.IQlËrüü çs¡rrfl¡ D@ .ffiGalûEfrÌ tt .CFüIFE ¡ræ¡rç* ¡r rrq.ffi

ñgtr¡rg rr¡*¡ t1*¡ç*¡ rffi ¡hrnrç Efmf

ûf

trü

'¿9-t

g!ATETEXI

llbr ¡¡trryl¡l ln tht¡ tÞmf'r htl not ¡ræi'rur\y

þüa ¡rraæted for rryr otbæ ilrgrcr f,a eag hlvrr¡lS ol,tlcr

hf 'lhû ar¡ålilrtr o8 by rryr etbrr pfioÃr

8!o thr¡!,¡ 1¡ Þ¡rc6 ea uert pelemrå bU &a

eraål(lrtr ræryt rþær l'niltortoô by tk rpprop*lrb

rllæuor¡ lr tb kr$r

ersrrå¡

Drt.n S H- Èr*"/^ t lqa,t .

åCKfrOIfI.EDOEMENTS

thc euthor ls doeply appreofatlvs of Ðr. B.g. Hetzclra

lnaplretlon and aávlee¡ and partloularly for his suggeettng ühc

laltlal ôlroctlon of tbf.e Fcsl¿rch. thc actebollc pork was

prrforncdl ln eollaboraülon ytth Dr. llet¡el¡ end he assiatcd ulÈh

the ellnlcal aspoets sf the eh¡oaatographlc uork.

Other uembcrü of tho [onorary Steff, of the eueen Ellzabeth

ItosBltal and thc Soyar Á,d¡la1ûr Hospltal gavc access to patfanüa

Endcr thclr €ãrtr I)r. Brya¡t Hudsoa¡ Dleb¡tte aad üctabolte Unlt¡

ÀIfroil Hospltal¡ Mrlboürrlt¡ and Professotr 0.H. Hllson¡ Dcpartucat

of PharaacoLogy and lhorapcutf.os¡ Unl,varslty of Sheffleld¡ U.E.¡

provldad furÈhcr plasne såmples frou patlents wfth thyrotoxlcosLsr

Aaknovledgcnçnt 1e duo to Mr. B.F. Good and Mtse !1.L. Isaeohaen

for thr ostlaatlone of pleena protein-boulrd lodlns. I an also

gratcful for thc tcehnlaal. a,sElstanco rGrdercd by ühe Junlor Staff of

fhc Dçpartosnt of lfedlelner Q.E,H.t 6nd psrtlcularly to þllçs P.

Devls for her cxpert and patlcnt aset ste¡rce uith the chronatograBhy.

lbc phoùography yae unüertaksn by !dr. l. Nolan¡ Dcpartnent, of

Hcdlalncr Roycl, Adelelde llosptÈa1. the Steff of the Ðivlsloa of,

Irfathcnatiael Statlstics¡ c.s. r. R.o", Ailelaide, perforøed thc

stattsttcal analyoca. 0ta¡o-Allonhrr¡re (Aust.) ?ty. Ltd. donatsd

gonerouE samplcs of varlous fodoenlno-acLde.

fhls work tdag oanateel ouÈ durtng Èhe c¿rnôtdetats tenure es a

fiú'l-ùtee Medleal Rcscarch Fellov wtth the Hati'rnal Hcalth and

lfodloal Rcsearcb Councll of Australla.

rtf*tr+{Ê*

c¡¡¡PrEB

-

TI

IIX

7.

Obco¡rEtl.on on the l{¡tebollo Eff,rota ofEhyrotrophlo Horoonc a¡rd In^activateilßþrotropbl,o ltsrnoÞô lL !lan.

A oomparlson of tho Barly MctehüoBf,focts of tl¡ynoglobulln¡ D¡¡looetrd8þroldr Ílr¡rrorl"n¡ aad Erltodothyronin.ln Han.

4. Suaaer¡r.

IY THTROIROP}IIC HOEI{OIE I

SI,'BJECTË.

OTBIÃ OF COTSEHTE

PBBFACE

ggËAET.

OE$EBAI¡ INfBoD{¡gfloil

Lr lfha Ch¡mlstr1r of thc 8þrrold Hornonc ¡Its Hlato¡t oal Ðcvclopannt.

2. lhe early HctaÞolfe Eff.sts ofll$rrotrolrhLo Hortsohor

2.

I

1

17

4

6

20

63

65

82

108

109

B.

-a-

ElË,Iûa.EgËAru

T ¡

avt

146

165

165

171

17t

17F

178

UI

f.¡2.

I.

l¡tu¡ê¿etlonolbr Frbtslllo btr lLrryrd ,.4 th¡ IÅ8þt

ct ghrosåto¡rcpbfo SldllnSÐr!!¡o Irtættflûrttffi ef D¡Î 1¡ tbc PI¡e¡

1l Elr¡*ns. to E$o!'d Stfueulr$.oa.

Îb ürdaalsa of tha Drl¡c¡l ol &[1.

fu gl5nt:ß¡Gaæ. of tÞt EcL¡¡r¡ of &!1¡ îhf¡old Ëtlrul¡tÉ"oa.

ETESgEåffi.

¿1.

Þ.

PNETACB

-thc rorh to be roportcd f'n thf's thrsl's eonerrna tb¡

ohcnÍael end pbyelologloal natu¡c of the thyrofd hornon

ol¡eulatlag ln thc blood ln nan. It utll bo dlvldcd lnto tro

broad elprotÐo

Onr eepcot Lnvolvca a ohrmLcal approech by thr drvclo¡not

antl epplloatLon of s pap6r ol¡ronetogra¡rhLo tcohn1.que to thr

otudy of thc blood orgenl,e lodLno oontont !'n yaaioua ¡tstca of

bcelth and èt ¡¡eor. Shc oh¡onatograpÞl,o pattern of th¡ hsmonr

ïat stuô1¡d Ln ranclon plesna renplca takrn f,ron normal ead

hypertþroÍd eubJcot¡. lh¡ cffcot¡ of tþrotrophle hormoaa oa

thc ¡rattcrn fn both gtoupt yrro lnvtotlgatcd.

lhr o¡oond er¡rcot le a pþr!.olegloal one. It eonaÍrtr of

e etucly of thc urteÞol:Lo ¡ff¡eta of, ednl,nletcrl,ng thyrold

horsoncs to uan, and tbc oon¡nrlron of thoar cffcots yf,tb thoer

Brotluocd by tbe sct!¡Lnlctratlon of tþrotrophlo hornons.

Althougb other studl¡s on ths obronatographlo pettern of

tbc ¡llaena hornonc ln no¡naL and trypcrthyrolô huuan cubJootr

hÂvo appcered¡ f.t 1e bollcvcel that the q¡¡rr.nt onc 1¡ norr

oouprcbrnelv¡ and, rnploya roll,abJ.e toobnLqu¡a tht'oh w¡¡r

thorough\r tcetcd. Þcf,orc dcduotlona urr. drårn. Dtrthrmo¡r

tho rcgurt¡ rrr rtl.yant to thc ou¡rcnt unocrtqlnty about tlc

-L

ohrnf,cal natu¡¡o of th¡ tt¡yroldal c¡s8ctlon¡ enð, 1B Partlculer,

rcfutr rccent olatnc that ôlledot¡rroel'n¡ fo¡'n a algnlfloeat

notrty of thc nornsL cf'roulatlng horilon .

In thc eondltlea of lry¡lorthyroidi,s a ¡rrcvlous stufly haa

roportcd that tho i,oêot¡rroalnrs ¡¡o prescnt !n the plaeoa¡

but lt Le bcl!.ovcei ttrc prcscnt rtudg doetu¡at. thl! flnttlng

norc 4ourcþ¡ aa ¡rarallcl, ehenloal aåd radloestlvc aù¡üLr¡

wcrc partoruecl in ¡ratbntc tr.atcd wLth radfoloatf.ar therapyt

aad ln oûdftlonr tt¡¡ plarne Þttt.¡u' 1¡l a lergr grou¡r of

untrcat¡il hypcrthyrold subJcotc Yal a*¡¡rln.d vlth clqlJ¡¡

rcsuf.tg.

Íbc roport on thc oÈ¡cnr¡tLoa¡ of thc .ally nctrbolle

cffoot of th¡rrotrophto hornoac cnd of vBrlous tb¡rrolil horsout¡

couelatg of, orlglnal rorts antl tbe ¡r.sultf Gonfl¡n tbr [ypotbcilt

aelva¡¡o¡cl by lh. 8,8¡ tctcol tbst thr tþroi.cl gland du¡ltrg

ttryrotrophle hornono stlnulua ¡.erotca s raplellg eotlag hotaoal

dlEtlnet fron lcæra th¡rrold hornontEr

lho sü¡dy of, th¡ ¡ff¡ots ol thgrotrophlo homonca ea thc

chronatographle pattæn of the tb¡rrsf.ô hornon. rovoal.d ¡

hl,thorto unrcportrd f,Lndlng; aaneþ tbst unilc¡ Eueh atlsulu¡

the th¡rrol,d gl'a,ud r¡basoa algnlff,oant asoust¡ of dlfedotyrollno

Lnto tbc plaane. thl.a rt¡rcstate a dcparturo fron vhet ttknorn ol thc nornal thyrold hornonc cynthcal¡ gnô rcllaar, and

-v

tt |s thought the phenogcnon nay be an inportant step !n a¡t

adaptlon within the th¡rrolrt gland to conditloas csuÊing ltg

aatlvation euch eo Ì¡rperthyroldiam and cnotionsl\r stressfuL

sltuatlons.

-4-

stmBl

1o å hiotory of th6 ohcntatr¡r of, the thyrotd hornoncc

lntsoduoce tho thc¡l¡. I{ctabolls obssffstlone by

Betz¡l and ooLlaboratore arc tbra dcao¡ibcd encl thcl.r

eoaoluelon¡ ¡tatod¡- thet tbyrotrophLo hornonc poaalbþ

cauaca thc rolcE¡¡ of, a rapidþ eoti,ng bornouc fron thr

tlqrroldr ôlctiaat fron trll,oclotþronLnor

2c A oh¡on¡tograBhl,o study ol the thyroltl horuom¡ dqnsn-

stretcd only üryrorln¡ aud asell a¡o¡¡nt¡ of H.lodotþ-

ronLnc ln nomal ¡llaana. Iherc ucrG lnerce¡cd anount¡

of, both ln hypertþrol,dlen, and the Íodotyroatntg e.I¡o

u.a. foundruf,th botb ehccloa)' snd redloeoti.v¡ ncthodorln

Wß ot, ¡ueh ssooa, uhcthtr u¡trcatsd or trcatcd l¡wo to

flvc daya prevlous¡ü wlth lrII.

l. lhr nctabollo pottulatc of äctsrl ct al. uea era$lncd,

oenfLraod, and ¡xt¡atl¡tl to shoy that thc carþ sctabolLo

eff,oot of tb¡rrotrophlo hornono 1a not roproclueod by

adnlnf-etôrl'ng an¡r of, thc knor¡n t[yrold hornoaot.

4. In aorual subJcota tlr¡rrotro9hto horsone adnlnlstratlon

preduoor ên laoraa¡¡ tn pl,asua bltrocloth¡rronlar coneoa-

tratl.onn end a rll¡sso sf êoflnfta aeounto of loclot¡rroa-

Ln¡s f,rsn thc gland. In þpcrtþrof.d cuÈJcot¡ thoec

lncrcas¡g vare leas ta enount end noro tranrltory.

v

5. Isor¡s¡c ln plarna totel r5\ and prot ln Þor¡nð It\

ooås.t¡tr¡tlonc ln h¡rpcrtbyrotd ærÞJrots u.l't fou¡d

tollovf,n6 tþroEophle he¡toaor A¡¡ iaorc¿¡r ln unlagly

oxorotton of l31I *". obr¡rv¡dr pr.tunåbþ ilur to thc

,[ nrt¡þollan of cs luoro¡¡¡ ln thr plnrnr ioiloQrrerlre'i¡

ooEteatr

6. 8b1¡ lcdotyaoslnr r¡l¡sæ fron e ¡tlnulatrd tt¡yrsLil gtranl

uea theugbt to bo poselbly rluo to r rooudLtloncê drtlel'eaty'

of th¡rrcld¡l todotyroalnr dr¡hilograaror

thr eign!,floaae¡ of th¡ pbonouraøa 1¡ dl.ser¡rrld La rcl¡tlo¡

to e poaalb1llty that lt dcBlrtra the sttnulat¡il 6l,and of

locll.atr caurlng th*rby an lnsrce¡ctt forsetf.on of ¡lthæ HSde-

tþronlar or anotbc¡ rclatlyclg ùralodlnstod hornon¡ vftb aa

ôycn Eorc repid ¡f,f,cot en n¡taÞslle ratc.

-6a

GEgËBAI, IgîBOÐUCîIO¡

I.

ETE!qE4E.

In I9L9¡ ËcndleL1 rcport.d tbat eftot fivc yosr! of labou¡

he haô succ..dGd Ln Lsolatlng 779. oî e eryatalllnr ¡ub¡tanol,

nt\rrorin+ tr, fron ! tone of bog tþrol-ct gle^aal (fcnaall, ¡.91h).

0n analyotng thl,o eubstancr¡ br found that lt oont¿1scd,65fl

loôl,nc¡ ead fron the rcsults ol fi¡¡thsr eaalytleel toats, hr

dlolded that |ttlqrroraai ya¡ a trlÞyilro-trlloctE..ev-1nd.ol¡

proprlonlo ¡ofd. õlfþrnoxlntr trg¡ retcr ehoun to Þr at lcest o¡r

of thr noat lnportant aubstÊneos thFough uhleh thc th¡rrold glaatl

rxætcd tt¡ eoatrol ovor nataboLtc ¡ata (rcnorlL, lgrgb).

Ia L925¡ trrtagûoa attæpt¡d to r¡rnthorle¡ thí¡ ¡uÞ¡tepor

rhl,ob raa EoH eellocl th¡rrortar¡ fron a oon¡Ldcratlon of shst b

thougbt ahoultl ùo lto etn¡etural :fomuln, but thr eubrte¿o.

prod,ucod Ìraô no phyrlologlcal. eotlvisr. äarlngûon thrrrfsr¡

ect sbout rvoLvlng a net. cfSl.ctent proocdurs for laoletl'ng

Iargc anot¡nt¡ of, tSrroxlac fren the gLand, ao that lt oould þ¡

ehemleal\r eharaotcrls¡d. tc ro¡llaold thc 5* faOn \ytlrcþsltsrthod of Ecada.l.I, ul.tb a ellluta na(OX), grdrol¡ralr. Bueh ¿

fryùolyaia waa rueeeesfuJ.l¡r uard by Osvald (fæg) to rrtr¡et

df.J.odotyroslns fros varlou¡ Lodo-prottlaor oth¡r then thoso ot

thc thyrol,d glaad. $ubs¡qur¡t and atrn¡lv¡ tr¡et¡e*t of thr

-7-

bar¡rta hgùrso\yartc yloldrd a erystalltn¡ euhet.Ber¡ ublob Êft r

pnrlf,lcatlen gavc 61f rca'g¡c, aaå bail th. øglstocl Íornrl'e

Cr5HffO*XI+ (Uerfngþnr 1926s). ßhc yl¡Id uaa tucnty-llvr tlnl¡

thet obÞtaod by Eenitsll (fgfg).

thr arst atca by Haringtoa (fOaeu) waa ta ¡¡tsbtlsh tht

cheoleal eatt ctr"uctural fsrnu]'a of thc dc-LodÍnntcd fo¡¡ sf

tbyrerf.nä, vhloh he found to þr þ(4f-lïydrery phcnsry) phruyt

o(-sutno proprlonlc ¿d,ú. lDht.¡ aubatanoo r¡c thrn o¡mtlrerl.trd

and nancd tþroaLro (Uartngbn, 1926b). Ihc orlrntetÍcn of &¡

lodt.ne ¿toes ef tbc t¡tr¡-lodlnetril drrivctfvc vaa aext l¡teb-

li¡hcd and thr fornule of tlryro¡l¡r cag tl¡us f,ound to br

7t5¡7tr5r trlreLoilotþroü.rr. 8bf¡ us¡ lato¡ oonflr¡,¡d ÈE lt!

synthralc (Herfngton and Bergæ¡ f92?).

It hsal bcrn show¡ by Dsuaenn (f8gø) that thc thyrold glênal

eontgfard a protrlnr llodotþrlnü¡ latrr oalled th¡rrogJ.ohlllnt

vhfob had thc plry¡Lologtosl pro¡rortlc¡ of lnoros¡lng thc ¡rhbo1llo

ratr and r¡¡lnar¡r attæegoü. orqr¡tloa aad al¡o of au¡tng cealr ot

GuJ.lla di¡ce¡o or ayrordtnr. Dotb th¡ or^ifetalltnc eubetaaoa

LeolEtrd f¡cn thc gleaal br Earr.Egton a¡d thr lynthotlo thyre¡lm

(tU) vorc fsr¡nd to ¡neer¡e a alÉ¿l"ar BÞ¡lelegle eotLvfsl.

Ilarfngtonl¡ acxt rtc¡l vrr alnstl to acsou¡t for tho d1aær¡n

Êney brtloea the tot¡l lodl'sc ooatcnt ol tbs glåaal antl thl r,uo¡st

of lstllnc r.oovcrcd f,ron tbo tþro:d.¡rr LedL¡¡r DlloôeQrro¡la¡

-8.

(Uft) hsal alr.cady blrn Lsolated tove¡d¡ thr ¡nd ol th. ai.n¡-

tornth ocnürrlr¡ fron ooral. aud alao f,loc artlf,lolaltry ledlr¡tad

protolus (Oaueld, 1909). OareJ.cl hed not euoo¡¡drct f.n lco¡stlEg

1t flo¡t tht t$rrold, hou.Y.r.. DII va¡ bløIogloell¡r lnaotlvrt

but }lartagÛon oon¡lel¡r¡ù lt uar probaÞþ c Dr.€ur8or ln thr

blooynthr¡l,r of t4 Alrd Efght Ecosu¡t f,or thc loctlar dlaorlpaaor¡r

ln thr glead. By s uoilllloatlon of thc ¡xtragtLon ¡¡roordurr

for Ea (usrfngton and Raailqlrr LgZg) lt r¡a,s ¡roaolblo to iaelstr

la orTetalLln¡ fern both å[8 antl În. Xt war eelculatrd thnt¡

aftc¡ nabJ.ng edJuetnrntg for dcootspotl,tlon of thr tro cnd proôuotr

durtng rxtraotl,on, end fsr l-oes of laorgnnl,c lodlao tlrrovgtr 1¡¡

adaorptlotr oa to prcelpLtatlc, tb¡ tro oon¡nundo eeaount b¡tv¡rn

tb¡u f,or tlrc tbolc of thr 1oülp vlthl'n thc glanê (Uartngtont

rgrrr.Subequcnt trork b8Ë lrov¡d thi¡ ruBpooftlos to bc lnco¡trot"

81Bk anð DlaE (fg*g) usf'ng th¡ t¡ohn1qur of papor oh¡ooeto¡tr¡Þhgr

afft thr radloeotlvc leotop. IIII, dcnonct¡ratcd tbc proaonot of

aoaolodotyroclar (Xff) ln beryte þdro\rtatts of ret t$rroldrr

Bre¡¡ and tr¡blond (fgl¡srU) roportcd thc prracno. of twe

ullåoua lotllnat.d oonpound¡ la both thc tþrold and tb¡ slrì¡n of

ratc ¡¡r¡vlor¡¡ly lnJ¡otrd ul.th IIII. Subaoqurntl¡r oar ef th¡s¡

eonpotrads vaa found al¡o is th¡ pLaene of patlrut¡ ¡ho hed blrn

trratod vlth thrrapoutlo ôo¡re of I5x¡ (oreas sad Pltt-Rlvæt¡

-9¡

195I). thla conpound rag ¡.etcr ldætlft'od a8 Ssit !l-l¡tlei[e-

tþrronlar (orocE and ELtt-Rtvrra¡ L*52). f,¡¡,whl.lo Roeh¡

!t BI. (fgSear¡) had ayathrai.¡¡d trllotlotlr¡rronlnr (tr) aaO

igolated lt l.n enal-l quantltlcs fr"on tha tlryrold g;Laaèr

In ¡r¡n¡sryr lt ba¡ boen sata,ÞIlahcú thet !a adtlfttoa to

lnorganío lodldrr thc tb¡rroglobt¡Utr of tho thyrold els¡ad

sonta:lne tþroxLno¡ trllodothyroalao; dlloðot¡rroalro aad

nonsloclot¡rrocLnc. À rccrnt r.port by PLtt-Rtv¡ra å8d Ba"L¡

(fge¿) gfvce the r¡latlvo prrecntagrs of tbr total thyrol,dal

lodlnc tn thc rat a¡ folloua ¡ lodldr, tfff uISr æ*¡ DItr a6ßt

84, I8S and Íy Vf. Ehlr ropoltr lncldoatally¡ le thr f!.rct f.n

whl,Eh e¡r estfuEate of tha f, eontoat of tho gland 1g nadtr

Untll f959 at Lcact¡ thcrc ïs8 mr¡oh oeufulfo¡ about tb¡

natr¡rc of thr forp La rhLoh tbc tþrold hornon. olrsuletcð.

It ve¡ tbought ltkoly thst lt va¡ oltb¡r thUroglobulLn or I

prptl.th derivcd fron t\yroglobullnr poeelbly oontataLßg DII e¡

urll aa 8a (garfnsto ns Ig77¡ f 94¡+) ' îh¡rrorf.no lt¡rtf wag not

f,avour¡d ae thc olrouLating foro bcoøugc of thc dolay whl.oh

clap:co after lte ad¡Elnlotratloar brfor lt¡ nctabollo rffist

Ls dæou¡t¡aÞlo. l\¡rth¡¡uoro thc horuono ta thc þlosd r*e¡ not

dla\yaabl,r, ffrd Lt vac tboqbt th,la proporry sould br con¡tstæt

ulth l,t brlng tþro6loh¡tfe or I prptldcr ratbcr tben 84.

lFrvsrrou (fgfg) ahourd, howcycr, tbat thr rndoglaour

-:L0Þ

tþroLù hornouc la thr blood behevrd Ln the atåro sa¡¡ touarûe

protrta pr3cl,¡¡ltaats, ðXe\yclr ènd .tùa,Eol lrtraotlou cs dld

8+. I¡ræ¡ (fmO) sborcd fusthersore¡ nith lsnunolegt@'l

trohniqura¡ {ftat 1t uag cxtrorcJ,¡r unlLkely tb¡t tbyrosloÞt¡l{t

rec rll.re¿¡d lnto th¡ elrci¡lstfoÊ .t(ÐPt tâ th¡ tàJ¡rotiT vsln

blooel t¡rd thea oaþ aftet nåau¡l traune to thâ glaad at oplra-

tio¡¡.

tJ.thotr6b itrarj.agton sqE partfy rt¡ponslbl'o f,or tbc vlr tbrt

thc t¡ue hornon ne¡r br ¡lepttôc eontel'nf.ng E4r ho r¡vl¡.al thLr

(gårfn$oa, I9,$4) Í¡ th¡ lfgbt ot thc¡¡ eh.nÍ.osl a¡rl L¡mraolog:

lca.l ftndln6er a*d al.¡s f,¡e¡s thc f,cct that thyreglobaU¡ ls

celerf,gonf.eiLl$ Êotl.vr wb¡n glvon by noutb to th¡ ath¡rrotio

anLmalr la whloh lts lntçetl.na} brsakato$B to Sa ¡uil oth.r

oonat5,tutnt¡ augt b¡vo talcrn ¡rl*crr Hr also polrtcd out tbatt

ch¡a coupared wlth tbr p$ralo3.ogloel aotlritl¡c of, otb¡r borsoat¡

suoh ee th¡ ¡ox hornor¡os aad tb¡ antsrlor pl.tultary hornoncsr thr

rtoll' knowa drlay Ln nrtebollo rtsgon¡o to aclnlnlctond f4 *

longrr sccm¡d unaoecpt*þb.

llaurog and Chstkoff (fg*e) produead cvcr! Ëore eonvlaolng

rvldrne¡ thst t\T?ori.ne ltaclf yes at lcaet thr prodonlna¡t

he¡nono 1n thc bJ"oêdr thry uoro thc flret¡ alocg vf'th tln¡End ltal¡ (rg*e)r Þ app\r thr lsotop. l'tr¡ to e study of try¿.ofå

¡lþaLele&r aåd cåønlstr¡r. l3e¡Eog r¡¡d ghrl,Eeff shorcil thst tht

-!l+

cndogü¡ou":.y llr¡-labolLcd horuon¡ bchnvcð ln th¡ ssn. $qlr

tora¡da p¡otel¿ preol¡¡trtatlo& aad org¿alo golvc¡ts. Shcy

el¡o eluold.¡trd tha rÉton ubÜr thr borton¡ nas not ûlaþcablrt

by ôrnonstratlnß tbât 1* t r transportcd bor¡¡d to vsrloul pl'earn

protcl'Btr

Souc ttec btfop thta, Coscetrr¡ et aI. (fg++) had dlvrtopcd

tho t ehntqur of paBer ohrouatogrepþ. Iaf,dler (fglg) ra¡ th¡

first to apply tl¡fs t¡ohnlqut l.n thc tåyroiil flclil. t¡ atlnl,l¡

letrpd ao uc. dsac6 uf lll¡ to rate, ¡t uhf'cb tloc¡¡ bf.rtologr./

rcvcalrtl no daoage ts tho tlr¡rrold gÈqnds. Oa abronatogreBhlag

buta&ol rxt¡aotg sf tho soruûf E* end lnorgrnla lodl'dc tt.lc th.

enJ¡r componrntc d,¡t¡stød,. [anrog snd Cbaihoff (fg+g) ooaf,lruld

thosr flndiago lu rats a fcw noaths lat¡tr. Ilr eddltlen to t*

and lnorganlc lodl'dc¡ thry fouad trao¡s of DI! þut sonel,d¡¡o¡l

thle rosultcð frop a brcakdovn ol lBn f.a thr Þut¡no1 rxtreet.

they illrl not croLudr thr poasf.bÍlJ.W thåt 14 *"V of,rqrlat. a¡ a

pcpÈldr of nnall noboular et16bt. Qsnff.¡rs¡tl'on of thl¡ oouorpt¡

that 84 ss¡ th¡ Eal.n horoonc¡ th¡n eaoc lroa stuêlcs 1n tho ht¡¡¡n

by Rall (fg¡o) and Rorrnbrrg (fg¡f),

Íhr ncrt atrp forvard uae an luportant oar¡ thc dl¡oovaty

ol, 7¡5r!r trllodotlgrroalal as a neü¡ral\r ooouulng hornoaor

g¡o¡a aad l¡blond (fg¡fart) r.pert.d that lE glacna fron aqtnal¡r

an ledlsc-oontalalng oomBouad, othu thsn E* and lnar6anf.o lodf.¡t¡

-f.Þ

us. for¡sd. thc¡r ðld sot aucor¡d Ln ldratLf¡rlng thL¡ ænpoundt

houcycr¡ Ore¡s ead Fltt-Bfvtra (fg¡f) found tro unldrntlftcl

fraoü.on¡ ln hmn pl,arna ln botb outþroldl¡a aaù t¡yportÞyroldr

laÀ. 0¡r of thr¡c a¡rpcarcd ldætÍoal vtth thnt founcl by Orom

Ead lrblsud (fg¡fort), thc fotl.ewlng ycar Grole ¡nd Pttt

Rivrrg (fg¡Z) 1d¡nt!!1¡ù thlô oonpound ¡¡ 5r5rtr trllodettryrroalan

and latrr (eroea aart FLtt Rlvorc, 19553) cffcot¡d lts l¡olatlonfron thc thyro1ô €Èaud. Hsapïhll¡ Soohs rt rL (fg¡ear¡)

shouod that !, uaa prco¡at ln thc tþroitl gtanrt ol rate follw-

lng adutnl¡tratl,oa of ¡51¡. subrcqucnt uorL h¡ ;hoyn tbat t,la ¡rroecnt þoth tn thr th¡rrolcl aad thc oi.reulatlon, but laenot¡ata vrry nuob lcoe than 1*. PXEat (fSlZ) Ìu¡ found ða

avcra€e osatcat of O.Lç1nSr prf srnt for I, U .crl¡u fros 22

cutþrolil aubJtotao

lhr poraibfalQr that tbc appcaraac. of !,1n thc aorun lta r¡ault of radlatlon dcnago to tbc glq¡d ra¡ ¡ubcoqucatþ

ruf.cd out. D¡n¡la and Dobyar (tgzÐ fo¡¡¡d n, b L9 ot¡t aî ,1patlonte¡ trretrd tor þ¡lortþrotdlao uttb t5lrr la enouste yhl,oh

auggratcdl ¡ rrlatfo¿ to thr dtrgrrc of þprrthyrotrdtca a¡d not to

thr cffeet of, rediatf.on. rn addlti,on thry fornd Hr! la l¡l ead

Drr ln 6 ¡ntÍcnts but eonctdorcd tbc pr¡¡.noa of Dr? to Þt dr¡r

to rsdlatlon dlongr. rn anothæ sù¡(7 õ.ùodotþronln¡ ¡re¡

nst¡d ln thr ccrue e¡ aooß er on. hour eftcr thcraprutle dosc¡

.lh

of lIlI, asè 1tc oonolntntloa ln tho a.¡'ug clld net lsor¡e¡o

uarktclþ th¡raftcr sa nould hsvc Þccn tho oe¡¡ lf lt¡ Pr'a'ûo'

v¡as ôuc to radlatlon dsmgr (B¡nua of rl'. ¡ t#5).

Uatil thls tlÉo¡ tsost rorkcra hnd onploycd butgnol r¡trao-

tlon pr€otatur.s, and eteo 1ãlI e¡ the srthod for drt¡otlag th¡

Lodlnatcd freotl.oas' Horlvfl, |n I955r s qcthoal obvlatlag thr

n.ccss!.t¡f fer uetng raelloaotlrrltg ¡rsa dnrcl.opeð. thl¡ wa¡

nadr poselblc by tho acleptlon of tbå oatal¡ttl.o c.¡lo rul¡lhatr-

arsrnlous aold r.agcat of Seltboff aad Sa¡ndrII (¡g¡+) dtrcotl¡r

on to tb¡ ct¡ronatographle filtsr pepor (Eoraen ct al.r X955).

Ufth tbl¡ pothod lisoiLaga¡r ct 8,lr (fg¡f ) fouud 8, la tbc ¡rlacna

of el'l ea"scs of lryprrthyroldl¡n atudLrdr antl lu n.ar:Ly el.l tb¡

outþrofd aubtcote. th¡y fatlod to d¡tost lllll or DI a

cf.the¡ goupr

l$rcrc h¡r¡ boou othor sà¡ôl.o¡ uhleh bve l.*rgrly oonûl¡a.ê

tho ooncr¡rt tbet tbr no¡'p¡I olrsulatlng for¡ of the thyrolê

hor¡¡on¡ h tl ulth trasc¡ of, l¡r but not liIE or DIt¡ (üyaovttl

entt Aroa¡, 1917, ûlnttrtcdou ct al.r 1960¡ Blrd end Farlrat

1960¡ Eose rt al,, 1960¡ Yenettt end Boreudr 1950¡ Pltt-

Bl'vcre strd Aal.tr l96t). In acldt'tlon, Rooho rt al¡ (f9lg)

oon¡ld¡r that thc hcvcrarË fo¡n of |!1r 7t7r5l Fllodottryronlm

and e]-so 5 ¡1| tttledothyro¡ltr. aa. nomal constl,tuæts of th¡

olrcuJ'atlng tlryroLd hornoan, at lragt fn th¡ rat,

-1¡Þ

In the osnctlùlor of þpætlryrolûiau¡ n'lny t¡o¡Ior¡ hsd

found thst agala f* and f, wtra tbl only orgenfc lotlln¡ oon-

ponnds tn tho blood (mnglrafnc rt aI.¡ 1955¡ Bü¡r¡8 an<l Dobynrt

Lgrr, Bcnu¿ of ¿1. t Lgrrl Haclagen ct ¡1., LgSTl årou¡ end

tfyeiovit¡r 1959)' Iaorcasas ln both t, aad EO ucæ rc¡rortrd¡

though tb¡ lnorcaso l,n Í, raa urueL\r tsoro st¡1&1n9. I{oroYltt

Fanan ct sl. (fff) havr rcportcd¡ ln addltton, doflaltr

ovldcnoc of elroulatlng !,odetgrroslncs {n h¡rportþrold oubJcete

foLl,ouLng therapcutls doã¡s of llll. g¡i,ns pua.¡.y chonloal

nrthoü¡ fn untrcatcd hyperth¡rrotd rubJcots¡ DII ua¡ sttll

drt¡ateblc 1a a fcs Gasrs although yi.th nuoh grratæ dtfftoul$(Ut¡¿ snd Fatrcn¡ 1960).

Ehæo hsa rocrntly rl,ecn a oontnor.rsy oyctr ubrth¡r or not

MI8 aad DfE elrsu.latc ln algnl.fl,oaat anounte ln noru¡l bloodr

Blooh rt eJ'. (fg¡e) rvolvod e aathod f,or atud¡rlng thr eLroul"at-

ing hornear ulth aæi,-treo.t d,esû¡ ol lII¡ ln orrl¡r to atntal.sr

thc poaalbl[ty of racliatlon al¿n¡go to thc gl'and. Uith thl¡notheô they eonf,l¡n¡d thc oonoluel,oas fn ûbc lftrrahrrc, tbat

the organtc ledL¡e La prlnot¡latþ Ln tbr f,orn of îa ritbnrgrt6lblc guaatttlcs of the lodotrroalnre pmarnt. rhry nort

drvrroBrd a nrthod mptoyLng r4r (tns¿r and Brook¡ 1959) and.

ualng thfs nrtbod wLth á.n¡u frop ns¡nal. subJcots thcy fotrnd

Eafk.d df.ecropanol¡¡ bctw¡cn thr dlaH,butlon of organfo iodl,dr

-1ã-

ac n.å¡Bl¿rGd by 12?¡ or¿ lSlI r"tÌ¡o¿¡. It lrêc formd thet wltb

ttro 127¡ nothod, yhf,ch eoployod tho oorlo culphato rcactlcn,

tlærc vsrc rarge epoto eoæ.sBondlng to thr looetion of Mrts and

DriI oa tho ohromatoËreue, but rftb tt. l51t m¡thod no pceka y.r.

föund ia tho sorrespondlag anaa (vrrnrr and Broey, L95gl Bloo&

ct al. 1960). îhc author¡ auggrcted that the dlscnpansy l.duo to the oonparattvrþ clor ¡"ab¡J.tl,ng of th¡ lodotyroeLnoc

rcratl've to tb¡ lorletþrenln¡e wtthln the tlgrrold gJ.and.

Sl"nl,lEr fi.ndtngc havc brrn roBortrd by anothca gtoup,

Ualng a teohniquc of ðoubh leotoplo ð!'lut!.on (Wnttrhoael aad

Bralc, 1959) for tl¡o cstlmatl.on ef f* wrd todo$moei.¡r¡¡ la

no¡u¿l huean ¡,laane, Brele anet Hhftehrsû (fgeO) l'n e prcI;lnr¡a¡t

oe¡uaunioatlon, lravc ruportod loðot¡rrorlnr Levrl¡ f¡ thr plarus

approxfnate\r .quåI to thut of t4r

Seoc doubt ha¡ born cast oa thcse rrporte of largo snol¡uts

of d.routatlng lodot¡rlo¡l,nc¡ in nornsJ. plaanan pertLcularLy inrcsprot to thc fl'ret g3ouB of usrk¡rs who u¡¡ th¡ corlo auJ.pbeta

rcactlon to d,rtcot tbc Lodo-osepounds on tho oå¡onatograal.

thlcuraoll vae edelcd. to tho ¡llaew b¡for¡ cxEaotfos Ln thf.¡

work, to ulnfnl¡¡ the rl¡k sf rlcn¡ntal todlse foraatlon drrrün¡

the exÈrgctfono rt hag been domon¡tratcd thst th!.or¡¡aoll

oata\rcoe thr gcrf.o eurpbatr r¡ectt on, thus ¡xoduoing a¡ntr oE

thr st¡¡onatograor. lEhlou¡aol,l a.Lco bes thc eanr R, varuc at

-16-

ü{It la thr Ènrtanol aortl,o ael,d ¡olvrat eyatæ (fono tt rl.¡I960f ûLnl,H.eéou ot el.r 1960). &¡rth¡¡uor.r GD. r¡er,at

cùrdy in rtts¡ r¡¡lag a nctlrorl of l¡otopr rqul.lrtbrl.ru, npertr

v¡luoa tor thr lodo$ne¡L¿¡¡ of b¡Bera onJ¡r O and, # of {rb¡

total, þLooê todln¡ (fttt-etvrm aad R¡lI, 196I). SÞyse¡lÐ

aeeouæteil for æ$ of tho total lod,lnc enû !, let j.îfi.

In suunarg¡ i't nay br aeld tkat ¡t thr grcacat tl,nt¡ th.r.1¡ s coatrovrrry cûlo.ral'ng tb¡ rdatlvr prrorat¡g.r of th¡

varlou¡ con¡nnrnto conpllrlng thr no¡nsl, etrroul¡tLng hornoaor

Uh¡rcag noct corEcra you.ld rgt. that Ea tr Þ¡r fer thc nrJor

oon¡$,ttrult¡ tegoth¡r rttb ¡'uorl aoouate of lETt thara ara ¡oÐ

rho ¡el'ntetu thaû th¡ llr|[ a¡¡el Dr'l! b¡tnttn th¡n reesr¡nt for up

¡o ÚOfr of, thc total orGeato lodtno, and th¡t thr rcmelndr¡ l,r

E* wLth tho æctptlea of, t¡aoc aao¡¡nt¡ of ln. tb chrs¡¡to-

grapht'o flndln8s L¡ nonn¿l mÞJcot¡ Ln thc ¡rroernt otu{¡r rtr¡bl dloouat¡d lste¡ ln tbr llgbt of tht¡ eont¡rovoftfr

-1?-

2c.

