viii Ministry of Health of the Republic of Moldova Public Institution “Nicolae Testemitanu” State University of Medicine and Pharmacy of the Republic… [600518]

viii Ministry of Health of the Republic of Moldova
Public Institution “Nicolae Testemitanu” State University of
Medicine and Pharmacy of the Republic of Moldova

FACULTY OF MEDICINE N2

Department Of Endocrinology

DIPLOMA THESIS

Thyroid Nodules & Multi -Nodular Goiter

Student: [anonimizat], group 1643

Scientific adviser:
Dr. Lorina Vudu ,

PhD, associate professor

CHIS INĂU, 201 5

ix LIST OF ABBREVATION S USED

MNG Mult i nodula r goiter

FNA C Fine needl e aspiratio n cytology

T3 Tri iodo thyronine

T4 Thyroxine

TSH Thyroi d stimulatin g hormone
TRH Thyrotropi n releasin g hormone
MIT Mono iodo tyrosine
DIT Di iodo tyrosine

WHO World health organization
TBG Thyroxin e bindin g globulin
PBI Protei n boun d iodine
FTI Free thyroxine index

USG Ultrasonography

STT Sub total thyroidecto my
NTT Near total thyroidectomy
HT Hemithyroidectomy
RLN Recurren t laryngea l nerv

1 CONTENTS
INTRODUCTION ……………………………………….…………..8
1 ANATOMY ……………………………………………….… ..12
2 Ectopi c thyroi d tissue……………………………………….. 13
3 Remnant s of the thyroglossa l duct…………… ……………… 13
4 SURGICA L ANATOMY ………………………………….….. 13
4.1 The importan t anatomica l feature s with
surgica l relevanc e are…………………………………… ……….14
4.2 THE IMPORTAN T CLOS E S URGICA L
RELATION S OF THE THYROID GLAND ……………..….16
5 MICROSCOPI C STRUCTURE …………………………… 1 8
6 PHYSIOLOG Y………………………………………………..…1 9
6.1 FORMATIO N AND SECRETIO N
OF THYROI D HORMONES………………………….…..……20
7 HORMONES ………………………………………….………. 21
7.1 REGULATIO N OF THYROI D SECRETION………….…. 23
8 CLASSIFICATIO N OF GOITR….. ……………………………… 24
8.1 Classificatio n by Hamilto n Baile y and McNei ll Love….…. 24
8.2 . WHO Classificatio n for endemi c goitr……………………25
8.3 SIMPLIFIE D W.H. O GOITR E CLASSIFICATIO N…….… 25

2 9 ETIOLOGY……………………………………………….…..26
10 HER EDITY..…………………………………………………26
11 PATHOGENESI S OF MULTINODULA R GOITRE……2 7
11.1 Endemi c goiter………………………………….……..… 27
11.2 Sporadi c Goitr e…………………………………….….. ….…27
12 PATHOLOGY………………………………………..…..….28
13 CLINICA L FEATURES………………………….…..……30
13.1 Growth……………………………………………………….. 30
13.2 Function………………………………………………….…30
13.3 Clinica l Sign s and Symptom s of
Multinodula r Goiter…………………………………………….31
14 DIAGNOSTI C EVALUATION……………………………31
14.1 THYROI D FUNCTIO N TESTS………………………..…32
14.2 Seru m thyroi d hormones…………………………………32
14.3 Isotop e scanning……………………………………………33
14.4 Othe r tests of thyroi d function………………………..…34
14.5 FINE NEEDL E ASPIRATIO N CYTOLOG Y (FNAC).…36
14.6 RADIOGRAPHY………………………………………..….36
14.7 ULTRASOUN D……………………………………………..37
14.8 CT AND MRI ……………………………………….……..37

3 14.9 THYROI D AUTO – ANTIBODIES ………………..…..…37
14.10 INDIREC T LARYNGOSCOPY………………………….38
14.11 COR E NEEDL E BIOPS Y………………………….. ……..38
15 TREATMENT………… ……………………………………….39
15.1 MEDICA L TREATMEN T…………………………….……..39
15.1.1 Levothyroxin suppressio n therapy…………………………39
15.1.2 Antithyroi d drug therap y … … … … … … … … … … … … … . . … … . . 4 0
15.2 Radioiod i ne therap y and toxic multinodula r goiter……..40
15.3 Alcoho l sclerotherap y…………………………………….…41
15.4 Radioiodin e therap y and nontoxi c multinodula r goiter…41
16 SURGER Y…………………………………………….………..42
16.1 Argumen t for routin e remova l of nodula r goite r…………42
16.2 Argumen t agains t remova l of nodula r goit re………………42
16.3 MANAGEMEN T OF CAS E OF
MULTINODULA R GOITRE……………………………………43
16.4 SURGER Y OF THE THYROI D GLAND…………………44
16.5 Subtota l Thyroidectom y………………………………………42
16.6 Near total thyroidectom y . Tota l Thyroidectom y…………42
16.7 Operatio n Step s in Surger y………………………………..…43
16.8 SUBTOTA L THYROIDECTOM Y…………………….……47

4 16.8.1 Skin Incisio n and Raisin g the Flaps ……………… …..…… 49
16.8.2 Exposur e of the thyroi d gland……………………… …..…49
16.9 Thyroi d Dissectio n……………………………………..…….50
16.10 Excisio n of the Glan d………………………………….…….50
16.11 HEMITHYROI D ECTOM Y……………………………..…..51
16.12 TOTA L THYROIDECTOM Y…………………………..……51
16.13 NEA R TOTA L THYROIDECTOM Y……………….……..52
16.14 TREATMEN T OF RETROSTERNA L GOITRE…..…….52
16.15 TREATMEN T OF TOXI C
MULTINODULA R GOITR E IN PREGNANCY…….………..53
17 POS T OPERATIV E COMPLICATIONS….……..………54
17.1 Haemorrhage……………………………….……..……….54
17.2 Respira t ory obstruction…………………….….…………54
17.3 Recurren t laryngea l nerv e paralysi s………………….……55
17.4 Tracheomalaci a … … … … … … … … … … … … … … … … … … . . . … … … 5 5
17.5 Externa l laryngea l nerv e injury…………………………….56
17.6 Thyroi d insufficienc y……………………………..………56
17.7 Parathyroi d insufficiency………………………..……….5 6
17.8 Thyrotoxi c crisi s (Thyroi d storm) ………………..…..…57
17.9Woun d infectio n… … … … … … … … … … … … … … … … … … … … … . 57

5 17.10Stitc h granuloma………………………………..……..…5 7
17.11 Hypertrophi c or Keloi d Scar …………………..……..…5 7
17.12Recurren t thyrotoxicosi s …………………………..….…58
17.13 Progressiv e or malignan t Exophthalmo s ..…………5 8
17.14 Tetany ………………………………………..……..…….58

18. Thyroid Cancer ………………………………………………59
18.1 Papillary carcinoma……………………………….………………5 9
18.2 Follicular carcinoma …………………………………,,,…….59
18.3 Hürthle (Hurthle) cell carcinoma ………………………,,,……59
18.4 Sporadic MTC…………………………………………….……… 60
18.5 Familial MTC ………………………………… …………..…60
18.6 Thyroid lymphoma…………………………………………….… 60
18.7 Thyro id sarcoma………………………………………………….61
18.8 risk factors for thyroid cancer ……………………………… ….61
18.9 Medullary th yroid cancer……,,,,,,,…………………………… …..62
19. Other thyroid cancers ………,,,,……………………………. …….62

19.1 causes th yroid cancer………………………………………………63

19.2 Signs and symptoms of thyroid cancer ……………………………65

6
19.3 Diagnosis………………………………..…………………………. 66

19.4tre atment…………………………………………………………….72
20.Conclusion……………………………………………………………81

20 REFERENCES…………………………………………………..8 2

7 ACKNOWLEDGMENT
I am grateful to the God for the good health and wellbeing that were necessary to
complete this study.
I wish to express my sicere thanks to DR.Lorina Vudu Head of the Faculty, for
providing me with all the necessary facilities for the study.
I take this opportunity to express gratitude to all of the Department faculty
members for their help and support. I also thank my parents for the unceasin
encouragement, support and attention. I am also grateful to my partner who
supported me throught this venture.
I also place on record, my sense of gratitude to one and all, who directly or
indirectly, have lemt their hand in this venture.

ABSTRACT
The term thyroid nodule refers to an abnormal growth of thyroid cells that forms a
lump within the thyroid gland. Althou gh the vast majority of thyroid nodules are
benign (noncancerous), a small proportion of thyroid nodules do contain thyroid
cancer. In order to diagnose and treat thyroid cancer at the earliest stage, most
thyroid nodules need some type of evaluation.

8 INTRO DUCTION

Thoug h the thyroi d and its disease s were know n to the physician s from
the time immemorial , the subjec t still continue s to evinc e grea t interes t
even toda y from the clinicia n and the pathologis t alike . As Willi s stated ,
for the thyroi d gland, workin g in continuou s state of interes t havin g
alternat e periods of cellula r activit y and quittanc e in respons e to an array
of exogenou s and endogenou s stimuli , it is not so surprisin g that it
suffer s from a wide variety o f disease . A constan t supp ly of thyroi d
hormone s is necessar y for growth, developmen t and maintenanc e of
metabolis m and functiona l activit y of most organs . Disease s of thyroi d are
manifeste d eithe r qualitativ e and quantitativ e alteration s in
hormon e secretio n o r enlargemen t of thyroid (goitre ) or both.
The thyroi d gland , reddis h brow n and highl y vascular , is placed
anteriorl y in the lowe r neck . Leve l extend s from the 5th cervica l to
the 1st thoraci c vertebra . Its weigh t is usuall y 25 grams . The glan d is
slightl y heavier in the femal e sex and enlarge s durin g pregnanc y and
menstruation . 1
The thyroi d glan d function s primaril y to produc e thyroi d hormones . It
stimulate s the oxyge n consumptio n of most cells in the body , help s
regulate lipid and carbohydrat e metabolis m and are necessar y for norma l
growt h and maturation . 2

