Alterations in Serum Thyroid–Related ConstituentsAfter Thyroid Fine-Needle Biopsy: A Systematic Review

Stergios A. Polyzos1 and Athanasios D. Anastasilakis2

Background: Thyroid fine-needle biopsy (FNB) is a simple, reliable, inexpensive, and generally safe diagnosticprocedure in the management of thyroid nodules. Local pain and minor hematomas are the most commonclinical complications, and hemorrhage and fibrosis the most common histological alterations after thyroid FNB.FNB can also trigger biochemical alterations in serum, since it may destroy thyroid follicles. In this review wesummarized the biochemical alterations in serum that occur after diagnostic thyroid FNB, aiming to reviewinformation that would be potentially useful in interpreting thyroid tests in patients who recently had a thyroidFNB.Summary: Computerized advanced search for primary evidence was performed in the PubMed(Public=Publisher MEDLINE) electronic database not limited by publication time and English language. Anincrease in serum thyroglobulin (Tg) ranging from 35% to 341% occurs in 33–88% of patients subjected to FNB.Serum Tg concentrations typically return to baseline about 2–3 weeks after FNB. The abrupt release of Tg afterFNB may induce the production of autoantibodies to Tg and thyroid hormones in a minority of patients. There islittle information on the effect of FNB on autoantibodies to thyroid peroxidase. No changes seem to occur inthyroid-stimulating hormone, total thyroxine, free thyroxine, free triiodothyronine (T3), or reverse T3, whilecontroversy exists for T3.Conclusions: The degree of increase in serum Tg after FNB is highly variable and not a predictor of whether thebiopsied nodule is benign or malignant. The increase or development of Tg autoantibodies that occurs in somepatients does not appear to be of clinical significance. Development of autoantibodies to thyroid hormones maybe more likely in patients whose biopsied nodule is benign than malignant, but further studies are required toconfirm this. If changes in serum thyroid–stimulating hormone or thyroid hormones are noted in a patient with ahistory of a recent fine-needle aspiration, they should be investigated since they are not likely to be related to thebiopsy.

Introduction

Fine-needle biopsy (FNB) is considered to be the mostaccurate and cost-effective diagnostic tool for the preop-

erative investigation of thyroid nodules, and it has beenproposed as the procedure of choice (1–4). The cytologicalresults after FNB are generally divided into benign, malig-nant, indeterminate, and nondiagnostic. The use of FNB hasalmost halved the percentage of patients undergoing thy-roidectomy and has doubled the yield of malignancy in pa-tients who finally undergo surgery, thereby decreasing thecost of medical care (5,6). Technically, FNB can be performedwith aspiration using a syringe (fine-needle aspiration[FNA]) or without aspiration (fine-needle capillary [FNC])

and can be guided only by palpation (palpation-guided FNB[P-FNB]) or by ultrasound (ultrasound-guided FNB [US-FNB]) (7).

Although FNB is an invasive procedure, it is consideredsimple, reliable, safe, and well accepted by the patients. Post-FNB local pain and minor hematomas are the most commonclinical complications, while serious clinical complications,such as massive hematomas (8), are rare (9,10). Post-FNBhemorrhage and fibrosis are the most common histologicalalterations observed in surgical specimens if thyroidectomyfollows, but some worrisome histological alterations mim-icking thyroid malignancy may also be observed (11). FNBcan also trigger biochemical alterations, since it may destroythyroid follicles, resulting in thyroglobulin (Tg) release into

1Second Medical Clinic, Medical School, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Greece.2Department of Endocrinology, 424 Military Hospital, Thessaloniki, Greece.

THYROIDVolume 20, Number 3, 2010ª Mary Ann Liebert, Inc.DOI: 10.1089=thy.2009.0157

265

the circulation. In this review we have tried to summarize allof the biochemical alterations in serum that occur after diag-nostic thyroid FNB. A major aim was to review informationthat would be potentially useful in interpreting thyroid testsin patients who recently had a thyroid FNB.

