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Pituitary disorders
Mardianto
Division of Endocrine and Metabolism
Department of Internal Medicine
Haji Adam Malik General Hospital
Medan
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Pituitary disorders
Anterior pituitary disordersPituitary Hypersecretion
Hipersecretion of PRL Hyperprolactinemia
Hipersecretion of GH Acrome!aly Hypersecretion of A"#H "us$in!%s disease
Pituitary Insufficiency Hypopituitarism Gonadotropin& GH& #'H& A"#H&or
Prolactin deficiency
Posterior pituitary disordersPosterior pituitary insufficiency "entral diabetes
insipidus
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Anterior pituitary
disorders
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Acrome!aly
Acrome!aly is t$e clinical syndrome t$at resultsfrom e(cessive secretion of !ro)t$ $ormone
*GH+
Its annual incidence is t$ree to four per millionpeople
#$e mean a!e at dia!nosis is ,- to ,. years/
Gro)t$ $ormone e(cess t$at occurs before
fusion of t$e epip$yseal !ro)t$ plates in a c$ild
or adolescent is called pituitary !i!antism
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Acrome!aly
"linical Manifestations#$e onset of acrome!aly is insidious& and its
pro!ression is usually very slo)/#$e interval from t$e onset of symptoms until
dia!nosis is about 01 years At dia!nosis& about 2. percent of patients $avemacroadenomas *tumor diameter 0- mm or !reater+
#$e clinical features $i!$ serum concentrations ofbot$ GH and insulin3like !ro)t$ factor3I *IG43I+&
)$ic$ is GH3dependent/ E(cess GH and IG43I $ave bot$ somatic and metabolic
effects *s$o) table+/
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Dia!nosis of acrome!aly
Documentin! E(cess GH 'ecretion 'erum IG43I concentration
#$e best sin!le test for t$e dia!nosis of acrome!aly 'erum IG43I concentrations do not vary from $our to $our
accordin! to food intake& e(ercise or sleep 'erum GH concentration
GH secretion in normal subjects is pulsatile& diurnal& andstimulated by a variety of factors& includin! s$ort3term fastin!&e(ercise& stress& and sleep
#$e most specific dynamic test for establis$in! t$e dia!nosisof acrome!aly is an oral !lucose tolerance test/
In normal subjects& serum GH concentrations fall to 0 n!5mLor less )it$in t)o $ours after in!estion of 2. ! !lucose/
In contrast& t$e post3!lucose values are !reater t$an 1 n!5mLin over 6. percent of patients )it$ acrome!aly
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Dia!nosis of acrome!aly
Determinin! #$e 'ource 7f E(cess GHMRI
7nce GH $ypersecretion $as been confirmed& t$e
ne(t step is ma!netic resonance ima!in! *MRI+ oft$e pituitary
2. 8 of patients )it$ somatotrop$ adenomas*macroadenoma 9 tumor diameter 0- mm or more+
It is important to remember t$at MRI does notdistin!uis$ bet)een functionin! and nonfunctionin!tumors
Ectopic GHRH secretion accounts for only -/.percent of cases of acrome!aly
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#reatment of acrome!aly
#$e !oals of t$erapy in acrome!aly are to lo)ert$e serum IG43I concentration
#o ac$ieve t$ese !oals& t$e adenoma secretin!GH must be identified/
:$en effective control of GH $ypersecretion isac$ieved& serum GH and IG43I concentrationsdecline to normal
#$e c$aracteristic tissue over!ro)t$ and relatedsymptoms !radually recede& and t$e metabolicabnormalities improve/
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#reatment of acrome!aly #ranssp$enoidal 'ur!ery t$e treatment of c$oice for patients )it$
somatotrop$ adenomas
after transsp$enoidal sur!ery& serum GH⇓ *0
to 1 $r+& and serum IG43I *2 to 0- days+
'ide effect
Deficiency of one or more pituitary $ormones¢ral diabetes insipidus& cerebrospinal fluid
r$inorr$ea& menin!itis/
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#reatment of acrome!aly Medical t$erapy'omatostatin Analo!s
7ctreotide *analo! of somatostatin+ in$ibits GH
secretion by bindin! to specific receptors forsomatostatin and its analo!s
#$e initial dose of t$e s$ort3actin! form of octreotide is
0-- ;! subcutaneously every 6 $ours
#$e s$ort3actin! form of octreotide ⇓ IG430 to normal
in .< percent of 00. patients& )$o received 0-- ;!