9 Nodula r goitr e is probabl y the most commo n endocrin e proble m in the
worl d today . 3
GOITR E : The commonl y accepte d definitio n of Goitr e “A Thyroi d
Gland i.e. , at least twic e its norma l size” . In general , the term is
applie d to the benig n enlargemen t of thyroi d gland . 4
Worldwide , nodula r goitr e remain s a proble m of enormou s magnitude . It is
estimate d that no less than 5% of the world' s populatio n have
goitres. Dependin g on the popula t ion studied , multinod ular goitr e
occur s in upto 12% o f adults . Multinodula r goitr e is more commo n in
wome n than men and increase s in prevalenc e with age. The incidenc e of
carcinom a in multinodular goitr e has been reporte d as 5% to 10%.5
Neithe r a well formulate d nor a simpl e procedur e is availabl e for the
managemen t of patient s with MNG . The main reaso n for such
situatio n to exist is, nodula r lesion s may represen t one of the many
differen t cell types that canno t be distinguishe d from one anothe r
withou t histologi c study . 6
Thes e nodule s may be benig n or malignant . Ultimately , it is this
threa t of malignanc y that pose s a majo r problem.
FNA C is a diagnosti c tool in whic h cells are extracte d from the
palpabl e swellin g using FNA C gun, syring e and fine needle . It is
simple, quick , safe and cost – effective . FNA C is increasingl y bein g used
for evaluation o f thyroi d swellings. 7

10 The study of multinodula r goitr e is essential , as it is a commonly
encountere d endocrin e proble m in clinica l practice . The majo r
concer n in moder n thyroi d glan d surger y is morbidity . Beside s
haemorrhag e and hypoparathyroidism , damag e to the recurren t laryngea l
nerv e is the complicatio n most feare d by both patien t and surgeon . It
represent s a serious complicatio n inducing , when bilateral , seriou s
functiona l sequala e such as phonatory , respirator y and psychologica l
problem s that limit working capacitie s and socia l relationship s of the
patients.
Post – operativ e respirator y complication s may need eithe r life saving
endotrachea l intubatio n followe d by tracheosto my or immediat e
tracheostomy.

11
Aim of the study
To determine causes of thyroid nodules &clinical picture,methods of investigations
& possibilites of treatment.

Objectives
Anatomy of thyroid gland
Physiology of thyroid gland
Prevalence of thyroid nodules
Causes of Thyroid Nodules
Diagnosis
Management&Treatment

Actuality
Thyroid nodules is a prevalent pathology , we face a lot of people in the hospitals
and our daily life with this disease

12 A. ANATOMY : EMBRYOLOGY13:
Thyroi d gland mainly develops from the thyroglossal duct. Parafollicula r
cells are derive d from the cauda l pharyngea l comple x (derived from 4th and
5th pharyngea l pouches ) separat e by midlin e swell ing calle d the
tuberculu m impar . Immediately behind the tuberculum, the epitheliu m of
the floor of the pharynx shows a thickening in the midline. This region is soon
depressed below the surface to form a diverticulum called the thyroglossal
duct.
The site of origin of the diverticulum is now seen as a depression called the
foramen caecum. The diverticulum grows down in the midline into the
neck . Its tip soon bifurcates . Proliferatio n of the cells of this bifid end
gives ris e to the lobe s of the thyroi d gland . This duct later become s
solid and finall y disappears . With furt her development , the thyroi d
glan d descend s in front of the hyoi d bone and the laryngea l cartilages .
It reache s its final position in front of the trachea in the 7th week . By
then , it has acquire d a small median isthmus and two lateral lobes. The thyroid
begins : functioning approximatel y at the end of the 3rd month , at whic h time
the first follicles containin g colloi d becom e visible . Follicula r cells
produc e the colloi d that serve s as a sourc e of thyroxin e and
triiodothyronine . Parafollicula r or C cells derived from the ultimobranchial
body serve as a source of calcitonin.

13 When thyroid tissue is present in the positions described above, an additiona l
thyroi d may or may not be presen t at the norma l site.
B. Ectopi c thyroi d tissue : Small masses of thyroid tissue have been observed
in the larynx , trachea , oesophagus , pons , pleura , pericardiu m and ovaries.
Masse s of ectopi c thyroi d tissu e have been describe d in relatio n to the
deep cervica l lymp h node s (latera l aberran t thyroids ) but these are now
believe d to represen t metastase s in the lymp h node s from a carcinom a
of the thyroi d gland.
C. Remnant s of the thyroglossa l duct may persis t and lead to the
formatio n of:
a. Thyroglossa l cysts , that may occu r anywher e alon g the cours e of
the duct.
b. They may acquir e secondar y opening s in the neck to form fistulae.
Thyroglossal fistula opening at the foramen caecum.
c. Carcinom a of the thyroglossa l duct.
SURGICA L ANATOMY14:
The thyroid gland occupies an important position in the centr e of the
viscera l compartmen t of the neck , lying astrid e the trache a just abov e
the thoraci c inlet , normall y weighin g abou t 25g.
The glan d has two lobes , shape d roughl y like slende r pears , hugging
the anterolateral aspect of the cervical trachea from the level of the thyroid
cartilag e to the 5th or 6th trachea l ring. The right lobe is often large r
than the lef t and the lobe s are joine d togethe r acros s the midlin e by a
thin isthmus plastere d quite firml y to the anterio r surfac e of the trachea ,
at t he level of the
2nd and 3rd trachea l rings . A variable – sized, but usually small, pyramidal
lobe arise s from the isthmu s somewher e alon g its uppe r borde r near the
midline. The thyroid gland is covered by fascia and the strap muscles and
more laterally , it is tucked under the diverging anterior borders of the
sternomastoid muscles.

14 Because of its fascial attachments the gland moves upwards with swallowing and
therefore slides under the examining fingers. The normal gland can be felt in
thin necks. It is soft and suppl e and the trachea l rings can be palpated through
it.

The importan t anatomica l feature s with surgica l relevanc e are:
1.THE MUSCULO FASCIAL COVERINGS: The strap muscles are
ensheathe d by the genera l investin g layer of cervica l fasci a and this unites
them in the midline . Thes e muscle s are applie d to the anterio r surfac e
of the gland, but separated from it by a loose condensation of fascia derived
from the pretracheal fascia. This false capsule covers the gland which is enclose d
by its diaphanou s true capsul e with its very rich bloo d supply, clearl y
visibl e just beneat h its surface . The nerv e suppl y of these muscles, the
sternohyoid and its deeper neighbour, the sternothyroid comes from cervica l
roots 1, 2 and 3 via branche s from the ansa cervicalis . These branches
enter the muscles at its lateral border and on the deep surface and though it is not
often necessary, the muscles may be divided transversely

15 to facilitat e acces s to the glan d provide d they are re- sutured , there
does not appea r to be any impairmen t of function.
2. THE VASCULAR SUPPLY: Each thyroid lobe is supplied by a
superior and an inferior thyroid artery and drained by three veins.

The Superio r Vascula r Pedicle : The superio r vascula r pedicl e contain s the
superior thyroid artery, which is the first branc h of the externa l carotid,
and its accompanying vein, which drains into the internal jugular vein. The
externa l laryngea l nerv e is closel y relate d to this pedicle . The
superior vessels enter the upper pole of the gland at its apex with branche s to
the front and back of the gland. These superior vessels are easily dealt surgically,
because the loose space between the two capsules is developed at the uppe r
pole of the thyroi d lobe and a ligatur e is place d close to the uppe r pole ,
to includ e both vessels and exclude the external laryngeal nerve.

The Inferio r Thyroi d Artery : The inferio r thyroi d arter y and vein do not
relate to each other at all. The artery arises from the thyrocervical trunk,
passes behin d the caroti d sheat h and then runs transversel y acros s the
spac e between thi s and the thyroi d glan d to enter the deep surfac e of
the glan d as several separat e branche s close to the tracheothyroi d groove .
Thes e termina l branches of the inferior thyroid artery are uncomfortably
close to the recur rent laryngea l nerv e and the inferio r parathyroi d glan d and
shoul d be surgically shunned . If the inferio r thyroi d arter y is to be ligated , it
shoul d be done in its transverse portion medial to the carotid sheath.

16 The Inferio r Thyroi d Veins : The inferio r thyroid veins , of whic h there
are alway s a few on each side, leave the lowe r borde r of the glan d and
pass through, require to be ligated singly.
The Middle Thyroid Veins: The applie d anatom y of the middl e thyroi d vein is
importan t becaus e it is a short , thin- walle d vessel , leavin g the middl e
of the glan d and directl y coursin g laterall y to pass in front of or behin d
the carotid artery and enter the internal jugular vein. It is the first vessel
encountered in thyroidectom y and merit s carefu l ligatio n when it is met
early on durin g the development of the intercapsular space mentioned above.
The Thyroide a Ima Artery : The thyroidea ima artery from the brachiocephalic
trunk extendin g in front of the trache a is smal l and surgicall y irrelevant.
THE IMPORTAN T CLOS E S URGICAL RELATIONS OF THE
THYROID GLAND : Thes e are the recurren t laryngea l nerves , the
externa l laryngeal nerve s and the parathyroi d glands . Like all importan t
relation s they shoul d be recognized immediately and cared for respectfully.
The Externa l Laryngea l Nerve : The external laryngeal nerve, a branch of the
superior laryngeal nerve, descends on the fascia of the inferior pharyngeal
constrictor , relate s closel y to the superio r vascula r pedicl e of the thyroi d
and the n leave s this at a variabl e heigh t abov e the gland to travel medially to
its destinatio n in the cricothyroi d muscle . It is functionall y importan t
for the pitch of the voice, because the cricothyroid muscle is a tensor of
the vocal cord . Damag e to this nerv e alter s the voic e quite
significantl y and is especiall y noticeabl e in singers.

17 The Recurren t Laryngea l Nerve : The recurrent laryngeal nerve is a branch
of the vagus arising embryologically in relation to the 4th aortic arch vessels.
Because of the descent of these vessels forming the subclavian artery on
the right and the aortic arch on the left, the recurrent nerves are taken
caudally and thus run an upward course to reach their vocal cord destination.
The nerve s usuall y lie in the tracheo – oesophageal groove and then bear a
variable relationship to the branche s of the inferio r thyroi d arter y befor e
enterin g the larynx. In very rare instances, because of failure of development
of the 4th arch vessels and a resultant anomalous right subclavian artery, the
nerve on that side will be non recurren t and then passe s directl y mediall y
at a much highe r level from the vagu s to the larynx . In this positio n it
coul d be in danger at the time of ligatio n of the middl e thyroi d vein ,
thoug h the difference between these two structures should be easily apparent.
The parathyroi d Glands : The numbe r of parathyroid s vary from 2 to 6
but in 80 percen t of case s there are 4 (2 on each side) . The gland s are the
size of a split pea. They are pink or brown in colour. The superior glands lie on
the posterior surface of the middle third of the thyroid, usually above the inferior
thyroi d artery , but well posterio r to this plane . The inferio r gland s are
mostly foun d on the posterio r surfac e of the lowe r pole of the thyroi d or
withi n 1 cm belo w the lowe r pole . They lie in a more anterio r plan e than
the uppe r glands. A parathyroid gland is located within the surgical false capsule
of the thyroid. Sometimes the parathyroids may be embedded in the thyroid gland.
A small parathyroi d arter y supplie s each gland . The lowe r parathyroi d
ar tery comes from the inferior thyroid artery. The upper parathyroid artery arises
from the inferior artery or from an anastomosing artery joining the
superior and inferior thyroid arteries. They will be at risk during ope rations on the
thyroid gland.