Methods—Literature Search

Computerized advanced search for primary evidence wasperformed in the PubMed (Public=Publisher MEDLINE)electronic database. The search was not limited by publicationtime or restricted to English literature. Medical SubjectHeadings database was used as a terminological search filter.From the combination of terminological (Medical SubjectHeading terms) and methodological search filters (‘‘PubMedclinical queries’’), relevant journal articles were retrieved (12).The bibliographic search was extended to the ‘‘Related Arti-cles’’ link next to each selected article in PubMed and its ref-erences. Finally, automatic alerts were activated in PubMed(‘‘My NCBI’’) to add relevant articles published after the initialsearch. A search for a relevant systematic review or meta-analysis in both the PubMed and the Cochrane Library re-trieved no result. Eight relevant articles were found in thissystematic search. All articles were prospective cohort stud-ies, some of which with a control arm, and are summarized inTable 1. According to the definitions of the American Asso-ciation of Clinical Endocrinologists, they were of level 2 or 3 ofevidence, leading respectively to grade B or C of recommen-dations (13).

FNB and serum Tg

As far as trauma to the thyroid is concerned, it was reportedas far back as 1982 that thyroid surgery was generally fol-lowed by an increase in serum Tg (14). Subsequently, it wasnoted that even minor insults to the thyroid, such as an FNB,were also followed by increases in serum Tg. In fact, in alleight articles relating to this, increases in serum Tg after FNBwere reported in some patients with the reported percentageof patients in whom the increase was significant (rangingfrom 33 to 88) (15–22). Initially, it was postulated that thedegree of increase in serum Tg could discriminate benign andmalignant lesions. This hypothesis was not confirmed, how-ever, and there was no relationship between the changes inserum Tg after FNB and the final histological diagnosis(18,19). Among individuals the rise in serum Tg after FNB isquite variable in most studies. The mean increase ranges be-tween 35% and 341% (Table 1). Enormous increases up to1500% (18) or 3000% (21) or even 12,500% (17) compared withbasal levels have been reported. Tg peaks quickly (between30 minutes and 3 hours after FNB) and slowly returns tobaseline within the next 2 weeks (17,21). The variability in theincrease in serum Tg occurs not only within studies, but alsobetween studies. This may be due to differences in the timeafter FNB that serum was sampled, but it also seems related todifferences in the criteria for an increase or decrease. In somestudies ‘‘increased’’ or ‘‘decreased’’ is defined to be values thatare higher or lower, respectively, than the interassay coeffi-cient of variation for the method used. In other studies thedefinition was any increase or decrease compared withbaseline values, and in still other studies the definition wasunclear. As is well known, there are a wide variety of methodsused to measure serum Tg in clinical settings and this was

also the case for studies on the effects of FNB on serum Tg(Table 1).

No correlation was found between post-FNB Tg alterationsand the age of the patient (21), Tg levels at baseline, the vol-ume of aspirate, the needle size, the nodule diameter (19), thenodule echogenicity (cystic or solid) (18), or the number ofpasses (19,20). However, in one study there was no increase inserum Tg in patients who had only one pass for their FNB(n¼ 7), whereas 16 of the other 42 patients in this study whohad 2–5 passes during the FNB procedure had an increase inserum Tg (20). In one study (19) the degree of rise in serum Tgafter FNB was related to the performer of the procedure, butthis study did not report differences in technique that mightexplain this. It is possible that the lack of expertise or a moreaggressive or clumsy handling of the needle might lead tomore extensive destruction of the thyroid follicles, therebyincreasing Tg release into the circulation.

In summary, an increase in serum Tg is common after FNBas well as thyroidectomy. Serum Tg concentrations typicallyreturn to baseline about 2–3 weeks after FNB. If the patient hashad a total thyroidectomy and serum Tg levels decline toundetectable, the surgery is complete and there are no me-tastases. Whereas it is current practice to follow serum Tg inpatient who have had total thyroidectomy for thyroid cancer,there is usually no need to check serum Tg after FNB. If suchpatients do develop signs and symptoms of a disorder inwhich serum Tg is useful, as is the case for differentiatingbetween thyroiditis and thyroid hormone ingestion, it shouldbe remembered that the results for serum Tg are likely to beunreliable if the patient has had an FNB within the previous2–3 weeks.