8b¡rc wfll ror f,ol.lotr Ê brlrf rcvl¡w of !úortr aarrldl out

b¡r }lrtrcl flacl qoll,aÞo"ator8 oE th¡ mrJ'y Eütebolio cf,f¡etl ot

ùhyrotrcBhle boruca¡ (tex). Iu thla rcvlcrr 1t vl.Il br lsdlo-

at¡d rhorcln fu¡tlrçr roas{rn¡ fsr etud¡rlng thr naü¡ra of tha

clroulatlag horæon. ucro csteþIlsbûd,, paetleularlg uatl¡r eo¡ûl-

tf,on¡ ol tSrrold atÉ,nulatl,on auch as durt¡g BSH Èrrpi¡r!,ôtû'¡tloa.

It bes boæ ehomù thet thcrc E¡F bo ragt,il f,luotustloa¡ lnplaeor protr!.nrbor¡ad foillno loveL (fp¡) ia nan eoeonpea¡rlng

addt tloa¡ raptd nrtaboLl,s ohalrgEa Brrr€ rlcsarlbed 1n ¿¡cool,atlo¡

vfth ruoh otrc¡aful ¡!.tu¡tl.ons (X¿tzcl of at..¡ f9t6a). ñlr"tlsrÐor.r th¡ aheneoa, nblch oonsl¡ted of a rapld, incice¡o la nrä-boLllo ratc¡ a fal.l ln th¡ nepprotcln roaplrato¡y quotlrnt rnð

an lsorcas¡ 1å tbc urtaaa¡ total nltrogan, coðluæ and ¡ntne¡lu¡(Uut not Bhoaphato) exoratlon, r.r'c Lcaa lra¡Lcd 1¡ \¡rgotSrotd

aubtootr nal'ntal,notl vlth cl¡olooctrd th¡rrol.ð. ?b¡¡c n¡trbolLo

changre urr. thrr¡f,ore ooasf,d¡rrd to Èc et lcast Eart¡y tÈpeldat

ln orlghr laù eltbougÞ thcy ucr slnL.l¡¡ l.n pattem te tbo¡r

fotlovlng !, adntnírtratlon tbcy appaamrl Eor. qutokl¡r (Ërtrtl

¡t al.r I956b).

In en rnütavour to olueldotr eh¡thæ thrsc olrangrt utro

4t¡o to û\¡rrotit stt¡uLatlonr lt uac dcoldld to ûako a, atud¡r l¡¡

-18-

nrrn&l sr¡bfrots of tb. Él¡Jr ¡ot¡bollo .lfcots of l[ôH å8d te

€enpe¡e th¡re rffrcta vt th thoeo follwlne f, eilnl.nfatratú,oae

FollorLng lSH a a1¡1,1s8 ¡lattorn of changce to thßt oaountlg

durirg tt¡rscË wss feuad, and agala thfu pattcra asulit nst þt

rcproduord tV 8r' Ehe nctabollo ratr fnorcae¡ tolloulag l8t

war slðnlfloantþ grratrr than that folloulng ?r. lrr hewwerr

prodnod el6nlfloaat lnor¡¡¡e¡ ln thc lgrcle of plarna aail

nrtnary lnorganlo pborphnr.Í lrhl.eb r.r. not fouad follorf'n¡8g[. $hc rarþ not¡bsrlo Lrr."t of EBII waa argnifrcantþ lr¡¡Ln s group of þpctþro!,rt eubJootr on metatüåuec tlryrrold

th¡rrBy sad lt tca concludad thcrcfore that tha carl¡r nrt¡Þollo

dl¡ot of 18H t'er tþ¡rroldal. in ortgln¡ Þut dlffrrs fron that of8t. rt vag tÞousbt ¡nealbr,r that uador ES}I eti.nulatEoa, thrtlqFold produore e rapletþ aotf.ng tþrrold boruonr dletlaet *o¡!t þtarr a¡Ét Pl¡cota 1955¡ Hctarr rt ar., lgi8, l96oa).

rn e ob¡onabgrrphlc ctud¡r of thc prasna tþrrolô hoxuoarr,

lt raa of inttrl¡t to ¡rarslr alao for l.edo-oomÞou¡rd€ aBart f¡s¡tho¡r etrædy [norn, fn thr ught of the ebov¡ euggectlonl.

Ia addltlon to a etud¡r of thc hornor¡r¡ uad¡r noruel or rut$rroùil

oonditlauat tt war thought ðr¡lr¡bl. to coEpar. thtor f,lnillagr

clth thoeo ln gtetra of tftæoiet stLnu^trEtlon¡ eueh a¡ follorLng8sË adnrnicþatlonr and ln thc eorcü.tlon of untrcatrd hrpæ-

tþroldtan. rf cueh un&l,eeov¡r¡d rci¡tlc¡ rrJ"et, th¡ro lay br

-lO-

g!.sator opportunltlcs for thrtr dlsoovory unöar aueh eeadltlc¡¡o

At tho saÉ. tL6r¡ 1t var frlt that chro¡atogsaphtct aote,boJ.lo

enri otber d,ats ml-gbt bc eollc€t.o, nhlcb vould br r¡lovnnt þ

c¡¡rr¡nt thco¡lre oã thÊ actiologr of grpertlqrrotdlra.

-20-

SHAPIBN II

a

l. IxrBourcrlou

th¡ o¡¡rront q¡nocpt on thc ch¡al,oal nåù¡¡o of tbc olrcn¡lat-

ing thyrold ho¡r¡one¡ has been fully <tleouss¡d in chaptor r -ocnc¡gl rrtroduatl,oa.. rt nay be mlt¡ratrd, hsywar, that attha tlne of urltl,ng, thls Ls s csatroyerglal aubJcot. lhctcs¡onc Doo.nt etud¡r (lftt-nfvcre anrd ßdr r 196¡) ln rata, oonflm¡

ths ordcr vf.cu (lor¡¡oe ot arr, lgSo¡ relcllev, ¡g4g) thet

tþroxlar (e*) re tho naJor ooastltr¡rnt ol thr orgaalo blood

lotlfne, la eddf,tlsn to æ¡r1 anounts of trtlodotlryrroaf.ar3 tuo

tcparat. otudl¡s (rtoor ct er"r 196o, Eca.ì,¡ snal thltrhred,1960) havo roportott that la nors¿I, h¡¡¡¡an aubloetrr Eo&olodo-

t¡rnoalar (f¡f) end ùtodotyroalnr (Uf) aooouat b¡tr¡rrn thrn f,or

,O-rOß of thc total organla Lodlne of thr blood¡

th¡ oeot¡rD.nio. of lodo$rrorfnos Ln thr btooct Ìrsa b¡en nrlldocuannted tn co¡ta1n caaos of, c¡nradLo gc!.trou¡ qretlalau, inuhlch a grnrtleallJ drtorafnrrl Þlooh¡nloal drfrot ha¡ þcra

ruggretrd f,o¡ tho cêus€ of tho lry¡rotþrrofdle¡ aaä f,o¡ tbr¡l¡ar¡ of thc lodoerrorlnrE iuto thr btooü fron tbc gtraarl

-2a-

(Uoelrr, fgOO). tyo dif,frræt enayuatl.e ctrf¡ots h¡v¡ brta

dreartbcd¡ a drfoet f.n eouplfng of th¡ tedotryroaÍnoa to fo¡¡

lodothyronls¡a (steaUuæy rt eI.¡ 1955), and a il¡fioÍrn€Ur ln

drehaloglnatlon of ledetyresf.mc ln the tþrold 6land ard

porslblg tlrronghout tho þody (StanUu¡T ¡t sl.r 19561 Qu¡ri,do

ot al.r 1956),

In trypcrtSroldtæ¡ thr ¡arJ'lo¡ ¡tuêl¡e uclng la¡gr êosrr

of tll¡ hsvc glrcn r¡rl,¡bLc rl¡ultr (pcnua *nð Þb¡rar, ¡,95tt

IËnghilf.eo rt al.¡ f955). torr mcrntþ urlag sEr,IL dø¡r¡ otrt\ (rarren ct n]'.¡ 1959) and ch¡ul'eel ncthods (af¡o end l¡.rrtr¡196O¡ YrItþ and H¡t¡rl, t9Ét) tt A"¡ Þo¡n suggratrd tbnt

rodot¡rrooL$s drû¡tÀtr l& qrdt¡ Lar6r çsouat¡ 1n ¡o¡o hysor-

trry¡ord paticntr' Anothe¡r r¡omt eùrdy (trona and {¡rdovltl¡1959) hes fstrrd to 6lvc d.cflnltr ¡rtdtaco of todoerroetrnra f.¡th¡ blood of þpcrtþrold øubJ.Gtg.

rn vlo¡ of thr eoatroverrl¡l ftndtrrgc tn bo& ruthyrotil ead

Ìrypcrthvrold rubtcoto lt yes drcrdoô to rc-invrotlgato thc ptartb¡rrold þoer¡oncs Ln the¡c sonôlt!.oru rnpleytng paprr eÌ¡ro¡¡ste-

grapbto trchnlguoa vlth botb t4¡ "oo

r[I r"thoda of drtrstLon.

2O HEIEOE

-êaærlr thr acprraÈ1on¡ d¡trsttoa and, lËtontl,flo*tloa of thrtlryrol'd bornome cl¡er.ratlng lE th¡ blood¡ haa provrd a dlf,ftqrlt

-2Þ

pro€rdur. owing to thr rllatlvcly nlnuto anouat¡ of thcer

hornonoE ¡rcl¡c¡cd f.nto thc oLrculation. It hag bc¡n thrreforr

nco.Ëaer¡¡ to lntroduot sptclel t¡ohnlquro ln ord¡r te aehl.lv¡

thc clo¡1¡od ernaltlvllr. Ialdlev (fg+g) uas thl tlrst to u¡o

Iil1 fo ooqbla¿tlon ¡rl.th påprr clrronatogråphy. Sush octhoda

euploylng radioaotlvi$ ruffor tron ecrtatn dl¡advantagce.

llhero te tho rlck of, radletlon artrfaots bclng rrloa¡rd Lnto

tho bLood (rrnue and Doþnr, f955) or boing produord durl,ag

rxtraotfon a¡d otrronatograBþ (fftt-nfv.rs ar¡d Uolff¡ 1959).

fharc la alao thc cthlcal problcs of lntroduslag rarlloeotl'vLty

into hunan rubJrcta rh:n not really ncooarary, fn Eonc oêEo€o

thcr¡ le al.¡o a poaslbilf$ that diaorcpaaelos Bay ¡xl,et b¡tt*os¡

tho uee of LZ?t *¿ 15r¡ ln thr aseeasdent of organia lodLno

(tltrner anct Bloak, f959).

â ecnELtlv¡ obcnloal teehnl.qur for dctrotf.neL27t oompounèc

has aLrcad¡r Þccn devcloped by Bowdcn ct ¡f.. (fg¡¡)¡ fhls ncthodl

vhl,oh enploya thc ccrle sulphato ar¡enLoug aoLcl rceetLon of

KeLthoff ancl gandrll (fgf+), did not provc satlefaotor¡r ln tbl'¡

laboratory rbca conblnccl ul,th th¡ cle¡stca,l ncthoila of bute¡¡sl

r¡traotloa oulng to th¡ hlgh oontent of thc oth¡r aonporrndl¡ ln

thr errun ¡xtraEt uhloh lntertrrc ulth thc rcaatf.onr cLth.r W

lt¡ l¡rhf,bLtlon or lte oataþole.

-2>

Ànlea erOhan6r r¡¡lns bav¡ bcen euggratod e¡ ¡u1t¡cl for

freotloaettng th¡rrolê bornon¡r f¡sp thr bl,osd (¡"Sbar of elr¡

Lg57) ånd s netl¡od fo¡ ¡cun aad varloua tls¡uc¡ ha¡ reornt\r

bo¡n drvclo¡rcd by Oaltoa åÊd Pttt-Rlv¡¡s (fg¡g). I aodltles-

tlon of thle proOtdur¡ yrs d¡nrloprd anû usod 1E tTP ¡rlræt

etud¡r, and th¡ alSrsota of srr¡¡n ¡o obteincd uor¡ fo¡¡¡d to br

euf.ncntly ¡uLtcd for the rnployncnt of thc ocrlc rulpbetr rl.as-

tLon followf.ng pal'.r ohroaatographlc Elparetloa. It wa¡ for¡gd

aeotgsa¡y to otanclerdla¡ rf,gtdly on the osntlitlon¡ of th. crrlo

eulplratr stelatng prøorer in ordor to produe¡ eoaal¡tcnt rcsults.

Erpe¡fgglle.L¡ Bl-ooct ls oollcEttd fro¡n hunan rubJeeto undrr

loclln¡-f,ror eondttlons, hoparlalardr end thc pleona rlparatod.

If radloaotlvc nrthods of, d¡toctl-o¡r ar¡ brlng urld¡ blood L¡

co]-lretcd l-¡[ days f,ol-loulnß It\ arl,FLnt ctratLon ta t1y¡rerthyrotll

petlrnte snd t-5 da¿ra followlag Ln rutltyrold f.ndlvldue]'c"

PIaEna oanplos follavlng þoth thcrapcutle (ff¿ ne.) do¡ra and

Sollorlng seÉLtr¿oar (0.a5-O.6o no.) aoroe arc o¡t¡t€tld.

AIL rorgGnta årc pmparcil ln trl.plc illatilltd yet¡r (tn¡

ti¡l,rd dlctt llatlon b¡l,ng over XcOH) uhioh La thon ¡naacd through

a eolunn of PErnutft litooedltc EFË rosl,n. Acotatc buff¡rs of

pH 4.6 and 5.6 arc prtpsurcd frsn O.2 F eo¡tlc eold and 0.2 [

sodlus acctatc. Aeotlc aoidt of pË 1.4 la pnpared by dfluttng

glaotaÌ ao¡tlc aetct LtI (vtv) t¡ vEtcro

-2þ

Ertraetfon¡ Drrx A0 I t -2t 2OO-¡IOO neah ln tho ¿o¡tntr f,orn

-

l¡ ur¡d. A tl¡gy of thc bulr 3.sln (6.0 5r. for 6 !l¡ t.rtr)

ln aert¡t. buffol (Bg +.9) te propard atrd Pourrd l'ato e gl'aer

golr¡¡¡n øl 17.5 n. l¡trmsl d!.ecctr¡ amel su¡lportrd ùy an lodf¡r-

f,rco gla¡¡ vool Flug. Ebc aolunn of m¡tn f'a paeErd ulth

grnth pr.!lur. ulth alr, and {O sl. aortsùo bnffrr¡ pfl 4.6 1¡

peaord through thr oolun¡ s1th gentlc prcBrur. to rquJ,llbr¡to

the rrlf,a at pH 4.6.

Plas.u¡ Le thu ¡neard througb the oolr¡oa uelng cnough

prassuta te açhlrr. & flou of ebout 25 clrope e nlnut¡. lthc

p).acna pacaing tlrrough thr oolr¡na ia ooll¡oted and pacerd

tÌ¡¡ongh ageln e fr¡¡ther 5r? tlnts. Eho Dorr¡ rcsla dL¡soclatc¡

tho tþrroxlno-protrin ooaplrr end tbc !a antl rrlatod ooapouncl¡

en ad¡orÞ¡d on to th¡ neln¡ aost sf tho protcln peac.a

throngh. lßh¡ r¡nain1ng E.n¡¡ Brotrfn l'a uarh¡d off tbr oolr¡¡n

rlth !O-40 do aGGtBtt buftcr þX +.6) ¡¡¡tlt th¡ cluaat 1¡

Bnotrl,n-f,mo vhcn tcstcd wlth lalfe,yl-rul¡lhontre a€l.d. Aocteto

buffrr þn 1.6) (zyþ nt.) is then actd¡d to tho eoltrnn, aaô

csu..o a fr¡ah dlrclrargo of protcf.n (proU¡U¡y tþrogloÞut.l,a aad

othe.r tSrroprotttn¡). Ehc top of tho ooLusn i¡ ça¡b.d utth

tl¡rc¡ 2 wL. lots of O.2r# (vw) ae¡tls aol.d a¡d 5 ut. ot A.Zâf

ao¡tX,o soíd la ¡roaerd through tho eoh¡on to rcuoro soall.ug lon¡.

-2r-

tho 8* and ¡rlatrö oonpor¡ad¡ an ¡Iutcd frou th¡ oolrn¡

vf'th !0 nI. of aoetle aol.ð, pH 1,4¡ ðlaoardlng tÞe flrct { nl.

of th¡ ¡luant. lPhc ¡lusnt¡ aro rvrgorattd l'n y*suo ¡t lÞ5OoC.

anô, aft.r ê.rt¡ting to Dcnov. the l¿¡t traers of rcrtlo acfð,

the rc¡ådr¡r 1¡ dl,c¡olvrd Ln 4fp7el¡ of ncthemlt Goasa@anLlÐ

þdroxldr (s.6., o,9I) (99¡t, v¡v).

Pepæ Ch¡op¿tocapüy¡ [hl,s l¡ eerrlcd out Ia en reændlng

rssnar on llhgtnaa !lo. I Beprr uslng oonvr¡tl,oaal tcohniqueae

Âft¡r aa rqufÌ:lbratl.on porÍotl of tFoa a balf to oao hout,

cþronatogaBtv lc alloutd to püDoo.d for l¿[ lror¡ra et 18ot2oG.

Sing.Ir-dt.n¡acional eh¡onato6rapÌry Le u¡u,ally æploycd ln tho

so1v.6t¡¡ n-butaaol aaturatrd vlth 2H aertlc a€ú,al (futetof

acatlc) and pbutanol¡rthaüolr¿ry snaonl,un }¡rrlrorl.dr (¡nf )

(4¡e¡e). In additloa tut-eqyl-eleohoL ¡].lgËtly u¡d¡ruatnretrd

ul,th 2[ rmoni.rrø hydrorl.dr (e],earoa, f.955) end co1l!'dlao a¡hr-at¡d vlth Gore¡ annonü¡n lr¡rdrorldr (s.e.r o.91) (mnrog ct aL¡1950) aro e€6.tfnoa uaed.

t &Btoytng 151r r-

Å fcr of,. thc ca¡Lirr radloohronatograus rrla s¡ros¡ad, for r¡,ilo-aet1vc ¡leake by euttlag thr eÌ¡rouatogrena lnto 1 cn. vl,dr rElgr

and cetrntfng the redj.oåatLyltår of caoh strip for 20O-6OO ¡co¡.

Ln an EfCo n'r, asaul,ar t¡rpe acintl,llator eo¡¡ntrr tl,tt¡d wlth

a lo ql. capaolþ plaetlo oupo ltoet racltoeotir. GbsoeatogEaø,

-ú-

houlvlr¡ Br. Ê¡caasrû by eean¡¡ttÊg the papcr atrlB vlth a ltslrer

Chloego trAotigfaph II Ë paprr atrlp ¡oaaacrlr eacl a Íuollar Chloage

rBs¡ Dlov n eor¡stctr ool¡logtad to s retc n¡to¡-re€ordlt.

Eg¡¡g¡¿gÃ$r- Pa¡nro are flrrt ttrled t'a torord elr

rtraught at 8ûoC. the st*lnf.ng aothod of Bord.oa Et al. (f9g¡)

t a urod¡ oploylag ra6fd ctead¡¡råt¡¡tloa. Both thr o¡*f.o

oul'phatc and tho arsaalous eold rcagor¡t¡ a¡o frrshl¡r prrparld

on thr da¡r of atel,alng. th¡ trnpcrattrrc clurlng atalnlng 1r

Eoat¡ollcd st tg t eoC. Stal¡rl'ng ttnc Ls L2 ntr¡utcs f,or pa¡rær

propercd f.a DEA but for Èutslol ao¡tLa ohrouatograus, 1r lna¡¡¿ee{

to 15 nl,nutce to oon¡ronÊBtr fot th¡ ialrtbLtloB of tho oateþttro

procCe¡ by rcel,tlual ao¡tLo eol.d.

Af,t¡r ståJ.alng fa oenplotcd,, thc oatatytfe proccae lrstoppod end thc papcrs dried by hcatlng fer 90 ¡¡oa. ln a foroûl

draught at roOoc. ct¡ronetogrêBc sr. casosecd vleuarl¡ unilce

urtra-vlotct rågbt with p¡åk onlaeloa at ló60& and Brraanont

blur-prf.nt rcgord,e of ths oh¡ouatogrenr e¡e nad,¡ the sano da¡r,

vhcn rcqulred. lhis 1s {io¡¡¡ þ rxpoalag ragld Þluc-Erl¡t ÞBpor

to th¡ urtrapvlorct ught aourÊ¡ vl,tb thc pa¡rn clr¡onatogrq¡

lnterposed l¡ctrrcn tho trøo ead, adJaceat to thg ¡¡u¡-prl,at paprr.

Ithc t¡l.urlrt"nt pap@r is dcvoJ.oprd. by uasbl,ng in ôlluto Ëroa

¡olutlcn and ll,rrd, by war¡dng Ln wai¡or. l!Ì¡ç iodLne 6e¡!¡{n{¡grpota¡ shlch en hlghþ fl,uorg¡ernt, ¡lroducc intcas¡ þlu¡ rpote

agsl,nat ¡ rbf.tr baokground.

-zl-

Cllnfsrlr gubftot¡ f,ron th¡rc cl!.nf.eaJ" groups soro otuètrd¡

a nornal grìoup rrltl ,ut clLaleal rvlduer of th¡rreld dl¡leao¡ a

gæoup ulth thr dlagnosl¡ of aoa-tsxl,c goÍtrcr and s thlrat group

wlth thr ellegnost¡ of byprrtbylotrll¡n. thc tllagno¡f¡ var eoÊ-

f,fltrd ln eaoh oaæ þ thc u¡ual lavrstlgntloar lncludJ'ng plrrlr

ptot¡i¡g-bor¡æd f.odln¡ lcvrl¡ and thc u¡rtah of llll

7. gl8ewslol on ttü HEtHoß

I

lht¡ ve¡ a¡a¡¡¡ld ln thc forlcvlng nå$rîor r- plaa¡n raepbe

u.rc takra frsn byprrtlryrol.cl patl¡nt¡ 48 hor¡¡¡ fol.torlng th.ingeËtloa oú tbrrapcutlo do¡¡¡ of 1!lr, and oxtraetloa wa¡ eerrl¡d

sut 1¡ tÌ¡¡ u¡u¡l vay ufth 6 üI. of planna. Íbf total lSlI *o-tont ef thr plashg vaa ncgaurcd. îtl lfrr *otæt of thc preana

aftor lto pacaa8o throt'gh thc roaln pJ.ut tfra lãI¡ æntent ef t[raortatr buffir (4.6 sn¿ I.6) Enil thr Or 2j$ aoctts aç1d va¡h¡o

Etro c¡a¡ur¡d. lhr dlff¡rrnoo brtvccn th¡ total lllr "oo

thl¡ü.asüT.srut orpr¡rr.d a¡ a Bcrcrnteg¡ of thr totaL lllt 1l oo

c¡tln¡to ef, thc anou¡t ot rllt adrorbrd on to tt¡c rcrln (lrutr r,Gslus a). th prrornta6c of thc adsorbed ISII nl*t.d tn 50f

aortú.o acld rer th¡a noeru¡rd (coruna u). îhc overslt" poroortegt

rc@Y.üI¡ of thr tot¡I tllf 1n thc cluant or extrest r¡as cgleu¡.Êtrd

(cotrna o).

t nrau of 9o.ãxí of thr tot¡r lllr *", ad¡orÞ¡ü oa to ürc

-zgb

ÍÀDI¡ I

r51¡ rnolr pr¡sxr

Plasûa obtaLn¡d f¡oa lrypcrtþrolô paü,rntr ¡[g hot¡ro aft¡rthæaprutlc do¡r¡ of rl\.

TLol?8,99O.5[8Arg

66.956.4

80.?62.265rV

61.7

78.779.560.6

&.5BO.6

94.285.8

75.267.2

85.?85.36?.1

85.092.4

95.6g6.o

96.6

94.7

9I.891.289.8

((

((

16.2

l,?.O

llo6Il.6I2.O

13.{

I2

,

4

5

6

1

ovrral..l þSrrnRroovtry efI'II

fi og edaorÈrdlllr .lr.t.d

É"e. llrr¡d¡orbcel o¡to reeta

PDtA'#Pla¡ae

Gba

-2)'.^

rosla¡ 0f th!.e , s .nea.n of 7A.# $et olutcd ånd ?L.Lß ronaln ê

on thc DCgID¡ tf,f¡ lSlI renal,alng oa ths oohm¡r Hss Ê¡srrqcd to

br fnorganlo lodtdr, and lt wa¡ oatlnstod thet th¡cr plaora

eenpler sont*r,¡cd a lcan of L!.LS of th¡ totar rlrr *" lnorgenlo1'¡r. th*t ls¡ ffi.* of thr tot¡t praena t!\ r"" r¡tinst d to

bo organl" llrr. rho arså ovæarr lltr oorrtmt of thc r¡traetwae found to br Îf.'¡f¡ houavcr, fhLe rpr¡¡¡nt¡ a oaloulatrd

E.an rff,lolmqr of 77.2É in tho ¡xt¡actLon of the oeloulatral

organLo tltt uy tho proo.d¡¡loe

rn thcfr orf.glnal nethoct¡ Galton ånd pltt-Rlvcrs (r95%)

rceoenorrdccl a pH of 5.6 tot thc ac¡tatc buff¡r usrd for rgull-lbratlon of thc r¡ain s6f'na. rt yas found f.n thr prcernt study

that at thtc pt tho ¡rl,aana trnclcd to b¡oour grLatlnou¡ ln natr¡rt

and fmqurntþ saT¡s.d thc solr¡m to blosr. lhl¡ rltf,floulty sa¡

ovorooqc by ehanging tbo pä to 4.6. ghc ovcrall. rcoovcry of tho111¡ to thc oxtracts sae inprovod at tbl¡ plt. rn onc plaøne

neaprcr for rænplc, thcre wa8 åR ovorall raooycry of praenat9lt or 6g.8fi at a prl of j.6, a rcoover¡¡ ot rr.üfiat a pH of5.1 and 75.tf, at ¡rH 4.6. rn anothorr plaala, thr r.€oy.qy ya¡

61.6fi et ¡rDt 5.6 aad TO.4 at pH 4.6o

¡

th¡ uf¡Lntu eËount of !* epplt cd to thr pa¡nr anal ohroüåto-

graphrd ln tho BEA oyetrn, ¡talnad aooordlag to Èho ot¡nd.a¡il

-tO-

û.thod ðnd rl,evtd und.r ulEa-vlo¡.at llght lc 0r0tr ,l..l-g. A

elnf'l,ar ord¡¡ of ¡¡n¡lü"ttü vas founel for B3r but for DI!, Etr!!

a¡rl lnorgên16 Lodtctr¡ O'OO! 1Lg. osuld bc dLecarln.d under threr

oondLtlo¡¡ (ltg. t).

Tarf,ous moùlfloatfons euggcatrd for fnsneslng thr ooloe

oontraet aacl thærby thr ænsltivlty of thr orlgln,ol nethoit of

Boudrn ot al. (rg¡¡) eppra¡ tn tha lttrraturc (utrtctrer aae

sts,Ãl!y, I955t IÞagunevs and lcagr, Lg,9¡6l €artmarnkl, I9g?l

stolc, 1958¡ Eutarn, r95g¡ Es¡lalL and Bloot¡ 1959). Eeeh otthoar uodltlsatfoaa hgs þr.n asEcs¡cd ln ürte leboratory butnono ,*" ¡¡tsrrght *o tnprovt on ari aasocsaont of the al¡rouatogren

etafnod by thl oÈndeað proerduro and vl¡y¡d r¡ndtr u1tra-rtol.¡t

Ueht.

A drtl.¡l,tr logg of aæslttvity ls for¡nd vh¡a ohroneto-

graphlng pr^acua rxtraote, pr.€u¡aÞl¡r due to tho rlptd and Blg:ucnt oontaLnod l.n th¡ c¡traot, Ehls ¡ff¡ot l¡ no¡t ngrkcd intho tlctcotlon of thc tþrontno ooapotrcnt¡ ln butenof,.-so¡tÍo

aelcl¡ and lnt¡rfcroncl lE ¡uch a¡ to ¡Eke lt dlftleult to oo¡psao

tþrronlnr osacoatrattroas l¡ di.ffcreat prarnr rrun¡rlrr. fhl¡dlff,ter¡ltu to of no grrat aooount¡ horcvcr, ag ¡lth¡r thc Bså olthr îÂÂ- rå, avrt.ot oa¡r br umd, not onl¡r to rlruonctratr

adrquetr\y both !a aad !, but al¡o to aohf,¡vr th¡r¡ erBaratl,oa

oa thc cluoutogrene. rn thrsr tro artalfnr ¡olvcatr tb¡ær 1¡

'51-

FIOURE 1

-CHROMATOGRAMS OF VARYING AMOUNTS OF

DIIODOTYROSINE AND THYROXINE

0.005 pg.

O0l ug.I

0.02 ¡rg. O

0.04 r¡9.

T4

Éa 0.01 ug.

! 0.02 pg.

D.t.T.

-0.03 ug.

l0'04 ¡9

o FBE.A. \-

-r:È

a t.nd*nc3r for thc î, Epot to Þaoonc oloagatrd cJ¡d thl,s l,¡

thought to bo ilur to tho pme.Boo of, lfpül or plgnrnt. In

adrH.tlon at4l_nrng bryond !, tn three AlraL:lnc eolv¡nta la aona_

tinca fouael and eor¡cepencla to a brsqd flat peatr of, nedl,oeetlyltü

ln the radloeotlvo oÌ¡ronatograros. Fhi¡ hae al.rcaéy Þr¡n oonnentld

on fn thc llto¡aü¡re and ra thought to bc du¡ to todlnatod llpl,ds(îaurog, lgt?).

rloopno¡ltloa of tn and r, ¡ h¡rther obsowetfoae oa thoplrfemaser of thr nethod¡ nlrc oÞtal,ard Èy r¡t¡raøttng ¡llareen¡lehtô vlth chroaetographl,cal.ly purf.flod radloaetLvr E, and

Í* ecpnratoly¡ togrther with ehcnleel oåtrl,,ore. lfhe oxtraot¡

satû th¡n ol¡ronetogra¡rhod atrat tbr redl,o-aotlvr ohronato8rau

ceenncd vitb the ger flor eor¡nte. f, and îa ucn al,so aild¡d

aoparatcly to 4ã st. lotg of ascti.o aolcl þn, f.4) and tho

¡oluttons qrspor.tod aad ehronatograpbltl. th¡ ro¡ult¡ (ltg. 2)

chow that nEfthor radio-ast!.vc 1O nor t* arc affcetrd tn th.t¡

cluonatographlo noblllty or lronogcari.ty by eLthcr th¡ ¡xtraotlo¡

proerdum cr by ahnonatograp&t. fro elgnl,fleaat enouatc of

rithcr redisactf.vr lottot¡rroclnoa or lnorgenl,o lodl.d. $.a¡ nottlsn thtso olrronatograna. tlhcrres Îa uaa f,or¡ad to nLgrato a¡ ¡sharp peek¡ oorñteponcllng to a dlaorota ohrøloal cpot, !,produord ea crongatod pcak vhlcb eo¡r.lpoada wlth an clongatrd

-53'

FIGURE 2

-

CI{ROMATOGRAMS OF RADIOACTIVELY LABELLED

THYROID I{ORMONES

I1

i1

IIltflfltr1fl{ 1Íf

I

Iti

0I

ÏRIIODOTHYRONINE F

r.Ì

il

l

Ji

tj

ilI

Iliffi

0 THYROXINE

EEA...............'......_

F

-U*-

€hf.eel apÐto In sddftf.@Br shronåto€Ferpr$l Ðl giatÉs

.81Êhad te LF.O *u€p{ uf.tb Eea¡-¡nailåoaottye !4r rb€uöd Ëo

chülcÉl Êodet¡rreelnc rpot,

ÂttcfqcÊt,¡ å p¡oatlcat fraturc ea all sþc¡l'osl altrs¡antâf,tqsË

Faotrlar3al frer plarm ortrrsÈ¡ (p¿g" I) r¡ r r¡rot of len B,

valu¡ (geUlr 2) rhloh la dur to tbe úIorldr sontesÈ of thr

glarner ou3¡r porü.oa of ulúch 1¡ ro*ovrú by thc lon .rehB¡åCt

oûlr¡¡a. thlr rpot la not l¡boLlod Í.n sbroaetograac f,ro¡ r¡ês,o-

aotlrr cxtraet¡. Doth [Gl aail r¡G[ Írrc fouaê to h¡n ln valuor

tdentlsal ulth thet of tbo plerEe ooElloannÈ anit þoth ¡uroôuocd c

rpot r*lth tho oosis aul¡rhatc srcrs!.ous acfô syrtcn. lhe¡¡ ccro

no rcforaac¡¡ l,s th¡ lltrratr¿æ at tho tf.¡c e¡ to thc n¡hrc ofthia ertrf,aat. rn crdor to dctcrplao tblr, aoo" oor¡nlaèa

r¡åatrd to lsell,no $tF. lnveaä,gEtcd, anù th¡ R, vature for ¡onr

of ttree¡ eno gÊvrn (lauh a).

It vaa thcn tlnught t3rat thc o¡nÈ night bo provontcd Þy

lnclu'rtng reduolng eubateaccs ¡uqh a¡ thlotr¡rec1l and llrentrtr-

thlctraclL la th¡ crtr¡otf.en¡ ¡ueh va¡ fs¡¡¡ô not te þr Èhr er¡¡.tbrs¡ nduclg ruÞskaeel, houevlr, produeed, epotr on Èhr ohrsop

atograaa vbloh @ulü br æafi¡¡od ylth tl¡o¡e of tb¡ orgaa!.o

fsdLn¡ conpo'"{dr. Ehla l¡trrc¡ting flncllag vr¡ pl,cæat to threoetrrovorslal nport of Block ct aI. (ffCO) Èbat lrrgr ¡sountl

of Lodot¡rorln¡s olrsrrlrto i¡ nornal plerm. rà¡y hsd addcü

-75t

'JICURI] '

CHROMATOORAMS DEMONSTRATING IOOOTYROSINES

STANDARD MIXTURE

NORMAL

THYROTOXIC

NORMAL

0RI0IN

rb

a'

-

PBl.6.4 ¡S To

PBl. 18'l¡goå

PBl.7.5¡s%

t .F

lfi

ct- D.r.T. THYRONINES

BUTANOL

., rl.'-äjl/iiìD l{rxr'uREe chron, toSrírl of a ml.xture sf Krr lirT, j-)I1, r,.nc-

T4 d1'çnoLvccl 1n eth¡¡noL-¿:r*¡nonl,¿r solutioR.

lll¡e other threa sÌrrom¡rto;;r'r.;rrs aro ûf lrIr:.eraa ;ii¡jiri.l-os obtainecl fro¡r

t:,'o noraal subJeots ¿¡nc1 one su'irject ç1th thyrotoxicosis.

,{11 r;l'i;:onaüogrlt^ur; vrere irsse-.ir,.6fl e¡tth tl¡e cherric:rl ¡tethocl .

TABIË 2

Iþl1

IUA0 = !,odoao6tfc aold + (I- proauoed by deoolpoaltton)rl.U. . thi,or¡¡.ecLlPnt - proplthtor¡¡Èof.Itg 3 ðllodotþrronl.ncÍRIAG a |¡|fir-trllodoth¡rroecrtÍe acldIEIBAC r 5t5t|rr5t Sotralorlotþrroaoctlo scl,ü

Other abÞreriatlo¡a aa ln tc¡t.

CoLltrdlnæm5

lA^-Itr,

B .Ë.4.

Buta¡rolacetLc

TODUEü!

O. ¡lO

0.lo

o.25

0otrO

cl

0.90

Oo25

0.,+5

O"2,

-I

-

0. ¡15

O.2,

I 2

-

0o8O*Qo25

HT.TG

O.¡lO

4.55

l! .ll.

-

0.80

PIIU

o.54

0.o5

0o5O

o.4t

ltf!

0.{O

0.O

0.15

Q.5l

UI!

-

0.65

0.80

O.@

!2

O.?O

o.60

O.7,

0.8,

î,

O.6,

O.¿lO

0.58

o.gÞ

r4

o.7g

0.89

Or85

TßIAG

-

0.5O

0.65

o.g5

!E¡nAC

'tT'

thleuracil to tbr plarae btfosa ¡rtraotloa. €osfl¡natísa thåt

thc art¡teot a¡nt ulth ¡ lor t, relucr rtforrcd to ebotor trobLerld¡r BIrI,.r$rd f,n e ruberqurnt papcr by Eorc ct al. (fg60)r

uho refcrrcd ¡1¡o to tho rpoto peodaord by thlouraolle vf.th tbe.tÍo ruJ.phato aye'¿.¡s. Eho lsttct yar eonf,l¡nett al¡o ÞDleltrl¡dou et cL, (fffO). ?he pns.nor of thc shl,orLilr rpot

1g of no groat acco'¿nt 1a ch¡o¡atrogranr ôovolo¡lrd 1¡¡ th¡ bnü¡¡ol-

aestic eyeicmr but ln BEA a?rroratogran¡ lt obor¡rc¡ rng tsrl! ¡ùlch

nlght be pnscnt anil gonotlnc¡ alro Drt lf thls ¡s ¡rnecnt lnenall qu.ntl,tles onþ (ftgs. 5, I?).

EvÈð¡nec of son¡ cstcrlfl.oetton of thr ledott\yrontno¡ 1¡

tire arkallnc sElvcnto, oeeu*l.ng rltber alr¡rtqs r¡tmstlea o¡r

ohrosatsF {pÞu raa ronetd.nc¡ ovldæt. li¡ol¡s¡,a rt ¡1. (rg¡z)

vho havo ¡tudlrd th¡ lotteuho ecld letrra, for¡nil that aold

e.lsohol:to aorutl,oa¡ l¡wur thcl.r for¡aü,on. gþc crt¡r¡ h¡rrY3$r kl€Þ I, vnluc¡ Ía the rllallao ¡oìvrnta, aad chtlc tbcæ

lr¡ broyn not ts eg!,¡etilc vlth fiht Brtr ef Ec.¡rn teetce¡lno

*ctdrn rouc mnr 1¡ nacôeel fn L¡torDr.tlag r¡ntr or ndtsrotlvepæLa 1r tho ¡ræ of tlre cbrse*togranr brturc¡ r, nod thc rolvrntfroat.