18 LYMP H DRAINAGE: Numerous lymphatic vessels leave the gland and drain
to lymph nodes situated:
1. In the midlin e on the front surfac e of the laryn x and trachea.
2. In the tracheo – oesophagea l groov e extendin g downward s into the
superior mediastinum.
3. Upwards and latera lly to the deep cervica l chain and node s latera l
to this.

MICROSCOPI C STRUCTURE
The gland is surrounded by a thin connective tissue capsule, which sends in
septa dividing the gland into groups of follicles or lobules. There is very little
connectiv e tis sue betwee n the individua l follicles . This connectiv e
tissu e give s suppor t to the abundan t fenestrate d capillarie s that are presen t
in the gland .

19
Fig. 3 Histolog y of Thyroi d Gland .

The glandular substance is composed of spherical (acini) follicles with a large
lumen . The follilcle s vary in size and are filled with proteinaceous
colloid , whic h stain acidophilic .
The epithelia l cells linin g the follicle s are cuboida l or columnar
accordin g to the activit y of the follicle . The averag e size is abou t 15 m.
The acini are arranged in subunits of 20 to 40 and demarcated by connective
to form lobules , each supplie d by an individua l artery . The size of
the follicles vary, being around 200 m in diameter . 16
The parafollicula r cells or “ C ” cells which stain lighter in colour but are
bigge r in size are presen t in the follicula r epitheliu m lying in betwee n the
basement membrane and epithelial cells. Some are also present in the
interfollicular spaces. 15
C. PHYSIOLOG Y17
The thyroi d gland maintain s the level of metabolis m in the tissue s that is
optima l for their norma l function . Thyroi d hormone s stimulat e the
0 2 consumptio n of most of the cells in the body , help regulat e
lipid and carbohydrat e metabolism , and are necessar y for norma l grow t h
and maturation. The thyroi d gland is not essentia l for life, but its absenc e
cause s menta l and physica l slowing , poor resistanc e to cold , and, in

20 children , menta l retardation and dwarfism . Conversely , exces s thyroi d
secretio n leads to body wasting, nerv o usness , tachycardia , tremor , and
exces s heat production . The thyroid glan d also secrete s calcitonin , a
calciu m- lowerin g hormone.

FORMATIO N AND SECRETIO N OF THYROI D HORMONES
The principa l hormone s secrete d by the thyroi d are thyroxin e (T4 )
and triiodothyro nine (T3 ), T3 is also forme d in the periphera l
tissue s by deiodinatio n of T4 . Both hormone s are iodin e – containin g
amin o acids . Small amount s of revers e triiodothyronin e (3,3' , 5' –
triiodothyronine . RT3 ) and other compound s are also foun d in thyroi d
venou s blood. T3 is more activ e than T4 . The naturall y occurrin g form s of
T4 and its congener s with an asymmetric carbo n atom are the L isomers . D –
Thyroxin e has only a smal l fractio n of the activit y of the L form . T4 and T3
are synthesize d in the colloi d by iodina t ion and condensatio n of tyrosin e
molecule s boun d in peptid e linkag e in thyroglobulin . This glycoprotei n
is made up of two sub – units and has a molecular weight of 6,60,000.
Thyroglobulin is synthesized in the thyroid cells and secrete d into the colloid .
The hormone s remai n boun d to thyroglobulin
until secreted . Whe n they are secreted , colloi d is ingeste d by the thyroi d
cells, the peptid e bond s are hydrolyzed , and free T4 and T3 are
discharge d into the capillaries . Thyroglobuli n enter s the bloo d as well as
the colloid . The normal serum thyroglobuli n concentratio n in human s is
abou t 6 ng/mL , and this level is increase d in hyperthyroidis m and some
form s of thyroi d cancer.
Iodine Metabolism: Iodin e is a raw materia l essentia l for thyroi d hormone
synthesis . Inges ted iodin e is converte d to iodid e and absorbed . The principal
organ s that take up the iodin e are the thyroid , whic h use it to make thyroid
hormones , and the kidneys , whic h excret e it in the urine.
Iodid e Trapping : The thyroi d concentrate s iodid e by activel y transportin g
it from the circulatio n to the colloid . The transpor t mechanis m is

21 frequently calle d the "iodid e trappin g mechanism " or "iodid e pump" . In
the gland , iodide is rapidl y oxidize d and boun d to tyrosine.
Thyroid Hormone Synthesis: In the thyroi d gland, iodid e is oxidize d to
iodine and boun d in a matte r of second s to the 3 positio n of tyrosin e
molecules attache d to thyroglobulin . The enzym e responsibl e for the
oxidatio n and bindin g of iodid e is thyroi d peroxidase , with hydroge n
peroxid e acceptin g the electrons . Monoiodotyrosin e (MIT ) is next iodinate d
in the 5 positio n to form diiodotyrosin e (DIT) . Two DIT molecule s then
underg o an oxidative condensatio n to form T4 with the eliminatio n of the
alanin e side chain from the molecul e that form s the oute r ring. Thyroi d
peroxidas e is probabl y involve d in couplin g as well as iodination . T3 is
probabl y forme d by condensatio n of MIT with DIT.
Secretion : The huma n thyroi d secrete s abou t 80 µg (103 nmol ) of T4 ,
4 µg (7 nmol ) of T3 . However , MIT and DIT are not secreted. TRANSPOR T
AND METABOLIS M OF THYROI D HORMONES
Protein Binding: The norma l total plasm a T4 level is approximatel y 8
ng/dL (10 3 nmol/L) , and the plasm a T3 level is approximatel y 0.15
ng/d L (2.3 nmol/L ) Larg e amount s of both are boun d to plasm a proteins .
The normal Protein -boun d iodin e is potent than T4 . This is becaus e it is
less tightl y bound to plasma proteins but binds more avidly to thyroid
hormone receptors T3 is inert.
1. Calorigenic Action: T4 and T3 increase the oxygen consumption of almost
all metabolicall y activ e tissues . The exception s are the adult brain , testes,
uterus , lymp h nodes, spleen, and anterior pitutary.
2. Effects Secondary to Calorigenesis: In hypothyroi d children , smal l dose s of
thyroi d hormone s caus e a positiv e nitroge n balanc e because they stimulate
growth , but large dose s caus e protei n catabolis m simila r to that produce d
in th e adult . Periphera l resistanc e decrease s becaus e of cutaneou s
vasodilation, but cardia c outpu t is increase d by the combine d actio n of
thyroi d hormones and catecholamine s on the heart , so that pulse pressur e and
cardia c rate are increase d and circulatio n time is shortened.

22 3. Effect s on the Nervou s System : In hypothyroidism , mentatio n is slow
and the CSF protei n level elevated . Thyroi d hormone s revers e these
changes, and large dose s caus e rapid mentation , irritabilit y and restlessness.
4. Effect s on the Heart : Thyroi d hormone s increas e the numbe r and
affinit y of P – adrenergi c receptor s in the hear t and consequentl y increas e
its sensitivity to the inotropi c and chro notropi c effect s of catecholamines.
5. Effects on Skeletal Muscle: Muscl e weaknes s occur s in most patient s with
hyperthryoidis m (Thyrotoxic myopathy) and when the hyperthyroidis m is
sever e and prolonged , the myopath y may be severe . The muscl e weakness
may be due in part to increase d protei n catabolism.
6. Relatio n to Catecholamines : Thyroi d hormone s increas e the numbe r
and affinit y of p- adrenergi c receptor s in the hear t and possibl y in some
other tissues , and the effect s of thyroi d hormone s on the hear t resembl e
those of p- adrenergi c stimulation.
7. Effects on Carbohydrate Metabolism: Thyroi d hormone s increas e the rate of
absorptio n of carbohydrat e from the gastrointestina l tract , an actio n that is
probabl y independen t of their calorigeni c action.
8. Effect s on Choles t erol Metabolism : Thyroi d hormone s lowe r
circulating cholestero l levels.
Effect s on Growth : Thyroi d hormone s are essentia l for norma l growt h
and skeleta l maturation . In hypothyroi d children , bone growt h is slowe d and
epiphyseal closure delayed. In the abse nce of thyroid hormones, growth
hormon e secretion s are also depressed , and thyroi d hormone s potentiat e
the effec t of growt h hormon e on the tissues.

23 REGULATIO N OF THYROI D SECRETION
Thyroi d functio n is regulate d primaril y by variation s in the circulating
le vel of pituitar y TSH . TSH secretio n is increase d by the
hypophysiotropic hormon e TRH and inhibite d in a negativ e feedbac k
fashio n by circulatin g free T4 and T3 .
Huma n TSH is a glycoprotei n that contain s 211 amin o acid residues , hexoses,
hexosamines and sia lic acid. Whe n TSH is administered , thyroi d functio n is
stimulated . Wheneve r TSH stimulatio n is prolonged , the thyroi d becomes
detectabl y enlarged . Enlargemen t of the thyroi d is calle d goitre . The negative
feedbac k effec t of thyroi d hormone s on TSH secreti o n is exerte d in part
at the hypothalami c level , but it is also due in large part to an actio n on
pituitary, since T4 and T3 bloc k the increas e in TSH secretio n produce d
by TRH . Infusion of T4 as well as T3 reduces the circulating level of
TSH, which declines measurabl y withi n one hour.