FNB and serum autoantibodies to thyroid antigens

Autoantibodies to Tg. Tg autoantibody (TgAb) mea-surements should accompany Tg measurements since assaysfor Tg are unreliable in the presence of TgAb (21). Only a fewstudies, however, have reported TgAb measurement afterFNB (17,18). In the earliest study, none of the patients whowere TgAb-negative before FNB were reported as becomingTgAb positive after FNB (18). In this study, however, thepatients were only sampled up to 2 months after FNB, so thedevelopment of TgAb at later times, which hypotheticallymight have been related to FNB, could not be ruled out. Incontrast, in a latter study (17), 7% of the 156 patients who wereinitially TgAb-negative became TgAb-positive when studiedfor 1 year, but not 15 days, after FNB. In the 57 patients whowere TgAb-positive in this study 12% (n¼ 7) had higher TgAbtiters 1 year after FNB than before FNB and 4 of them showeda clear time-dependent pattern of TgAb increase after FNB. Itshould be noted, however, that there was no matched controlgroup of subjects who did not have FNB that could provideinformation on spontaneous conversion of TgAb-negativeto -positive status or vice versa.

It should be noted that the ability of the mature Tg of660 kDa to stimulate the production of TgAb differs from thatof lower molecular weight forms. However, it has been re-ported that in patients with nodular thyroid disease, only themature Tg, with a molecular mass of 660 kDa, was noted inserum before thyroidectomy, while many different forms(50–300 kDa) were found after surgery (23). Whether this isthe case or not for FNB is not clear.

266 POLYZOS AND ANASTASILAKIS

Ta

bl

e1.

Bio

ch

em

ic

al

Al

te

ra

tio

ns

Aft

er

Th

yr

oid

Fin

e-N

ee

dl

eB

io

psy

Ref

eren

cesa

Stu

dy

typ

e=le

vel

ofev

iden

ceb

N=F

Con

trol

s=F

Ag

e(y

ears

)cT

ech

niq

ue

Nee

dle’

sg

aug

e(G

)

Ser

um

mea

sure

men

ts(m

ethod

s)S

ampli

ng

tim

eM

ain

resu

lts

Addit

ion

alin

form

atio

n

Lev

eret

al.,

1983

(19)

Pro

spec

tiv

eco

ho

rt=2

25=22

7=7

(pal

pat

ion

);3=

3(s

urg

ery

)17

–76

P-F

NA

20–2

6T

g,

TS

H,

TT

4,T

T3

(RIA

);F

TI

(cal

cula

ted

)

0,5–

30m

inu

tes

1)T

g:

in11

pat

ien

ts2)

Mea

nT

g:

35%

3)T

T4:

and

FT

I;in

on

ly1

pat

ien

t4)

TS

H,

TT

3$

5)T

gm

ark

ed:

inal

lp

atie

nts

insu

rger

yg

rou

pan

din

no

ne

inp

alp

atio

ng

rou

p

All

pat

ien

tsin

itia

lly

euth

yro

idan

dn

egat

ive

for

Tg

Ab

.C

on

tro

lssu

bje

cted

tov

igo

rou

sex

tern

alm

anu

alp

alp

atio

no

rth

yro

idsu

rger

y.

Cat

ania

etal

.,19

85(1

8)P

rosp

ecti

ve

coh

ort=2

15=13

No

24–6

0U

S-F

NA

22T

g,

Tg

Ab

(RIA

)0,

3,30

,60

,12

0,18

0m

inu

tes

(Tg

);0,

15,

30,

60d

ays

(Tg

Ab

)

1)T

g:

in11

pat

ien

ts2)

Mea

nT

g:

136%

at30

min

ute

s3)

Mea

nT

gre

mai

nu

nch

ang

edfr

om

30to

180

min

ute

s4)

Tg

Ab

rem

ain

edn

egat

ive

inal

lp

atie

nts

All

pat

ien

tsin

itia

lly

euth

yro

idan

dn

egat

ive

for

Tg

Ab

.A

llp

atie

nts

sub

ject

edto

thy

roid

ecto

my

atth

een

do

fth

est

ud

y.