4. RBåUTÌg

-rt nu¡t be cø¡rbelLccd thßg thl¡ lavætlgntlaa !.a stÉetl¡r

a*'rod et obtel¡illnt a guall,tatlt¡ isü.tæGat sf tbr neÊu,n e:! tkç

CHROMATOGRAPHIC PATTERN IN A NORMAL SUBJECT

M.W. d eet 3l

-

-lE ;

PIOURE 4

BUTANOL

t {orIo ct- THYRONINES F

Fo

tDct- 'r t,I-

B.EA.

-rv

cl¡sulßtfng thytoùd hortooa untler varleut eenalltlona. thÊ

ooaplJ-atLoa e data r!.thla Ê grosp of atrbJcotl, erè tha conpar-

lasa of dsttr b¡tnrrcc, grouge É,¡ heræ¡r laollltatËd by aerlgnLag

e¡oh qrot cn thr obroaateêtr¡r an ¡rbf.k¡¡.¡r v¿luc lroa I to ¡O

dcpondtnt utrlor thr ¡rta of th¡ eBot and thr t"atenris af ût¡

fluorc¡eûBgCo PceL¡ on tlrc ro¡n ùoo raô1o¡stlve o&soretasr¡Ët

r.r. lraf,lÂrly a¡lo¡r¡d fron tbo total ¡3Gr þet¡non thc sutline

of thc paeE end th¡ Èao&grouarl. ÎbÐ lLnÍt¡tlon¡ of ruch

aÊstranent froa thc qnaatltattve vl¡r pelnt aro üÈal.lmð, enè

tt 1a not Lntondcd thst ths ¡e¡ults roportrd belou Íoru noro

ths,n a rougb eorl-quantlbtLvc tctoa of thc ludtvf.d¡¡s,t oonpørntr

of thr olroul,attrEg hûrnena,

Euthvrol'd $uþlootr¡ Plase¡ fron 26 onbgeet¡ rlthout oXtnlo¡l

evLdmeo ef tþ¡rrold dl¡css. 18¡ ohronrtograpbrtl la at lcart tuc

eolvont¡, buteaol ao¡tte ¡,¡ril D8À. lfb¡ n¡an ¡rlaena prottiabourrd 1oü1¿o lcvcl (fn¡) of 24 of thcso aubJoote 1*q 5.9 ¡*&ftraaglag fro¡ 1.2 lø 9.Ð ¡t3.f.

În uea th¡ u¿1n oenpeacnt dttretort ia rvergr oaæ (nfg. ZII

fO ru dot¡stod t¡¡ 15 of tbr 26 rubJceta, and s f31nt tpot ulth* Rf v*lu¡ Jurt grratc¡ thaa thåt o !, iE th¡ BEA ¡elvrat

ryrtm ( ) !¡) ua¡ feund 18 tuo €etc¡. DI! ía¡ pmoøt f,n tÞ¡

pleæa of , euÞJrotr (trtg. z) an¿ tlr! 1n ono oeeo oal¡r (*nuro ,).

-þF

EABIË t

-

t â sln,Iar aastacntltt ús¡ ebta1¡sd alge t¡¡ t¡¡t - snÍl alcoho]'2H anoonlun [¡¡rlrorlilc ehronatogreoa fr'on thcoe rubJeetr.

I Dr¡lvcd by addlag th¡ aaoresscat ve¡u.s ef Ìfrt and Dr|[ {nbutaæl eortle to thc totel tå¡rrcaln. åarsa¡Eont ln BEA¡

+t sc¡ t¡xt (p*s. ) rot tho nrthod of, aeacellng tha osatratof eaoh oonpoEæto

o

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> !!iItE4thyro"af¡rs

DITHXÍ}?I 80rÀ& IDTTßota¡

lDh¡rro-l¡18a

crRoHltocnÂ?Hlo AsðBsst{EtE t*

But¡¡ol

-4.1e

t¡Ell 1, (CoDttô.1

7.81.2l.r I r.r5.7o.5O¡l5.9iì *I:T

LjEBABð

,[e,r526265tlrrqucEoy ot

Drtrstfon

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rcîlg ¡s[t>!t!t!4!Srrornln¡a

DIlüITPBIlg¡8u8ub-lrot

E.t ¡l rÞtâûÐl åeotlo

OHRO}NÎ(}GRAFTIG AA3flSSHffi 8

-{A-

In 5 of th. ! rublrot¡ la rhtoh III! rss dct¡otrd th. PDI lrvd

nae ?r0 /q.l or hlgh.!.

lbr naan valu. of tho vLausl a¡satsl¡o¡t v3s 5.? r¿nlt¡ fo!

1* a,nct l.! for t, tn thr EEA ¡olYcat. llIS a¡¡tl Dt[f va1u.l r.!t

rcrprotlvcþ O.l and 0.5 fa butaaol eo¡tlo. À aean valur ot

?.8 for thr total organto todldr oontcnt wa¡ dcrlwd by aild!.ng

the uean valu¡c rcrpeotlvrly for l4r !¡r and ) 8, la th¡ 8BA

rolv¡ntc to thr E nn valura for DI! a¡al tdl|f fa butanol aortl,o

¡olv¡nt (mlfr !). Aocordlng to thl¡ oûtt¡¡to tho 14 cont¡lb-

utæ 7#, ?, L7fi a¡d thr Lodoþroalncs brtsecn thcu oontslÞutt

8fi ot th¡ total blood orgaaLo lodLn¡ in no¡n&l eubJcotl.

Hvpcrtlurof.d Bubicct¡r Þjbf,gtlgilr- llaena fron 11 anoh

aubJcets uas GhroaatograBhcd t.n st ¡.cest thc tuo rolvontr¡

butenoL aortts aad BËto (naUtr 4¡ Flgs. 5¡ 6). Agefü 14

¡ våB for¡¡il a¡ thc Båtn coEl¡oatnt ln cvr$r oa¡.t 1, wec drtrottûln rrory oas¡ br¡t oao (ta whtoh th.3ÐI lcvcl vao onl¡r 1.5 þg.fl)end ) ?t uas fot¡¡d ln I of tbc 28 cubJtots. rn ùutaasl aortlo¡

Hr'lE vaa obacrvcd lq 9 oBaGE ancl Drr tn ?4 ca¡oa out of, th. tl(ne. 5).

thc n¡an ùotal a¡saaasont taluo vac l¡[.J ¡raltl, !4

aocountld for 6.6 r¡ntÈc (+eX¡, IO f,or !.1 r:¡nlte te#) a¡d uI!and Dr! togrther tot 7o9 r¡nlts (27*). thr acan pBr lovol fortirle group nas lJo0 ,þg.f.

_t5_

stBIE I

rlf

1.0

Lrt2llt7r4r5I6L7

18

19

20

?J

22

2'24

* A clnllar egalcsa@,t ua¡ obta!.¡od aL¡o la f.a.Ae - aqnonla,S &rlvrd ae l¡ ltsabh !.

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D.E.A çButanol lsrtlo

CEËOHASOFAPHXg A$SSSSHIST

-4þrr¡r¡ 4 (çeata.)

cHRO![AEo0nåPEIC l88E8SSntrî

E.B.lr

l4o!10.4Oo57.16a 67.03.50.61ã.O.#ì r.[8ABg

I5I,ot¡'tr219Pmquesry of

DttcotLe¡

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!'lG,,r.i,i 5

CHROMATOGRAPHIC PATTERNS IN HYPERTHYROIDISM

R.M. d aet 46

oRI0I

N

0RI

GI

N

oRI

GI

N

lt FR0N1d

oRI

GI

N Þo

cr- | Drf.

BUTANOL AC

TI{YRONINES

PB.l. 10.6 ¡S o/o

RA. d aet 19

PBl. 16.0 )Eoh

PBl. 10.6 )tgolo

Dl.T. cl- f- Tt

FRoNT

FRoN1

(" PB.l. 16.0 ¡s %

Fl,asn¡: tì¡:ì:l)l"es obùelnoC fro¡r üço dli'ferent subJects wlth

untre:iteC thyrotoxieosfs - Chfomatogr.rmo assesged cl¡enic,,_rl13',

BE.A.

'46'

;-ICiJRE 6

-

CHROMATOGRAPHIC PATTERN IN A HYPERTHYROID SUBJECT

QEg aet 20

o ct- l- THYRONINES F

o

oF

BUTANOL ACETIC

Cl- 1- T¿ T3 >T3

BEA.

?

-4?-

, Stet¡a rf* FIr- Dl*¡na fr'en ðrnÞJroto t"n tbf.s gËoup ras sEen¡þgr*Dbö 1¡¡ tlcc GÞovr túo

aelvætr aaå a¡ee¡sd chcsterit¡r (Ulfr g). !* uar fe@d, ls aJ.¡

trn I o¡¡or Ln ttÐ Eff ryaÈaro

In buteaol, acrtfo¡ Ht rar il¡trobd ln 6 ¡¡d IEE 1r* l* out of tblå0 æ¡og. lfh¡ tobl ess..rüEt raluo yrr 1å.5 rmlt¡, of rhfeb

8* aooo'usteit f,or W#, n, ør E* a¡¡d fI! ¡ed Ef toStth.r lor2rt. flhr n¡au PBI l¡r¡cl fo¡ t}rl,r group ra! not calsulatcd.

Ftf,tecn of &¡ abpyc placner rhl,oh Etrt r¡dlaesttvr¡ aad oæ

othar plesor tskra fæsn s¡ lryprrtùyrold prtlrnt ¡i{l þ¡¡ra eftrrlFh tn"re¡ry and not epptar{ng ia tàr ohæto¡llü a¡ars¡ld gróu3r

ver. eh¡ronatogagbsd ¿rnd thc chroutogracs a¡s.rnd for f[¡

ooat*nt (fEUh 5¡ RLgr. ?t B). ßa rea found in rll tÞ¡¡r oat*!¡

S, ü aJ.l but oEê Gs¡., E{IE i.n ? ¡n¿ AI8 tn 12 or¡¡¡ ou* of th¡

totaL of 16. lbr total ÈàcÐceaaü¡t ve.lu¡ ya¡ 12.2 nnd of thlr¡fla ceeouat¡d for 5$, t, f;ox 24{ NA tbt l,cdot¡ræortncr for 2Of.

l|Ísoellsneour Greu¿ r ,Il¡J's gr¡cup 1r oon¡xl,¡rð of tO grtlcrtrultb aoa-torio 6eltrr, threr rubtcds bæa to b¡ !E e rtetr ef,

acr¡te c¡¡otf.onal stresc, onc ¡Nrtlcnt y!.th acrorgrl¡r a¡d op

3ratlent þ'lth asut¡ tl¡¡rrotctttl,r. !h rc¡ult¡ of oÌ¡¡ombgrrBbto

aoalysle of thl¡ goup uith tÀ. lfl¡ .or.o¿rcat arc glvrn lnlabr¡ ?' îhq nran asaçaamat vaLuog fon chrontogru¡ for tbpatlonte clth non-toxio goltrc rrc 1* 1.9 untt4 t, L.?t

¿i.'{i,' 7"}-!,,

t Er¡rrcsaad ae porcentage ol doea sfI Dr-Lvrd a¡ fn fablo t.

clrEoErtoeEAPflIC Åg8Ë8SME !B. B. A.

o.{ a.92.95.16.91¡1O.5[rÂil8

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-51-

Ï'ÏGURE 7

RAITOACTIVE CHRONIATOGRAM SCANS IN HYPERTHYRqDEM

AS 9 aet 53

0 t- MJI IIITA.|TAN(L ACEÍE

-

ÏHYRONNES F

o otT. MII l- T4 T3 > T3

BEA

?Lr',s¡nr" obteincd f,ron a p.¡.tient Ì/1, th thyr.oto:rleosf s l;8 l:,;ur;

nfti r r{:cêlviüg þ nrC' of 1j1-I. 'Ii:'e fig.l.:re ís a i:hoto¡;rri;;h

of, ühe raclioactive .-icírnfl r-,f tlle chrour.togr,?ltLì¡

F

ill,li;/l.llti

ffi\t\i\\

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_þt-qICUN.E B

RADIOASTIVE CHROMATOGRAM SCANS IN HYPERTHYROITISM

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c¡ts!{IcA! $r80}taÍ0eB ÀPHIC AssEssMErî

þet MI

-rÞlt,-E'

I ,l'S, O.2t DtrE ead tlll O.9 end tho total anouat¡ to a nss¡ of

?.? unlt¡.

5. DrSCUSgloI

lßhr rcgult¡ of cluoaatogrephy of pl"eæa frs¡ aorn¡l rubtcctr

lndlo¡tr thstr aeEordLag to Soe¡ rcthottc, la L¡ tho pnôoolaaat

c1rq¡l¡tlng horgonrr îO san Þc dcteot¡ct fÞrguætþ but la ¡uoh

¡nall¡r quaatltlrs th¡n B* rad tbat DIl 1l aot a urusl eon¡nncnt

of tb¡ of¡oul¡tloa'

lhc no¡¡r asö.ütÐat valu¡ for !!O ls I$ ol th¡ total valn¡

for lodot!¡rronln¡¡ la thr nornal group¡ thL¡ valu¡ bowæ¡æ¡ Er¡r

not bo strí.ctl¡r proBertlonal to thr aot¡ral anount of !, ortrorlet-

lng I'n thr bleoct. ualag a ¡!.¡l,rsr vleuÊl arr.¡¡Eont, l{aol&gaá

rt al. (rg¡r) founit r, t thr plaam ot ? out sf I norg¿l aubJoetc,

encl wl,tb a rcnl,-quentl,tatlvr ncttrcd for¡nd 1, to anount to ag¡ror-

lnatoþ ilofi of thc tþronln¡ eonoutratf.on. p1¡d (lggù f,or¡nd

an cv.Þ aEaLlc¡ a.Eol¡rit of t, 1¡ hr¡tan aubJlottr Ia tvo ¡tr¡dlea

on rate, valu¡s ot ].0-æ/ (!ouæ 1959) and. jfi (rttt-ntv¡rs aad

Rallr f961) roa¡nctf.vrly hsvc br¡a fouado îhc hfghrr ya,Ir¡¡

louacl Ln thc prrneat Btudy La ¡rrobebJy dur p¡rtþ to tho ebrmc¡

of a strf,otly dLreot proportf.sn brtrroca the oonc¡atrctlon of spartloular sogponrat ta th¡ plaana and tho rc¡urt Es cet!¡atrdby thr vlcuel ae¡.¡cpcnt¡ rt la not dt¡r to th¡ br¡erdcra of!* to It durlag rxtractr.on aa thla poodÞ{u,ty u¿¡ lrcludrcl b¡r

-5r-

ohroÉato6rsphtt€ radloåcttvr 1* cnrl.chrd pleener and flacllng

onru s* (ltg. 2),

It rçoultl âppear fron thc r¡sulta rcportrd hrrs that nclthcr

DIII nor MM,g a ¡oruel oomponrnt of thc clroulatÍonr at l¡ast

not Ln thc anor¡rta rcportcd by Blook ct al. (fggo). DiIf uag

drtcoted Ln the pleana of tlvc ol th¡ subJectsr thr¡¡ of vhloh

had hlgh norual valuoe for PBI. Such r¡roradl,e flntll,age nay Þr

rclatrcl partly to a anall tÞrquonoy of, sub-ollnl,oal bl.oaynthotlc

tlcf,cot¡ auong an othcrulsr no¡ual, ¡ropulatlon and nay bc partþ a

sensl,tlv!'ty pheno[oaon¡ Sea¡f.tivlty ohoulcl not þE a problcn

though, aa Bouden et al. (fgl¡) polat out that thc nlntrun auount

of .DI8 drtooteblc with tho oe¡ùo aulphatr oyateo Ls le¡¡ than tho

asount of, clthcr I, or l*r thl.E uas conff¡mctl 1n thr ¡rrcoont

lnvretf.gatlo¡r. the vl,rtual absonec of f.odot¡rrosfnes ln tha

norneL elrcuLstlsn f'e oonsletent uith thc elasslca1 eonoopt of

hornoaal bloaynthcslr (noofrc lt al.. ¡ t952c¡ Pltt-Rtv.rå and tata,

1959) aooordlng to vhlch ilclodlnatlon of the todot¡rroclncs prooorda

vlthln the gland as a Ecane of coneerylng thc storcs of bod¡r

lsdlnr.

öloot of al. (fgOO) euggestld reasong at to why prevloul

volkcrs bave not found Drf ln the or.reuration ulth both 15rr otl27r r.thodo. t{ltb rcgard to thclr auggcstlons conc€rnlng tbor51r r"thorlo¡ dlsouaslon wlll appåar borow. ur.th trrr 14¡

-16-

ts.thodt, thry lnpltcd tbat thc ncthode uscd havo aot ¡rtreot¡d

thc lotlotyrsal.ncs frpu the blood¡ Hlth thc asthod as rcportld

hcrr, an caally dctGgtåbl epot nae proúuo.al lron a plaana

cnrleh.at to 1.0 /L&. uith DI!.

In vlcu of th. v¡ll-bmva end rfflotoÃt e.ohanltna f,or tho

dl,epoaal of, a.E¡t forlolrrorLnee ln the Þlood by drlodlnstlon ar¡d

dranlnatlon (fong Et al., Lgllt StanÞur", 1960) ånit by rc¡¡)'

elcarenot (Iascltcr end Stanbury, f959)r thc prteone¡ of cugh

la¡go anounts of f,odo$roel¡ce ôa suggcrted by BlooL ct ¡1.(fgOO) uould so.¡ Lâoongruoue. On ohtuleal gtound¡ elro f,tvould eren unllhr\yr Ês a tlBLeun vashrd butanor crtrsotabre

Lodla¡ (rhtch d,oce not ¡nc&!ur. Ðrl) ra for¡nd to bo no aor. tben

o., fg$- lras than q PB¡ estlnatLon on thc sano aanple f,roa

ao¡mal aubJcots (Uaa ana Bondy¡ Lgr,ll Oood, 1960).

rn th¡ untr¡atcrt þperthyro!.d g¡oulr, thr ebsolutc lnsr¡a¡rln tb¡ ass.asnoat valuo of ra o?.r thc noruaL group vouLd asoor¡at

for onþ a sÉall. pcrerntago of tho oba¡rvcd. pBr rLr.. ?hr ¡rcr-erntagr lncrea¡¡ ln thr s, ftgr¡ro rÊ¡ nuah 6rcator than th.lacrca¡¡ l.n !*. t, a,rnounttû to ]'Lfi ot thr total thyronlac¡ La

tbc þperthyrotet group but on\r tsÍ of, th¡ total ln thc ruth¡rreld

ffrouBr ra thcs¡ ohraÍoat :tndlce, thr Borelbirlty that th¡app.srrånor ot I, e þprrtþroldlæ 1¡ r¡tatcd to raûlat!.oa itraragr

and not to the h¡rpcrtfrrrolélan, a polnt vh!.oh ooäo.aard ca¡rl.!.or

-57-

york.ts (DtngLcatlnc et a1., f955), Ía obviously rulod out.

a¡ f,ar aa the blorogiealþ aotfv. LodÐ-Êonpounûe a¡a oanecrnod,

1.e. thc lodotþronlnca, thcrc ls nothlng to oupport a lugtrgtlonof, a cBcoffLo qualltatlvo Ð.orttloa ln tlypertþroltlLen. It ctoo¡

eoen llkely, houcvcr, that the ayaptons and ollnlcal eff¡cts oftprpcrthyroldlsn appGar to be rolatcd to thia largsr {ncrcase Ln

t, ooorction. rhe flnd.lng8 reportcd hcro eÌE ooa¡lgtont rlththosc reBortrd by arons aad Hydovltz (rg¡g) although as the

latter $cro radloactÍve etucllee, thc Lntcripretetf,on bo€oura

oouplt eatrd by the poealbilf t of tH.ffcrlng spcoffta aotivttlc¡beturrn thr f, and thc gn pcaLc.

tho euggeation that thc p¡ssrnos of r, lc mlatod to thc

eLlnlcal cffocte of the þp*tþrofd statc wourd bc grcatlyatreagthcncd lf lt uere poralbLc to oorrolate thc quantf.ty ots, founa 1n lndlvlduar eåscs r¡lth thE ollai.oal lntrnalty of thc

dielaao¡ such a ollnlaar ora¡elflcatlon ls, hovivcr, dlffloultand was not att¡apted Ln thle etudy, rt Ls of lntercst that tb¡ono BatLc¡t vho ahor¡cl no cvid¡n€a ôf c!.reuLatlng trl"Lodoth¡rroninr

¡¡ar subacqucntry troatad ufth thcrepcutt" lSlr end rl¡ sonth¡iat¡r naÊ rcpo¡tsd to bs oliaioelf,y hypothyrold.

Àn Lntcrcatfng flndlag uas thc ooouar.aec of &t! tn rlfi att¡ntrcatcd ¡latfcntg and Ln Tg* (aa cetlnatcd ohenloagr) of tb

-58-

DÊtl,.ntsr tuo to for¡¡ days aftrt lll¡ thlrapy, olr carþ Bû¡dt

ln lyprrth¡rrol.dlu (g*ur anê Þbynt, LÐ5) rrportod !{trî and üI!tn ns¡t rlra rnnLnrd, but it raa thougbt thr DIS rn¡ r¡latrd to

r¡dletlon daæagr 1a thc ti.and. Horo rGorntly FarrEn et al.(f g¡g) repertod tbr prre "rae¡ sf Loôlnatrd tyreelacr follovlng

eoal-trao¡r doara of l'l¡ l,n bil¡f of thrlr hy¡nrtà¡rrold group.

tshrlr pr.õoacr na¡ sub¡equcat\r notrd ln a cnalrer pcecrntagr of

unt$gtod Eacre of gçtrtþroliltsn, vlth pur.Ly ch¡ptoal rothsd¡

(fU¿ esd ¡atraa¡ t96O). tulrea ¡t aL. (f95g) suggeatoð thstiortotrro¡laes ræc proeoat in tbc pleena of oary tho¡¡ patlrntrvlth nretLvrl¡r largr gJ.aadc, uhtoh y.ru Eorr rad.Lo-m¡lotant

tban thoer ln tb¡ eFoup ultlrout þrorlana.rn an carLL¡r ¡trl,cg of patlcnta¡ Dr! vec f,ouad tn a sf,al¡år

prrolatagc of lryprrtþrclal iuÞJ.ota lq thl¡ laÞo¡atory (rrutyaad rrt¡rrr 1960). rn thle roport ao oorrolatlon eould be f,owd,

Þotuooa thr d¡t¡stf.on of DII and cc¡rtaln olLnlcal f¡aü¡¡¡s of thrpatleatan ruoh a¡ ollnloel 1nt¡nrfty of tho dlooacr, Blaeaa pBr

lcvol, slasd ¡lEr o¡r tannod rrd orrl rgglutlnrtlon tltro or thrhÍrtologr of th¡ gland wb¡n arellablo. rE vlcr of thlr, aad tbhlgh fnolðraor (ro*) of tbc ocel¡Ír.ser of Ert tn tho pnscat

rcport¡ further attrnptc at ¡uoh oourlatf.sa utrc not attcnptcd.

rt 1¡ pcrbapa e ltttlc surpr{etng tn vf,sr of, th¡ døflnlteanount of, DrE brlng lound horc anel thc flrqsJ8qt of thr f,lndltlg,

-rF^

tbnt other ¡osl¡cra havl aot roportrd ¡lsllsr fladlnga.

Itaolegan ct al' (fg¡f) l'n thtlr ttudy of þpcrthyroLd anbJcoto

uertl on\r nltalf.¡r rolvoat¡r 1n vhloh tbe iodoQrrolinc¡ lfthcr

do not ntgratc å¡nd Ëey thorctor¡ b¡ oonfuecd vlth protcln or

othsr origla natcrla.J., or havc a lon B, value aael nfght thcrcfon

bc obaeu¡od by chl,orldr. Arone and lþdovf.tz (rg¡g) roportcit a

radloactLvc paal ln thc !{r8, Drt Junotlonal arcs ln þpcrthyroldlcnbut dld not ld¡nttfy th¡ p.ar¡ la rctroapcot lodoþro¡lnc¡ ..G¡ a

dlstt¡ct poralÞlllQr.

rn tha prrernt âtudy thc lilutlfloatlon of DrÍ nao ba¡rd on

the fol,lorlng oriterle¡ thr epots ü.¡e f,ound Ín the hnoun üttaro&tr Ln both Þutanol asotlo q¡d BE¡l solvrat¡n although the c¡rot

1n BEA yat oooÊalonaIþ ob¡eur¡d by the ohlorl.de spot.

Csnf!.¡netíon ua¡ obtalncd by cnrlchtng Dl!-eontainlag pLaena wl.th

Eno*n DrEr thc¡ olrroratographlag t¡ butaaoL ao¡tlc enô BEA ts

ehov oolaeldtneo of th¡ rpotc 1n csoh ¡olvent. Furthor rvld¡nc¡

that thtc oon¡ronont rs¡ Dr! ugs dcduord fron l,ts clutloa troa tbq¡rron c*chengt oolu,na not onþ et pH 1.4 but slso

"a É pH f

J.o uhl.ob ts rnoyn to r¡eovor DI! and aot thc Lodotþroltnre.

rt 1s cf lntæ¡et that &rE u¿¡ found ualng ch¡ola¡l uthoð¡

la plasrs fron patl.tate both D¡fo¡r a¡ril aftcr rlctÍvlng ft\

thrrepy. lhl¡ orlrlnatl¡ tÞr porerþi¡ltt of it¡ oocurr.ßGa

brlng ln auy vay rclatrri to euoh r¿diothorapy. t\¡rthortsoEt¡

-6O-

EI! (a¡d rIE Dt.p.ottvtly) rorc foud La thr I5\ trcated hyprr-

tlryrofd group vlth tho saDr degrrr of froqucnory wlth È¡oth tbrl4¡ uu tur ltlt ncthodc, and ln a¡or¡nts approrluatsiy tha Gaü.,

rclatluc to tbc anaunta of Ear

ilfS cas found ulth e frrqucnoy of ebout snr thl¡d ta oao

h¿l.f that of DII Ln caeh of tho Lrypcrtþrold grou¡ro and shra

tl¡trotrd aar la a¿oust¡ ¡uallcr thsn El!. fhlc Lr probaÞIy e

r¡flrotloa of th¡ roratlvo eaount¡ of th¡¡r oon¡rouncla la tbe

tþrold gland. tr! 1s saltl to aeoo'nt tor N$ a¡rd rlrt to¡ l6fof the thyrol,ctal lodla¡ rca¡rootLyoly (pftt-nfvtr¡ aad RsL¡,, 196l).

Fos¡i.Þlrf.tfca as to tho nrohsnlsn of tl¡l¡ rrloaer of lodo-

tyroafnre rf.rl br diseue¡rd in cbaptu v to6rthc¡ ylth dEte

cboulr8 E r¡he¡¡ of Dlt tlon thc gland dr¡¡tng aeutr tlqrroEophl€

horuoul ¡tlruLatls¡. rt hae boon ausgcatoel (rrrmJu¡, 1960)

that thc ¡rbenenoaoa na¡r rofl.st a icondltLorldw drfiolonoy of tbrthyroldel .Esy¡.r Lodotyrorlnc il¡ah¿legrnasr. uhet¡vcr thrntchanl¡r lauclvrrlr enü vhatrvar aignlfloaaoo tho pboúonoloã E¡r

havrr 1t n¡u¡t raplasaDt a br¡atdoun of th¡ no¡ss¡' lntrath¡rrof,al8l

¡eqhenl¡n for thr oong¡natl,on of tt¡c Þodg iodlnc ¡terr¡.to4ntorlc coltrp¡ pltt-Rlv¡rs ¡t al. (rg¡r) havc aborya that th¡thyroLd gta¡d 1a aoa-bxio nodr¡lar 6oftr¡ oontein¡ lo¡¡ tþroxlætheã tht Lodot¡rroelnr¡ anrl aor¡ ürB üra¡¡ Drî, aad that f,otlovl¡gthr art¡inLctratlon ef 11r¡ * lor eonorntratloa .t rlL ua¡ fourcl

-6I-

Þoth l.n th¡ aodul¡r atrd th. para-aodulsa tl,¡ru¡. Apparcntþ

thcDt 1a an llabf.llty for aoec of thtsr gl.aåats to util¡'¡¡ lodi¡¡caurJ,ag ae tupafraoat Ln lla eJrnthrlf.a. lferatr ct al. (fgæ) aaO

Rupp ¡t al. (rg¡g) havc rcportcd ¡ratleato ci,th noetorl,e 5of.trrrl'th ¡lthæ 11, or * !, rit¡ ¡uÞataao¡ ss thc onl¡r elreulattaghorËonao

Íh¡'. e¡¡ aot ono.gh sssaå ta thc E)r.aaüt aorlc¡ to draradoquatr eonelu¡lo'D ar ¡rat, and thta date la sttll brtagaco¡¡nulst¡d- lfh¡sr aro dlff,icultlo¡ 1q sler¡lfyùng tht¡ eIln-fsar oouditlon iato itg v'rrlour ¡uÞ-¡¡etloar. îyo oa¡r¡ êrlghovn vltb qulto ¡a¡rod anor¡at¡ of, DrE (¡ut no xrt) (tauto ?).Pocslb¡J th¡a¡ sar.¡ (onr of vhlah ya¡ haorn te havc a rblgfealþ htrtery or gottno) rall iato a gror¡B vltb blorynthrtledaf.otr s{rtlar to ccrtatn t¡rp* of goltlou¡ erotlag (xocrrr,1960). fto nn¡l,nlüg €arr¡ ¡hou ¡ro aþna¡ralltr¡c ra th¡ trylotðhortonl dloH.butloq ln thr bloocl¡ although thr ¡rlarn" I, eoat¡nt1¡ rrll abov¡ thr av*agr for thr nornal praeae r, ooatrat rnaoso of tbou.

lltro of th¡ th¡1. oaa.¡ vlth ths ol.a¡sl,ft oat!.oa of Ë¡ttrogr E

and thr onr patleat wrtb aoro*gsþ chorrd qurtc rlgarfloantansuat¡ of Itrt. thr¡¡ ceao¡ vlll bc dl¡eu¡æd fr chaBtæ vundor th¡ hcadlng ef tùc rffrgt of llgfl cra th, clrûulatrag ho¡noarpattrrn.

-6?-.

6. GOTGII'SIOIS l[D Suütr^nr

Eh¡ r¡sult¡ af thie ¡tudy laclLoatr cacl es¡flrn tbÊt f* 1r

quantltatLvrly by f,ar tbc no¡t Lnportant clrculatú,ng thyrolê

hornonr¡ thåt æ¡1¡. but defl'altr etor¡¿tr of Í, aro fleqnrntly

clrtootrd acal tbat l"eelo$rroeÍn¡s Erc nst r¡tua¡.ly prscnt tn tb¡

of¡sur.atlon of aonal aubJrcta. rB þpcrtÈyrolilr¡n thtrr l¡ a

auall lnorcs¡¡ ln the ¡¡or¡nt of clroulatlng l4r e tuo to tl¡¡r¡folet lncna¡r tn th. a¡ot¡¡t ol tì1o ar¡d a drffnr.tc e¡onnt of Dt!nqy br dotrot¡d ln ?0-€ol of ctt Groo¡o ttho re¡urtc oro Éot

clgnlfloantlt ûlff¡rl¡t brtn¡cn ¡¡atnatcd aad lllr tr¡otr¿

þpætþtalett¡¡. In tfre tl¡atrd lll¡ g*..p, tht r¡ault¡ ero

rs¡stlaug at'll,ar uh¡tb"" r4r o" rEr aro bohg u¡rð fora¡a¡nrlng thr lod1¡c dl¡trlbuttroa.

rt lp oonoluürd that la SrBertþroldl¡l þoth th¡ inoroa¡¡ð

anount oî, 'lt, end thr oc€trrranel of lodofroalncç 1n tlre bLood,

arc eff¡otc dur to th¡ oonctitfso of þpcrtþroldl¡n aart not toother faotora ¡uoh e¡ radtetlon daoagr t,o thc tÞv¡oful gr.rad.

_6r_

SHAPIBN TII

fËrRo¡RoPEIC HoBmr8

À.- EgltolEo Et!8c!8 Ir ür

1. tSprxret¡or

å brL¡l dl¡Eu¡¡lo¡ of thr uorL x!.rtrorr.d b¡r Hrtrol ead

aolleÞorators o¡ thr rarl¡r reteÞolllo rft¡otr of tþrotrophlohoruo¡l (lSU) in nsa h¡¡ alrcedy bcrn presrntod fE CbaBtrr I¡re¡lrtre]" Intreduotlo! F.

Eroaus¡ of thc ob¡onatloa of ra¡rid fluotu¡txons 1a tbo

plaars PËr l¡vrr (uctart of a.1., LgSz) eooorpanlltl Èy eortst¡nctaÞslio ebsnSoe (nrtzol of s1,., l9568rb) ooourrlÊt tur ooneltrtlosr

sf rrottoner ctç¡es ln ran, Ìictc¡l rar rrd te [ôÈarF. tbo carþnrtabolla ¡ff,cct of, s9ts aad to oonparo tlrt¡ ¡ffrct ultb thetproducrd ¡y î¡ adntnl¡trattoa. (xrtsct ¡t el.r t95gr r96oe).

Follevln6 thr lnÈasr¡sa¡tsr lnJoetton of o.44 u.s,p. unlta of18ll p¡r 8g' to hcaltS volsntr¡m; I re¡rld rlco fa rutaÞollo r¡te(m) væ ob¡crr¡d, uhlch rnr llgnf,ftoaatly grrater thsn tb¡ rlroLa @ follouLag tho latrayanour lnJroüÅaa of o¡r to l.o rg. of t,ov.r thr olgÞt houm of ob¡¡rvatloa. !b¡ r1¡r tn m foltoringf8B uas eooon¡råalrd by rl"ra(ta psì,æ rat¡ ¡ad pular pr..ssrr,chloh vôFe not found forloutng r, adnlnl¡tratton. fb. nrtaDolloroal'o.¡. to tsH var rl5ntlr,eantþ lc¡¡ ln e gr'ux¡ of þ¡nthyrotd

-6{p

.sùåcct. ralãtelnrd oE d¡alooatrd t{¡neld. lhrrr v¡¡ ¡læ tq¡ralltatlvr ill,f,frreor brtn¡rn thr df¡ct¡ of Ëfl ¡¡d tho¡r of

8¡r ta tbct !, Uroductd ¡ ¡roæpt rtæ ln ¡rrrn atd nrlnr Lacrgnnlc

Bboaphetr lwrtr¡¡ Eo ¡uob chratlr urmo ro¡rortrd foJ.rortr8 ggt.

llh¡nr rsrter oorcluúed th¡t thr rarþ rot¡borLo rtfcct sfls$ dlff¡r¡ lror tbnt of !r, but yrt tr ot ylthyrol"úer orlglao

Ehry ruggrst¡d that 8EE lrt¡ sau¡r thr rrll¡æ f¡o¡ tb thgsolt

of a ra¡rldl,y aetlag boraoa¡ d"r¡ttnot frel rr. Horwer¡ othù!

¡n*rlbllltllr ts ¡eoou¡t tor tbl¡ ¡rt¡bolto ¡ffeot ol lgsr

ræel,¡ed. thry t¡¡olr¡ðrd thr ruotr ¡nraf,bürù thst th. rûfrstue¡ o:rtlsthyrotdal ln ori¡la, rhloh l.¡ unrlk.ty la vlor of thslgnifloaat].y ¡roduo.d ¡ffoct ln tbc lÜrpotàfeold rnblcotr. Ibæ¡vas algo th¡ ohanar th¿t tho offrot ra,y havr br¡s du¡ to Gor.

eontasi'n¡¡t tn th rgH ¡xcparatloa or ln ¡onc othrr uå¡¡ yar

rprotllo to th¡ ¡rrrgeratl,oaf u¡¡de îbora alro rcEaLaeit th¡¡n¡¡lbtll$ thst, altbugh tÞ¡ æE cf,f¡et u¿r aot ¡r¡¡rcôuerd ù¡

ft ft ntgbt Þc rcprocluocd, Þy otlnr tþrottl borzen¡ grc¡raretl,cat

¡t¡ch se 1!4r tþrnottl or tbyrogl.ebulln.

fo fqrtb¡r to¡t tbe lrypoth¡al,¡ ruggrctrrå by ll.ctrol thrr¡r+

f,orrr e ¡tud¡r of thr rar\y nltsboLte rf,f¡et of a èt'ff,oæ¡t

brlsda+ of 8ül f¡re¡ a d!.fúrrt¡t enlsal ¡ourGt ue¡ trda. IÀ

;tþrtro¡lartr, træur¡ ltÌiælr.Þrlnothyrol r, Eobrrf,ag A.Ê.¡ D¡rllE.

a

*Í

-3F-

eddLtloa a oenperùron of the ¡ff,cot ultb that produottl bU bo¡t

lnns$.vat¡d IEI r¿¡ r¡dr ln lutùyrold tubJtottr and wlth tb¡tproduoed by eCtrtalstelng th¡ ¡otlur b¡nom to a furthñ 5roup

of tþrrof,d-n¡latrinrô lygotþrotil rubJrotr. lßhL¡ rtrarl¡r cots

prlrtr ltst I of thlr Ghr¡ltæ. A rr¡prt oa thl¡ bal Þ¡¡a

aooc¡rtcel for ¡rublloatfs¡ {fcUty, Bood and Bctnrl¡ ¡96I).