24 D. CLASSIFICATIO N OF GOITRE
Goitr e is a clinica l term for any visibl e or palpabl e enlargemen t of the
thyroi d gland.
Differen t author s have classifie d goitr e in differen t ways
I. Classificatio n by Hamilto n Baile y and McNei ll Love18
1. Simpl e goitr e (Euthyroid)
• Diffus e hyperplastic
– Physiological
– Pubertal
– Pregnancy
• Multinodula r goitre
2. Toxic
Diffuse Grave s disease
Multinodula r goitre
Toxi c adenoma
3. Neoplastic
– Benign
– Malignant
4. Inflammatory
• Auto immune
– Chroni c lymphocyti c thyroiditis
– Hashimoto' s disease
• Granulomatous
– de Quervain' s thyroiditis

25 • Fibrosing
– Riedel' s thyroiditis
• Infective
– Acut e (Bacteria l thyroiditis , viral thyroiditis, subacut e thyroiditis)
– Chroni c (Tuberculous , syphili t ic)
5. Other
– Amyloid

II. WHO Classificatio n for endemi c goitre : 19
• Grad e 0 Thyroi d not palpabl e or, if palpable , not large r than normal.
• Grad e la Thyroi d distinctl y palpabl e but usuall y not visibl e in
position ; the thyroi d is large r than normal , i.e. at least as large as the
dista l phalan x of the subject' s thumb.
Grad e lb Thyroi d easil y palpabl e and visibl e with the head in a
raised position ; the grad e include s all patient s with a discret e nodule.
• Grad e 2 Thyroi d easil y visibl e with the head in a norma l position.
• Grad e 3 Goitr e visibl e at a distance.
– Grad e 4 Monstrou s goitre.

III. SIMPLIFIED W.H.O GOITRE CLASSIFICATION SYSTEM 19
GRAD E ‘O’: No palpabl e or visibl e goitre .
GRAD E ‘1’ : Mass in the neck is consisten t with an enlarged
thyroid that is palpab le but not visibl e when neck is in neutra l position ,
it also move s upwar d in the neck as the subject swallows.
GRAD E ‘2’ : A swellin g in the neck that is visibl e when the

26 neck is norma l positio n and is consisten t with an enlarged thyroi d when neck
is pa lpated.
ETIOLOGY 20
Worl d wide the most frequen t singl e caus e of endemi c Multinodular
Goitr e is still iodin e deficiency
In areas wher e the iodin e suppl y is scarce , a TSH mediated compensatory
mechanism is set into motion. As a consequence the thyroid gla nd diffusely
enlarges and as time passes by it gradually becomes nodular. 21
Iodin e deficienc y is not only the caus e of endemi c goitr e becaus e a
high prevalenc e of goitr e has been reporte d from areas wher e iodin e
suppl y is abundan t and becaus e Multinodula r Goitr e continue s to be a
highl y prevalent disorder in areas such as Switzerland, where iodine deficiency
has long been eradicated.
The foregoing section on pathogenesis should make it clear that non endemi c
nodula r goitre , are the late result s of intrinsic disorder s of
intracellula r growt h contro l mechanism , just as in othe r clona l and
polyclonal benign tumors. 22
Where as thyroid stimulating immunoglobulins cause the goitre of
grave s disease , specifi c Growt h stimulatin g immunoglobulin s are
considered by some author s to be a causativ e facto r in a fractio n of
nodula r goitre s. 23

HEREDITY
A clusterin g of thyroi d disease s includin g simp le goitres , in some
familie s or pedigree s has prompte d a host of investigatio n on the possibl e
role of heredit ar y factor s in the genesis of euthyroid goitre. Existing
evidence indicates that genetic factors held to determine the development of
goitre but no simple mode of inheritance can be postulated.24

27 PATHOGENESIS OF MULTINODULAR GOITRE
Endemi c goiter :
The deficienc y of the thyroi d hormon e productio n induce d by the iodine
deficiency leads to increase in TSH secretion, which results initially in a
hyperactive thyroid with tall follicular epithelium and small amounts of
colloid (so called Parenchymatous Goitre) and later in follicular atrophy with
massive storage of colloid, with or without nodularity (so called diffuse or
nodula r colloi d goitre ). In these endemic areas, the frequency of disease
at post mortem examination is virtually 100%.25
Sporadi c Goitr e :
Pathogenesi s remains unknown. Mild dietary deficiency of iodine, slight
impairment of hormone synthesis, increased iodide clearance by the kidneys ,
presenc e of thyroi d – stimulatin g immunoglobulins , and increased
production of insulin – like growth factor –I have been variousl y
suggested. Some cases are associated with lymphocytic or Hashimoto’s
thyroiditis and can be viewed as the nodular forms of these immune – mediated
inflammatory diseases.26
In addition to circulating thyroid growth factors, local autocrine or paracrine
growth factors may be implicated in the pathogenesis of multinodular goitre.
Epidermal growth factor has been reported to stimulate thyroi d growt h27 , and
transforming growth factor beta has been reported to inhibi t thyroi d cell
growth . 28
If a goitre were induced either by TSH or a growth stimulating
immunologlobulin , one woul d expec t it to be a diffus e goitre , i.e. all
thyroid cells in shoul d be stimulate d in a simila r fashion . Early studie s by
Taylor suggested that there was a progression from diffuse thyroid
enlargements, to foca l hyperplasi a and regression , to a multinodula r goitre .
Stude r and Ramelli hav e extende d these observation s and demonstrate d
that newl y generated follicle s involv e clone s at cells tha t may retai n
the abilit y to pick up iodine and synthesize hormone (e.g. hot nodules) or
that have (lost the ability to iodinate or endocytose thyroglobulin forming
"Cold nodules" with large "colloi d lakes" . Failur e of local vascula r

28 suppl y to the nodul e results in necrosis and scarring, which form fibrous septa
that further isolate the nodular areas . Thus a goitr e that begin s as a
diffus e hypertrophy , ends as a multinodular goitre.29

PATHOLOGY:
Grossly , the thyroi d is enlarge d and its shap e is d istorted, one lobe being
frequently larger than the other. The thyroid capsule may be stretched but
intact . On cross section , multipl e nodule s are seen , some surrounde d
by a partial or complete capsule. Secondary changes in the form of hemorrhage,
calcification and cystic degeneration are common. Microscopically, there is a
wide range of appearances. Some nodules are composed of huge follicles lined
by flattene d epithelium , other s are extremel y cellula r and hyperplasti c
and stil l other s are compose d predominantl y or exclusivel y of Hurthl e
Cells . Some of the dilate d follicle s have a conglomerat e of smal l activ e
follicle s at one pole (so calle d Sanderson’ s polsters ) other s have papillar y
projection s facing the lume n of cysti c follicle , a featur e that may
lead to confusion with papillary carcinoma.25
It is not unusual to find, within a nodule predominantly composed of
large dilated follicles, sharply outlined solid or micro follicular clusters of
follicula r cells . It has been suggeste d that nodula r goiter s grow by
episodic replication of these clusters, which have been referred to as foci of
secondary proliferation and which have been found to express
immunohistochemically the P21 proto – oncogene product.22
The poliferativ e activit y of the nodule s can be estima ted by immunostaining
the sections with MIB- 1.30
Rupture of follicles leads to a granulomatous reaction to the colloid, with
appearanc e of histiocyte s and foreig n body type gian t cells . Area s of fresh
and old hemorrhage, cause fibrous trabeculation and foc i of calcification are
common. Occasionally, osseous metaplasia is seen. Greatly thickened vessel s
with calcifie d medi a may be presen t at the periphery . A variable numbe r of
chroni c inflammator y cells are presen t in the strom a in many of the cases ,

29 indic a ting the co- existence of chronic thyroiditis. The larger their number ,
the highe r the chance s of postoperativ e hypothyroidism . The presenc e of
the highl y atypica l nucle i in a case of nodula r hyperplasi a should raise
the possibilit y of previou s exposur e to radioactiv e substance s if present
in the nodul e themselves , and of dyshormogeni c goitr e if present between the
nodules . It is not possibl e to predic t on the basis of the morphologic
appearance whether the patient has clinical or laboratory evidence of
hype rthyroidism.25

30 CLINICA L FEATURES : 31
Toxi c multinodula r goitre s usually occur in individuals older than 50 years of
age, who often have a prior history of a nontoxi c multinodular goitre .
Over severa l years , enoug h thyroi d nodule s becom e autonomou s to caus e
hyperthyroidism . The presentatio n is often insidiou s in that hyperthyroidism
may only become apparent when patients are placed on the low doses of
thyroid hormone suppression for the goiter. Some patients have T3 toxicosis ,
wherea s othe r patient s have apatheti c hyperthyroidism, atrial fibrillation,
or congestive heart failure. Hyperthyroidism can also be precipitate d by
iodid e containin g drug s such as contras t medi a and the anti arrhythmic
agent amiodarone.
Most goiters are relatively small and produc e few or no clinical symptoms .
Whe n present , the clinica l mani festation s of multinodular goitr e are
related to those of the following:
Growth:
An anterior cervical or retrosternal / intrathoracic space occupying mass is
present . Symptom s and signs rang e from none (incidenta l finding ) to
varying degrees of pressure symptoms and signs: from a sensation of fullness to
grotesque disfiguration with inspiratory stridor, disturbances in swallowing,
superior vena cava obstruction (rarely), and Horner’s s yndrome (rarely) – cause d
by pressur e on the trachea , esophagus, cervical veins, and sympathetic
nerves, respectively. Hoarseness is a rare symptom, but when present, the
possibility of thyroid malignancy shoul d be contemplated.