every ei!$t $ours for si( mont$s and in =6 percent of
t$ose )$o received >at& '& 'nyder& P?& @oun!& :4& et al/ 7ctreotide treatment of acrome!aly A randomi>ed& multicenter study
Ann Intern Med 01B 002200/
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#reatment of acrome!aly
Dopamine a!onists Dopamine a!onists& bromocriptine and caber!oline&
may in$ibit GH secretion
In a study of =, patients& caber!oline decreasedserum GH concentrations to C1/- n!5mL in ,=
percent and serum IG43I concentrations to C
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Mortality in acrome!aly
'everal retrospective studies mortality inpatients acrome!aly of bet)een 13< times t$atof an a!e and se( matc$ed
"auses of deat$ Deat$ from cardiovascular and cerebrovascular
diasease appear to be predominate in most majorepidemiolo!ic surveys/
Mortality and morbidity pro!nostic factors tumour si>e& suprasella e(tension& preoperativeGH levels& duration onset to dia!nosis& andoverall duration of t$e disorders/
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Hypopituitarism
Hypopituitarism is a clinical syndrome of deficiency inpituitary $ormone production/
Pan$ypopituitarism refers to involvement of all pituitary
$ormonesB $o)ever& only one or more pituitary$ormones are often involved& resultin! in partial$ypopituitarism/
#$e clinical manifestations depend upon t$e cause as)ell as t$e type and de!ree of $ormonal insufficiency/
Patients may be asymptomatic or present )it$symptoms related to $ormone deficiency& or a masslesion& or nonspecific symptoms suc$ as fati!ue/
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"linical manifestations
Dama!e to t$e anterior pituitary suddenly or slo)ly& can be mild or severe& and can affect t$esecretion of one& several& or all of its $ormones/
A"#H deficiency secondary adrenal insufficiency
#'H deficiency t$yro(ine deficiency
Gonadotropin deficiency 4'H ⇓ and LH⇓ causes$ypo!onadism
Gro)t$ $ormone deficiency s$ort stature *c$ildren+& inadult
Diminis$ed muscle mass and increased fat mass /
Increased risk of cardiovascular disease Decreased bone mineral density Diminis$ed sense of )ell bein!
Prolactin deficiency #$e only kno)n presentation of prolactindeficiency is t$e inability to lactate after delivery/
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Dia!nosis of $ypopituitarism
Hormonal studies s$ould be performed in pairs of tar!et!land and t$eir respective stimulatory pituitary $ormonefor proper interpretation/
A"#H and "ortrosyn stimulation test #'H and t$yro(ine 4'H& LH& and eit$er estradiol or testosterone *as appropriate for
se(+ Prolactin
GH provocative testin! Imaging Studies:
MRI or computed a(ial tomo!rap$y of t$e pituitary
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#reatment of $ypopituitarism
Glucocorticoids are reFuired if t$e A"#H3adrenal a(is isimpaired/
#$is is particularly important in sudden collapse due to pituitary apople(y oracute obstetric $emorr$a!e )it$ pituitary insufficiency/
Do not delay initiation of a possibly life3savin! treatment pendin! a definitivedia!nosis/
#reat secondary $ypot$yroidism )it$ t$yroid $ormonereplacement/
#reat !onadotropin deficiency )it$ se(3appropriate $ormones/ In men& testosterone replacement is used and modified if t$e patient desires
fertility/ In )omen& estro!en replacement is used )it$ or )it$out pro!esterone as
appropriate/ GH is replaced in c$ildren as appropriate/
GH is not routinely replaced in adults unless t$e patient is symptomatic/
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Posterior pituitary
disorders
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Diabetes Insipidus
"entral diabetes insipidus "entral DI is
associated )it$ deficient secretion of
antidiuretic $ormone *ADH+
ep$ro!enic diabetes insipidus
ep$ro!enic DI is c$aracteri>ed by
normal ADH secretion but varyin! de!rees
of renal resistance to its )ater3retainin!effect/