Part 2 con¡lgts of e¡ cxtøsloa of th¡ oÞacrvatton¡ er tþcarry nrtaborle cf,frot¡ eî .8, (nrtær lt 8r,.¡ r959t rg6orrb)

to e oonperleon of tbo oar\r acteÞoLlo cft¡ete of tþroglobulln¡elrclocatrd tbyrelar trr¡roxrBa sßd trtleiotþ¡oal,¡¡c ltr tan. Dert

of thl¡ ha¡ arroagr bæa ¡rubtfuhrd (wrtluy, Bood, chernoel erd

Hetrclr 1960).

a.

rt uac thougbt dcal¡ebb to trst tho tqrpothraLr or g.t".r

It al. (rfOoa) tbat gsH stl¡utatlon oeurtc thl Etcr¡ttoa of e

rapld\y aottng t\yrolô horsoac frou tho graadr by ruarurlag thr¡ffrots of a dLff¡¡ot E9Ë prrpErstion ln rutþrroLd enil þpq-tb¡rrold eubJoste and, also to oon¡rasr tb¡ ¡lf¡ote of thc cetlvrîsü fn tho outþrrof.d group vlÊb thoc¡ of b¡at ineotd.vetrd |Dglt 1¡ordcr to fi¡¡ther rvaruate tbe noa-apeo!,flo rffrct of fnJcotrdprotrln. 8bc lsE uæd provlour\r te ¡ Þeylna ¡re¡raraü,øa. rho

88Hr u¡¡d la thta ltudr !,s drrlvcd fr¡a hog pttnltarl¡¡.

+ Þrincttryroni, tlncüry aupprlotl b¡r soherrng a.o., Dlrünr

-ó5-

(r) egsEr!b 8tX ¡rrprratl.on ureü ü¡r r ¡tudrril gngarrttol

ill¡relvrê ln ncnrJ' ¡ltla¡ asd ¡å¡lnl.¡trrrü by itocp ln*rm¡eü¡r

laJrotlo¡ tn a ëor.Ct of 7.1 tgullrs plg r¡¡ltrF ¡nr 13, borlt

vd.gbt. lhr rlcrag¡ 1r rqulvalot to Or+t U.$.D. rnf,tt Drr Il.eeoordl,ng to lrtrÞ¡l ¡ad ËLtþl (fg60). 8or¡ of thr prep¡retlcl

raa L¡aotl.vat¡d ÈU Þ.atfng to 6OoC tor !O ¡l'¡nt¡¡ at pI ,l.O

fel'lerlag uhf.ch thr pË rar radJurtrd to 5r¡1 a¡¡d th¡ ¡rrqrarattoa

va¡ thca auteol¡vrd. fu a or¡Etrol'r nornal ¡all¡¡¡ y¡¡ adtl,ut¡t-

orcd 1¡ as idrat'l,oal f¡¡hioa epd i¡ ¿ volulo .qul.ralc¡t ts th¡tof tb ?8t lnJtetlo¡.

lVe greupr of rutJrotr ütür urrd, a rutgrretd aad e trypo-

tþrold goupr 8be rutþroful gnouB æ¡¡Lotcd ol ffvo braltþvoln¡¡tr¡r rrdt,oal ¡tudrat¡. thoy Frotltì¡û ¡e1l,n o¡ thr tLr¡têry of obronatf.ol, lû8t on tb¡ ¡lcond (ono nc& f¡tæ) es¡

l,naotLvo !|Br on tho tÞlrd alct (tur rÛ.Ì¡ eftcr tbr ¡reoad ôay).

À¡ a tlnlt.il tl¡r u¡¡ arell¡brc for the rborr gorforl of tbcæ

rhrd;hrr th¡ Îl¡¡t day of oÞ¡ævnti,oa üsa ¡ed¡ thr conbol alcy,

so ar to ¡voltl aa¡r lntæforæo. by thc prololgrrl ofloot of lEgt

e.rntn¿¡taatlon, åßd tÈßdorl¡eti,oa of th¡ tro¡b¡at¡ ou¡r the

th¡æ èaya rao not porof.blee

thc þpotþrold group oolsistrd of tb¡tt ïon.a rlth a8 eg.

rangl of 51-5'gr å.nö uho hail dtvtloped qrrerêre felterlry ruÞtetal

-6?-

tþrel'droto¡f¡ ülo for þyportþroldl¡n anil one f,or tþrold

caroi¡oas, llbry Bem oB ml,¡rtra¡aor thceepy sLth fuII d,ocr¡

of tl1yrof.ri utrest þ.P.). In thf,s gre¿p thc ¡a¡.18 $ôr ednln-

lEt¡rccd on tbr firet day and f8ü oa tlro rcoonnl rle¡r (onc rrtÈ

latr¡). ¡ th¡ roou tmpcra&rrc on th¡ ¡ceonil dqy trÊs r¡areetop-

abþ hlgh (lzoe), s¡¡d 80 blghrr tban or thc ooatrot ða¡r, a furth¡rda¡r of, ob¿¡matlon forlælag lgt rs¡ eedo thrcr sc€û¡ ret¡r rh¡n

tlre reoa tonpcreürr¡ ua¡ Z2oG.

Eve-horelt obeorvatlon¡ ucrc neel¡ o¡ sll aubJcets for rJ,¡ht

boer¡ on ths olt¡r,oal etatr, noteÞollo ratr¡ ¡rul¡r pro¡¡rrre anû

pal"ec rÊt.. 5lb¡ r¡Ëeblio retr (N.n.) rar d¡t¡r¡nLmd wlth a¡

oBen-olrcult a¡shl,n.. Slesd anil urlnr r.'t solrrotrd rhortl¡r

sftc¡ er¡f.va1 Et thr lsboretory üon -1ì ¡uþå¡ct¡ end thæ¡aftrrat tvo-hourþ perloela. precca protcln bo¡¡¡d iedlac (rg¡) rcvrtue¡ cgtl¡stcd by th¡ nrthort of Acland (rg¡z)" urlaery at4

¡rr,aua lnorganlc pbor¡futr vtrr t¡ttaaþil r¿ltþ th¡ n¡thocl ofEaureþ ead sMrr (¡95t) a¡rd or.stt¡llc rxcrrtÍoa by tÞr ¡rtùroâ

of ¡o¡m¡¡ aad Íatratþ 1føl)"Q) tr¡¡ult¡

-

cu,aÍoat Elf¡otg¡ ror¡¡1 ruÞJect¡ ns¡lrr1n6 ÎsË oenpLax.ard oflrrltatlon aad paln et thr ¡f,to of tho l,nlrotlon ea¡l al¡o ofaanr8es a,nd h.8deoÞa le¡tlng fer rcvcrar hour¡. tro rooal rff¡otrla thr tþrrold ¡¡.ra ¡uch c¡ paia or ¡y¡L[1n5 urre oÞ¡eryed.

-6E¡

Sh¡Er r¡n¡lbnr st¡'. suoh þlg tYld¡at t¡ tbc bqpettryrold gronp

glvre I8t såil eÞ¡rst ln tÞc ruth¡rrotrô group tollcrte¡ fn¡¡rtlr¡

tô9.

I A raBtd rt¡. 1rr E oøoÈrrr'¡ð ltr tàl

asrul rubJrote fellorlnS îSE (llg. 9t laÞIr 8). lh¡ rler v¡a

aot¡ð ll for¡¡ of tbr llvr aubf¡et¡ ¡nd tr¡olè anaþala otæ tÞ¡

shoL¡ prri'ort chorrd tlr ¡1,¡r rel àl'ghl¡r ¡lsntftsat wl¡r¡ o@ÞBrôû

rith ¡¡11ro (f. < O.GO¡). th¡n uar no rlgnfftoant r1¡c tn lEfollesl¡g h¡at lnsettvgtrd f$t.

f¡ 3hc þBotþrofö group (lfg. tO¡ feblr $ tronA aaalys!,r

¡hcvod a rlgnlfl,eaat rfet (f < O.o5) oa botlr Sf dayr oæ¡wrd

ul.th thr æatrel. Sone of thlr offrot, horwæ¡ t¡ a¡ tlr¡rarùEt

on¡ end 1¡ clur to a hlgh l¡f.tl¡I l¡vrl on tho oontrol day, Ol

botb daye thc ¡ffret of låä rar rignltlæatþ lec¡ than th¡

rtlrot of tBH ln thr rutllyrold group aoeordlEg to tra¡d analyelt

(f ç o.Ot). Îbo ¡¡en lrcreec Ln thr outgrroLd cuÞJcctr ver

16.ÈÉ eonparcd vlth e nran ínorcaac st 6.Tf lE th fpotþro1ilgroup (on tkr day thr rteou t*n¡ræaturo yr! 2Zog).

¡ In thc ao¡¡al rubtrotr

th¡ rff¡ots on thr Bulm ratr paralloled vrry cleorþ thr rffrot¡oã th. sotaÞorlo rato (nauo to¡ !lg. 9) eno l*era¡or u.r¡rccordeet la tbr flyr aubJoeta. üo rl¡t Ln purao rat¡ ra¡rroordrd foJ.lovl'ng ltl¡otlrr lfÊff. In the Srpothyrold, so co¡tt ¡tent

-69-

FITURE 9

-COMPARISON OF TSH AND INACTIVE TSH

IN EUTHYROID SUBJECTS

TREATMENT

JTSH

METABOLICRATECals.pcr Sq.Metre

per hour

PULSE RATE

PULSEPRESSUREì¡lms.of Hg.

INAOTIVE

OONTROL

TSH

lst{

TIME IN HOURS

o-o CQNTROL: o-. TSH; x--x INACTIVE TSH

ì.{e¿¡.n v¿rlues for 5 subJecta,

-?GÞ

TABIE g

rp FIVE È-oRrAIr ,SUBJECFS

(galE, per Sq7 Mrtre per nour)

SubJoat

frcnd anel¡rair ¡hoved a al'gnlflcantL¡r 6reater rlso 1:ol'lowl,ng tgll$b,cn oon¡lared wi.th sel,ino and laaøtl.v¡ lSH (p<O.OOl,).

48.,55.O

49.1

48.1j2t748.2

48.550c547.1

¡[9.0

4?.r47.,

SalincESH

Inao. t6ll

il&$r8

46.1,4.4

47.4

55.Q4?.0

49.O

5O.545.5

47.641.547.'¡

SalfaolsEInec. fSH

P

46.456.641.4

47.256.551.8

;i,52¡8

47.647.65r.2

SaltncrsHInac. tSH

0

{7.1,6.844.4

15.416.944.6

46.917o546.2

5l.o45.746.5

$nlf.norsHInao. l[SH

!t

5O.l

54.4

45.65r.651.?

50"450.249.2

51.647.746.6

SaLLncîsnInas, l8$H

H

51.8j2o745.,

51.85¡..¡$4V.9

17.5,L.24{.O

46.85O.O

44.6

SeLluarSHInac, 89H

L

7,I ,trcatm¡nt

lBlnc f¡ bst¡rc

-f1-

}'IçURiI 1O

EFFECT OF TSH IN HYPOTHYROID SUBJECTS[uEe¡¡ oF 3¡

NT lSH fR.T.32'Cl

TSH lRJ.22'C¡

TSH lR.T.32'01

TSH lR.r. 22'Cl

coNltot

METABOLICRATEGat. per Sq.Metrc

pcr hour

PULSE RATE

PULSEPRESSUREMms. of HE.

18

12

a

s6

x

0 4TITIE IN HOU

sx ln.T zz'cl

TSH fR.Î.32 'cl

tn$

o-o coNtRoL; o-oTsH f Rt 2z.cl; ¡_xTSH tR.T. 32.C1

-7ù.

IABTA g

HAIflTAINED ON THTBOID

(Cat¡. pot Seo t[¡trc per bour)

Srrnd e.na\rei'a showcd o rlgnlf,l.eant lnorce¡¡ wlth 1[SH (on bothda¡¡s) ooupancil .ulth control (p<0.05). Ibw¡vor tbc rLsc sitb$5II saa algnlff,oant\y lcgs thaa thst obsssad in norael subJcots(f 4o.Of) wt'th the trcnd anal¡nfro

45.'49.4

44.O

17.2

45.7

1r.2

Sa1tnc88ri 15aoc)BsH lezoc)

I{EÀ[ 17 oV

49.545.1

45.849.445.6

44.5

11.!¡1o.8

$e].l.ac

esn $z!c)ssn (e¿oc)

s 41.848,?17.9

{2.947.642.9

4þ"2

46.1¡[O¡0

P

¿15.8

49.149,1Sa,Llno

EBE 15aoc)rsH 6zeoc)

46.95Lo5

19¡2

17.8

55.741.2

\\

49'l'jLtS19..6

zzoc(ßfc )

)

$allnr18E

tgH

c 4?.948.?14.7

¡$?.9

44eA

12e9

48.9¡l8r?

45:ã

4?o6

19.244.8

5,L a*?SubJact lr¡atnrnt

l$lnr la hoì¡rt

(r)

(a) Purss EårB

PUIôE PBESSUnE )-Tffi=lrl-;r'

64

76**59

6'?U+r

,9

60

7?til62

62

66

59

69

6'62

8all.nc88H

Iaactf,Yr l[SH

I6420fna&ont

ßlrc ln hou¡s

+T

,L4'

41.

54st44

4I5**44

¡$8

49

1'

1'1'45

Sallnet8H

Ineotlvo f8H

I6+20lreabrnt

Sl.nc Ín hour¡

** P<o.or oonparcd uith sarlno at ¡asc tino uging anar¡rrtrof va¡l,aner,

.TÞ

f.¡æta¡¡¡ ï¡r. r¡eordld 6orpt ea thc nhotr !SË iley (tc¡fe lf,¡

Flg. lO).

Iul¡r l¡sls¡Er. Laûa.et.s Yar. Goillat.atly found lr

rutgrolrl rubJcotr fol,l"crl.ng lsH (¡auf¡ to¡ !lg. E) Uut th¡rl

vas no r16nlfLoant rlsr la eith¡r tb¡ cuthyrold group a.fter

Insotlvr 88H or l'a the h:'pet\yrold 6roup fol'loul¡g lSH on tltürr

rlay (tettc¡ Lo, l¡).

r Inomere¡ ia

thr ¡rlerna PDI lovr3'¡ v¡ro noord,rd ln thc ruthyroltt grou¡l tror

a E.åB sl 1.6 /Jg. Et u lO0 nI. '3o e nca¡r of 7.8 i2t. prr ltO nl.¡/-- - ./elght bour¡ follourng 88ã adninl¡tratl,oa (mlfc te¡ lt6. Il).

llbor¡ uå¡ å 3t¡rtÞor lnoro¡s¡ to a r.ea of 9.OiLgo ptr 1û0 ¡1.

trrnf-four hsr¡¡s eftrr laJceu.on. Inaotlvo 8SE proiluted r

rie¡ froo ¡1.8 to ,.1irt g. p.r ¡.OO r"l. rt c16bt hour¡ ulrteh J¡¡sù

roacbod elgalfloanor (U. 4.0.05) tut nevorthltEa rer rl,gEl,tlo¡.

antly loec ùhan tbst f,olloutng. tho sotLvr !SË tf< O.Ol).

ÍSB produccal no rl.sr tn thr ptema PEI tcvol 1n thc Èyper-

ttryrold É¡:nDurr, 4.9 yS, Þrfom snð, çe/ugr prt lo0 El. rtgþthor¡¡o aft¡r tSË (tatrr lll xtg. LL).

lhue Hes ao rfet in tbo rleana Lnorganlo pboaphatr l,,rvrl

f,ollorlng actfvr tgH ln tbr noraal eubJrota.

-Trp

DABIA II

oouparod uith oontrol at eano tlsr uclng analyalrof varlano¡.

(") Pur.ss nAsE )

(¡) PUI^58 PAES3URE (Moan Ve].ucs for threc eublcots)t"t". "t "g.,

t l<0.O5** p(0.O1

EÚ

98*rE6

8¡.

96*r86

a2gr*t?8

eI8æ

?I

8q

89

?8

Sell.n¡rsH (rzo

BsH (zzo)

)c

c

I)6¡[2o

!rcatocnt81no ln houra

60

62

#

62

59

60

59

56

65

6C)

,e67

59

60

59

$all.ntrss 1lesc)EsH çzzoc)

I640 2lrestn¡nt

tl'ac Ln bor¡r¡

-?5r

B¡BI8 L2

-

(Hrnn Yaluü fe¡ ¡ Subtrstt)

{f ".

pcr lg0 nt. pla¡c¡)

osupcrcd ¡ttth ooat¡cl et ¡aar tlnr urtag rseltrrlfof, ratta¡el¡

r F<Or05*t P<0.O1*tt P ç0.0O1 )

4.6?râ***5.¡lì

{.t6.1*5.1ç

1.64.64.8

Ê¡ll'or88Ë

Xnao. lDBs

I{o8¡csbe¡t

It¡r lrr bor¡¡t

1[h¡ lnsrrafo u!'th Êotlv¡ EEH 1¡ greÊtar tb¡s thst yltbfnaotÅvl 8$H at tor¡r bou¡c (fçO.Of.) sarl rtgbt bor¡!¡(¡<o.oot).

-T'l-

Ï'IGUT.¿ì 11

-

CCN4PARISON OF EFFECT OF TSH ON PLASMA PBI INEUTHYROID AND I{YPOTFIYROID SUBJEGTS

EUTHYROIDÍMEANFS¡

HYPOTHYROIOIMEANG3I

PLASMAPBI.

¡gms.o/c

TSH

INAOTIVE TSH

ool{rRot

ilrrE rN HOURS TllrE ü{ HOT RS

o-o ooNTROL¡ ô-ô l¡ilacllvE ISH; .-< TSH 1R.L 22'Gt¡

-x

ÌSH ¡Rt l2'Ot

-7ìÞ

E¡pr¡ rl

or, wnorp

jP*, ptr t9g ll. pl¡m¡)

l.I{¡8{.2

1.31.?{"1

9"44'94.1

8¡lLa¡Esn (¡fc)æu (¿fc)

I¡to

tæ8bst8l¡o l¡ þu¡r

-7y

r fb.:ta üarc ao €oa¡i.trat

€hÊnglc Ln laar3gnlo phorpbrt¡ rrc¡Ëoa ln ttrr agÐ81 6foa¡t.

fh.a. yer". no nlgrlfloatt ohaagrr ts nrlaar¡¡ el:tattnLat e¡oçttlo!

tn ¡tth¡r tbr rutftrrold er thr þrpotþ,tlold g.oEP tellovlng an¡r ot

tho Ër¡þ¡nta'(r) Di-¡€ur¡len

8þ ttlallegr meor.drd h¡¡r oa thc caaly nrtaÞolle eff¡ot¡ of

e p¡cpasatl'on of hog AtB oonfl,ru tbocr ro¡nrtlô prrvteurl¡r by

8¡tscL ot el. (fg60a) o* thr ¡f,f,rote sf bovi¡l Í8t. lollcringthe bovln. pr.patetion tÌ¡r l{R Laæca¡¡d bg lg.8f aoeoopanlrd by

a 6LÍl l¡¡orcesr ln thc araøua tBr lov¡J. vlthtn elght houm¡ th.hog preparatlo¡r produocd an rlcvatf'on o:ß 3l6.9f, t.a !A ulth ¡elnoreaae aî ?oí 1n th¡ pEr ln tào e¡¡nc ¡r¡ri.od" tEhr ¡lsllerltyof thc tro pæcpere$,on8 LE al¡c rsflcoted ln tb¡ ¡rulrc r¡tr aaê

puhc llra¡surl reËrpÞsla. ph¡ fellur. of, tõH to ¡*oduer e,B

lnorcaarö ¡rhosghatg rro¡¡tùon rå8 rsa{a notrd re tho invtetiga-tlon anü coatra¡te vtth tbe nerkld pboepheüo dtum¡l¡ follorlngüvrolil bornsnca (Baroou ¡t ar. LgSrl H¡t¡¡l of elo¡ l96oc).

!h¡ na¡L¡il ¡ln!.l"ar1g ln thr rsgnttuðo of th¡ cffæt¡ sE E a¡å

Flr oorrca¡rcnd rlth tbc nlsilar doaagr of thc tvo pn¡raratloe¡

ucodr naucly o.44 u.S.P. r¡¡lts prr f,6. of tho Èovtnc ¡nr¡sratlonand 7.1 gulnca plg rmlte pct Fg. of the bog gEA.

-aÞ

Is th. hfpet¡VroLd groug tbr heg EI preeiusoè ao r1æ l¡

the plaa¡c¡ FI a¡ed r algnlfloeatly sls¡Lr rlr¡ la fB th ta

tln rut\yrolet glûup. Strlr s¡taÞolle tf,f¡ot of 888 t¡ tåærfon

pftrunablt ntdletrtl th¡euch a¡l latest üryrold gta8d ¡nel l¡ *ot

duo ncnry to e eoa-r¡nel,flo ree¡naDl to ¡renatrlal grotd,s.

furt¡br¡cro¡o¡ thi sbsrpor of an¡r et6nlf,t oaat off¡ot on tbr t8,pulsr pr.ssurù aad pula¡ rett follo*tng th. ad¡{ErttDÊtlo¡ otth¡ lnaotl.vntcd pm¡nrattoa targoly ¡¡crudo¡ thr peeclb{rlty olno¡-!tr'tolfro n¡po¿3. to lajrettd ¡rotria. Goaorr¡|,tr8 tÞporrlbJ.llÇ thet thc ¡flrot n¡y br du¡ to ooatsâlnâlt¡ ls thrfSHr thlÊ ¡¡rcX¡s;ratioa lc ¡tatod to Þe fr¡¡ of ¡notcrlor pitrrlta¡.7

faotom, folll,ob ¡tlruLatlag aaal eds¡uooo¡tLootrophl€ bo¡roarl.

trt l.¡ alro rtatcil to Þo tÌce of lutrotroghlo bornoar, ¡pr'gÈ tàlr1¡ t&o rost rlhclJ eontrnt¡aat (rûnour, ls9). rntæbrophlo

hornon¡ haç bra¡r sôalnl,s,Ètt¡d to bypothyæoto¡l,r¡d retr rltþoutcuÞoqurnt rloc ln Hl (gvÊns of al.¡ lgi?).

lfåryolilltú.¡ I ]lh¡ r¡aotlet¡ hav¡ bten ¡..orntly nportrd(nano*tlO ¡t al,, IgúO) naatfoeting ¡¡ 1ooal Þelar rrtlì.Ieg ald

hr¡t ta the tüyretd Bro&e suoh rc¿sttor¡ rcr. not forud l¡ tbrBr¡mnt {tror¡D of rubJoatr, rlthough thry h¡yr btrn notrd ¡rv¡raltt^u¡e arrberqurat\r. l¡ tbrr¡ r¡aotlor¡ pÞebþ refLrot tbrlao¡¡a¡rd rat¡ of ¡rarnal e¡rathml¡ rttåln ttr tÞyrolal gl¡¡dr ttÊemg uau¡Gd.r tbat tlrcy esuld rauat tbr granrel tncæaar 1n lE

-&I-

aE rccsrd.d Þy [¡ts¡I ct al. (fgOOa) aaat eontlrald bel.r

gtall¡r ntebollo cffretc folloErLsg Í8Ë adslslatratlon ha'.

bsrn rc¡nrttd prevloual¡ {Barron, 195+f RsIl et aI. f954). Iâ

thrsr otuillre 88H r¡a¡ obscrv¡d to lravc a sot¡boLlo .ff.et Q.uÊlft-

atfvrLy eLsllar b î, aad !41 thl off¡ot of IEH wa¡ aþolllhrd

uhcn gùvrn b oao patirnt ultl¡ ryrocdora. lïos th¡ r¡culta ol

the adul,nfatratloa of fsË to onl eub$ret only 1t t*as thougþt that

tbr nctaþoLle ¡ffcot ra¡ ¡Lu1l¡¡ to that of !, but ¡orc rapltl

than that follorlnS !a, ìÍctabollo rff¡et¡ r¡pen lt pld uotaboll.rn

fotlewlng IHSH havt EIeo bee d¡¡ortbrd (frcfnfrf of a1., f96f)

bnt thog. arÒ prsuns,bJ.y utratþrof,tlal 1n orf6l.n.

(+)@B¡rlV nctabolio rff¡ota atel.la¡ ts tho¡e ¡rrcvlous$ re¡nrtoâ

(BetzeL ct al.¡ 1960¡) u!-th E bovlm proBsratton of têI hav¡ Þrrn

oþ¡c¡v¡û followfng e bot fSE ¡rrcperatloa. [o ¡r¡cb eff¡ot¡ u¡r.

obeervcd folloulag a¡ lEaotLv¡trd, 18tr ¡rcparatlen, furtb¡

oon¡.at o¡ tb¡ ¡nralÞJ,e ¡lgnlflæno¡ o,f thrao fladlngs rf.I[

appoar lte hrt 2 of thl,s Oba¡rttl.

-8þ

t.

t

Prrrlsu¡ ¡tr¡dlr¡ Ëy Eetar1 ¡t aI. (f95sr f96og) hava 6tEa

ovl.etæet of as .arlt ¡ot*þollo .úf.Gt of EË8¡ eB¡nrætþ crdlatrd

threugh en lntact th¡rrei.d glald¡ þut not r.produord by tbr edlrl¡r

l¡tratlea of !r. It ua¡ thought of Lnttrcst to .rt ad thr rùtQr

to a s1¡å1$ gran{n&tloa of tho ear\r r¡tabsllo rfftot ol t$rro-

$oþullar dceloaatrð tþ¡rrolil rnd t$rroxlno to aisrsa shrthor tÞ4r

oo'¡¡lil rrploduoe thc ¡f,frqt of, l[8I1.

(r) xnrgorɡ

-lbr grucrel' cxpcrlnrntal oonilltloas torc casoltlal\y tùa

sa&Ð as tho¡e reoordccl i.n Part I of thfs Chaptcr. A oon¡nrlron

of tho eat\y netabollc cff¡ote of tþroful, 1O aaû !, uar reðr flono groîr¡) ef ecbJects. In e¡othcr group, theol obccrrntlo¡¡

vcra extrllel¡d to a eon¡nr"lson of tlrr cffrot¡ of t, ¡Ioa. rtth

thosr of f¡ 1n th¡ ptostao. of î88, ¿net alao utth tbc rffrût¡ et

thyroglsbulin.

tl.ve hral.tg nal¡ vo}¡ntr¡r .ùtdürtc oonprlrtd thr ltrrt

Foupr on vhon obs¡ryatl.ona sare sôr on ¡loer oEea¡loar of r|'gÞt

hou¡s. Eaoh studtat rcorlvrd orally on ¡Eoh of thr f,or¡r day¡

clthor a p!.eorbo, vltaurn D1r 2i r,g. (r)l red!,rr r-tþrorlnr(ta)r 2,.5 lo l.o ng. (aeæreltng to Þody urraÈt)¡ drctooatrrt

-8y

tþrofd åO-3O greins (t.5 to 2.O g.) or ¡odùt¡æI-trllodothgrroalnc

(lf) (O.5 nt.). fho ptaeoÞo ya¡ adn{nl.¡tered on thc f:lr'st ilry'r

th¡rrof.et ead !* Utra randonl¡rd oY¡r the n¡¡t tuo days of abalrvE-

tle¡ anil !, rar gfvre oE the flnaì. tlay.

th¡ e¡ooad ÊIeuB eoa¡L¡tcd of a dlff¡¡rrnt lot of f,lvc ¡tudr¡t¡.

Eaoh ¡tuilcnt r¡scl,vrd orel vlto-rn 81 {a5 rS.) "¡¿ a¡ lntsanu¡culer

LaJcotfon of 2 tI. sf norual, ¡elln¡ oa th¡ flr¡t dag, oral t,(O.5 sg.) .o¿ 2 sL. lntranuoaular ¡ellac on tho ceoond, oral !,(0.5 eg.) aa¿ 0.44 U.8.Pe unlt¡ of lg$r la 2 r,I. nsrnal mXlm

tat¡a¡raoularþ oa thc tht-ril dq¡r, and thrte rrc*¡ latcr oa thr

fourth ùag thry r¡e¡lvccl oral th¡rroglobult,o** l" e doregc of?.O 16r Bor Í6. of body ve1ghî.

Obac¡rvatlons y.r. nEdc on oll¡¡loal atoto¡ pulac ¡ato a¡il

puLer prrscrra¡ åDd bleod a¡d u¡la. uaro aolrcetod et tnop

Þourþ lat¡rya.l.g as dc¡crlÞod cÈovr. rhr annly¡ir of, ¡llaneenai r¡ELac for placaa PEr end lnorgenio phorpåatc rev¡la y.rr

carrlotl out ulth tho aethoda cftcd aboyl.

þ) n¡su¡Æs

-Dellorlag tsË aad E1r lonr cubJrctr æn¡rratnrd of hcadaoho

a¡rd nau¡car and 2¡$ br¡¡¡ lortwtng thr ggt tnJrotioa tro rubJrotaoorpral'nrct of pala 1n thr thyrold ar.a on ¡rsl¡,erlq. !h¡tþrold glaad ln bth of thc¡r rublcotr ras ¡nlpabrr enlargod.!o oltnl.sel cffiots rhl.ch oould br ¡¡eriÞ¡d to aqy of thr tùürofal

¡lnd¡y ruppllcd by Sohrrlq À.Gr¡ D.t¡la.;.iH:.T ;i"}i:.Ïi il;.¡.". Þoc, re*r.a

tTT

-g{-

pra¡rsratlost oY6 thc pcrlod of obooçatlog rg¡ ¡strû.

r Io ocEll.teat cbt'Eglû

1a pubr rat. rerr [ot.al la thc ltr¡t gsoup fol.lorLng thyrotd¡

15 or ß4r (ta¡fr 1,$) nor 1B th. ¡eoo¡tl group folloutng tbr

pleorbo (S + nr), ¡allac ead f, (s + fO) ol af,t.r t\yro6lobultn

(fattr f5). t elgnLff.eaat l¡orl¡c la ¡rrrlcr rctr vet oþ¡etrrê

follor1ng ¡f,nnlt¡¡¡æue t, a¡d !8ã (tSX + !r) omnar¡d to I + 8l(raurr r5) (l4,o.or )

lhr adnlnl,otratlon ef !* ua^c lollev¡d by aû lncr.¿rr 1¡

both eyrtollo aael rllartollo brcod pr.aær. ui,thl,n tro boum,

rcaohl,sg a ¡ad¡r¡¡ ln fonl hourc. (r< o.or) (!a.lt¡¡ 16 ald l?),glnllar ohangoc f,ollery¡d tþro!.d¡ rcachlng a ErúrÌ¡r t¡¡ 6 bos¡(f <O.Ot). tro ohangra follorcil î, tn thío foup End noat otth¡ac prcparatlo¡¡ had. *n cftoot e¡ ¡rulæ ¡rrar¡uro. rn tho

aoeonð ¿FeuD of ruÞJrota, !, aad EËH bad tþc rff¡ot of preituoleg

a pulm lrrïoa¡r'. rls¡ (¡r¡rr rg) (rco.o1 ) t-brro roro !orffcot¡ follovüg S + E¡r S + !O or tþ¡rreglehlla.

Effrst¡ oa Hrteùells Bat¡¡ Âc notcd grevlonaþ (üttsrl of *1.¡

f960e) l'a l¡v¡¡ûtgatlaar of tble tp¡r thr t8 1¡sr¿¡¡il on btùcontlol \¡rr (feufo 19, ltg. tl) (eautr 2o¡ Dtg. 12) prr¡rnaÞl¡

clur to tlorcarLag r¡rtl.l¡¡ar¡¡ ef thr rebtest¡. In tbr fl¡¡tBfor¡pr !, Irroduocd ¡n l.nor.et. 1¡ ertaÞol'lo ratr ln alL fl.çr

rnÞJrotr et threr, fï,vr ¡Bd ¡lvæ hourl, (p< O.Ot) ruleh va¡

ÍtlltIrç{.<

?qta

sgrsra*flarli?r?ç

cr gìl Il

çtrltç*

útllsor*útçlì

r{ôr¿PIöC'

rtdâh.Ðe.!Ê

ñta

Et

05,tÍrl

c'tcaIICöå

tü0üÁrltJI¡{

+

-8úp

atü¡É ¡,i

OT PUISE NASB

82

66

6,?8**,8

6¡l

66gl**58

rÉr(

64

64T4

,7

6164

66

,6

67

T'68

58

Sellnr + 8l$al,tar + t53så + 8¡thyroglobrelia

þfEåTË

90

æt97962

TO

64

86

60

61

7+

87

61

62

6?

6q

66

80

?8

75

5T

SaLlrl¡ + 8ISs.lJ.nr + f5!sË + 33îhyreglobr¡ILa

ï

fO¡t

8t7'

lozl*

81

8¡95

74

8ti

T4

98?,

78

76

e466

72

90

7466

Eallnc + E1

S¡ll'nr + I5ts$ + 85flyrogloþ'¿lta

I

T2

,1,,66

48

5?

60

62

52

56

57

56

to

57

,+,s4'6

60

,,56

14

$¿ltar + 3lSel;lnc + ttlSH + f1fhgrogl.ohrlfn

Y

68

,,6,72

52

,764

?846

576I61

42

5760

56

16

6?7662

,8

Sal'lnr + EtSaLia¡ + IttSIt + !5!þrroglobull¡¡

v

?8

:T2

56

5462

e4

55

57

5e

61

58

ó66,6,54

52

65

?r6,

Jcot

I

Sub 21I6420Srcahe nt

üIJ{B IH HOUNS

*ìr P< 0.01 compared with Satlne and

varíance.

Bl using analysis of

-af-

gÂBrt t6

-

)

rt9128

Ltt120

Ir?rzsr2grtao

ll¡¡,26tL"*rr9

Ir81r9t5¡r117

LNT"128

119

tenFolEryDold

!4It

a6{2oßrcsfu.nt

8trnc L¡ Ëour¡

* P<o'ot Go*parcat stth eostrol for thr aau¡ porr.ed, uatngrtt F tc¡t.

.9T lTdi,cü EF Fr 9o.o)¡T

(

rr--Ë[w

TL

a8

rSl9L

9L

fert8

9L

6¿

rg8

aa

5¿

çL

t8LL

6L

GleCI8

88

lfr

'¡ P¡o¡.Q,¡

ïo¡+Eoc

lürq,Era¡,

I)Ì¿o

r¡Edl El rfrt

{8r

-gÞTA3I8 T8

OB PUISB FNESSTTBE

(r*. of Ug.)

1T

1T

t4 *rç

+4

45

15

4E

,$0

,e42

50**12

41

42

48

,9

48+9¡tl10

Sallnr + Bl8a11nr + 15tSH + 8¡fþrogloÞulln

ilEA¡8

60

to68

1.6

46

+8

,,50

5'60

60

t2

æ+,60

18

?o

60

50

12

Eell¡o + DlSalluo + !5lSB + 8¡EIryreglebulln

ï

n+8

5r.

16

,,,,48

56

15

t8,+,6

,o45

,5,1

to+,4'¡l+

8atrl,sr + BISatlnr + 15tsH + f¡8þrogloÞüll¡

I

+,5060

{6

12

to50¡[o

{o+5

58

,o

,lO

1'1'F

frt8l5ld)

B¡1¡

ÞuIla

U

5'4'æ41

,,{0{6

'8

,,,81?,

40

n,5,576

+,w,6,5

8ellnc + DIS¡Ilnt + !t88H + ItShgrogloÞut1À

r

2'&,,,8

{5&lo,,

20

t055

,1

w10

16

,6

4¡lo

28

+a

$alin¡ i BtSallar + fttSE + 8¡EbyroglobÈlle

I

I642oSr.abctJcot

I

I

Sub

111¡r La Essr¡

**P<0.01 compared with Sa1ine + 81 uslng analysis of variârrceo

t*T'Tl¿.9,¿'Ll¿'gþ

*r9' Li¿.rç

{5'6tç.çt

**L'çþ¿.T'E.zþ9'¿þ

B.tirf'Tl

9'þva'þ,I{TIÍH

T'¿ùç,.81L.8þ6.gl

T'9þl'çþ¿'61o.?f

ç.çlg.ùfç.çig'€f

ç.¿þg.lþl,gto'5ù

ç,8

t6Bto¡&¡Tc¡+l¡ocÍ.

g'oç9'¿þ0'¿tç,.L'

ù'gtf'¿lo'çþT.lt

L.LIg'Ttç,.¿þ

Bolt

T..çþ

f.¿þû.ç,þg.gþ

çú

tüpTo¡&U

To¡+r¡ocT

g.çç

¿.gtg'Llç. Li

L.Tçg'Ela'8þ9.çl

g'6t1..v.,

l.¿lC'¿l

L'8þ6.6ç.

¿'gl9'gl

l&tt

BTo¡&üTor+troof

l.lçg.gþ

l.6lL.gl

g'gt

'.9t l. Llf.ll

T'gl6.oùo.?,o.9þ

L.çþ¿'6ç9'ç,o'c?.

It,

'E pTo¡Âl{¡g

To¡+EooH

I.Lþo'6ûa.çl8.çl

6.L'ç.Íl6'Ttç,.d,

8'TT

O.TÞ

1,.G,

ç.8ç,

e.llo'Tto'çlL.çþ

5¡tE

pTo¡fr{t

Ta¡&]uocÐ

eT$s.Elno¡&

¡¡InoH EÎ eEËÉ

+o¡tqnt

Boçred e", s rq+ ùo¡ ror$u**;;l^'i:#3ll I H:Sì;t+f

cr?ü

pto¡Á¡.tü

TO¡nlso0

(laon ¡.¡ .4¡¡ rrranbg .rrd srpolug)gõcStEnB gârf, KI

6Ï EIS'E

.{6-

r9I-

T¡IOURE 1I

-COMPARISON OF THYROID, T4 AND T3

JMETABOLICRAT E

Gats. per Sq.M.per hour

PULSE RATE

PHOSPHATEEXCRETION

Mg. Per minute

--È -.-Ã

I'

0

TIME IN HOURS

Q-QGoNTROL.-oTHyps¡s)(-[1a a-ar¡

0

Moan v¡.lue,Ë fotr þ subJects.