Function:
Patient s with nontoxic multinodular goiter by definition do not have any
symptom s or signs of thyroi d dysfunction . However , many such
goiters have a growth potential and, with that, the potential for
increasin g autonom y and hypersecretio n of thyroi d hormone . Beca use
the condition is slowly evolving and most often seen in the elderly, the symptom s
of hyperfunctio n are at varianc e with those seen in graves disease .
Often , cardiovascula r (congestiv e hear t failure , atrial fibrillation) and

31 gastrointestinal symptoms are dominant . Frequently, over t hyperthyroidis m
is precede d by a length y perio d of subclinical hyperthyroidis m that may,
when looke d for, be associate d with a number of organ manifestations
in the central nervous system, heart, bone and muscluoskeletal system.
Clinica l Sign s and Symptom s of Multinodula r Goiter
Slowl y growin g nodula r anterio r neck mass Enlargement during pregnancy.
Trachea l deviatio n or compression , uppe r airwa y obstruction , dyspnoea
Sudden pain or enlargement secondary to hemorrhage Occa sional cough and
dysphasia Gradually developing hyperthyroidism Iodide – induced thyrotoxicosis
Superior vena cava obstruction syndrome Recurrent nerve palsy (rare) Horner’s
syndrome (rare)
G. DIAGNOSTIC EVALUATION
Diagnosti c evaluatio n in patient s w ith suspected multinodular goitre
shoul d be obtaine d to suppor t the clinica l impression , to establis h
the functional biochemical status of the thyroid and when necessary, to exclude
malignancy.
As in other General Surgical cases, routine investigations like bloo d analysis,
urine analysis, electrocardiogram, radiological assessment of chest are done
to acces s the fitnes s of the patien t to underg o majo r surgical procedures.
(1) Sleepin g pulse rate – To differentiate tachycardia due to anxiety from that
of thyro toxicosis, pulse rate is counted when the patient is in sleep.
A count of more than 90/min is suggestive of hyperthyroidism. A rate
of 90- 100 per minut e indicate s mild , 100- 110/mi n moderat e and more than
110/min, severe hyperthyroidism.32
(2) Serum cholestero l – In hypothyroidism, it is markedly increased (more than
300 mg. %).32

32 THYROI D FUNCTIO N TESTS:
The most important investigation of thyroid function is meticulous clinical
assessment of the patient. But clinical diagnosis has to be confirmed by
investiga t ions to know exactl y the hormona l statu s of the thyroi d and also
its relatio n with the anterio r pitutary and hypothalamus.
There are a variety of tests of thyroid function available. The number of
investigations requested should be the minimum necessary to reach a
diagnosi s and formulat e a managemen t plan . Only a smal l numbe r
of parameters needs to be measured as a routine although this may require
supplementation or repeat when inconclusive.
Seru m thyroi d hormones
Seru m TSH : The serum TSH may be used as a single, initial test of thyroid
functio n becaus e of the high sensitivit y of the TSH assay to diagnos e both
hyperthyroidism and hypothyroidism. TSH levels can be measured accurately
down to very low serum concentrations and if the serum TSH level is in the
norma l rang e it is redundan t to measur e the T3 and T4 levels. Interpretation
of deranged TSH levels however depends on knowledge of the T3 and T4
values. In the eruthyroi d state , T3, T4 and TSH level s will all be withi n
the normal range . Flori d thyroi d failure result s in depresse d T3 and T4
level s with gross elevation of the TSH. Incipient or developing thyroid failure
is characterized by low norma l value s of T3 and T4 and elevatio n of the
TSH . In toxic states the TSH level is suppresse d and undetectable.18
Thyroxin e (T4 ) and tri -iodothyronin e (T3 ) are transporte d in plasm a
boun d to specifi c protein s (thyroxin e – binding globulin, TBG). Only a small
fraction of the total (0.03 per cent of T4 and 0.3 percen t of T3 ) is free and
physiologically active . Assa ys of both total and free hormon e are
availabl e but the total values depend on the level of circulating proteins
which are affected by the leve l of circulatin g oestrogen . Thus , pregnan t
wome n and thos e on the oral contraceptive pill have elevated total T4 and
T3 levels without evidence of toxicity. The free hormone levels are unaffected.
Similarly some patients have low levels of TBG either as a primary
phenomenon or secondary to a reductio n in serum protei n level s as a resul t

33 of systemi c or liver diseas e and the total level of circulating hormone may
be low. For these reasons the free levels are more meaningful. Highly accurate
radioimmunoassays of free T3 and T4 are now routine . T3 toxicity (with a
normal T4 ) is a distinc t entit y and may only be diagnose d by measurin g
the seru m T3 , althoug h a suppressed TSH level with a norma l T4 is
suggestive , are usefu l in detecting hypothyroidis m or hyperthyroidism ,
but the majorit y of patient s with thyroid nodule s are euthyroid.18 The
majorit y of patient s with thyroi d no dule s are euthyroid. 33
Various combinations of these tests are used in different laboratories. An
appropriat e combinatio n is to establis h the functiona l thyroi d statu s at
initia l assessment , with TSH supplemente d by free T4 and T3 evaluatio n
when TSH is abnormal.
Isotop e scanning:
It gives information about thyroid activity and also shows graphic information
about the size and extent of the gland. This method is particularly helpful in
showing the retrosternal extent of the gland.
The uptake by the thyro id of a low dose of either radiolabeled iodine (I123
) or tecnnetiu m- 99m (Tc 99m , which is normally taken up like Il23 ) will
demonstrat e the distributio n of activit y in the whol e gland . This test
is inappropriate for distinguishing benign from malignant les ions becaus e
the majorit y (80 per cent) of 'cold ' swelling s is benig n and some (5 per cent)
functionin g or 'warm ' swelling s will be malignant . Its principa l valu e
is in the toxic patient with a nodule or nodularity of the thyroid. Localization
of over – activit y in the glan d will differentiat e betwee n a toxic nodul e
with suppressio n of the remainde r of the glan d and toxic mult i nodula r goitr e
with severa l areas of increase d uptak e with importan t implication s for
therapy. Routin e isotop e scannin g is unnece ssary . 18

Othe r tests of thyroi d function :
Som e of whic h are now only of histori c interes t and other s in
the province of the endocrinologist rather than the endocrine surgeon.

34 1. Serum protein Bound Iodine (PBI): In euthyroid condition, the range is
3.5 – 8 ng per 100ml . It is chea p and can be easil y assessed , but it lacks
specificity , in that it measure s non- hormona l form s of iodin e in the
blood.34
2. T3 Resi n Uptake : The patient' s serum is incubate d with radio – activ e
T3 so that the latter becomes fixed to any t hyroid binding protein not
carryin g T3 or T4 . The amoun t so fixed can be measure d and thus
the numbe r of bindin g sites in the serum whic h are unoccupie d can be
measured . Naturall y in hyperthyroidis m the numbe r of free bindin g sites
is low and in hypothyro idism this numbe r is high . The norma l range
bein g 0.91 – 1.21 µg. 34
3. Free Thyroxin e Inde x (FTI) : This is calculated from the formula that FTI
is equa l to serum T4 (or PBI) x T3 uptak e percent . The norma l rang e
is from 3.5 to 8. It correlates closely with the level of free T in serum and
thus accurately reflects the thyroid status of an individual. This can be
considered as the best single test available at present.34
4. Test of Hypothalami c Pitutary axis: When thyrotrophi n- releasing
hormon e (TRH ) is give n IV in a dose of 200 µg to a normal individual, the
leve l of TSH in the seru m rises from a basa l leve l of abou t 1 µg/m l
to a mean peak concentratio n of abou t 10 µg/m l at 20 minute s and
returne d to normal by 120 minutes. In hypothyroidism there is an exaggerated
r ise of an already elevated TSH level but in hyperthyroidism there is no response
of depresse d TSH level . Its importanc e remain s to certai n exten t in
the diagnosi s of T3 thyrotoxicosis if it is not possible to measure the
circulating
leve l of T3 .34
5. Uptak e Tests: The rate at which the thyroid gland traps iodine reflects the
rate of secretio n of the thyroi d hormone . In hyperthyroidis m both the
proportion of the tracer dose taken up and the rate at which this takes place are
increased . The best time to measur e the isotop e uptak e is between
10 – 120 minute s after administration . At this stage there is no additional

35 discharge of radio – activit y from the gland . The trace r dose of I131 is
5 microcuries . The uptak e is first measure d and then the radioisotop e
pass es back into the serum being incorporated into the T3 and T4 molecules
and can be measure d as protei n boun d 13I I. Thyroi d radioiodin e uptak e
(RAIU) is most often reserve d for dosimetr y calculation s prior to
radioiodine therapy.
6. T 3 Supressio n Test (Werner) : This test differentiates thyrotoxicosis
from other causes of raised uptakes e.g. iodine deficiency and the autonomous
thyrc i nodules . The initia l uptak e is measured . 40 µg of tri- iodothyronine
is give n 8 hourl y by mout h for 5 days , after whic h the uptak e is repeated.
T3 is used because of its more rapid effect and its shorter half- life.
Considerabl e suppressio n in thyroi d uptak e is note d in the rang e of 50
to 80 per cent by this amoun t of exogenou s hormone . Sligh t suppressio n
in the rang e of 10 – 20 perce nt is note d in thyrotoxicosis . The TRH test gives
simila r informatio n and has replace d the T3 suppression test in centres
where a radioimmunoassay of serum TSH is available. In patients who are on
anti- thyroi d drug treatmen t for thyrotoxicosis , this test ma y be used as
an indicato r of remissio n of the disease . A retur n to norma l suppressibility
in treate d patient s usuall y indicate s remission . 34
7. Miscellaneou s Tests : Thes e compris e the BMR , serum cholesterol ,
serum creatine, measurement of tendon reflexes, ECG etc. Of these BMR and
measurement of tendon reflexes may help in the diagnosis of
hypothyroidism . Othe r tests are of little value.34

FINE NEEDLE ASPIRATION CYTOLOGY (FNAC):
This is an excellent , simpl e and quic k test for thyroi d nodule s which
can be perfo rmed as outpatien t method . Thyroi d condition s whic h may

36 be diagnose d by this techniqu e are – thyroiditis , colloi d nodul e (quit e
common), benign tumours like follicular adenoma, follicular carcinoma,
papillary carcinoma , anaplasti c carcinoma , medullar y carc inoma and
lymphoma.34
FNA C of multinodula r goitr e can evaluate any suspicious nodule, defined as:
1) A palpably prominent nodule,
2) Any firm , hard , or fixed nodule,
3) Any rapidl y growin g nodul e or
4) Any nodul e in a thyroi d glan d expose d to previou s irradiation.
FNA C of one or two of the most prominen t nodule s in each thyroi d
lobe would be reasonable.
In studies comparing preoperative cytodiagnosis with histopathologic diagnosis ,
the predictiv e valu e of benign , malignan t and indeterminate
cytodiagnosis averaged 94%, 96% and 73% respectively. 35
RADIOGRAPHY:
Chest and thoracic inlet radiographs are only necessary when there is clinical
evidence of tracheal deviation or compression or retrosternal extension.
This is helpful to diagnose the position of the trachea whethe r
displaced or narrowed . Straigh t X- ray is also helpfu l in
diagnosing retrosterna l goitre.34

37 ULTRASOUND:
It has a value to differentiate between solid and cystic swellings. It also
demonstrate s impalpabl e nodules . But its valu e to diagnos e malig nancy is
limited.
Sonography demonstrates in some patients that a single, clinically palpable nodule
is one of many sonographically visible nodules is of the most likely diagnosi s in
Multinodula r Goitre . The clinica l differentiatio n is important since
the risk of cance r is less in Multinodula r Goitre .36
Recen t data sugges t that 50% of patient s with a singl e nodul e have
other nodule demonstrated by careful USG. 37

CT AND MRI:
Thes e newe r method s have not yet prove d themselve s very helpfu l in
detectin g da y- to- day thyroid disorders. These are still in the experimental
stage.34

THYROID AUTO – ANTIBODIES:
Seru m titre s of antibodie s agains t thyroi d peroxidas e and thyroglobulin are
useful in determining the cause of thyroid dysfunction and swellings. Autoimmune
thyro iditis may be associated with thyroid toxicity, failure or euthyroid
goitre. Titres of greater than 1:100 are considered significant but a proportio n of
patient s with histologica l evidenc e of lymphocyti c (auto immune)
thyroiditis is seronegative.