Lin

,19

87(2

0)P

rosp

ecti

ve

coh

ort=3

49=n

aN

on

aP

-FN

A22

Tg

,T

T4,

TT

3,rT

3(R

IA)

0,10

min

ute

s1)

Tg:

in16

pat

ien

ts2)

Mea

nT

g:

182%

3)T

T4,

TT

3,rT

3$

All

pat

ien

tsin

itia

lly

neg

ativ

efo

rT

gA

b.

2p

atie

nts

init

iall

yh

yp

erth

yro

id.

Su

ssi

etal

.,19

87(2

2)P

rosp

ecti

ve

coh

ort=3

15=12

No

42P

-FN

A22

Tg

(RIA

)0,

3,60

min

ute

s1)

Tg:

in12

pat

ien

ts2)

Mea

nT

g:

78%

(3m

inu

tes)

and

341%

(60

min

ute

s)

Un

kn

ow

nif

pat

ien

tsin

itia

lly

euth

yro

ido

rn

egat

ive

for

Tg

Ab

.

Bay

rak

tar

etal

.,19

90(1

6)

Pro

spec

tiv

eco

ho

rt=3

12=9

No

26–5

9P

-FN

A22

Tg

(RIA

)0,

5–60

min

ute

s1)

Tg:

in7

pat

ien

ts2)

Mea

nT

gin

crea

se63

%A

llp

atie

nts

init

iall

yeu

thy

roid

and

neg

ativ

efo

rT

gA

b.

All

pat

ien

tssu

bje

cted

toth

yro

idec

tom

yat

the

end

of

the

stu

dy

.B

env

eng

aet

al.,

1997

(17)

Pro

spec

tiv

eco

ho

rt=2

214=

175

No

na

P-F

NA

na

Tg

,T

gA

b,

(IR

MA

);T

HA

b-I

gM

,T

HA

b-I

gG

(RIP

T)

0,1–

3h

ou

rs,

3,15

day

s(T

g);

0,1–

3h

ou

rs,

3,15

day

s,1,

3m

on

ths

(TH

Ab

-Ig

M);

0,15

day

s,1,

3,6,

12m

on

ths

(Tg

Ab

,T

HA

b-I

gG

,T

PO

Ab

)

1)T

g:

in11

5(o

f15

6T

gA

b-

neg

ativ

e)p

atie

nts

2)M

ean

Tg

incr

ease

66%

(1–3

ho

urs

)an

d35

%(3

day

s)3)

Tg

retu

rnto

bas

elin

eb

y15

thd

ay4)

Tg

Ab

rem

ain

edn

egat

ive

in14

5an

dco

nv

erte

dto

po

siti

ve

in11

(of

156

Tg

Ab

neg

ativ

e)p

atie

nts

(1y

ear)

5)T

HA

bco

nv

erte

dto

po

siti

ve

in9

(of

214

pat

ien

ts)

400

pat

ien

tsw

ith

scin

tig

rap

hic

ally

cold

no

du

lein

itia

lly

enro

lled

.N

ot

all

pat

ien

tsin

itia

lly

euth

yro

id.

All

pat

ien

tsin

itia

lly

neg

ativ

efo

rT

HA

b.

156

pat

ien

tsin

itia

lly

neg

ativ

efo

rT

gA

b.

(con

tin

ued

)

267

Ta

bl

e1.

Co

nt

in

ue

d

Ref

eren

cesa

Stu

dy

typ

e=le

vel

ofev

iden

ceb

N=F

Con

trol

s=F

Ag

e(y

ears

)cT

ech

niq

ue

Nee

dle’

sg

aug

e(G

)

Ser

um

mea

sure

men

ts(m

ethod

s)S

ampli

ng

tim

eM

ain

resu

lts

Addit

ion

alin

form

atio

n

Lu

bo

shit

zky

etal

.,20

06(2

1)

Pro

spec

tiv

eco

ho

rt=2

25=25

25=n

a(p

alp

atio

n);

15=n

a(n

oin

terv

enti

on

)

28–8

0P

-FN

An

aT

g(I

RM

A)

0,60

min

ute

s,15

day

s1)

Tg:

in22

pat

ien

ts2)

Mea

nT

g:

303%

(60

min

ute

s)3)

Tg

retu

rned

tob

asel

ine

by

15th

day

4)T

g:

in4

pat

ien

tsin

the

pal

pat

ion

gro

up

(ns)

and

inn

on

ein

no

inte

rven

tio

ng

rou

p(n

s)

All

pat

ien

tsin

itia

lly

euth

yro

idan

dn

egat

ive

for

Tg

Ab

and

TP

OA

b.