-9ÈEåEIE--39,

OB MBf,AEO]¡C BATB

Trend. analysis shor¿ed a sign.tficantly greater rise following

44.O

47.744.844.8

satlne + Bl8a,l1no + f58S8 + E¡th¡rroglobulln

HS¡ÀH$

49.441.L49.846o4

41.614.848.847.6

47.7*8.251,O48.I

44.511.64O.9¡[O.O

45.î12.945.9üf,.o2

47.24Ú .641,946.6

47.945.O47.747.9

Sal'l,nr + 8I8a1l¡¡ + ItlsH + 31fhyroglobulla

I

1

T

T

9sll!.sr- + 8lSallne + 1,SSH + f5thyrog.lobt¡¡.ln

45.746.749.848.2

¡[8.2

9O.55L.55L.T

40.948.9¿$5.O

¡$?.8

!oo?fi.256.O46.9

fl

9ol1n¡ + BISalLnc + ?,88H + f1thyrogÈobulfn

44.850.7,L.619.7

4¡l.o49.74?.241.9

?;

I¡

i-'

15.)45.849.4d8e5

15.2¡i9.15O.7

48.4

,

:ÁI

{td

Sallno + BlSalLno + î,r$ts + 15

EhyrogJ.obulla

Y

5I.1.4'î.445.547.5

iÈ'Ì

v¡a

Ë

h

È

:.

t6.94?. ¿l

jOc5

ãO.4

49.2,2.85O.lN.6

19c211.551el¿$6.0

:a:

i¡l

í,

:t

$ellno + 81SaXLnr + !,rSË + f¡tWroC].obutln

t,9.647.L47.744.0

42.144.052.2¡$4.4

47.6¡[4.]'jAoS

46.7

47.644.0¡$8.9

45.8

SubJcot tr¡ataent

ttnc 1n lþllrs

2-4û-2

TSH + T, when compared wíth saline + B., (f 4O.Ot ).

-93-

FISURIï .I2

-COMPARATIVE EFFECTS 0F T3, THYROGLOBULIN

AND ITSH and T3l lN EUTHYROID SUBJECTSIMEAN OF 5I

52

ISH & Tg AI50

METABOLIC

RATE

Cats. per

Sq. M. per

Hour

48T¡TG

46

ü

o44

T IME IN HOURS

CONTROLO-O THyRoGLOg.f-O rg X-X TsH & 13 [-[

-9þ

Grnftr!.ð Þy ¡ trcnil annl¡rrLa ov.tr thc nhob grrto<t (f < O.Ol).

Îþrold ploêuccå a tr¡rc ¡a¡t¡é lrorcatr uhloh r*l ncst rp¡nræt

st flvc þnr¡ (f4O.Ol) *ft¡.qg¡ not al3si.ftc¡¡t rlth tbo Èæ¿

eaeþrl't o.r.a th¡ rbsb ¡nrûcde So el¡rstloa yeo ob¡crç¡d

fellælr¡ !a rhra aon¡nrlê rfth thr eoatrol et tàror¡ *lvo anð

r.y.D bcur¡ altho'¡gh tho tred analyria rhsrycrl aa rpp¡8Gt

lnorca¡¡ (f aO.Ot) ov.r tÞ¡ vholr pcrfcd¡ thta Èrl,ng duo to

th¡ ono bur reluo bcfng illeær¡nrtry thor¡gh 3t5nu1oå¡tly rou

vb¡n oompamd vlth tht ærrcrpeed1l¡6 sont¡ol yarur (rrrrr lg, ).tn tbr groond, geuÞ of, euÞJrota, ao cor¡l¡tcat rff¡ota on

Il8 urrc produord rlth th¡rrogloùuxfn, or rÍth l!, + E¡ elthough

elgnl:8loast lnor¡a¡¡¡ $lth ,l!, etoac Þve brrn t ûerdod ¡ncrtoerl¡r.!5 * !EË produord a ri¡¡ rbtob rrs rl¡niftcaatþ grratrr tb¡n throontrol da¡r þ qo.0o1) rf.th tr¡nd enar¡rr!,r (naurr zo). thl¡ rlrvac of thr ¡q¡ ordrr e¡ that fol.lortng lgH eloar ar Flsord¡d laPa¡t I ef thl,¡ Cb¡ptrro

Eff¡etr en Ple¡¡a IDI¡ Ehr ed¡lnl¡tratl,o¡ of tgrrold proöuotd a

rlrr la ¡ü.ane Br (leurr ar¡ Ëg. l¿l) flon a Doå¡ lov¡l of1.9 ,tS. pæ lO0 nl. to lO.2 ltg. ¡ror tOO alo rltbl¡ tre houra,./ -/aad thlr rorol ve¡ ¡sl,ntEla¡d tbroc6hout tbr perlod cf oÞ¡c*r¡-tlon. 8þrrcrl,al ¡rroduord a ¡iotl¡r rGsrþn¡rr È[d thc ru¡nnmto t\yroglobulln så¡ totrcvhat grr*trr rlth tht doaagt ured, th.terleu¡ rrvrl rraohtag L2o97sr pæ loo nl. at { Þour8. sughtlnoroeara u.r. noordcd foLLovl,ng !, aloae ln tbo flr¡t groug ald

s,.ç

9.5l.oro.l

slør'0ï1.t

L.gT'OT

ç.6l'ç

ç,.9

o.6

¿'oTl.l

g'lg.l6.'r.f

f¡t¡'

pp¡&¡to¡î'Eoo

I9,¿0$srßÙs¡¡ú

r&at lf¡ tüÍg

(wug Òtr! oot ma .*ll

ffiws

4C,-

-96-

FIGURT¡ 14

-coMPARlsoN oF THYROID ' T4 AND T3

¡THYROIDJT4

I

g

PB. I.,¡9ms. per

100 mittititresptasma

7

6

5

T3

CONTROL

TIME N HOURS

O-O CONTROL;o-OTHYR0ID;X-)( 14, A-

Hean velue for l subJects.

Ars

-9T-

fotl'eulas 8, * Ba ln tbe ¡¡ooacl grouB (tattc zel Dlg. I5).

fhc rcepons. to t, + l$X saa sfn!,ler to that goüolleg tsä

e:.one (raur¡ rz¡ DL6. 1l).

¡ thcro flas an eaalY rleo

1n ¡rlaeaa lnor6anlc phosphatc tollovfag !!t tn thr ll'r¡t grouB of

suÞJcots (eautr 2ã) uf¡fofr wae ai.gníff'oent Þy four hour¡

(B< o.O5). Flasps lnorganlo phoephatc lev¡ls at O and I hsur¡

on$r rerr rotlsatrrl Ía thr groonct atuit¡r åad thr rceulta vorl aot

ana\rocd (fattc a4). thcrc was an Lacrccao fn pboepbato lcvol

ín both f, + Ba antl !, + 8SH of thc ee,Bo ord.t ar tÈåt folloving

S, tn thr flr¡t group. fhyroglobulln productd a rdat alneet of

tbt ¡anr nagnltudr. îho r1¡r follorlng thyrold ooor¡mtd tn th¡t¡out of, tho f,lv¡ aubJccts ln tho flr¡t gtoup and dlcl not qultr

rrach algntlloanooo ßh¡ro rraa ao rlsr folloslng 1+.

¡ lfhetc vaa e ngrked

phocphato ül'uæ¡L¡ þ< O.Ot) tofforfng I, b elt of thc tour

aubJrote of the ft.ret g¡or¡p uho¡¡ wl¡e coll¡otf.on: u.r. fo¡¡¡d

to Þ¡ oonphto fron thc ôctcrsl,ngtlon of tbc cr¡atl¡lno sontmt¡

(faUfr Z5l P[S. Ir). â rle¡ ot a ¡l¡llar ord¡l rae fouaü

fotlorlne E, + Ba la thr aoeoad grnu¡l (fqO.Ot ) a¡d a rlfsbtlygrratcr rlsr rre¡ fornd follswfÁg E, + 8Sln. (faftr a6¡ ttg. 16).

Bla¡c w.r. ¡coord¡d follovlng both thylolit (r< o.o5) *"¿ tþro-globuttn (rç o.ot ) rhrn oom¡ramd vith tbr lrepoottvr eoatrol¡r

t.6r.6z.¿lL.Lt'l¿'g

6'arÍ.L6.9¿.1

t'lo.lL.l,.ç

rß¡lE{oÉû¡&f¡ + gg¡

É¡ + .sftrBlC + .EytüS

EidIto

î,úta$a.¡¡ rGail úI útú

(wtltt 'Tt oor ara' '*l¡

€6-

-99-

FIOUNE 1 6

-coMPARATtvE EFFECTS oF T3, THyRoGLoBuLtN

AND [TSH ANd Tg] IN EUTHVROID SUBJECTSh4Eltt oF sI

THYROGLOB

12

t0

PBI.,ug Per,l00

mtof

PLASMA

TSH & A

CONTROL

2 6

TIME IN HOURS

l1

I

4

T

It,

CONTROL +o THYROGLOBUL|N H T3 X-¡ T.S.H.& T3 r-ô

'tls€ u *¡ãu¡cn po¡¡od oEB¡ .rot Tqr+Eoo q+TA pa.ttrduoo

((

TO'O>t 0Igo'o >t r

**l'ÇT.tl.t¿.,

r*6'io.tl.to't

19'tr'iTot¿.1

ç.oþ

6.1g,çg.ç

T'tL'ç9'çB'l

Ës

t¡pl6¡lhtü

IO,¡rluoctfvEll

6.tr'tg'fç,'l

L.ll.tç.,l.l

t'tç.1g.fç.1

ç.,l.lç.þ¿'l

ç,.þ

0'lg.Íç..,

lúiú

BTorÁttú

Ts¡+uocT

ç'çg'çL'tL'l

6.1l.ct.tr'ì

t.tL'ç,g.ç

' ç.1

6.çT'tg'çgrç

o.tg.ç,

6rç,

6rç,

fetü

pTo¡¡ttõ

To¡suoct

6.çL.lL't6.'

z.çg.ùL.ll.t

o.ggct6.þ6'l

l.lç.16.ç9'þ

0.6þ.,6.Êç,'l

çeT¡

pTa¡.6qü,

1o¡+lroc

ü.6grl9'çl.t

6.1TÔTg'ç8.É

o'g6.ùlÒcL.ç

g'tç.Íg'ç¿'ç

g'tç.1,.çç.ç

çú

ttplorÁ{$'

To¡+uoc

L'þo't9'l6.ç

L.þi.ls.ll.c

r.fl.çg'lç.ç

1.,a'sl,'çÍ.1

L.¿g.¿

I-'ç6.¿

çett

pfo¡fqú

To¡¡*r¡oco

g9,¿+BoElE.¡E+or9qnS

f,

H

-rOlrrÀBr8 24

(ng.¿/too nt. )

7.?{.84.94.9

7.17.55.67.8

S¡lllar + DlSallnc + ftîSH + 85lbyrogloþrrllE

I.tBags

4.75.24.15.V

ï.74.15.7Vc6

SalLnr + ElSallno + ItEsH + 81

thyregJ.oÞulln

r

7.11.55.O

5.O

j.57.6!.84.O

SalL¡ro + Bt8allnr + E5

8BH + î¡8þroglobulln

x

5tT9.4j.44.9

5.77.54.11.7

SaLf.nr + E¡Sallnc + It88H + î5EtVroglobulla

U

t'B{.95.O

l-i

6.4

7.V

5.17.51.4

9allnr + EIS¡llac + E,rBH + S¡fbyrosleÞull,n

v

9.27.9

(g ur - 4.o){.I

5.22e'l

9.1).6

Sallar + El$elLnc + fttsH + !5Ssrroglobuttn

tE

IolrcatuætSubJcot

81nc ln Hour¡

.lAtS o$a9sTen poT¡cd .urrs üoI To¡+uoo II+TA po.rtrduoo

09'0Tg.0

o¿'0lg'a

çær$E

f To'o)¿ r+( so.o)a *

+o.ßqn

*196'09ç'ø

*9L'oTE'O

08.0

6E.0É9'o

z9'Q

o¿.0

9E'O

ll.ozç.a

Lg.oof '00ù'oç.ç.. a

EE

'E pTo¡6qS

tossEoorYìsDf

çg'o8t'Oç.9.t)

Lþ.O

99'ot9'o69.089'0

¿ç.ogg.o

lç'o09.o

6ç.'()

81. O

gÍ. oLç,'O

fE+ú

pTo¡&ü

Ts¡ilùsoc4

6T'T

09'o68'olg.o

¿L.at9'o9¿'O

çg'Ð

6Ç'a09'06ç.o09'o

Eç.ogt.oç,1'oçç.o

ç,ú

'E Bfo¡rtq¡,

To¡+EocT

¿9'o¿ç'alç.aç9'O

zr.1gÞ'0

ol.o¿ç.o

g6.a

9T'O

6i.0¿ç.o

çE

TE

plo¡¡t{E

TO.¡+EO0f

8e 'Ti9.og¿.o

6z'o

96.O

I"9'otg'0Tg.O

ggoo

89.0gù.0

gl'o

0t'0rf 'ogl.0¿¿ 'o

ç,ú

tepTo¡f¡tü

To.suoc0

8:99-,,.8?-0Ðlfoq?o¡iD3AraH l¡T ruË¡

-tOT-

_IOÞ

NABTE 26

(¡ne.P/"la. )

SubJeot

*P < 0.05**P< 0.01

***P< 0.005

U

)))

Compared with control (satine + n., ) for the same

O. ¡18

Or89**l.O9#0.9!*x

or48O.66r+

o"?l*0.64*

0. ¡lI0.450.4'oO.45

().r,Ð.7'lO.t,o.tg

SÊllÃ. + BlSall.nr + |D5

rsH + 85

fhyÌoeloh¡1,t.n

HEAñS

O. ¿16

o.74Or?4

0¡ 9O

O"4,o.42o.6goo5g

0.40Ao25A.r9Q.57

0.ã80.7Lo.10O.5O

SeILn¡ + D¡

SalLn¡ + f$'t

rBH + !1Slvroelsbultn

T

O.45

I.121.ltO.90

A.420088Q.67

o.6l

0.46o.55o.460.4¡+

0.280.4,0.44O.r'l

3a11n¡ + B¡,

Sallne + 15

SStl + î1fh¡rrogloh¡Iln

I

0.594.9,1.52I¡15

0.600.45O.35O.?,

o.650.640¡81O.88

O.4?

Q,72o.3lo.57

Sel.ine + EI$elf.ne + f,SSH + 15

EÌ¡yroglsbulln

8.570.86L.08O¡81

Q.55O.520.5O

0.41

O.22O.V2

orlSO¡1?

Or120.200o 2I,

o.10

SaLf,n + BISaltn¡ + S5

fSH + f5thgrrogloÈulln

T

Q.51O.82l.2Oo.89

O.5¡$

0.820.88O.?l

Oo19

0.69O.560.54

o.40o.580r5¿$

0.56

Eallno + BlSallnr + f,lSH + !1IhyroglobulIn

t

6€4á210-¿lnsetacat

Stse l¡ Hotrre

period using trtrr test.

-104-

FIGUIìA 16æ

COMPARATIVE EFFECTS 0F T3, THYROGLOBULIN

AND [TSH ANd TA] IN EUTHYROID SUBJECTS'lueAru oF sl

I TSH & T¡

1.0TO

Tg

URINE O'8

PHOSPHATEEXoREt'O*o.u

0.4CONTROL

0.2

TIME IN HOURS

CONTROLO-O THYROGLOBULI NO-O T3N-¡ TSH & T¡ AJA

-loh

þ) s¡sgsågg.

Thte ¡ù¡dy eeaf¡ c{tñflt'E.tl tb¡ ¡fleotr of It feqd

prtvl,ousfy fi¡ tÞls l¡brÊùoly (grttcf tt al.¡ t95A' fgCOf) as¿

by ethore (Beveon .t el.r l95tf Àepor ¡t al. ¡ L%5). 1lbat

yaå a n¡rlcô lngr¡a¡¡ lE ¡llareø ard reLaarjr plne¡rhato æatl¡t

ulth a rtoc !,4 netabollo retr ovfêst 1¡ tho faoe of onl¡l ¡lalrel

obaagra ln tho plesoa IËI. tlbc Lesh of rftoot oa ¡rleæe tBI lr

not aur¡rl¡lng Enrl l,e clur part\y to thr aæellor a¡nouat of tL¡moltÐ

Lodl.nr s¡nt"nlstr¡rd anð partþ to tho &¡osa rapld uptahr ef !¡ ËU

thr pcrtpb¡¡al tlcaucer oost rcorat\r ooaflrnoct b¡ larson ead

ÂLbrlsht (rg¡s).

Uhon tlffrold and tìyroglch¡Iln rtr. er¡nratc$ ailnl.etrtcr,¡d

ln ðos¡s ar¡fÍLel¡nt to clovste tbr EBI to e lcrcl of, ap¡rroriratcly

l:ù.L2/114p plr IOO ¡1. tÞ¡rr osquared e rl¡e fn netabollo ratr aed

tn urlaary Bboogbat¡ sisllar to but not a¡ grcat ae that follorylrg

tr. Íb¡ rffrot of tùyrold tÞ¡¡¡ oonflrus the fladÍaga of Iy1¡ ot

Bl.¡ (fg¡e), BoÍ.y.r, other at¡¡el!,r¡ ln thl¡ laÞoratory (ur¡¡¡yt

trevrcsec a¡è Ert¡el.r f999) oa tho ¡ffcot of alall dally do¡ra cf

E, (færng. ) and thyrolil (a-fO ng. ) la ¡ntlantr ulth ryzocÔrn

ehoc tboro lE ¡øsc quel.l,tettvc dÍffuræor botvoca the n¡tsbollo

offccte of I, aad tþrrold. Illcaool,atlon ol thc fal.l fn plarno

olplcat¡rol tÞoa the rl¡a Ln Þssal notabolle ratc could Èo dlæû-

Etratrd followl,ng f, but sot foll,srlng drsf.ceatcd, tlryrrold.

-106-

It l's aDlra .Bt tÞat th¡ acl¡talsbstLoa of thc aor. llov\r

aotl.ag ffr f'E e¡rltc o! ea elovatt'on of tbr plaane DD¡ to

*LO /*e. pcr lOO EL¡ rBÊ not a¡aoot"atrd vlth a algnffloa¡t

cloyatlon of tbr lB at th¡or flvo ¡nê acv.n houra as obrcncð

wfth I, a¡d to a l¡¡g.a uteat tþrold and tùryrogloDnlla. AIlo¡

unllhr !1r tlryrroful anil tùyreglebulÍa¡ !4 bÅd ao rffrot on

uriua,r¡r f,norganlo pheaphetr o¡æotloar.

ilo o=planatLon eeo Þo glvcn for thc rbvatlons in syetoll,o

and dlastolle brood proscurr as obgercd forLoving tbyrold aad

!4. lhclr ooouËrene¡ forlorLng !O ruggostc that thry arc not

rcletcd to nctabollo ohan6rs. Boarlng la nlnd tho lablllty ofthle tyBc of reasurcnont rt ls poealÞll that tho ohaugÐo yo¡r.

fortuLtoue qnd aet r¡ret¡d to the a¡nol:fto trrafucnt givan to

the tubJcotr.

rn eplte of, lt¡ obecrv¡d raplct effect fn crcçating tho Dg,

Îs[ hgd becn ob¡crv¡d not to produec a pboa¡rbat¡ d,lr¡rr¡le aa ètd,

It aacl oth¡r thyrofd bornoaes. For thls r¡asou 18H ys6 ¿rrn{¡¡-

lsterocl togctÞor rtth !, to assora rhcthot BSH ntght cau¡¡ coeo

rrtsntlon of thc lacrrarcd pboepbatr ¡rsrctlo¡ duc to lr. suob

houtyor, va¡ for¡nd. not to bo thc ea6c, tho phorphato ellur¡¡i¡folleulng ît + r88 vss of thc sane o¡drr ss that folloutng 1Fo

alono. Ehc oauae of thla lao& of pboephste dl,nrcsLs yltlr tgfladsL¡lstratl.on ronalnr unorplalned, but lt nay bc r¡latrd to thc

-lo?-

EoÞl,ll¡atlon of phoapÈato as pþoaplæIlpldr rltbln thc thyæld

glanit a,a Bn acooupanl,nrnt of tho lnercsscd ratc of horao¡¡

btooynthcsis undcr lte cff.ot (¡fn¡ora¡ 1958¡ Eog:L a'acl v¡,4

Dotnra, 19é1).

?br oarly notebsLLe tf,ftot of !8H tr¿s not bccn roproduolût

ttrcr¡for.r by ri.tbrt E5r !4r cle¡looattcl tþrotô or tþrogl'obu}!.4.

It rcnaf.n¡ poeslbll thåt th. eft¡et aoulè be 4proiluord ÈY a

¡ultable so¡blnotloa sf S, antl !a. In thls ooÊnoêtJ,on f.t vould

b¡ d¡¡l¡eblc to know thr prreltc prolrortlon of thr¡a ag.ut.

åcù¡alJ.y s.o¡ctcd by the tl¡rrotcl.

thr effrsts of trtlodotlyroaootlo eoLù aaê totrE-lor:lotftrrro-

ao¡ü,o aoá.it dlo not allftæ gualttatLv.ly f¡oa thsoo øt' !l, aail !{

(Aaff ct al., 1956). Although thero 1a eous .YLdtnc. that tht¡

ef,f,rot of EE t¡ ntdiettit through afi lntaot tþrrolil¡ !t 1g ltill

pceoibll that a p.rtphqral elfrot, for rrsrnplc an lntrrftar6c.

Ln pleooa protrln Þf.ndlng of, t$rold hsræn. eay bc íavolwô¡ ß

Lt osulrt be poetulatod tbat ¡uob an effcet I¡ noa¡o¡¡olatlür ir

thÐ tl\yrotd-na1¡teLsrtt ä¡lg€tÞyrotrd rubJeetl. E¡urrthrlrarr la

vley of ualtcrttt ttrnovcr ret c ol rsdLoactlvr ta and !t mite

tbo 1ÉIr¡rûo. of î$E (stooy anal F€rEl.nr¡ 1959)r auol e¡ ¡ff¡ot

on btadlng rould sü3o un¡l¡oly.

A¡oth¡r peralÞl,lÍþ to aoæq¡t for thla oêrly lctaÈoIlo

rft¡ot ts ttr¡rt prrvlous\y suggr¡tod þ ErtzrL ot aL. (fg¡9, 196O¡)r

-I,O8-

Eegrly thet ESä stinu¡st ¡ th. soorrttlon et a rapfdfy aotls8

t$rold horuoro clfstlnot ñou tbocc a¡-!.aaly l¡ota" l!hl'.

h¡rpotboafu oaa b. fr¡rthcr lavr¡tÍ,gatod þ the appll,eatl,sn of

pÊptr ah¡ooatographlo ¡¡tboó¡ ûo a rù¡dy of thc otrenlettng

tbyrolil hornonor paltlor¡lår¡ü lE etatcs of tþrotd ¡tlnu¡.atien.

Suoh a otudy Lo re¡rortcd Ín tbc fellerilg ohaptrr,

(+) sH$tABr or cË s[BE r¡¡Ear¡y setabl!'e ¡f,f¡ota atrltåE to thoao pruvloueþ

rcportrd (fctacl rt a1., l960a) wltb a botanr proparatlon cf

l$8r bavo Þern obe¡rvcô follovlag a hog lEt prcparetlo¡. Io

suob tffect¡ uttrc oÞsrilrod follovlng aE 1aa€tf,yatcd l[SIl prcpara-

tloa, or follovlag th¡ aantnl¡tæetlon of astlvt !õH b thyrold

nst ntalntri bypotlryrofd aubJootro

lfbcsr aotabollo offrota of fSË souJ.d aot br rc¡reriuocd by

adnln!¡teatl.on of !, (ooaffnfng trtnl et ¡1., l95oa)¡ !*rcl¡cfeoat d trryrrcld o¡ t!¡rlogleÞulln. ![hr poeelbre oer¡¡cs olsuoh an cffEet vtr. dlsouE¡¡d¡ ineludfne tho h¡rpothor!.¡ adrnno¡d

by SotzcL ct sl,. (fgOOa) that tho th¡rroÍd ho¡uonE productc a

rapldly aotfng thyrotil homonc unclr¡ îgH ¡ttni¡ratfoa, dl¡tLaot

frou tt¡ee¡ alrcad¡r Elsrao

-lo!Þ

C¡TIPEEN IY

B.

îHTROID gUDJB€lg

Gbapte II of thlc thal¡ oon¡lrtrd of a r.polt o¡ ¡

ohroustogrslft!,o str¡dy of tbE olroulstins thyrslct horno¡r !n

üêrlaal tabJ.ota, aaö fn ÞPcrthyroliltrsq a¡tð otbtf uLso.Il8.olr.

condltloaâ.

Àc s r¡sult of, thf,¡ etu{y anal fioa a surt ¡r of thc n€at

lltc¡aù¡r¡ Lt ra¡ ooaolud.d tbÊt ln no¡ral ¡uÈJ.otl tb slrsul-

attlg trornoac oonllotl Eostlü of tryrodlt (fa) uut tbet srßll

a¡aouat¡ of, þlloðotft¡rroll.nr (fr) cordct t!¡quratty Þr detcotld.

$t¡rtbo¡mor¡ lt såa un6o@oa to drtoot elgntfl,es¡t a¡Ou¡ts of

el,tbcr ¡onolodoQrrorlnr or dlloaloq6oaln (X¡l or D[!)r elfiùougb

thero us! àoeo ooËtrovrrry aÞout thlr Bolat la th¡ lttcreù¡fr.

In ElrrtåUrold rubJteta¡ cü.th¡r untr.ato¿ or 2-5 cþgrl

ferlonlng rll t**tr¡¡tr antt v!.th rl'tù¡r r2?r o" rlr¡ ..t¡"¿"

ol drtrctlon, th¡r¡ utt olroulåtlngr el:l'Sþtfy lne.¡a¡od tnoüütr

ot, îf aa¿ Larg. laor¡a¡¡ð of lITe In adclttlsl¡ qnltc d¡*ltrl.tc

e&unts ûf q[Î u.r. drt¡otcd La ?O-&fi of aLI så¡car aad. ramtlnlr

-llO-

aLls ËX!. Ihta tl¡d.lag t¡ hypcrt$roldl'm of el6ntfloaut

anounts of lodotyroel,nce La the plaeær not onl¡r rlth redf'o-

activ? nrtlþd¡ brt partlotrlerly vltih ohcnlsal, nethoda¡ l'a aa

lntrrcotlng ono as f.t ra¡rrrsa[tr a efgalflgant rltperturc froa

tho oonorpt that thr todct¡rrorLara at. nornalþ mtal¡cd vl'thLa

tho glend fer rutLll¡atLoa ef thc Lsdlac follovlag dceÞa1ograo-

tl.on (Aocnc ¡t aJ..¡ 1952o).

Sono tllcoueElon of thc posaiblc ¡tgnlf,l'oanoc of tbr flndla6

uaa prcsrntod oarller, but ln ordcr to aaeess EotG fulþ ttastgaLfiea¡c¡ lt vas docl,clcd to lavectågatr tho otfeot of 8$t on

tltc oLraulating hornorc ¡rattcrn f'n euth¡rrof.tll¡n and Ìrypcrtlry-

rofdis¡. It yas fclt altelrsbh to aaerea, !,f, poselbh, rhrthsthc prcaoaoo of Et f.n thc plaana ln hypcrtbgroldl'æ vac duo to

atr t'noreaaod tlryrrold acttvlQr ecoonpaa¡riag tho b¡rpert$rotd

statr¡ or sh¡th¡r tho elroulaü.ng DIt uae rclat¡el to gonc othcr

pri.nary factor ln the artt olory of h¡rperth¡rroldlou.

Such an l'nv¡stlgatlon uac f,olt to bc rrl¡vant alao to th¡

auggcstlon tbat fSH prodnocs a rapf.itly acting thyroíd homom

dl¡tLnet f,ron thosa alrcady hown þetarl rt al., 1958, l.960a¡

Uc1lby ct al.¡ 1960). It vaa folt that t'f cuch a þpothrslruaa oormct tt Efght bo ¡nselbl.r ts ldrntl{y ¡ueh a nolcty

chronatoeFaph¿ea.lly 1n thc blooti fron eubJeete durlng fSB stt¡u-

Letlon' Eveu ff suoh a fractlon roqalaccl u¡rclteæverrd lt ra¡

-11I-

felt tbat o etnil¡r of th¡ tltfføruttot od.rqrlntlug lËttrs.a of tb

hcr.ooD.s *or¡Itl b¡ of 1n¡nrtanec. EuOb 4 Itattül¡r lf ¡rroðuæü

.fogæÐtrs1y hy Ednla¡lt tltng thl aÞ¡Ëo¡tr--|,Êt¡ ntxü¡rc oJ f4 åaal

f, æV poôstbt¡l rcXÌ$odr¡o. th. tür\y Ëbbollc tff.ot ef 89t .Yta

lf Sr lÉatlvlalual brErmonr fat.lod to do lor

r. ryluoËth¡ sh¡onatographlo nrtbcl¡ have b*¡a d¡sorl'bral ln ôrtatt 1¡

tb¡ llrthôd¡ ScetÍeh of QhqFtæ IIo

Blood ïBs €ÐIlcetrtt esd thr plsrna ¡altÊrtt il undor l'edl¡æ

frcc æt¡dltlop¡ ñon caoh rubtoat. SutrJcots Èon trc ol:l¡leal

gtor¡FE y.ro ¡hd,lrdl a nonal troep vltb no oll.sleôl ovlaltco. of

thgrolil rlt¡¡a¡r a¡d e grcqp ulth þrpæt$¡oldl¡E. lhr dlaSnorl,¡

re¡ oen lrÐ.d l.a eaoh oso. by tbo n¡¡¡s,l tavrrttgntlonr¡ lroludla3

a pleena prutcll bouatl 1oô1¡¡ (¡g¡) lovd, a¡d thc 2l þs uptalr

of llh. Studl¡¡ yoro pæforncd s¡ r'.ght nonsl aubltota, ¡!cÐ

of rbo¡ Í.r.l gÍ.?.rl l'lf se thEt eh¡sn¡togreu ûe¡ the.. ¡ub!.otr

v.D. eege¡¡rd rlth 14I ..tnrdr enl¡r¡ that ta rt'th tÈr er¡te

eulphatr er¡rnlou¡ eelð crtþil of Doutca öt ÊIo (fg¡¡). Stnttlrr

ror. prrfcnod es fou¡' u¡tret¡d \ypcrt$¡old subtrete¡ asd a,bc

rlght rrypætryrold 3r¡þJrct¡ tuo to to¡¡r ûeyr tolloui.a¡ fll¡

thora¡ryr. Glntosstotfas. fior tbr l¡tt* patlratr r.F. Brf,rarlly

a¡s¡g¡ld rtth X5\ r.thoûl by aoannf,ng t¡ a tuc.l¡a¡r ChtcaSe

Ëlettgreph IInr but shrn poaclbtr oäd.cal atuttlrr rlth orrf.e

-:L18.

rulphatr ret ¡nrf,orp d on tbc ohr¡o¡tograns eitor thly hd brm

9GêFIilGdo

tt8Ë- was aÂa:rßlgtet.d Èy derp lnt¡e¡u¡sufar latrotion 1l¡ e

d,oaagr of !O U.8.P. unltt d:L¡¡elvrd l'a 2 sl. of lolueL EelLnr.

gtnorl tra¡ ooJ-lrstrd Þelorr tbc tnJostlon and 2¡ 1¡ 8t 24v {8

hor¡¡s and. ¡on¡tl¡l¡ ?2 hor¡rs eftcruard¡" thr eubJrctË l.Portod

ls a fmtlng statr to thr teÞorabrT f,tl tht mrnls€r aqô reat!.d

f,aoùtng ¡nd rrctía6 for thr cuberqneat 6 hs¡¡¡e. ObEsrrÊtloaÊ oa

nctabolls r¿t¡ (F) w¡r¡ oatlr brforc 8f¡g âuat 2ù end 5 houre ÉrÈ.r

l8! lE al.l rutlryroåd and Ln tro àyporttVrold auÞJcata. ÛÞ¡lrr¡-

tloas on puler ratc and ¡ruler grasaur. rrf,ra redt Juat prlor to

lrcû.Dunet¡ct ln el]. rublaqùå. url¡o vas eolLot.d ûou tho¡¡

þpcrth¡rreld aubJreta rþo had rcorl"vrrt tflt, urua!.ly Juat eftor

vonopu.noturco

In on¡ brypcrtbyrolè subJoet blood ¡ra,a tal¡rn prJ.or to thr

ad^øLn1¡tretloa of tSlf thra l, 2, 5r ¡¡d ? days latcr. lBSt wa¡

thon adnlnletæcel and bloerl talcrn 8¡ 24, 48 and 72 hsur¡ lstæ.

In anotbor þr¡relthyroÍil cubtrct, bloott saa tahon Juet ¡rrter tot51¡ thæepy and thca 1, V¡ 5¡ and 9 cle¡ra latcr. ro tÍlB vas

glrcn to thls aubtoot.

I ÞinothyrenF¡ partly suppll,cd by Sohcrlng¡ A.Oo¡ BorLln.

-tl5¡

2. tü¡u4rg-

-*rt¡þo.Lls Ètar It bad b¡¡¡ fsund ln carllc rtuül.r o¡¡ tå.

EotsbXfo .ff.ûtt of 388 tbat Eot rrrr¡r ruÈJcet llrlпuord a

lrtsbolle FrDDoar. þ fÊS. Eþ. E ¡að oftrr rrt¡Þello obrcr"rp

tÍoa¡ t at undortal¡¡n 1¡ thlr ¡ürdy to an¡r¡¡ rhrtbu rash ruÞJrot

tld re¡nnd rrt¡Þollecl\r. Io æalrol rtedy rer pæferrrd rltÞaa¡r ruÞJcot, a¡ thl,¡ rat eoa¡ldrttd qrafgGt€ar"¡r rbLLr u¡1Eg tht¡oteÞoXLe ttspoÉrce mrrþ ar trrærælngn t¡¡tr. Aatfl¡l'¡U ilt.rut$rrold ruÞtrct¡ ¡nû thr tryo hy¡lrrt$rrold rnÞtrcta 1¡ uboc lC

ncåü¡aanant¡ ror¡ n¿dr dl'cl shov I railrtrs.. !h¡ m¡¡ ¿rtsbolle

ratc f,or cutErrold rubtrctr r¡¡ t?.1 oclorl¡a Di:r .qg¡.r ¡rt¡rbody rurfac. I¡ot hour brúoæ EgF, Ê¡0d lnorrsrod to 48.9 ¡Bal tc

5lo9 oaL at $ anrl 5 Ì¡our¡ rts¡rrotLroJü.

th¡ uona guloo ratr Ln tb cutþrrold greup rå. ?9 bcf,orc t!8ú

and rceclrel a saxi¡rn of 9¡l et rlght horsr (feffo 2?l). lho ¡r¡¡pulao lrr.asnro laoreatrd f,rsn 45 ss. of Hg. ø 5? at I hosr(naufr ZTE). sbo þpetþ¡rolü aubftotr aI¡o rhou¡d a rl¡Þoi..ln Þoth puler r¡to and pufur ¡rntrsua., tht pular F¿t rl.rlag t¡cn

9? to a ¡s*lar¡E of lO8 ¡ad, tbo puÞr plürü¡r. rlatng û.cL 64 tû

?ó at I houre (mUtra 28r ¿g). OnI¡r eac Þgprrtþrelit anbJrot

faitrd, te ¡lroduog a ænvl.noing rls¡ oltÞrr 1¡ tbc putn xl¡ìr¡üura

or th¡ p"lao r&ta.

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the groap dsonstretûd en f¡crcascr thc caaLle¡t l'norce¡¡ tli,a6

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increas¡ vas Or{ tfrfe uaa reoorctrú La a patlctt yho fellrd to

show a ¡lulec r¡Eponsrr but cLld shoc a pursc prtssut. FrapgDotr

Sbr larg€st inoreesc i'n .PBf r¡oorctrd væ 8.8fgr ptr l@ nl.I[he EsH oauo¡d tho neaa 88tr revr]. to Laoreasr f,rs¡ L2oø76. bL5.7 r*Uc par I00 r¡1,', thL,s uax!.¡u¡ Þo1n6 ¿rttel,n¡d at trrcat¡r-totst

hourg.

Effecta os ghranôtoslaobf.a P¡ttûrn¡ Dollortng thc lntra¡u¡oular

LuJeot1"on of SSIi to c*al¡ of thc otght norrpal. eubJrote, elgnt.f-

Loast a,nounta of ü!f r.!r d¡t¡etod¡ rreral\¡r in both brrüsaol

ae¡tÉ.e and butanol ctÌranol amnonta (EEô) golvcats (Ësr. I?-êO).

In onr suÞJcet DI8 rac not ôotectrd r¡¡rtil ?2 lx¡r¡r¡ aftrr Etadnfuleþstlon. ra oa{5r ogo Eorgs,l subJcot etuclleci vee üIE

prcøcnt Þeforc E5Ë adntnt cbatlonr th¡ lDtr &ea brlng gol /tg.por lo0 nrr of placxao usuelþ thc ärlB eppeeroô la for¡r houre,

aonctf.n¡¡ l.n t*o, and vae ae¡lnal at bctucen trtaty-3ot¡¡r husg

e¡d fort¡r-rlght hsurs. ¡slttresy valusa u.re aoctrgned to ragh

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FI0U8¡I 17

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EFFECT OF T.S.I{. ON CHROMATOGRAPHIC PATTERN

lN THE NoRMAL v.M. d rt 68-

t1 PBl. 8.s ¡e %

ÏHYRONINES

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cr- 0.r.T.