38 INDIRECT LARYNGOSCOPY:
To determin e the mobilit y of the voca l cord s is widel y used
preoperatively, although usually for medicolegal rather than clinical reasons. To
see the condition of the vocal cords to exclude injury to the Recurrent
Laryngeal Nerve during operation . So laryngoscop y shoul d also be
performed jus t after operation . Only in 3% of case s there may be
symptomles s cord paralysis. These cases are to be segregated from
cord paralysis due to Recurren t Laryngea l Nerv e injur y durin g
operatio n by Laryngosco py preoperatively . 32

CORE NEEDLE BIOPSY :
This is done unde r local anaesthesi a is occasionall y of valu e in
establishing diagnosis in patients with a large often hard and fixed mass in
the neck frequentl y on the basis of anaplasti c carcinom a or t
hyroid lymphoma. Core biopsy produces a small cylinder of tissue which is
subjected to histopathological examination because of the caliber of the needle and
the consequen t hemorrhage , haematoma , perforatio n of Trache a and
damag e to Recurren t Laryngea l Nerve.38

39 TREATMENT
Ther e are three main approache s to the treatmen t of this condition.
MEDICAL RADIOIODINE SURGERY
Non specific measures such as rest, sedation and ß adrenergic blockers are
helpfu l to treat this condition.
Indication s for therap y inpatient s with multinodula r goitr e including
hyperthyroidism.
1. Compression symptoms attributed to the goiter.
2. Cosmetic concerns of patient.
3. Concer n abou t malignanc y base d on the history , examinatio n and
fine needle aspiration cytology.
4. Recen t growth.
MEDICA L TREATMEN T
Levothyroxin suppressio n therapy
The use of thyroi d hormon e in suppressio n of multinodula r goitr e is
controversial . Thyroi d hormon e prescribe d in an attemp t to revers e or
prevent thyroi d growt h by suppressin g TSH' s direc t thyrotrophi c
effec t and any indirect permissive effect on other growth factors such as
epidermal growth factor . The goal of suppressio n therap y is a serum TSH
level in the low norma l range . Furthe r TSH suppressio n is not
recommended , in orde r to avoid possible untoward side effects of subclinical
hyperthyroidism. A modest dose of levothyroxine (100 fig) is usually adequate,
but monitoring of the serum TSH is recommende d to determin e dosag e
adequacy . Both levothyroxin e and levotriiodothyronin e are equall y
effectiv e in suppressin g TSH levels but the forme r is preferre d becaus e
of its much longe r half life, whic h render s it potentiall y less toxic and
aids in ease of patien t use. Patien t complianc e with therapy is important,
because multinodular goitre growth resumes if treatment is interrupted or
discontinued.39

40 Antithyroi d drug therap y
T he reporte d succes s of long- term antithyroid drug use in the treatment of
toxic multinodular goitre is extremely poor. Of the 41 patients studied by Van
Soestberge n and colleague s41 , 39(95 percent) developed recurrent
hyperthyroidis m followin g cessatio n of antithyroid drug therapy. The
mean time of relaps e was 5.2 month s with 95 percen t relaps e occurrin g
withi n the firs t year . Becaus e prolonge d antithyroi d drug therap y in patient s
with toxic multinodular goitre seldom results in permanent remission and reco
mmended only as adjunctive therapy when needed for the initial control of
hyperthyroidism . The preponderanc e of the evidenc e suggest s that it is
not helpfu l to use combine d antithyroi d drug- thyroxin e therap y to
enhanc e the chance of remission. 42
Radioiod i ne therap y and toxic multinodula r goiter
The clinical utility of radioiodine therapy in the management of toxic multinodular
goitre is well established. So as not to skew the results of reported successful
radioactive iodine therapy in patients with toxic multinodula r goitre ,
however , one must be carefu l to separat e patient s with multinodular goitre
from patients with diffuse goitre5 , Graves ' disease , and singl e toxic
adenoma . In addition , thyroi d size and nodularit y are assessed only by
palpatio n in many s tudies , and other s do not clearl y defin e the
duration of follow up in assessing response to radioactive iodine therapy.
Nevertheless, a large number of patients with toxic multinodular goitre
eventuall y achieve d a 92 per cent euthyroi d succes s rate follow ing
treatment with modes t dose s of radioactiv e iodin e (25 milli Curie s of
I131 of less); others have reported similar (70 percent to 88 percent) results.40
In patients with toxic multinodular goitre studied by Jensen and colleagues
(estimated average gland weigh t by palpatio n 61 g), the mean radioactiv e
iodin e treatmen t dose was 37 mCi of I131 , whic h yielde d a 57 percent
probability that the patients would become euthyroid after one year. Twen t y- five
per cent of these patients required a second radioactive iodine treatmen t
withi n the first year for persisten t hyper – thyroidism . A statistically
significan t associatio n was not seen betwee n successfu l treatmen t of
hyperthyroidism and estimated gland size or radioactive iodine dose

41 administered per gram tissue. Although some authors report only a 3 per cent
to 7 per cent persistenc e rate for hyperthyroidis m when a much
large radioactiv e iodin e dose is used , this has not been observe d by others .
Thus in treatin g patient s with a large toxic multinodula r goitr e surg e ry
is preferred over radioactive iodine therapy, because of the more rapid
resolution of hyperthyroidism.40

Alcoho l sclerotherap y :
In use for the last few years mainl y in Italia n center s in solitar y hot or
toxic nodule s and solitar y cyst, alcoho l sclerotherap y coul d theoreticall y
be used in Multinodular Goitre. The drawbacks are related to pain risk
of Recurren t Laryngea l Nerv e damag e and the possibilit y of
extrathyroidal fibrosis complicating subsequent surgery.

Radioiodin e therap y and nontoxi c multinodula r goitre
Surgica l excisio n is preferre d in patient s with nontoxi c multinodular
goitre when treatment is necessary to address compression symptoms or
cosmeti c concerns . If, however , the surgica l risk, is high or if patien t refuses
surgery, radioactive iodine therapy is a reasonable alternative. In two studies using
RI to treat multinodu lar goitre causing compression symptoms, median
reductio n in thyroi d volum e was 40% and 60% after one year and two years,
respectively . As with radioactiv e iodin e treatmen t of toxic multinodular
goitre, there is no relationship between initial goitre size and thyroi d volume
reduction . Althoug h it is not uncommo n to see an initia l increas e in
thyroid volume at one month after radioactive iodine therapy, treatment does not
aggravate obstructive symptoms 44 .

SURGER Y :
Argumen t for routin e remova l of nodula r goite r :

42 This subject supports the view that the incidence of malignancy among the no
n- toxic MNG is quite high and the most or all such goite r shoul d be
removed as soon as they are detected, because of the risk of cancer. It has
been claime d that many lives coul d be save d by systemati c searc h for
the remova l of nodula r goiter s base d on the followin g co nsideration.
a. Many surgical centres throughout the world have statistics, indicating that
4- 17% of all non- toxic goite r remove d were malignant.
b. Even though nodular goiter may be benign at the time of detection, it is
likel y to becom e malignan t later and sho uld therefore be removed as
cancer prophylaxis. Lahe y state d that prophylaxi s remova l of all discret e
nodule s woul d do much to lower, if not abolish the occurrence of thyroid
cancer. This history of pre- existing nodular goiter often of long duration was e
licited in many series of thyroid cancer. Some authors cited the individual
history of patient with quiescent benign nodular goiter, which began to grow
rapidly , and prove d to be thyroi d carcinoma.Soka l state s45 that some
nodules might be malignant fro m the start for whic h serie s of
histopathologica l studie s durin g ever y stage of evolutio n of th e goite r
may be helpfu l to come near to conclusio n and to find out that the
histopathologica abnormality is the earlier stages to predict malignanc y later.46
Vini L and associates reported that differentiated thyroid cancer found
incidentally at surgery for hyperthyroidism has a good prognosis.

Argumen t agains t remova l of nodula r goit re :
The selectio n of statistic s from the centr e is highl y selectiv e and is not
representativ e of populatio n in general. Nodula r goitr e is quite commo n
in endemi c areas but the thyroi d cancer is rare. Clinicall y correc t
diagnosi s may be made betwee n benig n and possibly malignan t swellings.
Benig n goiter s rarel y underg o malignan t transformation and there is no
assuranc e that surger y will preven t the thyroi d cancer.

43

MANAGEMEN T OF CAS E OF MULTINODULA R GOITRE

MNG
NON – TOXI C TOXIC (Normal TSH)
( TSH , T3 /T4 )

FNA C I131 SURGERY

BENIG N SUSPICIOUS/MALIGNAN T

LT4 O BSERVATION SURGERY

SURGERY OF THE THYROID GLAND:

44 Bliss R state d that surger y in elderl y patient s is as safe as in younger
patient s with no increas e in morbidity . Benig n MNG is the most
common indicatio n for surgery .

47 Followin g are the operat ions done in non- toxic and toxic MNG :
Managemen t of patient s with MNG band on thyroi d functio n (serum
TSH , T4/T4 ) and thyroi d fine needl e aspiratio n cytology.