Co

ntr

ols

sub

ject

edto

vig

oro

us

exte

rnal

man

ual

pal

pat

ion

or

no

inte

rven

tio

n(n

ofi

ne-

nee

dle

bio

psy

,n

op

alp

atio

n).

Alp

ayet

al.,

2007

(15)

Pro

spec

tiv

eco

ho

rt=3

25=19

No

22–6

6P

-FN

A18

Tg

,T

SH

,T

T4,

TT

3,fT

4,fT

3(n

a)0,

1,30

min

ute

s1)

Mea

nT

g:

16%

(1m

inu

te)

and

37%

(30

min

ute

s)2)

Mea

nT

T3:

18%

(1m

inu

te)

and

14%

(30

min

ute

s)3)

TS

H,

TT

4,fT

4,fT

3$

All

pat

ien

tsin

itia

lly

euth

yro

idan

dw

ith

soli

dn

od

ule

s.U

nk

no

wn

ifp

atie

nts

init

iall

yn

egat

ive

for

Tg

Ab

.U

nk

no

wn

the

nu

mb

ero

fp

atie

nts

wh

oin

crea

sed

Tg

and

TT

3.N

oin

terp

reta

tio

no

fT

T3:

by

the

auth

ors

.

aR

efer

ence

sar

ep

rese

nte

din

pu

bli

cati

on

dat

eo

rder

.bA

cco

rdin

gto

the

defi

nit

ion

so

fth

eA

mer

ican

Ass

oci

atio

no

fC

lin

ical

En

do

crin

olo

gis

ts(1

3).

c Mea

nag

eif

ran

ge

was

no

tav

aila

ble

.:

,In

crea

se;;

,d

ecre

ase;$

,n

oal

tera

tio

n;

F,

fem

ales

;F

NA

,fi

ne-

nee

dle

asp

irat

ion

;fT

3,fr

eetr

iio

do

thy

ron

ine;

fT4,

free

thy

roxi

ne;

FT

I,fr

eeT

4in

dex

;IR

MA

,im

mu

no

rad

iom

etri

cas

say

;N

,n

um

ber

of

pat

ien

ts;

na,

no

tav

aila

ble

;n

s,n

ot

sig

nifi

can

t;P

-FN

A,

pal

pat

ion

-gu

ided

FN

A;

RIA

,ra

dio

imm

un

oas

say

;R

IPT

,ra

dio

imm

un

op

reci

pit

atio

nte

chn

iqu

e;rT

3,re

ver

setr

iio

do

thy

ron

ine;

Tg

,th

yro

glo

bu

lin

;T

gA

b,

Tg

auto

anti

bo

die

s;T

HA

b,

thy

roid

ho

rmo

ne

auto

anti

bo

die

s;T

PO

Ab

,th

yro

idp

ero

xid

ase

auto

anti

bo

die

s;T

SH

,th

yro

id-s

tim

ula

tin

gh

orm

on

e;T

T3,

tota

ltr

iio

do

thy

ron

ine;

TT

4,to

tal

thy

roxi

ne;

US

-FN

A,

ult

raso

un

d-g

uid

edF

NA

.

268

In summary, it is likely that the abrupt release of Tg afterFNB may induce the production of TgAb in a minority ofpatients. The clinical importance of this is probably minimal,however, not only because of the few patients in whom thisoccurs but also because human Tg-TgAb complexes do notseem to activate complement in vitro and are therefore unlikelyto be harmful in vivo (24). However, TgAb measurements maybe misleading as markers of thyroid autoimmunity if per-formed within at least 1 year after FNB. On the other hand, thisis an unsettled issue. Thus, it is not clear if conversion fromTgAb-negative to -positive after FNB occurs only in patientspredisposed to thyroid autoimmunity. Nor is it known ifsubjects who convert from TgAb-negative to -positive afterFNB remain TgAb-positive.