I0RIGIN OD Dt

BUTANOL

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PBl. 6'5 ¡e 9b

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Í.IGURE 18

-EFFECT OF T SH. ON CHROMATOGRAPHIC PATTERN

IN THE NORI4AL

K.C. d acr 52

O HOURS

2 HoiRS

4 HOURS

8 HqJRS

48 HotrRs

0RI

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EFFECT OF T.SH. ON CHROMATOGRAPHE PATTERN

IN THE NOMNAU

0 HotRs

2 HqJRS

4 HOI'RS

8 HCI.,,RS

24 HOURS

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T'TOURE 20

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EFFECT OF T. S.H. ON CHROTIATOGRAPI{O PATTERN

IN THE NO RMAL

O HCIJRS

2 HOURS

24 HOURS \G F

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r¡rot eoærórrg þ th. orürct¡ of r¡nt l¡Fol ¡lt l¡tæltriV of

flrr¡r¡mor a. dr¡sï.Þ¡d la GÞ¡Dtæ fI. l&o æ¡a e¡æ¡¡mt

rslu¡ fcr ft r¡¡ O¡2 ¡t O Þcs¡ std hsô rl¡¡a to 4'2 ct ¡lt

bocrl (aatf.r !21 ltg, 21). (æ r.ar er¡ersrlt v¡ln¡ glt E

tor X[! ¡¡d fcr !* aaô t¡r rñr Þe¡rô ea rl¡ cl the rubtætr orl¡r¡

l.¡ cheü a oelpLrtr ¡ætcr cl chæntoSrrr¡ ra¡ oÞt¡tn¿. )

EhGt y.r. coD|i.¡tæt â,Ed ¡âlÈ.û llrælar.¡ lE th. !, GoeùD¡¡

lretl'ea êvr¡r tb¡ r$ol,r prrfod cf cb¡ær¡tlen, DaaD ¡alu¡r rtrtl3flo¡ 1.2 to o boræ¡ ic 1.7 rt ¡18 bo¡r¡r¡. llb rcepcur 1r tüo !+

oor¡nlrat, bcrlrlr, üar tultr vsrl¡hl¡ ¡nd tÞr m¡a r*lnr(feUfr le) cppa¡rd to ðo€rreæ rl!'ghtly tbltsrtng H¡ brcyæ

th¡ v¡¡L¡tfo¡ rÊr to rÈðo ülth sr !* qF.¡ that tt ¡r mt F..lÞ¡¡to ænalrdt tñrt !a oroætratl,sat iß ü. plema aehrtly f,¡LI'

afts !8t ¡d¡lsl,rbatte¡. 8on ovlê¡ror ôf a cor¡red rhLcù

rcds¡ed tà¡ eæ1e æl¡ibnt¡ r¡eetlol and rbtcb Þsü an t, rrtEr

å¡¡t b¿ehü üriû tbåt ef !o ( > lo) va¡ fcrail tn tüo anblrete

¡ft¡r 19Ë only. I ri,rl,r¡¡ oolpouð x¡r rofærrd te 1n sbptrr rrf.r tho oFcrgtogrsphlo tl¡*tlr6r o! &l/InütÞ¡rretrdLrr. lt'h. tcblt$rorfu a¡!.tælÄt val.w rlrop¡rit rllgbtly ûrcn ?.{ ûe 5.i ¡t2 þur¡ sDó tcto rüCbt\y to 8.5 et ¿18 botgr. Ovrrall. trt¡l*¡r¡rær¡t v¡tru¡r lacü¡.d froa ?.6 to X.2r5 ¡t ¿18 bogr.

rn tår fonr oaæç ol uatrratrô þpetsrrolitlc¡ Ëtr prortuard

r¡ taoro¡¡e l,¡ both tb lorteerro¡la¡¡ and tùe lcrxctbpoElrr

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PATTERN IN EUTHYROID SUBJECTS[ue¡¡,¡ or sl

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PBI. 9ICHEMICAL

ASSESSMENT

ArbitnryVatues

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TIME IN HOURS

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T4 O- O IODOTYROS¡¡,¡E5I-tr T3 O-O

IOTAL x- ¡ p9¡.1-l

Arbttrary values for eneli con.Ðiin€nt derlvsd. fron the are¿ of tlie

,spo t rnd the intenslty of l, ts fluorêsGènoÊ¡

33o

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SotaL tlt¡¡runtu lncrca¡cd fro¡¡ 8.4 to 11..8. lotel lodoftrre¡¡.r¡¡

lneroas¡d fro¡ x.¡8 ¡t o bsr¡r ta {.8 at I horu¡ rnd üro toblovl8sll as¡.¡¡E.Bt velus ua¡ lorS at o horcr, 16.6 et g hot¡r¡

(trhr nsxf¡u) aa¿ l{r4 Þ 48 hsutrr. sú DDr seeû valm æaoù¡¡l

,'6.6itLgr pB r0o r,rr at 2r borre¡ r,nerraaLaü ftol Lz.t/Lgo prlr

lgo sL boSorc 1:Eü.

rn th¡ þport\yrold cublcota trcatrcr ylth lrr¡ nara,[eroÌ¡roo¡tegrapàle a¡¡ææet sf tb¡ offrot¡ of gBü ræ. ¡qd¡ url¡gbotb 1l\ *a l4r ..ttod. (tlgr. 2$ Zi, 26). !Þo rr¡¡¡tt¡ arc¡l¡llar to thoro for¡ad la th¡ r¡atroatrrl hypertlyreid tfoupothero úE! LnEra¡¡a tn both thr f.odoþro¡lar¡ aed tb. Loåothrro-nlm f!¡otlona. &c lnorraæ 1n thr t odotgrroatm fastloa rerfound to bo dur to snarl laercs¡r¡ tn ûhl îa eoElroarnt ea r¡LLae rtoflnltr lrwcaEca la to urtb Þoth t¡. t2?r eud tb r'L(rte, ?l) ag¡¡ssn.ûts (nabloa fi, ,r). Ih¡ l¡or.a.r¡ ln ¡Eru.r. not¡d f¡roe¡rrotivo of rbothrr D[! uq¡ drteot¡d Þrforr ggtr

ctÍsulåtÍon.

lbr abgolutr lno¡oasc rn n[f tn both Êrûups oi þpertþr-roldlen wa¡ Lcss and nero tran¡t¡nt tlrgn that ¡etocl l¡¡ tb¡ ao¡r¡l

-1|2u

FIOUNE ']2

EFFECT OF TS.H. ON CHROMATOGRAPHIC PATTERN

IN ]{YPERTHYROIDISM

O HOURS

4 HOURS

O HOURS

0RI0IN

0RI0IN

it o3e

Do.t.T.

UTANOL ACETI

cr- t- T4 T3

o.n $ eot. 2o

*' P B l. 9'1 ¡Solo

THYRONINES

PBl. 11-7 ¡Soh

PBl. 9'1 ¡tS 0,6

PBt.11-7 ye%

-li

D CFR0NTa

il O3CFR0NT

Fol{f4 HOURS

BEÀ

Fl¿rsn:l obùnlned frou e subJecü 'r¡lth untre¡rted Ëh;rotorict¡sie,

O HOURS

2 HOIJRS

4 HOURS

8 HOURS

2t HOURS

48 HOURS

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FIGUR¡; 25

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MIT tltt

HITANOI ACFIIC

o-HP I aet 21

PBl.12'8¡4 o/o

PBl" 13.6lg o/o

PBl.15'9¡4 o/o

PBl.ls'1 )E olo

PBI l9'3¡.¡g o/o

PBl.2l.2¡q olo

EFFECT 0F T SH. lN HYPERTHYROIDISIvI

O

,

ID

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oRI

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a DO

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.ra;THYRONNES

PlaEno obt¡¡ined fron a, su'ujecü with unüreated thyrotoxlcosJ.s.

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-151-

lIIüUÉiF 24

EFFECÍ OF TSH ON THE CHROMATOGRAPHIC PATTERN

lN r3rl TREATED IIYPERTHYRoIDISM

Ri,i.ô aet 46

0 HouRs

1 HOT RS

G PBI 14.9,pg.o/o

Ptsl 16'0/'¡9.o/o

PBI 15'2¡g.o/o

ilet flÇ

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If-¡r24 l{ot Rs

o THYRONINES F

A,ITANOL ACETIC

FLirena oÌrt;rinoC fron ¿r sui:Jcr:t u'¡ith t-Try¡ste ::ico¡;lr': 1i] I:ourç of tcr

adnlnistri..tiOn Of ? m.C. of 171-I. 0hx'oí!,ltto-;rlinr che:;:icl:) 1,,'

.i-:Sl:1C;.r:,l]ot1 fo}}.;r¡i: ; l]ÇflElT]iIiíj f clr *gr}1o:ct1Ì*e .,ìCí-ìj';'s E

ltt 4DIT.ct

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FIüURil Zri

-

EFFECT OF TS}I. ON RADIOACTIVE CHROi'IATOGRAM SCANS

lN HYPERTI{YRODISM LM.drt 43

o Hotns PBl.124¡¡ %

¿ Ho[ns PBt 13.6.t¡ o/r

26 HOT RSPBl.l9'lr¡90/r

¿8 HOLnSPè1.i?'?14g'lo

il{fRoinEs

aJlAmL ACEIE|

¡ll"rsnn obtalned fro¿t a lu-bJect wtth thyrûtoxj.âJl:li¡ 4 cir::yr sfter

\

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-135-

I'TGURTì 26

EFFECT OF TSH 0N RADþACIIVE CHROITIATOGRAM SCANS

IN HYPERTHYROIIISM

ASg e* 53

PB.-03¡9t/c0 lltns

0 T}IIROMNES F

8 runs ftl.112¡tflo

l¡|tr+ flll Îr{YRot{hEs F

Flr,-¡g¡,¡, obt:'lj.neel fron lr lrt,len'b w1 th ùlr¡,r¡¡l,cxicorrf* 120 irl;urs afÈer

the ¡:,dullnistratÍerl of $.0 ril.cn of 1r1-I.

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-1)4-FIOURE 2?

EFFECÍ OF TSH ON THE CHROMATæRAPHIC

PATTERN IN HYPERTHYROID SUBJæTSIMEAN OF 5I

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ë;;at cn,;i thc lntenclty çf i+"s fluoresc€ncê¡

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group fellculag !tË. thlt l,¡ tn¡r ¡lro o3 th¡ !, rrr¡nltloI¡ beth 3Il aad !, thr nerl¡e u.!. unelly rcc€ûrod ln 4 b Ihour¡ f'n th¡ þprrtlryrol.cl greup, rhtr.ar tÈry yota ¡tlllLno¡roe¡lng at 48 hour¡ la th¡ outtgrold ¡rougr !h¡ ohmlo¿l

atalalag notrd t¡ th¡ Êa.& Þryonô !, vhrn rtotcrt¡d tl tm llll

tr¡etrd ¡ratlrEtc uB¡ ¡..a to oc¡rrrsDetd ulth e Èroad ana of

raclLoaotlvltyo

In tvo ¡latlcnta ¡¡¡Lal oh¡nloal aadl radioaotl.vr olr¡elate-

tran¡ Yar. ¡rrrforrcd for slv¡reJ' clayr follcvtlg thf ecl¡1n!¡tr¡-

tlon of a thcra¡nutlo do¡r "r rt\, end oenpatad vtth ohrnl.eal

olrronstograns lrr.parocl fron the pløena ¡f raoh patlrnt bolorcIll¡ tn.rap¡rr In both rnÞJrotrr Cr¡lt¡ l¡rgr anot¡ntr cf El!(vrth .otc ttr!) r¡r. ¡rr.t.nt t¡ tho ollouletlcn ù¡lero trtetno¡t.lorloring troehet¡ aarl ulth tbo ch¡¡lËar a¡.or¡E.nt thær ca¡

no varlatlo¡ ln th¡ a¡o¡¡nt ef f,odofrerlar r¡latLv¡ to tho s¡o¡r¡t

of lotletþlcalm ethtr thgn thst yhloh ¡lght Èo or¡notoö frcnrrporlDatal trror. 0f glratræ latcrc¡t rae th¡ flnûlng thetboth llr! aact El! v¡r¡ lab¡Llrô radloa¡ttvcly la tho 24 hota

Blarna antt tbat tho r¡reeltlo eettvlt o:? th¡ lctteþro¡lnl rpotrthr¡¡aft¡¡ lnonasrd onJ,y ellghtly end to th¡ caB¡ ¡rd,rr er dldthat of tht ttryroaln¡ eoa¡retut (lfe. 2E). gtËttar r¡rult¡ uoar

obtElmd ul.th thr Ercond rubJrot¡ although th¡ rpoolfle *ctlvltyof th¡ rlr! a¡nt dld epprs,r to Èr lnorraslag ¡tltr at 14 houre,roratlvr to tho tþrrenr.ro rprt¡ but cqurlrþlru va¡ r¡aohccl Þ, {gheul¡o

-'l ]ij-

.t'IùU?.8 28æ

RADþ¡CIVE CHR(nIATOORAM SCANS IN I{YPERTI.IIROIDISM

W.K. rt 52 tl?lat}l -t0 nc. lül.

ii r-'_l

ï1t5tCl

2lt4t6t

!rl

o t- .H.l.T. ol.T.

BUlANOL ACETIC.

THYRONINES F

n

t-0 tltl OI THYNOìnES F

1+

ti silirlt1lllì

lt+l]

1fr1

-1tÞ

r. rgoü95¡0r

Drtlnlto aylalaBco ha¡ ¡cry born aoqÈrnulatrct ln th¡ eor¡r¡o cf

thls lavt¡til,gpttcn¡ tbat ln ¡tat¡r of thysolal eünrletloar sucÈ

aa L¡ l¡yprrttryrcldl¡n a¡d aftor lEH ad.einlgüatlonr thorr an not

o¡¡Ly obaagre ln th¡ tlqrrcnlrr eonlloa.nt of tho ol'rculattng

hornonc, nalaly ae lnoreagr¡ la lrr but aL¡o tlrf,l,nltrr and et

tLa¡c qul,tr largo¡ laorrasrE ln thr locloSte¡ln¡ fraot!,on¡ ælnfy

ü!.In osntrast to onr grrvtoue rcport þtool ¡t al., fg6o) t¡o

oooulrono¡ ol fE ln thö pla.rm heE brrn clrnoactretrd Dcth

oh¡¡lsally and wltb lSlI ..thode ln tabrll¡d hy¡ruthyrold

¡ratl,rnte fcllerlag lbæepy delo¡ of f1\. Eloel ¡t al. (fg¡o)

ha€l olalnrd that thc fallur¡ to cl¡ron¡trstr lab¡Lbd lotlofro¡L¡e¡

ln th¡ plaraa of ¡orn¡l tuÞJcots ve¡ du¡ to Larnfttcl¡¡rt leDolllag

of tbr Et (Dut not of !a and !¡) by thr ttno th¡ btrooct ve¡

renplodo lvrn el,loyl,ng for ¡ Eorìt rapld rqulllDlatlo¡ tn F¡rrtþrclcl auÞJoctr, tblr poe¡lbtltty te.oa un¡fh.lt tn v1¡r of tb¡

aôoquato lrÞrl.llag o! 81l¡ rrletlv. to th¡ tV¡¡e¡rl¡¡¡ that yer

ôlnoncttatod l¡ tvr pathntr 2{ hor¡¡s follovlag thrre¡rrutlo do¡uor llk. rt Lo ueua¡ to Örley eenpllng Etrl 2-l daye for,lorLrgrã\ la ¡utlvrotd ruDJretro

rt hB¡ plrvlourry Þ¡cn auggratrd (umue and ÞÞynr¡ r95ã)

tl¡åt thr eBpreraao. of E! ln thr plarne foLleriag ¡uoh do¡r¡ l¡

-1+O-

dltr¡ tc redl'¡$.cn ôelegl tc tb¡ 3l¡!.ô. ihet ttùi¡ vu urlllrlybar ¡lrce4y br¡a cuggrrtrð frur¡ tÞr lfrdå¡g of Et rhraterlþ

la u¡trret.ô o¡¡or ef þperthpol,dlæ¡ rr rqlortrd re¡}l¡rr h¡t

la natir rvc¡¡ 1¡¡¡ lllr\y Ëy lür ch¡nl,oel ftarllng trn th¡ec tno

ruÞJootr ef a rl.nl-lar ¡¡cuat of Et Þcferr ¡ad Efllr rueh tMnry.It lay br qu¡stlcl¡d s¡ te ulry tblr fl¡Alng cf lar6r slu¡tr

of S! ta th¡ .1loulet{.c¡ l¡ Fc¡tÐar. þ t3t her nct Þr¡¡ fcudprovlcualt fa rl¡!,la¡ lnvutÉ.¡atlo¡¡. GE¡r¡tr¡raphl,o aarl¡ltlr

o8 tbo leÞrl.lrcl lodoe¡i¡s aol,cl¡ ln th¡ lüUæofal Yrl.n Dlootl ef do¡f

hav¡ fndloatrdt ttÊt troaty ¡l¡utrr ef,tol Sl ednl¡l¡tretlonl thr

}ìDryr¡ lnæes¡¡ vhtch oltrrcrril va¡ cluc lo na lnorra¡l la ta alcm

(fcfuraa a¡ù Arer¡r t9l6). 8! rs¡ ¡ot lôratl.ftrd trn ttroÞropetogtr¡¡rr Þut tb¡ Þloed yar fantÐlod 2t üeutr¡ rft¡r !3t

onþ¡ El eeuld üaLl Þ¡ve Þrcn rol¡a¡lcl aftor thl¡. ÞLt!¡

entl llrsth (19t5) la pa¡nr obrønetcarapb¡ of er¡rLoa.l þryh ln

dcgr fol.lruln3 f5\ *¿ ôun¡ry lOI ¡tl¡uLetton¡ feurd l¡cr¡¡¡¡d,

lnorSanlr Leclldr, !a aail $r ùut thr rort ¡rr{Eânünt f¡¡tun ca

thr el¡ronetegrapb¡ var e ¡uÞ¡taqer vlth e ytìf for f, l¡ Þuta¡ol

dlÍ¡¡a¡r amoal'e anö vhlch tbrü dld nct lalatlfl Þst tbouCht !ûthtÞr tlgrreSlaDull¡. llhl¡ tuÞrtanor ooul'al havr br¡n El, et thr

l, vnlur of E! hs¡ bæ¡ ¡tatrct to Èr O.Ig (ercrr, fgfl) a¡it

O¡gi (fftt-ffvrr¡ ¡aËt leta¡ I95g) t¡ thl¡ rclr¡nt"

lydovltr snat ¡¡cn¡ (f9tf) b¡vr lrvrrü.gatrit tht tlroüstinglaþrll¡d hernesr pattrrn follcrln¡ lgE ed¡lntrtratlon 1n tors

rt{lr

.utryreld subltot¡ end lh!û. þprrtÐlrlal rubtrotrr erry

rqrortrd oc¡r ¡na,rlloastl,vlQl ln thr Et ¡nrl E! funotien ¡rer

rhlch apprercd tc i,aæracr ellghtþ follovlut !8t ln thr hypæ

thy¡¡oltl anil qtÞrol¡l rubJrcto. Elrl'¡ ouÞ¡t¡ner ra¡ n¿t ÀôGt-

ltlrd but th¡'g¡rt to br art th¡r El nol lü8 ¡a ltr ç lay brtrcathr I, valul¡ of El ead El!. I¡vrrtbrjlttt¡ tr tbo I, v¡Luc¡ rtDr! c¡al lc! ln tb¡ alralLm rolv¡nt¡ u¡¡d en t*t.q.Ly clcæ ltlr qul,tc prcbabb tbat thry rlgbt rlgratr Br o&. raallogot!.vt ¡m&

rlth er l' valu. þ¡ürrra th¡ tyo. they u¡rleyrd tnro rcl.rotryrtme ¡ ÈutanoL - iû esorlru þrûel,Öa ¡¡nd trr. nrylEl'oeåcl -2l ¡¡æ¡tu þrcllorl,dt. [hr fo¡xæ aolv¡nt ls not f'd,ral tolrrparotlns !t anð !, rhwrEs th¡ lstt.r l¡. tle¡¡e lrer om

outh¡rrokl rubJrot ra¡ oluonetogtaphod ln th¡ ¡ooonit ¡olv¡nt a¡û

qulto e lergr p.elß epprarcd la thc !, erre by {,0 houm but eotrld

net bo fcu¡d la th¡ lfr¡t eolyøt. plasna tFsn tb¡ oth¡r thæ.Eüb.{¡str¡ ra¡ ohronatograp}nil oaþ la but¡aol amoaLa er tal a¡

oan bo neÕo out fron thrlr pgprrr tholr failur¡ to rl,rtrct E,

ln thrcr aanprre mlght b¡ dur to a Door rrl¡alottsn o! s, en,r ta

ln th¡ þutaml-eo¡onlao to uro found f,n thr thlra oeso¡ cfhyp¡¡tÞ¡e!.d,laE foilowlng t8I, uclng thr t¡rt.al¡rl q,Loohol

ryatto

ra E etudy ef thc lnoor¡roratúen ur 1l\ '.¡to

thtrelcl horeo¡¡e

(ruer Eaô v¡hrrall, t95g¡ true¡ lg59) attontloa rsg cl¡ern sc e

red'f.oasttvr ¡na,t rlth an B, Jurt grret¡r tbqn that of t, h

-I¡}F

Dute¡ol-cll.on¡r-eononluo þilrod,tb ctrrolatograar flon rrtrert¡of rat plarne. lbor¡ euthon¡ vho had ¡xrvl.outty tll¡csv¡¡ril

thie ¡ubstano¡ la thr thyrold Sfsad of r¡t¡ (.3lam rt el.¡ f$?)roon¡ldu thl,s ¡ub¡tanot ls e nry thyrolrt þornolar I¡ thr p¡¡¡.otstudy a ohrnl,oeJ. apet and a radioectú,vr p.a¡ yf,th a rl^rtrlan B,

valu¡ ln r¡latlon to !, ( > t¡) L¡r Ell a¡d trrtr a{fl eloobol-

a¡nnsnLu¡ \ydlorlda y.ra tcr¡nd. It wa¡ ran\y toon ln ao¡nal

lndlvtdu.la la tb¡ r¡etlng atate but aorc ft¡qurntty forrovlag

lBH stLnulatlc¡ E¡cl va¡ areo elr¡ ln þprrtþlclctl¡nr rt wourô

apD.er that th¡ prro.n@. et ) f, le nLatrcl ürty o:ßtu to tb.pt.tan€a of laol¡agril eøor¡nt¡ of !¡r Èr I, yalu¡ t6 vtlt¡¡Àll¡r

ld¡¡¡tlcaL ylth thst of H.icelothyreaortto aotd (o.al) anct 1t l¡ooaoelvab¡t thet tntlodotlryrroeoottc sol,ct ¡f8ht Þ¡ d¡tostrd Ln tht

Èlooil 1l a vory hlgh eonomtratton of !, Lr ¡rrerntl ar it hßt

Þ¡¡a rbora¡ Þy both tn r¡l,tro (rrurrgnt ¡t al., l9t9) ancl l¡ rlvc(Oatton aad lttÞtLy.tt, ¡.9F9Þ) nthoctr, to bt a n¡lebelltr of

lr, chlrfly ln thr trtil¿lfr Þut al¡e ln th¡ ltvcolh¡rr a¡o tttftlourtl¡¡ tn th¡ lntrrpntati.on of thlr area

of st¡renatogfane pr¡¡remtt t¡ erhqìlm rolyrnt:, hoylyÉo

tlaolagg¡¡ rt al. (fg¡f) hsv¡ ¡b¡vu that tÞr tþreaL¡¡ lrtors hevr

Rt varuu avæa,siag abcut 0.90t leure¡ (rg¡r) har potnt¡d out

that lf lsdLnetod llplal¡ a,r. lounct ln an ¡rbastlon plcotdrst

thry rlll nl'grato wltb aa t of epgrc-r-ctrry 0o6 l¡ Þubnol-

Itlrancl-anmnlr¡¡ þdroxldr¡ ullrlnron (¡,gfr) ha¡ rrf¡lroal ts

-l¡lÞ

lntrrÍ*aaoa ln thl¡ asra of a olr¡opatcgran by a brroral¡h

plgnrat. In vl¡r ol al,]' tbr¡¡ oon¡ldrratiom it reulel ¡aG

uprctl,æt to br æaÐ.nra$,vr Ln lntrrlrctlng thc o¡l'gÅn ef thr

) \ rpet. ft r¡¡¡¡o guf.tr a Boraib$tty tbÊt lt 1s rÍth¡æ

trtlodotþrrreertto eot'd or sone !, anlLt cft ftn tho ntn !,aBot by thr ¡rracnoe of suoh an lnte¡forl'ng p!.gnrat or llpldia tb¡ r¡sfui Brr¡rar.at pl.arne afuGtr end thr¡r ¡neslbllitl¡¡nay rqusffV afnly to hr¡orfr (fglg) $FLrro¡r¡ r¡nt alee.

lhc ¡rrormt lsvratl,gatlon h¡¡ r¡vrs¡.rd no rlofl¡¡ltr rlrlilæ¡of en unhcrn traotLon brlag rol¡¡¡¡ô frsa thr thg¡roful 6!.erd

ulal.t !3I rtt¡nletloa. Sm tlndù¡g of largr ¡rcr¡nte ef Eltn th¡ clrtrlr¡tto¡ clu¡ to SBH ¡tt¡uletlen l¡¡¡ not ¡rrvtornJ.y

Þæn r¡rortrcl, lln r¡¡ult¡ l¡ mlettren to thr thyronlEo¡ ¡rloon¡let¡¡t vlth tbo r¡¡ulte rrpcrtrd l'n thr li¡d.toct lltoratil¡c.

avallebl. on thfr ar¡noto

D¡rlng !C[ et!.¡ulatlon¡ rqll¡r ead nor¡ tren¡lont !,lerrsre¡

!.n bsth El anrl t, oeorurrct tn hy9ætþrcldlæ¡ thê6 1l ¡ttþroidl¡n. bvrvtr¡ tùr ¡nttrra 1¡ hyp¡rtþrroldtrn brfon tûl¡tlnulatloa olocol¡r nmnblr¡ thr llnat r¡ault fa th¡ loru¡leubJcot at thr hrt ßbt c:f !Êt ttt¡ulstloa. It ¡trnr FrebsÞbr

thr¡ofcrr¡ tbet thr pettrm ln lfportþ¡ttallü l¡ dur to

rnclr¡trou¡ !88 ¡tú,nuletlo¡. ü¡rthrr frcgtnou [ßf, ¡ü,¡ulatl,olo¡¡not tbrr¡forl gloduoc th¡ ¡aqr fu¡æ¡s¡ral tflllct. FctunÞþ

-11¡þ

"hßt le clru ln þprrt$poldt¡¡¡ follcrlg t8ü 1¡ ¡ rryll¡l,

snd Eûrt lraa¡l,eat oúfcot oa thcrt æE¡ro¡¡rttr rbl,oh s¡r

u¡rh¡dlg aff¡otrd, ln no*zaL¡ æorly El and lrr lhLr tr¡

oon¡l,¡tent vlth thr æ¿11¡! rDl rler a¡d at¡o the acreltrr

rfðst oa let¡þol:Lo retr &ad. pu'¡ac ratc in bypæthgæ1rfls¡,

Íbl'r þpeth¡¡i¡ rsuJ.d tr¡lly tbat tho r¡au¡ual rln.tri€ otelfoulelÉ86 Et tr þprrtþlcl'(itü te tn nÐ ray ¡ Ffüanf*rtåelogicai fEete¡ ln üyyrrtþrrolriln. rt my, howüürr,

nfÅtct aaother artlologfeel tactor; naml¡r tnærestal lgt¡rreùlotlea. ¡t lFarno to ùe crylafncd uhy approd.natrry eof

of tbc \yprrtlryrold, oubJcet¡ cholr ro cvl,itrnoe ot cLraulatlng

&[1!. It beo blä ltrggoetrcl tbst 1¡ üyDs'th3nolilL¡n tFr plrræccef rl tu tbû flarn¿ 1¡ dur,3o E lEoadf,tion¡dr clrtletoacy of thloôrQne¡1n¡ derhelograaso (rrrn¡ue, 1960). lhat lr, tbc

aer¡al l¡vrle ln th¡ &l.aaa sanrot ooBr wlth f.ncrrar¡d ctæsadc.

rc'¡lvcr¡ la blolo¡{oatr øyotroe actrgtloar to a¡r sltnsæ.ons ôo

prteuroabl¡r oeerrr aail lt uay Þr 8r6Uaa1 $¡at there 1c e tradøeyto edept te ånoroan¡cr trctlcgrrcrrnr rcr¡rrs ult&rn tåo gr¡nd ng

hyprrtþreldl¡s Ly as lno¡ra¡¡ 1n thÒ eottvltü of ll¡ls regiyror

thf,¡ ino¡ca¡r ca¡r br largn rnougi¡ in corc lndlvlduat eer¡ leplovrnt thc rclr¿.. c¡f ted,fBatad grcrlno¡ l¡to th¡ btocdr

rt fu ml¡rm¡t that ne drf¡et ln loaoqrrnatn dG¡hsl,ogua¡r l¡htDlrthürÌct,tllæ ha¡ È¡.n for¡nô f,e et¡ ,Ud¡r (Ocr! tt ¡l.r ¡g5g)

-l¿$Þ

1r tgot rl:ftÈt trôtrrrt t 1¡ lt¡ eot!,r¡ût r r.Fr nnortlL Olorl¡ttcthæ vo¡h oa tàc a.ttÉlü e! tbt¡ .attt 1l þlclüfrfütnr¡tth* W f¡l vltso ruryrrfoÉc¡l' tmH,qn.r e! Dt laålr¡t lr rtrratrillcr¡ i¡ rrldld.

-L+fu

sËugJ

O.-

IE¡OID O¡¡ID

In tÌ¡¡ ceurs. of lnv.åttgptÀng thc llf¡st of !8H on thr

ohlonåtcgrephÅo D¿tt.e of tho olroulstlng üryrolit hor¡¡cro t!Itygcthyreld, ruÞJtrt¡ rho had rcor!,v¡d, th¡rr¡nntf.o de¡t¡ efltl¡ lt va¡ frlt tbat r¡¡efi¡t gueltttettvo data oa thl ratl af¡¡er¡tLcn of U\ ,*arl t8H stlnu.lat¿on d.ght Þe eolllstcd etthe ea,Dr tl¡t. rt v¡r lor¡ncl arrÞrcquontltr that thr oÞromt-

ogra¡lhlo clat¿ ctcrlved bed en l,aportaEt Þærl,a6 on th¡ latrr¡uv-tatles cf tús qr¡entltetlv¡ d¡ta, antt alco en ürc wsrt of ethær

ou thc ¡lfrot cf E8r oa thr uptako snd roLrss¡ of lrlr *to" tu.tþrolil g.lrnite

lo

r¡ tb¡ latt¡r part cf tbr ala¡tænth omtu:ry a plttriürytþrold lrleu.cn¡h1p us¡ ¡uggr¡trtt ftor tho oÞrclvatloa cfrnlergrd pltuitarl,¡o ln oe¡.. of gel,trour srtlul¡¡ and aræ intþnotilrstonlard raÞblt¡. lhra¡ rhortly aft¡r ¡goo, tt rerrroordld that þprpþrrobry oautod tW¡.old atrcpby l¡ varlcu¡aal¡al¡ Dut thet thtr oor¡rd lr ¡xrvotod Þy thr ecl¡tntrtçallca

-Å¡llt

of $po¡lbyæel dnttr ¡ thuc lr¡d,l.¡q to tÈr nosglfüoa of a

ål.otlnet th¡rrolå sütrulatd.ng faotor rÉthl,n thr plttrita'ryr rht'ù

rrâs nsnrtf thf¡eÞophåo horuole bry S¡rev aud l{teeao* 1¡ 19!10¡

loll¿urtug thf,e¡ rrlth th¡ erudc ehælcal BsstyË tbæ ev¡lleÞ\t¡

8811 ws¡ ¡Ì¿eus to ¿.eDråôö tho glunduler t e{lá,nr ¡Sre¡ by ¡rslraÉ. of, 1oôln¡ l,¡to tl¡r b¡ocd. thi¡ ua¡ ooufl¡nocl rlth tba

u¡¡s of Ìlfl ¿"r the Êlr¡t t¿ø by r.btond s¡¡d t{it (rgæ). thftlnt¡rducticn of çrdüedLa¡ b¡¡ rnoþI¡d varl,cuc þ¡¡cs ef r¡r¡r¡¡rncnt ef gJ.åudu.i¡¡r actf,vlty to bl dryLgrd.

l$eåt end Foehln tÞant tt el.¡ L949) Åntraduocd th¡

&eefrura¡¡¡at cf l'h o¡,."ra¡cc reto¡ lerr thr vsllsr of ptrrrua

cl¡er¡ü ocraplotrþ er f5\ Þy thr tl{trold tr rmtt tlnr, uâfouno tl'¡L¡ to b¡ J,6 rl. pla nln¡ùo f¡ n*¡al atrbJrota aarl

486 al, prr nlautr le uatrr¡tr¡l celr¡ of eyputþrrd,dlrt lhl,r

lcd r¡tbör¡ to {¡¡¡ec¡ uh¡tbrl iËBH raninl¡lrrtLon vor¡Ið. lnorea¡l

tl¡c olca¡¡nEc ratt and ethcr prranctrr¡ ef tlV¡eolil t¡¡ctf,on t¡the lev¡l ol¡sôstccl lu þprrt$tcldl,nr

Such ånrcril¡etÅeu¡ (o.g. Ståa.I-ü and Aetrood, 19{9)

revsel¡d thqt tlso r$,r¡ttd ¡ trr¡oref ¡r tji,t,erocfetloa of tte¡ffeots ef &¡[ eu ieÉlm cllaren€o or r¡eul¡l¡tlor¡ a¡0 cr

r¡I.eceo of ltl¡ frcs th¡ ¡laaêl rr.l¡r¡æ cecurrlng ai¡¡¡lü¡ecdiatrþ, rbrrü¡e tbo i¡erle¡r ln ugtekt råt dtl,ayrd frrsonG horse. l¡¡rnæ (fglgi for¡¡ð thst 3EH fell¡d ts lnorraæ

uptakc of rll¡ la garqa cf åypcrtsrcÍdl,r¡ Þut ll¡ho¡a (fgts)

-I|8'

¡hwad that ltÍll ¡¡oulutratlc¡ rr8¡ å !c!o æn¡lttvo rte¡ur¡nml

th¡a lãl¡ opt"¡a la ¡rylD.¡rûry¡¡ldllre¡ la rhúoh trdlttrc! üo

aoctrsr¡latfon of f!\ t'n nr¡rclc. to 88ü dl,{i rt¡c n¡¡trit$ eft¡l

toro örla¡r¡ tho rtfrct cn nptalr þrrng eq¡¡l,voeal. Il a¡¡tryfrt'û

rubJtota th¡sl Ie! 8n I boer latrac¡r l¡ ecsuøt¡¡"süen fellorlag

!8I¡ anð tilrr æ¡14¡¡ ve! r¡eüod La 18 to 34 houe¡ ycf th

lologr. or *rr3\ Íår t e.u¡aÞl. la 9o ú,autc¡¡ goôtrb.tt

(fg¡g) eopSl¡nrd tlnrc flaetlngr of il¡hora ln ruthylold ruDflotrt

eûdt ro El¡c har Oooldecr (f9t9) ln both rutiryrotdll¡n and bVpe

t$rol,dh¡r Êlthough Þoth s5r.t ùlrel tÞ¡ laoæ¡all in cræ¡tlel

fol,Iorlng !8I i¡ l¡¡s ln þpctþroldlrnrtno potat¡ Ero lücglÃt tro¡ th¡¡¡ l¡v¡¡ttgatl,ôane ODa

oono.lnð thr poealbb ¡att¡æ of th¡ tbülrolal ¡rsrtf,s¡ tollerl'ltË8X 1a thÊt låtcnt ¡lrrl,od eoor¡rrln3 Þ¡lore aeq¡nuletion ¡oflso¡ro

Ih¡ ¡¡eond polnt l¡ad¡ ts th¡ suggrrtlon that¡ 1n o¿ntre¡t tc

u¡rmr rg (fg5¡) sug6rctl,en, tbr lryp¡ltbvtof,d gle¡ü ïill ru¡nnd

to rrograor¡s tBE stlnulatlon, $¡¡rr anci $ohrll3. (fg¡Z) hed ¡hcrû

that þpelthyrold g¿snú¡ mtd 5 to 5 t1¡¡r¡ aa Euoh E6ð ar clo

¡¡ornal tlryroüi g].anria to ¡recluoo thr ganr l¡¡oc.ur" in t!\

eoc¡'rtlon rate¡ and ån orilcr tc protluoa au l.noreE¡¡ Ln ¡rerttlel¡eto gt aII ln l¡ypæthyrcltltco¡ lt rould bo a¡cratar¡r to at Xrsrt

.roaod thr rndograous 88H lcvll. 3hl¡ çould ¡ttll bo eou¡ntlblt

vlth thr throqy that Qxens I dl¡¡ear ta proclucad bry en lnelre¡¡

tn üÐH by tho pftultaqy.

-l+Þ

ü,rour¡l,oD on thr net¡um of th. telly rrlla¡t of l& fcr

tho tsü rtl¡¡uletoct th¡rrold nor felLerr. toÞÞlnr rt r1.¡ (fgl¿)

Eotrd thatr eftrr !8Ir I,n mth¡rrold rubJrct¡ thoro ua¡ & nlat-lvrþ grratæ l¡or¡a¡l la urlaaly 1'\ .r*.tú.oa tbe¡ t.n t.ruPEDh or þt¡l ttl¡r ruggratlng that tt-Ëlt orur¡¡ aa lasree¡¡ 1l..ru¡ of, an trcdc-oon¡roruô vhleh lr ropLdL,y or¡and Èy thr hlillry.

Ð1¡¡ rt El. (rg¡g) rrerur¡ct tDrt\ a¡ð tota1 lt\ cllrap¡relatrs.

tlnoe anil I¡v¡lc Ln eutþrolil rubtretr aact þprrt\¡rrold rubJootr

foltovlng l8H. Ehry fouart reBld !,¡oroa¡r¡ in rtslll¡ trv¡h i¡all rutllyrola rubJrote, but tbet thr plam* lllln¿ldo d!,repp.a¡-

aner tl¡. vee slgalfloå¡ltly l¡or¡aard, and l¡ eono cubleotr thrplarna lllteal¿¡ eeiually lnorla¡cd. sÍ¡rLar rosulto yora

Íaoctd.d lu thc lrypcrthyrolcl rubJoote, ancl ln Þoth 6tcuÞB th¡rtwsr a oo¡rlaspoadlng rarr¡r l¡or¡a¡r Ln urln¿ry lnor5anlsr!ll,odl,l.. fhcy coariil¡r¡d th¡ r¡r¡asr of rsdloeotlvft (over

aad êÞoyr that rrl,¡egld e" ¡1151¡) to oonr alao fro¡ tbr gla¡d

and to oon¡lst of lEorcanlo l5lr, and. to bl du¡ to aB Lnblbitlea

of tbr r¡utf.l1¡at!.cn of, thr l!1r ¿.rlvrd þ ctolodlnatloa ulthtathr glaail.

fagatcs. of a¡,. (fg¡g) chowrct thst lBH oau¡¡d a grratrr

lnor¡a¡¡ ln total 1!r¡ ttr* 1n t.O.A. pmol¡rl,tablr lttr to oog.