I)Subtotal Thyroidectomy :
It is a standar d operatio n undertake n for toxic MNG . Approximately
7/8th hyperplastic gland is removed retaining the posterior margin in order to
maintain a euthyroid level and to protect the parathyroid gland the recurrent
laryngea l nerve.
The care of no n- toxic goiter, it is advisable to leave an amount equal to a
norma l gland. Only the enlarged amount is resected.
Contraindication : Subtota l thyroidectom y is contraindicate d in person s
with thyrotoxic congestive cardiac failure. Particularl y when cardia c
reserv e is low and the goite r is smal l and adheren t such patient s are
recommended radioiodine therapy. It is also contraindicate d in
ophthalmoplegia , for rapid reductio n of the toxic stage may worse n the eye
conditio n and at least 6 month s contro l by anti – thyroid drugs such as
carbimazole should be under taken before subtota l thyroidectomy can be safely
performed.
II) Near total thyroidectomy . Total Thyroidectomy :
The reporte d incidenc e of nodula r recurrenc e followin g subtotal
thyroidectom y for MNG rang e from uncommo n is 10% . Kraim p
and colleague s reporte d that following subtotal thyroidectomy recurrent
nodularity develope d in 25 to 735 (3.4% ) patient s with MNG . 25%
of nodular recurrence s occurre d in each follo w up perio d of 0- 5 year s
and 5- 10 years. 50% of patient s with recurrenc e had so more than 10 year s
after surgery . Immediatel y post operativ e thyroi d hormon e therap y may
have delayed , but did not prevent recurrence and once post operative nodule
recurrence was documente d thyroi d hormon e treatmen t did not inhibi t
furthe r growth . 48 Most likel y the best prevent ion of recurrent post operative

48 MNG is near total thyroidectomy. The experience hands complications of
total thyroidectomy are no different from those of subtotal thyroidectomy. 49

Operation Steps in Surgery :
Preparatio n of the patien t – the fitnes s for t he surger y is decide d by the
statu s of the hemoglobin , cardiovascula r condition , respirator y syste m
as usua l oral hygien e is improve d to avoi d post operativ e respiratory
complications.
When the patient is toxic, the toxicity must be brought down to the euthyroi d state
befor e surger y eithe r by sedatio n alon e or in combinations with anti –
thyroi d drug s carbimazol e 30- 40 mg/day in divided doses until toxicity
comes down and followed by 5mg every 8th hourl y as maintenance does .
The respons e to the treatmen t is assesse d by subjectiv e improvemen t of
the symptoms , slowin g of the pulse rate and thyroi d profil e tests .
Iodides alon e are not advocate d but some prefe r to add Lugol’ s to
carbimazol e 10 day s prior to surgery . Propranolo l may be used alon g
with carbi mazol e in the management of very severe toxicity and to reduce
the length of pre operative preparation.
Anaesthesi a :
At present , the most preferre d anaesthesi a is genera l anaesthesia.
Pethidin e 100mg , Phenerga n 25m g and atropin e 0.6m g are give n one
hour befor e surger y as premedication . Inductio n of anaesthesi a is by mean s
of Pentotha l sodiu m intravenousl y and after scolin e (50mg ) is
injected. Intubation is done and anaesthesia is maintained with nitrous oxide
and oxygen.
Patien t is in supin e positio n and the neck is made prominent by its extension .
The extensio n can be obtaine d by placin g a sandba g or a cushion unde r
the shoulde r blades . The neck is thus extende d and head rose
sufficiently to prevent venous engorgement and ring to support the head.
Towelin g :

49 In order that the anaesthetist can perform laryngoscopy during operation ,
the swellin g must be so arrange d as to allow his access momentaril y
to remov e the endotrachea l tube and immediatel y to replac e it with
laryngoscope without contaminating t he wound area.

SUBTOTA L THYROIDECTOM Y :
Skin Incision and Raising the Flaps
The skin incision can be marked by pressing a length of thread on to the
skin befor e using the scalpe l keepin g in the of skin creas e 2- 3cms
abov e the sternum . The colla r (Kocher ’ s) incisio n is then made ,
extendin g to the lateral borders of the two sternocleidomastoid muscle. With
larger goiters the incisio n is made little highe r up. In orde r to give a neat
scar, the platysm a is divide d at a slightl y highe r level than the skin. The
flaps of skin, superficial fasci a and platysm a are divide d at a slightl y highe r
level than the skin. The flaps of skin, superficial fascia and platysma are then
reflected upwards to the level of the thyroi d cartilag e and downward s to
the sternum . Skin edge s are held wide apart. The anterior jugular veins are
divided between ligatures.

Exposur e of the thyroi d gland
The investin g layer of deep fasci a is incise d verticall y in the midline.
Any anastomosin g vein s bein g secure d and the interva l betwee n the
infra thyroi d muscl e is opene d to expos e the sheat h of pretrachea l fasci a
covering the glands if additional exposure is necessary then the infrahyoid
muscles are sectione d abou t an inch abov e the skin incision . The
pretrachea l fasci a is now incise d and finge r is passe d over front of each
lobe to ascertai n its size and extent . As a rule, large r lobe is dealt with
first and by retractio n of the infrahyoid muscle and fascial sheath the greater
part of its anterior surface is exposed.

50 Thyroi d Dissectio n:
The latera l surfac e of the lobe is cleare d by finge r durin g this
procedure . Middl e thyroi d vein if presen t is divide d betwee n ligatures .
The inferio r thyroi d vein , whic h form s a venou s plexu s anterio r to the trache a
is carefull y dissected . The muscle s are retracte d strongl y in an upwar d
and latera l directio n and the uppe r pole if the glan d is delivere d at the
wound. When the vascular superior thyroid pedicle becomes apparent this is
divided betwee n ligature s with a doubl e ligature s to the uppe r stum p
preferably.
A finge r is swep t aroun d the lowe r pole , whic h is delivere d forwards,
after the inferio r thyroi d vein s are secured . The lobe is draw n forward s
and medially and search is made behind it for the inferior thyroid artery.
Thus vessel should be ligated well away from the gland in order to prevent
injury to the recurren t laryngea l nerve . The arter y is ligate d in continuity.

Excision of the Gland :
Afte r takin g the decisio n abou t the amoun t of glan d tissu e to be left
behind , severa l pairs of arter y forcep s are applie d to the capsul e of the
lobe in its postero – latera l aspec t alon g the line of propose d position . The
lobe is then sectione d from latera l to media l side, in a place toward s
the front of the trachea.
The opposit e lobe of the glan d is then treate d in a simila r manner , an
equa l amoun t of the glan d tissu e bein g left behind . All hemorrhag e
points bein g arreste d eithe r by fine ligature s or by diatherm y
coagulation . The woun d is close d in layers , first the deep cervica l
fascia , then platys ma and finally skin. Usually drain is kept deep to the deep
cervical fascia.
Mattioli found that subtotal thyroidectomy is adequate intervention for
multinodular goiter, as long as the number of clinical recurrence is not
significantl y high . 50

51 HEMITHYROI D ECTOM Y :
The lobe of thyroid gland is mobilized as in the first stage of subtotal operation. It
is particularly important to trace the recurrent laryngeal nerve through out its
course and to divide the branches of inferior thyroid artery withou t damagi ng
the nerve . Ligature s of arter y in continuit y is not required, but it may
help in the avoidanc e of damag e to the nerv e by reducing
hemorrhag e as branche s of the arter y are divide d close to the
nerve. Parathyroid s are presente d preferabl y with their bloo d supply .
The entire thyroi d lobe is then remove d togethe r with isthmu s and a
thin sleev e of opposite lobe to give a better cosmetic result (Taylor 1969).
The wound is close d in the manne r describe d for subtota l thyroidectomy.

TOTAL THYROIDECTOMY :
Tota l follow s the techniqu e describe d abov e excep t that the entir e gland
is remove d from one tracheoesophagea l groov e to the other . The
technique of this procedur e is essentiall y a bilatera l versio n of
hemithyroidectomy . If it is not possibl e to preserv e parathyroi d gland s
intact , it is preferabl e to implant them within the sternocleidomastoid muscle
rather than to remove them completely. Total thyroidectomy may be successful in
effecting cure of carcinoma, and should be advocated in those cases where
the growth is sufficiently mobile or if tumour is found in one of the lymphnodes
outside the thyroid (Hurgreaves, 1981).52If the tumou r s f papillar y type
and is confined to one lobe, lobectomy with removal of isthmus is usually
sufficient. Dissectio n of lymp h node only is carrie d out when they are
involve d by tumour. The discovery of isolated lymph node metastasis from a
carcinoma of the thyroid which is undetectable clinically (lateral aberrant
thyroid) requires total of near total hyroidectom y combine d with removal of
laterally placed nodes especially n the younger patients (Frankenthaler 1990).53
Khadra M and associates stated that in view if the risks of reoperative surgery, total
thyroidectomy should be considered the operation of choice for most benig n
diseases affecting the whole thyroid gland such as multinodular goiter,
thyroiditi and goiters affected by thyrotoxicosis.54

52
NEA R TOTA L THYROIDECTOM Y:
Surgeon s who are uncomfortabl e performin g total thyroidectom y can
decrease their patients risk of hypopara thyroidis m and recurren t laryngeal
nerv e injur y by using procedur e designe d to minimiz e dissectio n in the
contralateral tracheoesophageal groove. Near total thyroidectomy minimizes
dissectio n becaus e it leave s a few gram s if thyroi d tissu e alon g the
posterior aspect of the contralateral lobe. If near total thyroidectomy is
performed, no more than 25% of one lobe (approx 2gm) remains. The surgeon
may decide to perfor m a near total thyroidectom y routinel y in situation s
of relative indication s for total thyroidectomy and possibly in selected
situations in which precise anatomic dissection is technically difficult.

TREATMENT OF RETROSTERNAL GOITRE:
If obstructiv e symptom s are presen t in associatio n with thyrotoxicosis i t
is unwis e to treat a retrosterna l goitre with antithyroi d drug s or
radioiodin e as these may enlarge the goitre. Most common substernal goitres
arise from the thyroi d lobe . 55 Resection can almost always be carried out
from the neck and a midline sternotomy is hardly ever necessary. The cervical
part of the goitr e shoul d first be mobilize d by ligatio n and divisio n of
the superior thyroid vessels, and by ligature and division of the middle thyroid
veins and the inferio r thyroi d artery . The retrosterna l goitr e can then be
delivere d by tractio n and finger mobilization. Haemorrhage is rarely a
problem because the goitr e takes its bloo d suppl y with it from the
neck . The recurrent laryngeal nerve should be identified if possible
before delivering the retrosternal goiter, as it may be abnormally
displaced and particularly vulnerable to injury from traction or tearing. If
a large multinodu lar goitre canno t be delivere d intac t from the retrosterna l
positio n it may be broken with the fingers and* delivered piecemeal, but
this should never be done if the lesion is solitar y and there is the possibilit y
of carcinoma . Armou r and Colleagues,56 describe d morcellemen t can
be a mess y proces s and partial claviculectomy offers an easier method
while removing difficult retrosternal goitre through the standard approac h to

53 the thyroid gland. This technique was helpful in an obese patient with a large
retrosternal extension of the goitre.