Autoantibodies to thyroid peroxidase. There is little in-formation regarding the effect of FNB on the generation ofthyroid peroxidase autoantibodies. These were measured inone study, but only in those who were thyroid peroxidaseautoantibody-positive before FNB (17).

Autoantibodies to thyroid hormones. Autoantibodies toL-thyroxine (LT4) and L-triiodothyronine (LT3) are the rarestthyroid autoantibodies and occur in a small number of pa-tients (0.04%) (17). Studies have been performed to determineif FNB induces the formation of antibodies against LT4(T4Ab), LT3 (T3Ab), or both LT4 and LT3 (T4T3Ab), which aredescribed as autoantibodies to thyroid hormones (THAb). In awell-designed study, THAb were increased after FNB in 4.2%(n¼ 9) of the 157 initially THAb-negative patients (17). Thisprevalence was about 50-fold higher than that reported inconsecutive European patients attending thyroid clinics (17).All nine patients first developed IgM antibodies (five T3Ab,three T4Ab, and one T4T3Ab). One month after FNB, four ofthe nine patients developed IgG antibodies of the samespecificity (three T3Ab and one T4Ab). In one of them, the IgGT3Ab persisted for 1 year after FNB. It is of interest that allpatients who developed IgG antibodies had Hashimoto thy-roiditis. It seems that the primary immune response (IgMantibodies) is followed by a secondary response (IgG anti-bodies) only in a percentage of the patients, and the secondaryresponse is long lasting in only a minority of the latter.

Benvenga et al. (17) concluded that post-FNB Tg release issufficient to induce THAb synthesis. This synthesis occurred 10times more frequently in patients with autoimmune thannonautoimmune thyroid disease (21% vs. 2%). In patients withHashimoto’s thyroiditis, TgAb levels below 400 U=mL beforeFNB that did not increase after FNB and cytological diagnosisof benign colloid nodule were risk factors for the developmentof THAb after FNB. A possible explanation for the first riskfactor is that high serum levels of TgAb can buffer the releasedTg. Therefore, TgAb sequester antigen that might have beenable to trigger THAb synthesis. With regard to the second riskfactor, the association of THAb with benign colloid but notsuspicious or malignant nodules resembles the significantlyhigher frequency of THAb in benign goiters compared withthyroid cancer (3–11% vs. 0–1%) (25). Since it was previouslyreported that Tg expression is lower in malignant than in be-nign thyroid nodules (26) and that cystic fluid of malignantnodules contains less Tg than benign nodules (27), it could behypothesized that benign nodules are more likely to store andrelease Tg molecules immunogenic for THAb.

In summary, it is likely that the abrupt release of Tg afterFNB may induce the production of THAb in a minority ofpatients. Although further evidence is required, THAb afterFNB could be proposed as a predictor of thyroid nodulebenignity, adjunctive to cytological diagnosis and other de-mographic and ultrasonographic data (28). However, thecost-effectiveness of this approach is questioned, since THAbare converted to positive only in a minority of patients sub-jected to FNB.

Effect of FNB on serum thyroid hormones

There are limited data regarding the effect of FNB on serumthyroid hormones (Table 1) (15,19,20). No change was foundin serum thyroid–stimulating hormone (TSH) (15,19) or inserum reverse T3 (rT3) (20). There were no significant changesin total T4 (TT4) (15,19,20) or free T4 (fT4) (15). One patienthad decrease in both TT4 and fT4 index (FTI) (19). There iscontroversy on the effect of FNB on total T3 (TT3): no changewas reported in two studies (19,20), whereas significant in-crease immediately after and 30 minutes after FNB was re-ported in a third study (15). However, in the last study, serumfree T3 (fT3) was unaffected by FNB (15). The sampling timewas similar in the above three studies, but there were differ-ences in the needle size (G) (Table 1). There is no reasonableexplanation for this discrepancy. In our opinion, there is noobvious reason that could selectively lead to increase of theTT3 without affecting fT3, fT4, and TT4.