2-5 daye efter 1!\ *arlnl,etrat!.o¡, and a¡¡r¡¡cd thet th¡ tot¡r.r - FBr dâao'panorr¡ v¡. duc to a r¡ha¡r of lnrrSanr.o rcdi.doo

-15Þ

lhry itld¡ horwæ¡ leof for E! 1¡ th¡ bloodt by ohronatogrr¡rþr

but for¡¡ct no ¡vf.donor of lt. loernb¡¡f rt Bl. (fgeOerl) fcurd

r¡¡rntlally etrlLar rorult¡ ta dogr¡ e¡d la ailclltlon¡ thet tbriiod!.clr I r¡L¡a¡l ve¡ ¡nhaacrct by tht arl¡lalotratlon ol pæohler

atl¡ and oonoludorl tbat rgH had e prcrnpt rtlnuratorlr of,frel upon

an lntrsgl,aaclurar dofodlnatl,on plDgorao îhry ooallrnrd th¡¡lf,lndLn6a ln hr¡¡a¡ra aarl rat¡ þ døonrtratlng a proupt l,ncrcarc l¡urlnar¡r lrltr .**otlon¡ end vhrn organi.o blndrag wa¡ pr.vrat¡d

ancl lodLao tlappJ,ru was tnpal,rlttrîËË nrualty 1oö to a ¡rronpt

d¡o¡¡a¡l ln th¡ glanelular 15lr *r.trut. rbry ahovrd ar¡o ¡aabe¡aot of thte ¡t:8¡ot Ln n¡¡xordr¡atous ruÞJrots and in tþroLd-rçtenlsod ratl.

Halnl (fgff) had rhown by dllf¡r¡nt n¡thoct¡ that a cl¡ElLar

pbononrnon üBy ooour 1a ratc. Ehr ttryro!.dl gorun ratlo of11lr ouotrnt tlrop¡ for thc f,LrEt I hor¡rr att¡¡ !gr, and thr¡oonn.no.¡ to rl¡1. Shoy alror¡d lst.8 (xarar ¡t a1., ¡960) thettho ¡es¡ phlnouonon ìtaa obs¡rYrcl rv¡n uhrn thr glaadular loclldrstou hatl brcn clrplotrd by thr arlnlnt st¡ratLon of antfthyroldclruga and tr.

lho prrerat study of th¡ ¡ff¡ot of !BË on the glarne pBx¡

totallllr, ¡¡1!rr l¡vrrs and cn th¡ trrrnår¡r .xorotroa or r!\

rr rlh-trret¡cl þport&yrorct cubJrets ulll nor Þo clreor:lËrd¡

-t!!t-

?¡ E!H9,P9,

B15ht hrprrthyrold rubJlete rÇtc ãtuctl.d b7 daga aft.t'

raob had rrotlvtct a thrrap.t¡tlo üogc of ltll. lhr ¡ratlratr

mpor'tadl to tho laboratory fartlng¡ l¡ tha aornlrg¡ and aoÛalrr.ô

fartlag for 6 hour¡ and r¡¡fttag tor I hor¡r¡. lggl wa¡ 6tvla la

a el,nglr lntsaousgulsl. tnJrou.on 1¡ 2 aI. of nolnal ¡a114¡ tloaego

of !0 U.$.F. r¡nlte to ¡aoh suÞJrot. Bloo¿ v¡¡ colhct.al bofor¡

!8[ an(t sl 2. ¡[r ¡on¡tlprn 6 and 8 lrourr eftward¡. Ela¡ne ve¡

arparetrtl uûd,.l lodtn¡ t}rr eontlittons.

thc plarae PDI lcvol wee ¡atlnatrd by th¡ aothod of Aolanå

(fg¡Z). À ye1r¡n¡ of I nL. of pl,aana va¡ d,llut¡ct to I0 sI. rlth

eatr¡ and oeunt¡d la tbr lI00 SolntLl,letor oountor to givc tho

total lllt o"ntmt. PmolBltatlo¡ of thlg ¡ano ¡aüplc ol ¡llacne

rar prrlorÉcd vlth clno culphetr anrl eodlu¡ lrydoxlcl¡ eosordlns to

thr nrthod of Acla¡d (fglf) and th¡ Bnrol¡lltatr wa¡ sa¡horl tnlor

vlth ratlr¡ and r¡dl¡eolv¡d ln LO ¡rl. rlllut¡ hyilroohlorlo eold,

end th¡n rcoorut¡il to gl.vr Ðft\. IFin¡ vaa oountrcl 1¡ e

volu¡¡ of, 1O ¡Io undllutld.

l. n¡su!ßs arD rgGuSEIo:

lbt r¡sulte of sI¡. oouatl¡g on pletra et. rrprrerld ar

pæorntas. of tho dosr of 15lI adslnl¡tcrrd ¡rcr lÍtre ot plaraar

t Prtnethyronr ¡rertþ luppJ.lrrl by 8ob¡rl¡g A.e.¡ Btrlln.

-Lï¿-

thr n¡se tota"L ltfr ocntürt bolor¡ sH ail¡qL¡t¡trat!,on va¡

L.L# p.¡ I for ¡.y¡n ot th. .1gbt rubftote (!gUr tÕA).

thrro re¡ e rtrady laor¡a¡¡ up to I hou¡¡ vh¡n th¡ lovrl wa¡

L.lrt prr l¡ and thle drcpprcl ¡llehtly to l.40f et ?4 hotÈ¡.

*" lot'lI aad o.1!Í a¡ holuÈLc, tIL. lollorlag rsH ¡ti¡ula-tlon th¡ tDl'lI rost !.n a elr',lar faohl,En to thc total, Itff

('rautr V6D) rc that tlro ¡f,f¡ot on thr i¡ol.uÞlc " f5\ ra¡ v.rl¡

Ênslf.. {ho nra¡r tor r¡sLubho f!\ ¡ìos. f,ron o.llf of tb¡

closc per lltrc of plasne to 0.16 at 4 iro¡¡rs, but dropprd tco.aïß at p4 ho¡¡¡e (naufe 1?).

Ag nrntloarcl fn tho Introiluotlon, varlour rorkæo havo lsuact

atgnl,flcant tot¿l ltll-lDultr ¿f"olr¡ranolca folJ.orlng ISH¡ l,n

both outh¡rælcl ancl hyporthyroLrl eubJretr. fh¡ a¡thod of prrct¡rr

ttatlng protol,n eae, howcvor, dLfforont to that us.d in thr

proartlt atudy. In th¡ I'ap.tt quoåed nbovt¡ trlohleraootfo aet,d

was uoetry ucrd for lh!.c plllpoeor thl,s 1¡ knovn not to pilcl¡rLtatc rltbcl Lnorgento lodLdo or tho lodosrroslacg (norg ct ar.¡L9-51t BLla¡r¡sd¡ of al.r tg6o). rn thr plrrrnt .tudy thr Eoao6ry1

naglnts, aø uatd by Aolancl (rflz) Horc rürDloyod. !h!.a ¡rooxplt-atoe not on\y tbe todetþronlnoa, but al,eo a largo porooatag€ eftho lorioffroglEle. Fho parorntage of âodeþrsslnls ¡a{d, to be

prcolpltatcd slth tho latttr varÍce wlth tlfffcrrnt autl¡orltlr¡¡

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-ltÞ

long rt elo (fg!+) sletn thc tlgun La 651¡ Hsn snd Ecrd¡r

(rg¡r) suggret tbst 84Í of th¡ loillno ol xrt 1¡ ncovoreblr¡

rt eBprar¡ fton th¡¡¡ ¡rtlaatr¡ that th¡ ilfff.r.ast b¡ty¡¡atotel 111¡ *¿ tho ¡lno prrolpltatlr 1!lI gtvcc a brttrr Brr..r-n¡nt sf thr lnor6an!,o lll¡ a]'slr¡ rhorrae thr total f!\,

lGl preolpltaÞlr rll¡ or,rf¡rmo¡ ¡oan¡r.r both incrganlo t od!,do

and lodcþrreslalar rov¡rtholr¡r thr fo¡u¡r oorblnatlon nlgbtrcfr¡at Loctot¡rroala¡ oont¡nt to a onall r¡trnt ac rrlL Ee tb¡tnorganlo 1!1r. !h. diffor.no. of 0.lrÉ ot r!1I prr l (1.r.].]'ól of tho total rt\) as r.asumd, utth thte ¡rthod t¡ prflll¡-abþ clur to th¡ lnorganlo rlk oont¡nt of tho plaena, Ln addltiorto an unknorar though nnar!,, traotLon of thr Lodotyrorf.nr rhornby papor ohronatograpþ to elreuratc !.n thr plaena of þpentþ-rolcl ouÞJrota. lgH produorø e ¡uall Lner¡ae¡ in th¡ absoruto

asount of thr Ëtolubl¡ n lll¡ tho naxl¡r¡n brLug attalnrcl atbrùmn ¡l and 5 hor¡rl (teUfr t?¡ Flg. Zg). lbls mall fnorreæna¡r br rcfr¡otlng rlthcr e nodraat¡ !,ncr¡aro 1n thr l0closros!,nof,¡aotlon¡ rhorn rarll¡r to ooour rn Ìryprrtþrorclla., o¡ nay

r.Dr.E.¡t ln addltlon e yqy snall lnorca¡¡ ln lnorganlo lodldrorf ¡uoh an lnor¡a¡r tn lnorganio loctld¡ o¡lsts tt fu qul,t¡ urrþto br elu¡ to n¡taboLÍen of th¡ lnor¡aard anount of olrouratlngloclosnoeln.e. l[hc naxl,nun lnorras¡ oooure approxf.natoJ,y at th¡sano tl.nc as trrr uaxtnun lne*ase of, l0dot¡rro¡r,áe.

-156.r

flIOURE 29

-

It3tEFFECT OF TSH ON " INORGANIC t'

IN HYPERTHYROID SUBJECTS

60

PERCENTAOE

CHANGE 30

-30

0 H

x

024 ?,0ITIME IN HOURS

ô-A URTNARY r3tt ExcRETtoN

O-O RESIN : RESIDUAL I3II

X-X PLAsMA ToTAL l3rl minus PBr3rl

-15?t

l¡ a fic'thrr ¡h¡CI o¡ thr naùrrt, a¡ouat and Ul¡ rcln'lloa-

shlp of thlt lno!.el. rtbr a,nouat of lll¡ ryElntlg on tho r¡olr

ooltun ve8 r.êsurld¡ thlr rbculð rqre.lat epprod.retdy tbe

Enor¡nt of Lnol5anlo r'h ln tbr ¡rlnele, thr rr¡ults (uurr ll8l

1lg. 29) o¡pr.¡catl a¡ oot¡Et. p.r. lOO ercoad¡ l¡.ll lI. plar¡¡ ¡horr

sonr varlatLcn Þ¡tnr¡n patLonta Þut th¡ ov.tall ofl¡ot 1¡ a lacll

lncrlaao ulth e Dåd.lr¡E brtuæn ¿l a¡d I besr¡r

Iho r¡rlaary rlft rxsr¡tloa Þ¡tn¡tn 0 anrl I houre ve¡ al¡o

n¡asr¡r¡d and ¡hors a alnLlar¡ thougL Eora plot¡or¡¡o.d rl,¡¡ vlth

Ðarinun ooourrlng at ¡lthor to 3-4 hour or thr 6-8 beur ¡rælocl

(na¡tr ,91 }lg. 2gr. lhe lnor.ar.a tn tho r¡rtnr r!\ oottrat

ar. nor. aetlorablr¡ thle la proÞatþ eluo¡ partþ to ceoh url¡leBrclnru r¡flretiag an lnor¡aEo fn redloaotil.vt$ tlrroughout a trchour prrlorl¡ and pertþ to th¡ obr¡¡vrd rapld renal daiodlaatlon

ano oloa¡ano¡ of laÞ¡ll.od, Et (Iaaatter and Stanbury¡ l95g).

Ëonr oonll¡natlon that thc loclotyrorlar¡ ete e!.rculet¡ ln

þp*tlryroldl¡n was oþtaln¡ct ln onr ¡latlrnt by ronBarlng I81t\çra¡u¡tntut þrr¡ramc wLth SnsO*-IeOf) wfth nflãt¡ soanu.on¡nt

aft¡r tlDlauF waeh!"ag (taUto 4O). In thla ¡ratlcnt qulto a laegr

pall\ - 3¡l5lt dleær¡rano¡r $ss obteLËtd Þ¡fom lBfl ua¡ adala-

!,strncl and osrroe¡nnrird to qutto a oonepLeuous epot of IIE oa

th¡ oluonatograoo lolLorLng t8H tt¡oro ys¡¡ a nochrqto tnorta¡¡ln thr illsolopanry nraeundo rhLa eormepondrd wlth a nod¡ratl

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Talur¡ ¡f-f) erpr.Earcl as pcreentage og ailntnl,¡t¡nd doel pcrl1$.r plarraa.

Yaluc 6 8¿dleaotfve agao¡aßcnt ve.3.r¡r of Di[Î flon üh¡ Cbs¡nato-graBhfo aoatr¡

(a) - (f) Àa¡tu¡d to Þo dur to taÞrtl¡d thyrogleÞtrlf.asonocnbatXon la thc ¡llawar

(+) - (f) Brpnaonts tn¡¡ r¡fll¡ attor d.dr¡ottrEg thc valuofor %hV¡o€B.fobulLn r.

(o) - (¡) Eh. p3]tl¡ - ¡¡lllr ¿teorep¡Ewt assuncd to Þrdu¡ to tho lab¡lloal DIB csntcnt ot tb¡ ¡rlaræ.

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¡. !eÞ¡ 15Ìr

2 lobl BE

t (a) - (r)4 Ðrttr5 (*) - (r)6 l{ashcdt BE

r (s) - (l)

t 5¡.I

t 9lr

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48 Hour¡24 llour¡I llorsc

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åqv ¡ .ley XfVal,uc

Afttr 88t

-1fl-

lngt¡erl la tho elo¡ut of D[! a¡¡ot¡¡d vleuellyr Þoth taôlo-

aotivr\y and e!ølqnllyr ancl al¡o vlth tb¡ nsdrratr trnerca¡¡

of urt^anry 151¡ o,.t¡rut¡ and å EEåII l¡orrerl ln tl¡c tete.T.

rtlï rgrlh ¿isrnnrüeor

tn thta la'trcratory rct! f,¡ Ln progrrss rhloh 1¡ ft¡rtb¡r

esnfi.¡t¡l,ng i¡hat lotlot¡rrealnre a¡rpral la thc plaua ln r¡ttpoa¡a

to tiürro;l'd cti¡Êillation. iÈrelinlnary uorh be¡ shoyn ü¡st rDI-

EBr dlsorupanol,ce rxl,ct ln uatr¡atrtt üyprrtþrelrtirn¡ psrtlou-

larlv in ti¡es¡ öÊ.8.s i'¡ shioh thr larg.r agount¡ of lodotrrcrl¡¡¡ogol¡t.

Dor rxamBle Ln trro patl,rat¡ !.n wl¡loh a d¡fl¡ttr BlarmlodoQrre¡lno lcvol wae f,otrad¡ thr tEiI hvolr u.a. ?.9 aad

L2.7 /t'Lso pot L00 nl" r.ðpoot¿vrJ.y¡ uharca¡ tho BEr bv¡r¡wtr. ão6 aad 8.9 /t-g. ¡rcr loo nl. rn anothor gett,rat ln th¡

¡llarue of whlslr aô foriotyro¡i"ar¡ voao alotoct.at, thr DBI lovrru¡s llo4 anit th¡ Bll lcvoL Lþ.r)iLg. Dlt IOO nlr

rn a furtbrr l¡y¡n¡tüyrartl patf.oat tho plr ra¡ lLo snd thrEII 912þ1,. yrr lûO lrl. thLc dl'¡¡æqg¡aqí of lc8 1LEo Fa.//l0o el. søou¡trð to f6.41 et thr IDf lw.l. Eo¡t E! uerqlrtrotod ln thr prerna of thi¡ rubJcet a¡u follov!,n6 ltf Efl¡l¡-i¡t¡etfor 6$ l¡c¡eaæô aaount of, rrs uan ¡elrs¡ed tnto ü¡ plarna.

lhLs oomrrponctld to an. lnoreo,¡r ra thr rBt-Brr drræ.paaelr¡ to1.2 1p{re por 100 o.3.r (n.4) at four hour¡ a¡¡,ü D.! (zz.tfi) at ¡lg

-1óÈ

hcur¡ aft¡r !88. rt i¡ ¡neelbl,o that oo¡r of thl¡ inorcaelng

dlacÐpaaoür wes du¡ to th¡ ob¡¡¡vrd lnorracr fa !O oonolnt¡atlo¡

ln tbe plarna of thl¡ eubJrct aft¡r sBH. lhr prrorntagr t.ævalãr

of !t 1¡ th¡ Btr n¡thod hÂc b¡ra fsuad to b¡ about goÉ (nqn âå¿

tsoncty¡ r95?). rt i¡ unllkrry that thr prri,ooctagr moovrry tnthr af.no pmol,pltaÞrr pDr nrthod veuld b¡ nuoh lceE than thi¡flgurr ancl thrr¡fort aut lr-tnduoral cHeorpaaoy bctrrrn th. r,!rand, EEr lrvrle ln a lo-rleh plaeua le llroty to br qr¡lt¡ spallo

rn saÞlo ,?r lt oan br ¡¡¡n that thr ¡ur'\ r.¡wll ¡tao fnrasBoaa. to 18Ë. Ehl¡ oannet neo¡eaartrg Þr tekrn ag tndloatlvrthat th¡ hyprtlryrold glaad ia nepoadlng to tgñ, hovrvrr, bosau¡¡

thFc 1¡ et lra¡t oae othol fao,þr o¡rcratlng l,a thts l¡ortseo a¡¡ct

rhl'oh Le Lndtprnct¡¡t of fst ¡tf.luletlon, end thet Lc the lno¡reroln rproi,flc aotlvLt of thr thyroldar ¡romtlcn uhloh La str,llooctrrr!.ng e¡ roon et !-4 ctaryr afto flk thcrapy. pltt-Ilv¡r¡ead RgIl (fggf) ¡hou¡tl lhEt th¡ cgr¡lllbrtr¡¡ lc not rraohrel ln thtrutlryrold rat t¡¡tll et l¡ert 14 dqya aftrr ItL. Horrvrl, thrPEr rcrpon¡r in untrratrd þprstþrold!,¡¡ a¡ ¡hoyn ln thlri.nvrat!,gatlo¡ in thr pnv!,ous ohaptor (and el¡o ln tho gnslntohe¡rtcr for th¡ rlght petttnte oXtcd) ia cttflnltr rnough end

anet¡nttd to an eÞ¡olutr lno¡raoc øt 1.5 7 S. Btr 100 nL ¡ll,aruln tho l¡yputhyroldl group anô l.jr*t g. fn thc outÌry,rold groupr

-1óÞ

tho trs:cißu! DGÌoeolte,8l lneroe¡l tn tbc byD.rt¡rysotû gfouD he¡p

ovot, Lt ?1.5 enê ooffias at 24 horu'l¡ Yhrr.a¡ la tt¡¡ rutltylolit

FS11D 1t LE ,7.4f and ooEur! åt 48 hor¡r!. !h¡ de¡r et !8H

gtv¡a te oublretc !,q both SrouDB va¡ llo u8D unltr' lhlr doregl

nuct rurtLy cxooró th¡ r¡¡dogilnou¡ !g[ Itnt Llr thr try¡ltthyrold

rubJrotr. Slæo an othor faûloetlone lE thr fftrratrùr that

hyprrt$!.ld 6tåÁd la rroponrlyt to rægraouc Ei, orgr Ogeltlo

(fgpg) ttrlËs dc¡o¡ at rnsll e¡ ! U,ã.P. u¡lt¡¡ ahovtcl that

clrar¡nor sl 1!\ ,". lnsroa¡o d W Ðl rn hyperürurslel gtallr¡

and Ð æO-WO/ ta outþrottt glandr. ,Ln¡olÊ and la^r¡¡on ò9..6O)

for¡dt that tbr 2¡[ hou¡ u¡rtakr nt ttll raa l,nsr¡e¡¡ct follonl,ag !8f

prmrctloatlo¡r eoolô¡¡ (fg¡g) hact polntcd out tbßt tho uptalo

"r fI\ wa¡ not a¡ rln¡ltlvo ê üånrranmt of lnsroe¡ed eettÉt

rlthl¡ thr tþrolô gla¡it a¡d that thlr l,¡ e proDaùIc crpla¡¡tloa

rh¡r renr lnvoetlgatore (o.g. Ulrmr, Lgrr) hatt nportril tbr rypeF

tbyrold glla¡d to Þ¡ lndr¡rrnelrnt of !l8H oortlelo

^[ ¡hort nv!"rr of sçs,r acBooür of llII p¡tabollgp aad

kl,,artiee ln nor¡El aubJccta a¡d fa hyptrtt¡6ol,dten rar pnetnttd¡

tcllcvrd by e då¡oucsl,on of ¡osr of, thr dt¡erlÞ¡d rffrotc ct !¡lin þoth ooadl.tic¡as. In perttc*Ler f,'ù yas shoun that aon¡

wolborg bad cletoot¡cl total rt\- !.0.Å. ¡rroof"¡rttatte lllf

-L6Þ

dlacnBanolr¡ ln mtt¡yrsl,d aad fqfpa'tÌryreld aubfrotr eact l¡âd

ooneLudrcl thrs¡ r¡r¡ duo to en .Êtly rrlracl ol lnosgnnto 1!l¡

from thr EtL¡¡uLatrd glandÌr

0pportunfty vae tak¡n ilurl¡g thr lnvrotl,gatLon ef tho offcot¡

of, St o¡ thr plaena ohrooatographlo pettrn tn ÌeÞ¡Llrcl þperrtþrettl rubfrotr¡ to rc-rxam!.no thtø þBothrglo. fba lDlt\

Bnolpl,tatlon uae pælors.ô wlth thr 6onogrl rregratar horlvll¡

rhûoÌ¡ er¡ thoqght to prrotpltatr b¡tno¡¡ 6þ8rß of thr lodoSr-

rosl¡c¡ plrarat tn th¡ ¡rlarne¡ 1n dl¡ttnotl,on to tlr¡ E.C.A.

nrthocl vhfoh ¡rr.rd.¡rltatrr oaþ ,fr of th¡¡r oon¡louadr. E¡*ì,I

dllconpaaolos olllr bctwt¡a DDlt\ ancl total l,L *.t¡ ton¡tl fn

thcr¡ byprrtþroltl lnöLvLtluale¡ Ênd tbr!. dlrorrBanoloå lno!¡aretl

¡tlehtty up tlLI 4 to I hour¡ follsulug !8f lnJrotloa¡ Ia vl¡rof, thr ¡alf,lu d¡uorsttêtLon thet larg¡ a¡sount¡ of loôoSrrorlno

ar¡ lrl¡ertd tron th. !8H ¡tl¡ulst¡d nonnl glancl¡ anü thst

tûsll.! Lncnascr s.L lound ln thr lryBtrthyrold ¡ntlrstr¡ ltve¡ lrlt thet thr lerg.s ctfuorqrnnd,¡s fouarl Þy oth.r¡ ¡ac dB.

aalnly to thtg !.Lls. of lodoQrro¡l,nr lato thr pleane¡ althongh

a e¡all ameunt nay br attÍ,þuteÞl¡ to an l¡one¡rcl tnoagÐnlo

leôldlr oontrnt drrlvod lron th¡ rrlaÞoLlsn ol tht loôotyrr¡lm¡o

thtsr lnerae¡r ln ù¡¡a oau.l thr obmrvtd tnsr¡srl ln urlner¡r

exættlen uf 1t\, vhloh 1s ¡exl¡el at g hoqra follouÍlg !8n 1r

tho [rprrtþrolrl ruÞJeetrr

-I:1,-

cH^?l!A W

OEFFRAI{- DIS.EIIBB IOlt

r. uæutguglfhc obr¡olsal oYialono. ln thla atr¡dy of th¡ netur. 6f thf

ol¡sulrtlng ttVrold horuoat hac lnelloatrcl that th¡ thyrol'dl

durLng î8H ¡ü,aulatfon¡ aaô th. hyprrtlryrold 3land ¡oelat. lâto

thr Þlooel ¡troqo òllotleþærlæ¡ ronei.edo$rrorlar¡ en lncr¡a¡¡d

a¡ouat of tnl,lcdothyrcata¡ a¡dl ls atldi.tlen ¡lthor th¡ nornøl

a¡ount or ¡Ilghtly laor¡a¡rd quaatttl,rc of tlry:oxlar. lo

tl¡fl,altr .vldæo. of en¡ etb¡r orgenlo eon¡nmnte rlæetod Þthc tlryrolÖ glaaei uiller th¡¡o ooadltloaa yan fer¡nö. fbporrl,bl,llfir that en unlacm fraetLon nlght Þe r¡LrEa¡d $ar

orrtefnþ not urludtd by tbt r¡ult¡ of thlr ltuèy.

2t

earFHIç rtrplr-ø¿

ln e bûlcf rceapltulatlon of tha arteÞoll,o ftndln6r¡ lt my

Þc aaict that oenflrnatory ¡vl.rlrnor of an rarly aEcl rapltlþooeurtlng rtlaÞolto rlf,oet ¡roduorcl þ tSH (nrtaot anct lJ.cacf,e¡

Lgril y*e obtslanrl. l\rrtbrrrert, thr þpothrctc tbat thi.¡

cffcot ef Í8II oennot br acæuatrd te¡ Èy arlúnl,rtril.ng !,(nctr¡f of ¡L, ¡9t8, 1960E) wa¡ oo¡rf*rntd a¡d r¡tmd¡d to eclmoastlatl,on tÞat tho ¡ffrot os¡¡not br rrçreðuc¡d Þy tür

-Ió5-

eclnlnlatråtlcn of rltbas E5r !4r <l¡¡!,caat.d thulctd cr QrlF

gIcÈulln.

Oar poaalblc or¡rlangtLoa for thr cllff¡¡¡nt agal aoa. rapld

.ff.ot of !ÊE t.¡ thr ¡ugg.ttlog (Xrt4t ot al.r 1958) thåt üA

Caus¡t th¡ ¡¡¡ra'¡lon of e¡othrr th¡nold borno¡¡r al yat r¡ntll¡-

eoy.tod, rhloh hs¡ a nor. ragl,d Eotten on PaÉph¡ral ¡rtabotrlr¡

thån dooa !O ovtao Suoh e flEctlon YB! not ûoflnttrly tounÖ tr

thc prrrütt ¡tudy. ÀD 1oôlnr coatet.nlag ooqlloaont gth.r. thÁa

th¡ lodoQrrerlara, !a or t, vea horrvrr for¡ncl ( ) !f) e¡d 1.

poralÞ\y ldrntLoal vlth that drseÉblat þ lrulr enil V.X.r.ôl

(fg¡A). Son. ðupport that tbte l¡ a ¡lrptal\y aotÍng holront

nlght Þr prremt lf any rcIlanoo oe¡r b. plaercl on th.lr .ubt.qu.Bt

suggoltÍons (truor, f958l llurr of aJ..¡ f958) tbst thl¡ ruÈltelo¡

¡nhano¡tl th¡ exl,datÍon of Sl.uooar antl .uoolnl'o aolil dlrrotly¡

thet le¡ wlthout funoouBltagi¡ esd that Lt rahaaorc Þlologloel

aoetylåtÅon rlaotÍca¡ vhotpras !4 a,nd tO lnhlÞlt .uoh aoatylatil,on

rraotl.on¡. lhl¡ ¡ub¡tsnocr vhLoh haa thr oano Bt vaLul el

trtlodethyroeo¡tú,o acld ln thr ort ¡olvmt ut.il for lts ot¡rost-

ographlo l¡olatLonr Í! cald by th¡n to Þr an aortyl drçlvatl'vr

of aa organlo lodtldr oon¡nurd, end la lhottght to þ¡ dl¡tlaot tron

trllodotlr¡rroaortt o aEld.

I¡ tho ¡rroÊont study thc ooourrmo¡ of ' ) t, tr wa! l,aval-

labþ oorr¡lattct vlth lner¡a¡¡d anounta ø1 lI, on tho ohloaatcgran.

-1,6?-

It var aot ldmtllbtlr þut lt Y4¡ ¡on.lôor¡d to È¡ olthot e¡

unlr¡er¡ artrfast, orl tcE. of tbr !O epllt fror lh¡ rala tlaotloa¡

or Sllodoth¡rroaoltl,o qeld¡

It aay Þr rrprat¡d that thr feLlun !,n thÍ¡ ¡tudy tc

cl¡flnf,to\f ldeatLtlr a lraotlos ln th¡ plerna vhleh eoulil acoorul

lcr th¡ rapld rrteDell,o efftotr ol !8f, rloo¡ not by ery n.en.

rxoLurl¡ thr ¡rerrlblllty thåt ¡ueh a conl,onont tr ¡¡crtlad by thltþroldr By aaåIogr r"!.th lhr ¡rlryrlologå.cal vr!.u¡ oh¡nlcal

proprrtlr¡ ef l, oonlarccl yltb E4r lt rlght Þ¡ e¡rttolpetrd that

this oonpcund¡ tf lt rxlata¡ al,ght bsvr e v.l¡f hteh tr¡¡r¡ovæ

rat¡ i,n tht glaana sail bo rapldþ tak¡¡ up by tho tl¡au¡r ¡¡el

th¡rtf,c¡rr br vrry dlfflloult to looatr l,a th¡ plaana ylth thr¡cohrnloal nrtlroûao

It nlgÞt Þl quoetton d th.tbcr th¡ otceuatographlo lorult¡of th¡ ¡fl¡ot sf E8H tn ruthyrolct auÞJrotr tre¡ rlvlahdt l,¡another Tay E ¡naalbro rxplanatlon of thla ¡arJ.¡r uotabello

rff¡ot of !EH, that Lo¡ otho¡ then thc n¡oreotty tor e,a uûncrnfraetl.on. lollorlng th, actntala$atloa of tb¡ ¡tanderrl do¡rof î8I¡ (5O U.S.f. r¡nLt¡) to a ruth¡rro1d fnélvldual, th. plarmPBr lrv¡L sa¡ for¡ad to incrcarc by l.i ¡tgo lrF loo El. llelth¡ onroaatographlo ¡¡¡uLt¡ lt nleht Þr r¡tLnat¡d that st La¡ttvo-thtrdE of thla rier f.g du¡ to an lRæ¡a¡r r¡ thr t, contratof thc ¡rlarna¡ ee thr l!* oonornt¡catlon ya¡ found aot to rl¡r

-158-

foll¡uiEg !8Ë. þLttülng !t ln tbo do¡r¡ adul,nloterotl La th¡

nrtebolle etuaËrr, whrthr! Þy th¡ lntravenout or thr olaL routtt

tho EEf ¡lsr va¡ ol th¡ orclor of 1.9 pgp prr l0O nI. ?hir

rlE¡ uer r.Gordoù rlthln tro hour6, rh.r.a¡ th. aad,nt¡n EDI

lrvrl foltrorlng !9H rea not Ettel,nrtl t¡ntfl 2þ{8 hou¡r¡. If th¡

nld-potnt of thr n¡tebollo oÈ¡rnatlonr¡ leo. tho tor¡r-lptr

polnt¡ la u¡¡d for ocupel!.ren¡ thrn tl¡¡ r1¡¡ ln !, felloulag

EÊH nu¡t v.r1 n.Brly tquEt tho rfa¡ ln nlaana !, (1.r. DDI)

foll,ovlng th¡ adalnl¡tratLea of Orll !9. !, tt¡rlf rhrthuoralþ cr lntrayuousl¡r.

Iroa thr ocnpa¡leoa of thoeo flgrrroo lt nt¡¡t br oenolud¡ð

that thrlr le ao ebvLouE faotor Ln thr clr¡onatographl,o fi.ndllgr

to aooount for thc dLffrrf.ag nrtaÈollo lrrBon¡r foLlewlng !8Iand !¡.

llhr gucrtlon na¡r noxt br a¡I¡cl, as to wh¡ther Lt v¡ould Dr

orprctrd that a partloula¡ r1¡o 1n rrogwoueþ adnlal¡t¡nd !¡roould preiluot th¡ ra,¡o utebotls ret¡ hor¡a¡¡ e¡ th¡ eanr ¡:l¡rln !O producrd tndogrnourJ.y tturlng !8S ¡tlnrlatLoa. !!¡¡r¡ 1r n¡

date ln tho gmarnt ¡trrrdy vhl,oh uor¡ld brlp to anryat thlr qnr¡tfe¡¡

Onc poaelÞlt rey la vbtoh ¡ dlffærncr rlgbt r¡l¡t botron tbr tno

ooncl!,tlenr, voulÖ Þ¡ lf a dlfftr.noa l8 tlryrold hcraon¡ Þt¡dtas Ùy

tho Blarne protrln¡ oogr¡rnrl. rf thop ra. aa lnt¡rf¡rono¡ l,n

Þlndlag of thr hor¡olr¡ durl,n6 !8f eot!.vetlon, th¡ horlon rqf¡ ¡rtot

-15Þ

thr tl¡ru¡¡ at a Eort raplcl rete aad oaust an lntrta¡r lnoaX.crtglrlslrr l¡t ee !, la hora not to hsvt a strong afflrttyfor ¡rlarua ¡rotrla (¡rte ¡ lt el. , Lg72t l{enolelg tt al. r f95?)

tt l16bt Þr ergurcl ùet Lntrrf¡r.nso ylttt homon¡ Þlndlag

grn¡ra,lly uould hev¡ llttl¡ etfrot on thc EvaileÞlltty of I, bthr tls¡u¡s. Iì¡r'üh¡mort thr nrtabollo tlata ln th¡ pnsrnt ær¡At

choyld thet ßgH d,tal not ln ery yey alter th¡ oalorlgralo ¡ffrcto1, Ìr.

lbr ¡ffcot¡ of lEt lt¡rlf on protoln btEtllng hevc probabl¡

not Þr¡n lnvretLgsttd þut lt ls ho¡ncl to oarryy out ¡ush a¡

lnvratlgetÍon ln thla l¡boratery. Sonr lncli.rrot ¡vldrasr Bl&tb¡ drrf.vrd fron a atudy o1 th¡ rlf¡ot of lEH on th¡ tu¡nov¡r

ratr of tlryrotct hormemc. gtory and p¡rhl'ne (fg¡g) founcl ¡c

chaa6r Ln tbr bll llf¡ of eLthor !, or !a follorlng !8H lnruth¡rrold aubJrotr. lhrl.r ruÞttotc r.ra, hoyry.r, on &rgolr

lodLa¡ therapy yhloh Eay hÀy. pnvmtcd an laorrest ln thr

tu¡¡ev¡r rat¡. îho altttloultlt¡ ln ntaeuring ¡uob lnor.a€a¡,

paltloularlf a ¡nsll lnor¡s¡¡¡ rhl,oh na¡r nrvrrth¡l¡s¡ havr qulto

nrl¡ttl rffotta, nu¡t þ¡ oon¡fuleabh, parlLoularf.y lf an ratþohangrr oay Ln th¡ fLral 2¡l hour¡r Lr brlng aougbt.

.lt loa¡t tno ¡tudlr¡ (Strrfhg anct Ohodct¡ l9É6t I¡tÞ¡ra¡at t!.l¡Let, l9f5) hert rtvral¡d that 1n untnatrd þpottËy-roidl¡n thrr¡ la a nallrcl lnsæe¡r ln th¡ tr¡¡¡cyr¡ of lebtlhrl

.tj

It

-l?lÞ

!ht'¡ 1¡ ruggrrtlvo of an rtf¡et iltrt te aa lnomarlcl

tlen rat¡ to no¡ra]' ha¡ Þ¡¡n obr¡w¡drrü¡rn of thr

l8H l¡vel t¡ tht¡ ooactltloe. ff thr aeauaptlon 1r oerrrct¡

hovlylr, 1t ¡houl.cl heppln that lollorlng adequatr t¡ratn¡at of

thr þputþroltl otEt¡ th¡ turnoy.! rate ¡lroulil el¡o dfú'al¡h

t f tho rtt¡ot ol t8l ln procluolag en lnor¡*grd tt¡,rnovrr u3¡

nrdlatral through thr lntaot þprrtraetl,onlng thylolclo Sush ¡&,

orer/aa

(gtrrlr-ûgr 1958) Eftlrcr¡gh a¡oth¡r ctutly (¡ae¡¡r anal lïolnk.l,f95S) suggretn that thr turncvr¡ ratr¡ although doorcerd

followlag tbrrapy rarlrþ ¡rtt¡rne oonplotrþ to nornal. thlrauggætJ.on togrther yltb thr llnclLag of a elDllar lno¡la¡¡ l¡tu¡acv¡r of !* Ln rut$æÍd r¡Latlvrr sf patlrutr vltb þptætþretdlru¡ reLote tho peralÞlllty tbEt an eÈ¡crnal n¡teboll¡u

of !* rey Dr an latrgral ¡lart ol thr dl¡ta¡r proo.at f,n þprnthyrelell,en (bS¡ar, f9S). ltrla prrl¡¡hrnf rftret r¡y clr.lat

ln adôtttea to a ¡ru$al oflrot thrcu¡þ GE, a¡d aosd uot alttrthe htrpætrü,oa d¡duord abovr tbst a¡ l,açram 1¡ rnôeglnur

88Ë bvotr ta¡r proôBor eq lnerre¡r 1¡ turnovæ rttl¡ aad thGrþproelucr a ra¡rlô lng¡err l¡ ¡¡t¡bolle latr¡ vlthout jnoêueL¡g a

relLtd lænsre !'n th¡ circrlatlng bvrl of !, ol ta.