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Antidiuretic Hormone *ADHB
asopressin+ #$e major renal effect of ADH is to increase t$e
)ater permeability of t$e luminal membrane oft$e collectin! duct epit$elium via t$e ADH3sensitive )ater c$annels
:$en ADH is present& epit$elial permeabilityincreases markedly& and )ater is reabsorbed
In t$e absence of ADH& permeability of t$eepit$elium is very lo) and reabsorption of )aterdecreases& leadin! to polyuria/
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"entral Diabetes Insipidus
"entral diabetes insipidus *DI+ is c$aracteri>ed bydecreased release of antidiuretic $ormone *ADH+&resultin! in a variable de!ree of polyuria
Polyuria can be arbitrarily defined as a urine outpute(ceedin! < L5day in adults
Lack of ADH can be caused by disorders t$at act at oneor more of t$e sites involved in ADH secretion t$e$ypot$alamic osmoreceptorsB t$e supraoptic orparaventricular nucleiB or t$e superior portion of t$esupraoptico$ypop$yseal tract
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7nset of polyuria #$e onset is usually abrupt in central DI and almost al)ays
!radual in nep$ro!enic DI or primary polydipsia/ #$e ne) onset of nocturia in absence of ot$er causes of
nocturia is often a first clue to DI/ 4amily $istory
#$ere are familial forms of bot$ central and nep$ro!enic DI/
Plasma sodium concentration Lo) plasma sodium concentration at presentation *less t$an
0
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Dia!nosis and Differential
Dia!nosis of Polyuria :ater restriction test
:e !enerally recommend t$at t$e patient stop drinkin! t)o tot$ree $ours *administration of $ypertonic saline -/-. mL5k! per
min for no more t$an t)o $ours+ before comin! to t$e office orclinic #$e measurement of t$e urine volume and osmolality every $our
and plasma sodium concentration and osmolality every t)o $ours/ #$e $ealt$y individual )ill soon reduce urine flo) to -/. mL5min at a
concentration !reater t$an t$at of plasma&
#$e patient )it$ complete diabetes insipidus )ill maintain a $i!$urine flo) at a specific !ravity less t$an 0/--. *1-- mosm5k! of)ater+/
#$e test s$ould be terminated if t$e body )ei!$t falls by more t$an
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Dia!nosis and Differential
Dia!nosis of Polyuria asopressin #est
#$e ADH3insensitive *nep$ro!enic+ disease must be
distin!uis$ed from t$e ADH3sensitive *central+ form
#$is is done follo)in! )ater deprivation by injection of
aFueous vasopressin or desmopressin acetate/
Give . units of aFueous vasopressin subcutaneously and
measure urine osmolality after 0 $ourB patients )it$ complete
central diabetes insipidus )ill s$o) an increase of .-8 in
urine osmolality& )$ile patients )it$ nep$ro!enic diabetesinsipidus do not respond/
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Etiolo!y
Idiopat$ic DI
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#reatment of central diabetes
insipidus #reatment of t$is disorder is primarily aimed at
decreasin! t$e urine output& usually by increasin!
ADH *e!& ar!inine vasopressin or AP+ activity/ Replacement of previous and on!oin! fluid losses
is also important/Most patients )it$ central DI $ave a normal or only
mildly elevated plasma sodium concentration
"orrection of t$e $ypernatremia reFuires repair of )ater
deficit/
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#reatment of central diabetes
insipidus Desmopressin
a t)o3amino acid substitute of ADH t$at $as potent antidiuretic butno vasopressor activity
It is usually administered intranasally and in an oral tablet form #$e intranasal preparation B initial dose of . ;! at bedtime can be
titrated up)ard in . ;! increments dependin! upon t$e responseof t$e nocturia and t$en additional daytime doses added/
#$e daily maintenance dose is about . to 1- ;! once or t)ice aday/
7t$er dru!s "$lorpropamide "arbama>epine or clofibrate #$ia>ide diuretic or 'AID
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#$ank you