In summary, the little or no T4 and T3 leakage that mayappear after FNB is not sufficient to alter serum concentra-tions of these substances. As a consequence, serum TSH is notaffected by FNB. It has been proposed that a post-FNB in-crease in serum T3 might cause unfavorable cardiovasculareffects, especially in patients with heart rhythm disorders (15).T3 may lead to increased adrenergic activity by increasing thenumber of b-adrenergic receptors (29). Since serum fT3 wasnot altered in the same study (15), however, there should beno T3-mediated effects on the cardiovascular system afterFNB.

Comparison between different techniques

P-FNB versus US-FNB. To date, no comparative studybetween P-FNB and US-FNB had serum post-FNB biochem-ical alterations as its primary or secondary endpoint. Limiteddata can be extracted from the unique article evaluating theimpact of US-FNB on Tg and TgAb (18). Mean Tg increased by136% 30 minutes after US-FNB; this increase is in the middleof increases that have been reported after P-FNB (35–303%).Further, Tg was increased in a similar percentage of patientssubjected to P-FNB and US-FNB (Table 1). TgAb remainednegative in all patients subjected to US-FNB (18), but con-verted to positive in 7% of the patients subjected to P-FNB(17). However, the cohort of patients was significantly smallerin the study of US-FNB than in the study of P-FNB (15 vs. 156patients respectively) and sampling time for TgAb wasshorter (3 vs. 12 months, respectively). Therefore, no solidconclusions can be made, so further comparisons betweenUS-FNB and P-FNB are needed.

FNA versus FNC. There are no data regarding the ef-fect of FNC on thyroid related tests in serum (Table 1), socomparison of the effects of FNA and FNC is not possible.

POST-FNB BIOCHEMICAL ALTERATIONS 269

However, since there is evidence that FNC is probably asso-ciated with less trauma to cells and tissues than FNA (30–32),one could hypothesize that FNC might lead to lower Tgleakage in the circulation and subsequently to lower alter-ations in thyroid hormones and autoantibodies than FNA.

FNB versus large-needle biopsy. Similarly, there are nodata regarding the impact of large-needle biopsy (LNB) (ei-ther large-needle aspiration biopsy or core-needle biopsy) onthyroid biochemical tests in serum. Again, however, sinceLNB is more traumatic to cells and tissues than FNB (33,34),LNB should be associated with more Tg leakage into the cir-culation than FNB and likely greater alterations in thyroidhormones and autoantibodies.

Conclusions

Thyroid FNB is a widely used diagnostic procedure with alow rate of complications. The effects of FNB on serum Tg,thyroid hormones, and autoantibodies have not been ade-quately studied. From the limited data it has been noted thatTg increases quickly after FNB and slowly returns to baselinewithin 2–3 weeks. The extent of this increase, however, ishighly variable and poorly correlated with the histology of thethyroid nodule and its benign or malignant nature. In somepatients the abrupt release of Tg after needle biopsy appearsto be sufficient to induce the production of TgAb. It is unlikelythat this has clinical consequences other than possibly affect-ing Tg measurements. In a few patients the increase in Tg maylead to the production of THAb. There is a suggestion that thisoccurrence is more likely in patients with benign than ma-lignant nodules, but this has not been clearly established.There are no clinically significant changes in serum TSH, TT4,fT4, fT3, and rT3 after thyroid needle biopsy. In one of threestudies (15), there was an increase in TT3 after needle biopsy.In the other two (19,20) no change was noted.

Acknowledgment

We thank the librarian of Ippokration Hospital of Thessa-loniki, Dimitrios Vlahoudis, for his help in retrieving the fulltext of older articles.

Disclosure Statement

The authors declare that no competing financial interestsexist.

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Address correspondence to:Stergios A. Polyzos, M.D., M.Sc.

Second Medical Clinic, Medical SchoolAristotle University of Thessaloniki

Ippokration Hospital13 Simou Lianidi St.

55134 ThessalonikiGreece

E-mail: stergios@endo.gr

POST-FNB BIOCHEMICAL ALTERATIONS 271