-1ll-

l.IHZROID gU¡g¡^8¡OT

lbl oooturmot of Et f.¡ th¡ ol,rouLatfon Ln rutÌlyrold

Lnalltl,duelc follorlng 18H adnlnl¡taatlon lrea probaÞþ not Þra

pr.vlou¡\r rcportrd. Bremt rcportr (floot tt el.¡ 1960¡

Dralr andt lhl,tohrad¡ ¡960) havr auggeotrð tlrat thls oonponrat

aeoot¡¡te for ¡Þ-56f of thr clr¡ulattag tht'rÉld hoamao fsrsndcs rer¡lloa fron aotr¡al lndlvtd.uah¡ fhlr auggtstlon wa¡

queet!,oned hsv¡vrr 1¡ tvo ruÞrcgucnt ctudlrr þeno rt al.l 19601

Dlnlt¡tadou tl a-l.r 1960), antt ft¡¡th¡r data yar plor¡ntrcl aåal

tll¡ou¡¡ld rarrf.cr l¡ thc prrsrnt rrport oonftrming that lt l,r

unl,lIrly th¿t thc loetctyrc¡lnt¡ ata a noruel etroulattng

ooupcmut.

la n¡ntlon d Bnvlouel¡rr E! hes b¡rn ctctroträ rn jcf ofoal ¡¡rl¡e of r¡¡tnrat¡d þprrtlryrcld auÞJtotr (rerraa of el.,19t9) lollwlnt l!1¡ tn repfr and ln a m¡eh ¡narx.cr Brrorntagrof untr¡atrd trypættryrold rubJrotr (rrra and talran¡ 1960).

a df¡sr¡¡rlol apprelrd rerllü ol tbr pcaa!,blr rcaeonr rþcuoh agout¡t¡ of u? h¡d aot È¡ra rtet¡ot¡d gnrvloucþ ln rlnltarrttrdlr¡ en thr rffrot of EBE ea thr slroulatl,ng thyrold her¡on¡

gattrm. Ya!¡¡ trr rtr¡dlo¡ of thÍ¡ na.tr¡r¡ haro bæn porfcrttd,and lt ra¡ fclt thßt ln ¡or of tb¡r (nuyar ancl H!¡set¡ ¡ LglSl

lyitevltr e¡al A8oB.r rgt?) an lnd!,oatto¡ "f bC Droo.Bo. rrar/pcrrlbþ not1ord,, but tbst thl¡ ve¡ not rraognl..d et th¡ tln.

-lT¡'

fb¡ ortt.trle oA whl'ob tbr prarat lê¡ntf.fìloatfon 1¡ ba¡¡il

havr brca cllsouoerd snrl ar¡ bråof\rr-

l. thr flndl,ng of s r¡rct 1¡ at lcast tvo ¡oLvrat ryrtur,vlth thr l, ln raehr th¡ eauc as thEt of, rtaÉale¡ô D[ll

% lla¡ oolnel.dooo la two rolveate, sf, thr r¡!¡üoun vlth tbr

epot produe¡d Þy Þora E,I uh¡n erJilrd to tbc cftleottboúsrc ohronatoEråpht t

V. !h¡ ¡Iutlsa cf thl oonpou¡nt ño¡ tho toai.a ooluu at spI et vhtoh El (aaa ffi|!) al¡ar ar¡ bor¡ to b¡ olutod

(earton aüd EltlBi.vrrs, rSOga)t

{. flha llnðlne tbst th¡ oeråo rulphet¡ r¡aotl.ÞS ¡Fct

oolåolalaal rr.th ¡ ¡redleactlvr ylako

D¡¡thrr rvlalüoa th¡t tà|,¡ eongo¡¡¡d f¡ E! uar obtal¡rd

Son tb¡ -¡¡ultr of s8H acl¡fnlstretloa l8 thr lil¡ t"."ttaþgrrtþroful rubJooto. Har¡ ønfy ôrnLl Inroâr.¡ l.¡ ttr ú,rer

dlsorqaary brtrcn tlr¡ tot¡l ptarnr ftt aad th¡ ¡lno pno!.9-

lt¡Ëlr ft\ .tæ. fcr¡¡il fcllerln¡ lsl â&lal¡lratl,ol¡ ubrnm

uuoh lergrr cllrær¡laac!,re her. Þ¡æ, fouact Þy othrrr (r.g. Dtlr¡ct al.r 1959) urlng th. S¡ pnoctplta$.oa nrü¡¡rtl.

Eirp¡nrtlry lho cuggrrtj.oa tbat E! l,¡ rrhe¡rd t¡to tbr

ofroul¿ttea La þpcrt$rrefull¡n tr thr deaoa¡tratLcn Þy Oaorlcn

(fg60) of E{ ancl tl¡c corrrepcndLr¡ illloêrghrryltacü,o ecld¡

t¡ oitdl'tloa b f,¡crgaal,o Leôldr¡ 1n thr uri,¡r ef þprrtryrolal

ruÞJrota afi.tr rl\ tn *w.

-LTY

tt¡rtb¡r cup¡nrllvr ryt,d¡nor 1¡ Þl ng oollootcd ln thl¡

IaÞæatcr.¡¡r whurby i,t ls Ërlng shom lhat PRI - Úf cËeær¡r

anolr¡ .d.st 1n ths¡c oatot of þportbytoldtsn ln vbloh låa8ú

arpuata cf E! elc aletrotrd ohronato6lephloa.lly. lurtbr¡norr

ta thc rutlyrold rub$æte, no cllaonpanoy Dqrond the rqltctrd

Bvaragt vaLsr oî, A.l ru !r La pnlrrat.

¿[.

thr qu¡¡tloa th¡n arld.¡ a¡ to thr porrlbì,¡ ¡su¡¡ of ,t¡Irl¡

lo¡a of If! So¡ thr 6laait t¡ ¡t¡tls of tryrcol,it ac.H.vet!,o¡.

that IEî tt lo.t 1¡ æ¡¡i,dr¡eÞL¡ quantltt¡¡ la cth¡r ccadlttcar¡

notaÞþ tht of oortat¡ù typ¡¡ of 8ottrow ært!,alal¡ l¡ srr.ldcounrutod Enel ha. Þos ¡oat rao.at¡ü læ1,¡rril Dt teor¡r (rgco).

rn th¡pr statra¡ horwrr, tho pprrnc¡ ef a¡r aaEr¡Er drfrcû La

thr bl'oryatbrlÉ,o qcl¡ lor tþrol,d bs¡uon¡ l¡ r¡tabrl¡brdt.

oar ¡uoh G$/n. d¡trot ls L¡ tbr thylr¡dtel lodcfioelnr do.hal-cglnao. (guaurry lt al., rgt5). gbo poeal,Þürty that E ¡hi,lerdrfrot la þprrtùyrcldta¡ lrlete, nurt Þr oca¡ldlrrel. !Èt úeot

thet rn the cn¡ oondl,H,sa ¡rpæt¡rrclctlrn lr ¡xoðuood anal 1n ttrethur thr c¡r¡n¡tt¡ ctlnl,oel rtfrot¡ 1¡ not egateet tbir ¡nrri}-lltlt, es thr þgrttryxrlill¡¡ 1l thl¡ gpr of gcltnur ærtlat¡ul¡ thc-ght tc Þ¡ ctu¡ to a drttct ln dr¡halcgraatlon rf lcdcgrrer-lnrr tbcu¡bcut tb. Doôt (Onurfcæ lt et.¡ f95O) ¡IthåuSh ilrirtdr¿ har Þy Dc r.asr son Ercherlra8rd (nettlr t9t9). lrl lt

-L7þ

ttc¡ @rce.tary b pæfufata arr aott¡al drfrct t¡ thl,¡ .!ryrÐ

rLthl'n thr thyrolit 1¡ hqprtþrcldttcn¡ Elnor tn tbr rutÙryrrtd

rtatrr e elaglr lnJrotloa ct ær wlul oa¡rr. a rL¡tlar loa¡ cfDII :Èon tbo 6l,aael wlthln { hor¡¡ t¡ pegt !,ncta¡or¡. ft yor¡.ltl

¡.oE tåat tù,l rug¡rol!,oa (urmJru¡ lg6o) trrat e rosndlltto¡¡di

rl¡tlolmqy of tb¡ tllbalcarûas. lr ¡reduoeê, lhould. ¡ufflor brrglrl¡ thr¡o lrvrlr of ¡ú,rn¡tetlag El ln Doth ¡t¡tro ottþroJ'it ¡etlv¡tic¡. loar rupport f,cr thl¡ ir grtard Þy oÐrtudt (oarl rt al., lggg) tu vbr,eh no üof;tslrrqÍ of, thr tüyrolitrnSl¡d. coulal þr elcno¡¡tretrel, tr feat lltgüt lnc¡ra¡r¡ nrarrocrdtd.. lEtlulrorr¡ ln aaf.ra.tre gÉ.wn alaf\y !.alrctlons eflEHr an lnær6¡e ùr f,oôaþrcrl¡r clrrhatogeatLsn bn¡ þ¡arcportrd (noelo rt ¡1.¡ 19ã!). ÞarlÞþ thls tnor.as¡ ooçucr

aa a oen¡naoetoEy phanoDoaôi¡ !h1ø æuprnrrtory lnæceol mq¡r

r4gtraln e¡ eflect ¡aan la thr ¡rrlrrnt ntud¡r, who?rr it la ahor¿

that not Ell þportþrold rubJcotc havr clroelatlng !.cdrtyror-Lnra, and rh.tr all hyprrtlVrcLd euÞJoete ro¡rald-h¡e of uhstùtrDr! L¡ ctrt¡ctrd or aet þasn sË talrau.on¡ ¡roduæ a unÌlrrEnil nor¡ ùaarttorT rtr¡ tn r! thea th¡t ¡..r¡ la thr rulþrrotûruÞJoctr ü nr¡na¡¡ tq güc

-L7'--

jo

l$¡r¿r aaû Dr.sG¡t tn thr tl¡rues, Þaattcular\r ¡rlthLa tho

kldnryc s,ad tbe lf'vts¡ vü? stfl.elent nothoüg of sl¡arlng thr

ûl,¡ouletleq cf thr løilcþroelrnr (ncng ¡t eI., I9t4¡ gtae¡ult

¡96t)l and thr hÊlf llf¡ ef trnjootrd Iü8 Lnto ret6 !.¡ ar short

et ¡ fw rLnutr¡. In hr¡.ra¡re thr ha,tf lLf¡ l¡ ls¡rcrterl to Þ¡

¡1¡ br¡¡e ås enr ¡h¡qy (¡"*oO, 19@). In vL¡u of tta reBtdl

¡rteDell¡r Lt tr probcblr thEt th¡ anss¡t el IEI drtrotrð þohroratogrqlþ rr¡xr¡rnts a v.*y ccn¡ídæabrl le¡g f¡¡n tbrthyrotô of thtc anbatanol. rn eûdlt¡,sn th¡rr Às lhor¡ te bt rvclr ¡ültsL¡¡lû real oÀ¡¡¡aae¡ sf Et (rrrltrr aad StrnÞnr¡r,

1959) and thl'¡ tn¡rli¡r tt¡at ruoh of tho Loril.¡r ¡oatut o! tÐslrouLatl¡g ãÍ la lc¡t qnd uot roo6¡ortci to th¡ tixyrefil glenôo

lhle ¡ltuetlc¡ t¡ ún dl¡¡oi¡ ocatre¡t to thet vhåsh l¡ nov

aocr¡rtrð a¡ th¡ lrrter, j.a whl,cb thc tcEtur eente¡t of, thrtrdrQcerl¡¡¡ reLor¡rd by ¡rotcoþcte of tlryro6reÞulln trnryolrô utthln thr tþrold for furthæ i¡o¿zoa¡¡l Èle¡yr¡tà¡rlr(¡coUr rt ¡1.r t95t¡).

l¡ thl¡ 8[t rrt¡¡¡r thrn¡ a rcoha¡-løs fer thr pur¡ne¡¡!\¡l

tlrplrttca ol tl¡r th¡æclð 6l,aail c! lodl¡¡o ia rtatle of tþzotrlrtl¡ulaüo¡t r! tho pn:at rùrðy qBö tos ¡th¡r ¿treta i¡¡ thru,t¡relurr thlr erlnptiea l¡ prrrþ o¡recrrlativto t¡¡lürrr dBtB

th¡rfore 1r rrqulrcd ï1th ¡ vlrr to oaroul¡tú,u¡ th¡ ane¡¡at cf

.LTf-

lcdeQnctlm, anü of lcðl¡o l¡ thL lrlrsl¡r lhtr ¡boulô Þr

aeËtv¡d by e guantlkttrr st¡.rmoÊt of tho Beptl oh¡omic-

gråEs, a¡rtl ¡lrould r¡la?r to th¡ .ilftt of thr ñ1, ¡g d!.rcrr¡r-

a¡o1¡t.

A ateá,htng fcahrrc of thl'¡ Loclln¡ de¡rlrtton l¡ $lat ltls eoourrfn6 la e ¡lü¡atisu nþr¡t thero lE a r.et\y lnorra¡od

rato ef bioeyntbrcl,e. Ehlr re¡¡¡ in tum, fevorn th¡ toraetlon

of a hornen¡ clth lc¡¡ lodinc eantu¡t than B4r Ëuoh ea !, er

es¡¡r othra freotÍo¡ wfth 4p .van uoro lapld nrtaboLio rff¡ottban tr. SoEr aupport fcr euoh ¡n altered blooyrithrtlo

ø¡ohqnLe¡ aay Þr gntmrl fron thr et¡cll¡a showlag tlrat cllrtalyleûlar drprotlofi @r.¡r.¡ sa iaorussr ln tlrl aøsunt of d,rcul¡t-ing !, (Qucf¿o ot alo, IgE?l bloup and treohåyrr, L%rr.

firr tludlnge of, Hetset ct at,¡ (rg¡a) of ÍBr-Bü d.l.corc¡n

anoh¡ ln rubtrct¡ rurd¡¡golng ¿¡ür.re onstl,oaal etúc¡¡ å¡Fa

roiÃ,orant hotr¡ ln that !.t wso ahovn that auotr tubJrote nsnj,ftrtrapid s¡tebol'to ohaugoe ainller tq tt¡s¡o producrd by ggt

a1ùmfn1¡trat5,on þtror et al.r r9!6arÞ). Erro of thc tbnreubJeota reported la¡'Li.¿r tn tt¡ås study to br in a eo¡¡ðl$.oa

of aoutr istr.ss n rhowld eS.gnl,floant an¡ou¡rts of üg fn thrplaauec Hh¡¡reae Ít nay b¡ dt fnf oult tcr rcLetc aetlvertlea

wi.th tho twnrdletr produotlon of en e@.rgency hor.nono rlr¡lod.lnat¡cl then !a and pocclÈþ lgr 1ù ctc,ra appcar oLçer th¡t

tlrrtrr

'Ats|t¡æ Ünt} }F$;¡ F fFI rB Dlqr üF ür fl .* t p .ür r.rlilr s qr lnnür frPrF;[rtWrrmH.Hlr¡iltt

..r*l

çF .rir¡rm !r æ ü Èrænr }[ tËtä '' .:

ra¡ß|tË ftF rÐ rrrq*a p {t

-1?8-

BIETIOû8åPET

-

ACKEBT{A"$¡ B.E. and åROfSr ld.I'. (lg¡g)r J.clin.endocr.& Hctab.¡

lÉ,¡ e26-

ACLA.¡ÈD, ü.D. (tg¡Z)¡ BloshEu.J., ÉgJ I'l'|-.

¡LåBICHΡ 8.G., TO¡lIlA, ß. and Lâ,ASOñ, P.C. (fg:g)t ßndoeri.aolory

641 2O8.

AnOÍË, I,J.L. and ñïDOV¡ÎZ¡ if ,D. (tg¡g)r J.cltn.endocr.lt Hoüab.¡ $[5r$8.

AStsBr S.P.¡ SÈLENßOU, H;4. and PtÂt{O!{DO!¡} c.Â. (tgll)¡ &¡llrJohns

HopIlua Eosp. !¡lt 1641.

¡^ûttHA,ffß, E, (tAgO)r Hoppe-Seyl.Z.¡ ll ,19.

æALE, D. ¡¿d WltItEItEAD, J.tr. (tgeO)r Clln.chlra.ÀeÈa¡ !¡ 15O.

BE$UA, R.s. sßd ÐoBÍFsr B'M. (tg¡¡)r J.erln.€Ddoor.& Metab. t 1l¡1

t t8.

8BËUAr B.S. ¡ DODtrFSf 8.01!. a:rd HISÞIER, A. ('lgøù¡ .f .cl!,n.endoer.& Met

lüetab., J,!j 1167.

BER.AUÐ, 1. (tggO)¡ Ácto Endocrlnologlca¡ !å' supp. ,5.

DIRDr R. a¡rô Få,AIÌAI{, H,E.A. (tfeO¡r J.clfa.enðoorr& t{etab.r -4¡81.

BI¡IZZAAD, B.¡¡1. (lgeO)¡ Metaboltsm S9 ZtZ.

Br"ocKr R.J'¡ uËBfiB8r s.C' and !{ANDLT B.}I. (tgæ)r Arch¡bloehon.

Elopþe. fl¡ 9.

BtrOCßt R..I.¡ WERI{EB¡ S.C.¡ MAIDL,r R.It.¡ ROU? V.V. alld RÂDICIIEVICHT 7.

(tgOO)r Arch.bloetrou,Btopl¡re. @¡ 98.

BOSS$ES, R. and tAUssKI, H.$f. (fg+¡)r il.btot.Ghaa. g[¡ ,BI.

_l?9-BTDD¡|, C.H.¡ lrÂCû.êeåg¡ B.F.¡ and üILEINSOn, J.H. (tg¡g)t

Bl.oqhe¡r.il., åtf 9!.cÂtûERO¡[, Br (tgeO)r Eioehca.J,¡ f,dt ,Zg.cÂvrr 8qÂ.¡ ærBRHl,rrE$r tf.H'¡ $IAEFOBD¡ B.B.r DUüC¿N¡ f,&. and

glArF¡oEoEcIt' R.A. (tggg)¡ J.ella.sndoGF.& HcÈab.¡ Jåt lz}z.gHoUFoER¡ tr.c', E.ASSE¡IÁ,ÁR, a.å.8. aad QUBETD0, r. (rgeo)¡

tl.cllu.cadoer.lÈ llotab,, &l ggr.

@NsDEBr 8" ooRD0l{¡ A.H. and MÁ,RTtrfl, A.J.p. (rg++}¡ glocheu.J.¡

.flt 224.

CEBY, F,.A.E!. end YIESSEB, B.p. (tg¡O)¡ ErlÈ.ucd.J.¡ l¡ 777,

DÄ¡{ol{strr¡ T.s.r I{ATEER¡ F.M-, tüErtr,El l.o.¡ B0RESKY¡ D.c. ånd

ÞfosEsr Qnt (tgoo)t J.crln.endoor.& Hctab.¡ @¡ r5ar.DErssr u-P.r .ÀLBarûi{Tr E.c. a¡rd LÀBSOH, s.c. (rg¡e) r iI.crfn.

Iuveet, r .ã!¡ lt09.Dgrss¡ 1ü.P. r otsitA'.rG;rI$EBsy¡ p.J. , and t/yNt{, J.t. (rglg)¡ J.ell.n.

Invest.¡ fg t 4.

IlrMtrlRrAD0t, À.r trRÅssflr 1.R.r SLATERT J"D.lt. and 1ú&ÌëEt¡ p.C.ñ.

(tgø) ¡ Betu¡rcr J.gjb 69t.

Drñcr.EÐrnEr rt's.¡ Prrl-BrmRs, B. â¡rd srANBUBr, cr"B. (twr),J.ol,l,n.goêoer,& Hstab.t Jfi 724.

DOB.Íls, B. and HIascH, E,Z. (tg¡g)t J.erln.endocr.& teü&bor

757.

DBA0U!ÍOVA, f.r and trANOE, p. (rg¡e)¡ Baturer lJg.i 5r7.

EItH0&ft J. (t gFS)¡ Acte Radtologtaa¡ Snpp. 16O.

ßrrüo&8, Jr aûd L¡,Rgsos, I,.-û. (rggo)¡ Acta gadocri.nologlea,

l29.

¡

-180-BVA.ts, 8.8.¡ COB?0POU&OSr l.B.r aBd slÈtlgorr M.E. (fg¡Z),

Bndoarlmtssy .ggt 4,Ql'

FABR.â,H, H.B.À., LEA, å.J.¡ COO&DFrr 4.U.0. and ABDåTT¡ J.D. (rg¡g)¡

Lanceù !¡ 791.

tglBn, c. (tgæ)r Ëlosh¡ø.il. !!¡ 549.

FEIIBB, C., mmgsr ¡,. aadl EERBSSSr &. (tgæ)¡ aeta Phyatologlcar

tung. låt ?91.

EEuEB, c. aad YEKERDI, L. (tgøe)r Aote Pþstologlca¡ Hung. lf,¡ ,o7.

FIE[, E. and FIüN, R,¡{. (tg€)¡ Solenoo !99,1 îfr.gI¡EfgHSR; ß. end STAHL8T, P.c. (tgþlr Bature jJZt '|.7Q.

PRIEBELT D, a¡¡d HIftEI,r ll. (tfeO¡¡ PcrEonal eoanunfcatloc.

PREII¡SEL, ñ. (tgAf )r J.clln.InvesÈ.¡ 3p¡ 476.

oAI.lOF, V.A, and PIÎÎ-IIYERST B, (qgçg")r Bloel¡co.8. !/l ,79.

eÁ.L10r, v.A. and Plll-RfvBnsr 8. (tg:gt)r Biochoa.J. ILt ,19.

OÂUIEI{ows8I, P. (tg¡Z)r Ana.lyaf 9g 452.

cI;EAso$, O.tr. (tgE:)¡ J.blol.thGB., 2721 8r7,.

tæÐ, B.F. (tgOO)r Unpublfshed ob¡¡rveül,ons.

OOOLÛENT A.tl.E. (tg¡g)¡ J.cll,n.cndocr.& Hctab., JlJ 1252.

0&SER, S.A. and gHttLLr H.F. (fgff)¡ J.clln.endocr.ll Mctab.r llrloJo"

oBosgr J. (t gS+l l Brit.ncill.c*t nrll. !!t 2tB.

oR06sr J. end LEBr'oNDr c.P. (tglt")¡ Prcc'soo'6xp'Elol'e l{'1"

|Ét 686.

CEOSs, J. antl IúBLOHD, 0.P. (tg¡tu)¡ Eaclocrtnology $; ?14.

-181-

omsgr t. aud PIlt-RIuERs, B- (tg¡f )¡ laneet $!l '166',

Gnossr J. aail PIlf-RIvEBsr R. (fg¡z)r lancet !¡ 479',

GEOSS, J. aad PI11-¡IVERS¡ R. (tgE¡")r Blochêú.J. þfi 64r.

cngssr ilr a¡âd PI13-RIVEES, B. (fg¡fU)l Biochen'J' !l¡ 652'

HåL|{I, f.S. (fg¡f)l Clba Founctatlon GolÌoquia on Enôoorl'notogyr f9¡

79. Ghurel¡lllr l*ondon.

HÂI¡l{Ir il.S.¡ ûBA.l{l{BBr O.K.¡ mUGiil{Añ, O.J.r PEI¿IS¡ }3'H' and FîIILÏ¡ER, O'

(tfOO¡ r EnrlocrlnologY¡ [l¡ 70.

HÂHgLSff¡ t{.U., SSEIN¡ ü. end FHtsEDEGR6¡ A.S. (tg¡Z)¡

J.ell,u'endocr"lt llctab'r 1?,1 J5.

n^å,RINGTOA¡ G.B. (tgZga)¡ Bfoohcm.J-¡ @í 29J.

HARff0fOFr C.R. (rg¿et)r Btochcu.J'¡ S,l tOO.

HÀRIÌ{elOü¡ C,B. (fgf¡)¡ the lbyroiô Gland¡ Lts Gheulstry and

Physüology. Orford Unlversity Fress¡ &ondon'

HARIUGtog¡ G.R' (tgff)r Ergebn.Physlol.¡ lJ.l 21O'

ilAailqcf0ü¡ G.!l' (tg¿+)t Proc.&oy.SocrB.r ll3l 225'

HA6IDOTOH¡ S.R. aad BARGER, G. (fget)¡ B!.oohen'J. ?! 169.

ltABIt{CTOf, C.R. an<t RAI,fDALL¡ S.S. (f gZg)r Bloehem.J.; !fu T7!.

HETZEL, Ð.S.¡ SIAüOCK¡ t.S. and, oOOD¡ B.F. (tgæ)¡ Hatursr .LBl

1166.

HE5ZEL, E.S.¡ OHAANOCK, J.S. atrd eOOÐr B.F. (fg6Oa)¡

J,cll,n.enilocr.è lloù4b., 4i 156.

uBruEL, B.S.¡ 'gHAR[ocK, J.s.¡ x,Ar8ENCts¡ .I.L. a¡ttt I{ELITBY¡ M.I¡.

(tg6ot) t å.uet.J"erp'BLol. , Ei 227.

I{ETr.EL¡ B.S,¡ OnACE, W.J. and W0IrÎF¡ II.6" (195',;a)¡ ¡f .psyeho$gm.Ses.

u 186'

-782-IIEIUELT B,S.¡ dle 1¿ ËABA¡ D's¡ afrd HINK.LET Ir-E.¡ Jr. (tglZ)¡

lraag*An.Goltre Aseoo.¡ p.242' C.C. thouas. Xlllnola.

mtZ&t"r B.s. Brid PL,ESCIA¡ fl.D. (tgl¡)¡ J.Enôocrlnol. !|t 111.

IlglzgL, 8.8.¡ SC$ûÎTSÎÂBDT, |r.U.¡ ORÁCE, W,J. end HoI¡ÍPr H.g. (rg¡gt)

il.psychosoulBas. 1¡ 7?7.

HtttsEf,, Í.r (tg:glt J.Çhromatog. 1r 91.

ffiDOIÆfZ¡ J.D, and AnOfS¡ Y.L. (tg¡Z)t rt.ell,n.eadoGn& Hetab.¡

Ij:z trrz.ISOBAR' S.H. (fggO)r fn rGliniçat Enelocrlnologyr ed. 8.8. Astwood¡

0nue aod Stratton¡ 1960.

IN0BAR, s.fl.¡ DOH¡,ING, J.T. and FREI[KErrr X. (lg¡Z)r

Bnêocrinologyr 9$ T25"

I$cBABr S,H. end trRBIN&EL' [. (tgS¡)t J.elf,n.Invesü.r ått 8O8.

IEOBAR, 5.8. Brd TBEINEEL. U. (tgæ)t J.el.fn.InvGst.¡ !f¡ 1605.

fEüDåtrnLo E.C. (tgtg")¡ J.ÞloI.Chêm., 22i 125.

EË!¡DALLT E.e. (f gf gu)r J.bl.oL.Ch;m. r *9,i 269.

KOOJ,T t. arrd ysil EBEHEIfT L.t.ll. (f gSt)¡ Acta Bndocrinologtca É¡

921.

KoLtHoPtr¡ I.M. snd S^NIIEIiL¡ E.D. (tgf+)r tI.Àtrer.GbeE.Soc.r 5É,I

1426.

n0n0r 1.¡ yan uIDDI'BsgoBtHr L., ånd AgthlOODr 8.8- (f ggO)¡

Eudoorlnoroeg gE¡ 847"

KTLE¡ I,.H.¡ GA¡¡ÀBÏ, J.J.¡ t4ÞlTERr B.J. and PAE¡ F.F. (tg>glt

J.eItn"€ndoer.& !{ctab.t lg¡ 950.

LAIDLAU, ¡t.C. (tg+g)¡ Eature, 7641 927.

tå,RsoÌ'l, F.C. and ALBRIGHI, E.C. (tgæ)o Endocrtnology gãJ 78r.

_tgr_LÅSSISER¡ W.E. anil S1ÂNütRYr J.B. (f ggg)r JrcXLn'Inneeü.r lgl

784.

LEBIOSD, C.Pe arô Sífu, f. (f gtO)r C.R.Soc.Bl'o1., Perls¡ llll,i

545.

I¡SúoUP¡ H. ênd LÅg$Mn, f, (t955)¡ G.E.8oc'B1o1.e Parls¡

Z4t ¡ 5O9.

lgail¡,N, ;I' (f gæ)r J.el'tn.Iav€8t. , JLI 555"

lleoIBR, E.ì1. (rgeO)¡ srlt'Eoü.Bt¡rl.l LÞ.3 l1l.'

!{ACLAOA¡g¡ S.R,., BOWDEU, C.H. åait UILKII{SOHT J'tf. (tglZ)t

Dt.oohen.J. r .9-I3 5.

Uåü, E.B. and EONDI, P.K. (tgSl) t J.c11n.cnðoof.& Êletab', JAI

757V.

!fAlDI", R.II. arô BLOCß, R.J. (f g:g)¡ Areh.Biochcm.Elophys.t 91¡ 25'

tfAÐt, S,B.¡ POCHIFT E.E. eüâ 0OLDIBT E'A' (tg49)¡

CIt"n. Scl. ¡ Pf f 09) .

ffAûÂTArI, S,, sHIZU¡{g, [., llAtgUDAr E. s.nd IsHIIf J. (f g¡g)¡

Proc,Soor€ïpÊr'biol.&$led.r .83.1 765'

OstdALD, ¡, (fgOg)r z.BhyeLol-Ghea., &t 472.

PIUDr ß. ('tgll)¡ Acta 8aêoçrlnol.r 3g¡ 267'

pIIl-RIVEnÐ, R.r HUBD¡.g, D. anù H6ATIIERT f.H. (fglf)¡ J.cll'n.endoct'

å !{cùab' r Llt |5tl .

PIIT-BIYERS, R. aild RÀ[,Lr J'8. (fggf )¡ Bndocrlaology¡ 68¡ '09'

plltt-EIVERS, B. Ðd tAiÂ, ¡I.8. (fg¡g)¡ lhe ltryroLd l{orøonee¡

Pergamon Frcss¡ Londou.

pIlf-RIVEBSl Ê. *nô FIOLF, iI. (f g¡g)¡ Esd,ocrlnoteryr ,qL¡ 841'

-19¿Þ

QUERIm, 4., gÎåHBURT, J.B'¡ Eû,SllEÈAABr A.A.[I. and MEIJERT J.lf.A'

(rg¡e )r iI.el!.n.ea¿ocr.& Hoteb.r !Ê¡ 1096'

QUERIDO, 4., SCHü[, E. a"ad EEEPSTRA, J. (fglZ)¡ Clba Colloqula on

Badloerinolotrr lgt 124. Churehlll. London'

BAÊL¡ J '8. (tg¡O), ,il.clln.cndoet.û Þ1eùc'b. t .!9t 996'

BÄL&r J.E.¡ PBÂBSOE,0.1I.¡ LIPSEÎIT H.B. and R.åld$oÑ, R.U. (tg¡e)¡

J.olln.sndocr.& l[otab.r 1û¡ 1299.

R.åLL, J.E.¡ BOSBIES, ¡t., mst, c.D.¡ ?8ARSoffr 0. and nå'ldso¡lr R.tt.

(tgl¿): J.clln'cndoGr.& !{ctab" J3¡ 769.

RAYSONr R.tl. @Z+J¡ Fetleretl'on Proc. !2t 661.

RAWSOU¡ R.lf., AAIrI,, J.8.¡ PEAnSOffT O.ll.¡ RoBBIflST {t.r POPPEI'L¡ H'F.

enð ldEST, G,D. (lg¡l)t lrarie.Agsoc.Á,aBr.Phye.r !Ál 86.

pBBIUS , õ.t BAü, J.B.¡ BECKER, R.V. attd R.AlfSOf r B.tl. (lgZZ),

J.o!.l.n.cndocr.¿D üctab., 72t 856.

nocHE, J., TISSIîZtrÏ, 8. anû MIcllEL¡ R. (1952E.)¡ G.R.Acail.Sef.¡

Parls¡ pl{i 997.

R06ffi, J., LISgITZKI, S, anô MICIIBL, R. (tg¡ZU)t C.R.Acad.Scl.¡

Parls¡ !l{¡ 7?'?.8.

ROCEE¡ if.¡ MICHBL, 8., ¡.[ICHEL, O. enal LISSITEßYr S. (tg¡e),

Blochem.blopfty.Âcta' ¡ !¡ 161.

AOCHts, J., tdICHtsIl, B" anô ffiIfEZ¡ {. (tg:g)¡ Aota Endocrlnol'oglca

æt 142.

mgEBDERo¡ I.H' (rg¡t)t J.clin-Invegt. æJ l.ROSBfBEBft¡ I.H'r ffiH, C.S. ard CIiAI'r'BHr È1.$' (f Sef )t

J.cltn.eaêocr.¿t tctab.r åU 554"

_tg5_

EOsEf,BEno¡ I.$.r AlILå.Us¡ nl.c. and BBHåBr Â. (fg6O*)t

Enttoerlnology €f 185.

BOSEIEERG¡ Lñ., ATIIAIS, J-t.¡ SEflAR, A. end Âltflr 0.s. (rggot)¡

Fourth Int.Goltrc Coafeîêrcê¡ Ereerpta !{edtca¡ S¡ 26.

Êttpp, J.ü.¡ GIIATAHRIAT C.r PASCIIKI$¡ l.E. a^nd CHUBLARIHT E. (tg¡g)¡

ânu.Int.l{cd.r åLt r59.

gODEREER0, v. (rg¡g)¡ P?rystol,R€v. :g¡ 777.

sÎâSBtRTf .Iò3. (tggo)¡ AnaaIE E.l. acad.Seloaees 86î 477'

STAFBUSS, J.B.¡ IIEIJEB, J.l,ú.4. agd f,åssgl{ÂÂB, .4.4,.[i. (tg¡dt

J.çlf.n,endoer.& ilete.b.¡ $i 84S.

glailBuRY¡ J.8., oflBËÀ, 8. end PIÎÌ-RIYERST B. (tSE¡)¡

J.clln.endosr"& Þleüab.¡ fJg 54.

SlAltLET, M.Ì1. snd trSnmOD, Ë.8. (fg+g)r Endocrinologrr $¡[¡ 49.

SgÊRL¡Nôr X. (tgæ)r ü.cll¡r.Invsst. t l$t 1t48.

S!EA,LIN0, E. aîr:l €HODOST R'8. (tg!6)! J.clù¡.Inroet.¡ tlf 806.

stol,c, Y. (tg58)¡ Baturo¡ lBt 52.

SlORl, U.ê. and PF¡nEINS, U,H. (fg¡S)¡ J.cl1ñ.sndocr"& t'lçteb" l,ÍLt

757.

SZAÊO, g., PBUER¡ O. and BALO0H, I. (tg¡Z)t åota Ph¡rslol.I{uag.¡

&t 25.

IAUROGT A. (tggZ)r In dlecr¡aalou on Yanotül¡ A.¡ t0lbe

Foundatlon Golloqule on Enôoorlnologrü G'hurchill¡ london. i9.¡

215.

ÎAUBoc, À. anð CHATEOFF¡ I.å. (tgæ)¡ il.blo}.êbco., 3fr¡ 659.

TÂUmG, A., eHåIEOFF¡ l.tr. and. lost¡ U. (tgæ)¡ iü.biol'6h8m.r llls.¡

99.

-186-

tagssEl, Ë.Ë. åDd sttoRRr g. (rg5r)¡ ü.bi'oL.€trets'¡ lpflf 6?5'

toxg, g., îÀuBoc¡ a. e$ô cHÀrEotr¡ E.L- (rgfi). J.bior.ch€üt'¡

ilATt 59.

lR8VoR8oÌf, v. (19t9)¡ J'bl'ol'Ghæ'¡ !Æi 'L7'

IRIfoiIUs¡ Y"Èt. (tggO)¡ Pørsonal CoøealeaÈlon'

IBO¡TBB, W.n. (fglg)r 1n rfire lhyrold gornonGsq¡ n" ?ltt-RXvers

end J. lat*¡ Pcrgamon Preggr London'

vrggttl, À., ar¡d BßRAUD, 1. (rggo)¡ Pourüh lnt.ooLtre couf6tte1'ê1

E¡cerPtB l{eôlca¡ ff¡ 62'

uEI¡Iðr¡ É,L,t GoeD, D.F.¡ cHAR¡{ocxf J.S. arð HEIZELI B'S' (rgeo)¡

ü.c1ln.cndocr.è Hctab', ÐJ 1t84'

rgLLBf, M.L.3 &ooD, B.F. and HsrzBL¡ il.S. (rgçr)¡ J'clln'cnöscr'&

Hctab. t ?IJ (nov.).

UEI,IEî¡ ü"L. an¿ HETZEL¡ B.S. (fgeO)t Aust.arnsls'Hêd'r ål 247'

lËLLBy, Èå.L.¡ LAUEEUqB¡ if.R. snô HErZELI E'S' (fg¡g)r Unpubllehcdl

dats'

WERñEB¡ 5.C. (rg¡l)t thr fhyrol¡l. l{ocbor-Earkcs¡ scv York'

t¡iç¡{Bn, S.C. anô Dtrgç&¡ B.J. (f g¡g)t Éatursr lgZJ 4O5'

tfBBÐEB, S.0.¡ ¡OW, Y"V. end BADXCHEVICII¡ I. (f gOO)t J'c114'enôocr'

ê ltotaÞ. r .39J ll17'

HHITEHEAD¡ ¡I.B. a,nil BEALS, D' (rglg)¡ Clln'chln"Aota S; ?10'

HILSISOB¡ J.H. (fg¡f)¡ In etlseusslon on Vaootttr A' nglbe

Þr¡adaÈlon cglroqùla on Endocrlaoreg¡rE Ghurchlll¡ rnondon'

lfl(l{llr J. (fglg)r J.clln'Inv€st.r 2!Ð 1a57'

YrgNr J. (rg6o)t ,arcb"biochea'Blophya' flfl 120'