TREATMEN T OF TOXI C MULTINODULA R GOITR E IN
PREGNANCY:
Thyroi d diseas e durin g pregnanc y is a significan t issue , especially
becaus e the incidence of autoimmune disease of the thyroid approaches 10%
in women . 57
A retrospective study suggested that the increased prevalence of thyroid nodules
among women may be related to pregnancy. The prevalence of nodular
disease is detected by USG, was three time s as high in woma n who ha d
experienc e at least one pregnanc y compare d with wome n who had never
been pregnant.
The evaluatio n of thyroi d nodul e discovere d durin g pregnanc y is
simila r to that of the non pregnan t patient . Nodule s with benig n cyt
olog y should be observed and followed by an endocrinologist.
If the FNAC is consistent with thyroid cancer surgery is recommended. Som e
expert s recommen d operatin g durin g the 2nd trimeste r befor e 24 week s
of gestatio n to minimiz e the risk of miscarriage . S ome expert s advocate
postponin g definitiv e surger y until after deliver y in most patients.
Radioiodine is absolutely contraindicated because of the risk to the foetus.58
The danger of surgery is miscarriage; and that of antithyroid drugs is of
inducing thyroid insufficiency in the mother, of the baby being born goitrous
and hypothyroid.

POS T OPERATIV E COMPLICATIONS
1. Haemorrhage:
A tension haematoma deep to the cervical fascia is usually due to slippin g
of a ligatur e on the superio r thyroi d artery : occasio nally haemorrhage

54 from a thyroid remnant or a thyroid vein may be responsible. It may, on rare
occasions, be necessary to open the wound in the ward to relieve tension before
taking the patient to theatre to evacuate the haematoma and to tie off a bleeding
vessel . 18
2. Respira t ory obstruction:
Suffocatio n from laryngea l obstructio n is the most seriou s immediate
complicatio n of thyroidectomy . Surgeon s woul d probabl y agre e that any
death from this cause could be avoided if the obstruction were relieved sooner.
Lahe y and Hoove r wro te: 'In practicall y ever y case in whic h the patien t
dies after a tracheostomy, which has been done to relieve obstruction to breathing
followin g thyroidectomy , one can say that the patien t woul d have lived
and been a normal individual had the tracheostomy been done earlier' . They
emphasize d that the time when tracheostom y ough t to be performe d is
the moment at which the surgeon first considers it. racheostomy in his conditio n
is almos t alway s temporary . Abde l Rahi m and colleagues,59 conclude d if
four or more of the predictiv e factor s for post- operative respiratory
embarrassment like goitre for more than 5 years, preoperative RLN palsy ,
significan t trachea l narrowin g and/o r deviation , retrosternal extension ,
difficul t endotrachea l intubatio n and thyroi d cancer are present , a planned
tracheostomy at the completion of the thyroidectomy should be considered.
The four main causes of obstruction may occur alone or together: an expanding
haematoma in the neck; laryngeal oedema; vocal cord paresis; collapse of the
trachea . This is very rarel y due to collaps e or kinkin g of the trachea. Most
cases are due to laryngeal oedema. The most important cause of laryngeal
oedema is a tension haematoma. However, trauma to the larynx by anaesthetic
intubation and surgical manip ulatio n is an important contributor y facto r
particularl y if the goitr e is very vascula r and may cause laryngeal oedema
without a tension haematoma. Unilateral or bilateral recurrent nerve paralysis
will not cause immediate postoperative respiratory obstr uct ion unles s laryngea l
oedem a is also present , but they will aggravate th e obstruction.
3. Recurren t laryngea l nerv e paralysi s
This may resul t from pressur e on the nerv e by bloo d clot or by oedema
in which case recovery can be anticipated. It may be unilateral or bilateral,

55 transien t or permanent . Transien t paralysi s occur s in abou t 3 per cent
of nerve s at risk and recovers in three weeks to three months.
Permanent paralysis is extremely rare if the nerve has been identified at
operation.
Loss of functio n can be cause d by transection , ligation , traction , or handlin g
of the nerve . In unilatera l recurren t nerv e injuries, the voic e usually becomes
husky because the vocal cords do not approximate one another. The voca l cord on
the side of the nerv e injur y is paralyzed , since the recurrent laryngeal nerve
innervates all of the muscles of the larynx except the cricothyr o id
muscle . Usually , voca l cord functio n return s withi n 6 to 9 months .
If no functio n return s by that time , the voic e can be improved , if necessary ,
by injectio n of the paralyze d voca l cord with collage n or Teflon, whic h
usuall y help s to bring it to the mid line. Ofte n the functionin g cord will
compensat e by approximatin g the paralyze d one, in whic h case the voic e
will b e good and no treatmen t is necessary.
Bilatera l recurren t laryngea l nerv e damag e is much more serious
becaus e both voca l cord s can assum e a median or paramedia n
position, resulting in airway obstruction and difficulty with respiratory toilet.
Often, tracheostomy is required. Later the glottic aperture can be widened by
arytenoidectom y or arytenoidop exy, whic h displace s the voca l cord
laterally. While this improves the airway, the voice deteriorates. The
advantage is that the tracheostomy can be removed.
4. Tracheomalaci a
Tracheomalaci a is a complication of very large goiters and is therefore Seldo m
encountere d in surgica l practic e in the develope d world . It presents
with trachea l collaps e after thyroidectom y when it is recognized
intraoperatively . An electiv e temporar y tracheostom y for airwa y
obstruction during post operative per iod may be necessary . 60
5. Externa l laryngea l nerv e injury
Injur y to the externa l branc h of the superio r laryngea l nerv e is not as
serious as a recurrent laryngeal nerve injury. It should be avoided, however,
becaus e it result s in a limitatio n of the force o f projectio n of one’ s voic e

56 and impairs a singer's high tones. Not infrequently these disorder improve
during the first three month s after thyroidectomy . 18
6. Thyroi d insufficienc y
This usuall y occur s withi n two years , but it is sometime s delaye d five
years or more . It is often very insidiou s and difficul t to recognize . The
incidenc e is considerabl y highe r than used to be though t and figure s of
20- 45 pe r cent have been reporte d after operation s on diffus e toxic
goitre s or toxic nodula r goitre s with internodul ar hyperplasia.18
7. Parathyroi d insufficiency
This is due to removal of parathyroid glands, or infarction through damag e
to the parathyroi d end – artery; often both factors occur together. Vascular
injury is probably a more important than inadvertent removal. The incidenc e of
this conditio n shoul d be less than 0.5 per cent and most cases presen t
dramaticall y 2- 5 days after operation , but very rarel y the onse t is
delaye d for 2- 3 weeks or patient with marked hypocalcaemia is asymptomatic.
Devascularizatio n can be minimize d durin g thyroi d lobectom y by carefully
ligating the branches of the inferior thyroid artery on the thyroid capsule
dista l to their suppl y of the parathyroi d gland s and by treatin g the
parathyroid with great care. If a parathyroid gland is recogni zed to be
nonviabl e during operation , after identificatio n by froze n section , it can
be autotransplante d at that time . The glan d is mince d into 1- to 2- mm
cubes and placed into pockets in the sternocleidomastoi d muscle.

8. Thyrotoxi c crisi s (Thyroi d storm)
It is an acute exacerbatio n of hype rthyroidism. It occurs if a thyrotoxic
patient has been inadequately prepared for thyroidectomy, and is now
extremely rare. It is thought to be due to excessive release of thyroid
hormones into the circulation when the thyroid is handled during surgery. It is
characterized by tachycardia, hyperpyrexia, de hydration, delirium and cardiac
failure. It is treated by mechanical cooling of the body, oxygen inhalation,
intravenous fluids, diuretics for cardiac failure, digoxin for uncontrolled atrial
fibrillation, sedation and intravenous hydrocortisone. Specific treatment is by

57 Carbimazole 10- 20m g 6 hourly , Lugol' s iodin e 10 drop s 8 hourl y by mout h
or sodiu m iodid e lgm, intravenously . Propranolo l 40 mg 6 hourl y orall y
will bloc k advers e beta adrenergi c effects . This agen t may be give n by
careful intravenous administration (1 – 2mg) under precise
electrocardiographic control . 18
9. Woun d infectio n
A subcutaneou s or deep cervica l absces s may form and they shoul d be
drained.18 Incidenc e of Woun d Infectio n is almos t simila r to any othe r
operation ; this has been extensively reduced by achieving proper hemostasis
at the site of surger y and by the use of suctio n drainag e instea d of
conventionall y used corrugate d rubbe r drain.32
10. Stitc h granuloma
This may occu r with or withou t sinus formatio n and is seen after the
use of nonabsorbable suture material. Absorbable ligatures and sutures must
be used throughout thyroid surgery. Some surgeons use a subcuticular
absorbable skin suture rather than the traditional skin clips or staples.18
11. Hypertrophi c or Keloi d Scar
This is more likel y to form if the incisio n overlie s the sternum.
Intraderma l injection s of corticosteroi d shoul d be give n at once and
repeated monthl y if necessary . 18
12. Recurren t thyrotoxicosi s
This is due to either inadequate remova l of thyroi d tissu e or subsequent
hyperplasia of the tissue that has been left. Further operation should be
avoided if possible and the administration of radioiodine may be considered
as an alternativ e to antithyroi d drugs.
13. Progressiv e or malignan t Exophthalmo s
Occasionally this may occur after operation while thyrotoxic feature
regress, exophthalmos may increas e .32
14. Tetany :

58 Damage of the parathyroid glands resulting in tetany has been repor t in
abou t 1 – 3% of case s subjecte d to thyroidectom y for thyrotoxicosis .
Majorit y of case s presen t withi n 2 to 5 days after operatio n but a few
case s may be delaye d for 2 to 3 weeks . Mostl y it is transien t recover s
spontaneously . The serum calciu m level falls and the treatmen t is
administratio n of 20 ml of 20% ca lcium gluconat e solution with some
parathormone . 32

Thyroid Cancer
Malignant (cancerous) thyroid tumors
There are several types of thyroid cancer.
Differentiated thyroid cancers
Most thyroid cancers are differentiated cancers. In these cancers, the cells look a
lot like normal thyroid tissue when seen under a microscope. These cancers
develop from thyroid follicular cells.
Papillary carcinoma: About 8 out of 10 thyroid cancers ar e papillary carcinomas
(also called papillary cancers or papillary adenocarcinomas ). Papillary

59 carcinomas tend to grow very slowly and usually develop in only one lobe of the
thyroid gland. Even though they grow slowly, papillary carcinomas often spread to
the lymph nodes in the neck. Still, these cancers can often be treated successfully
and are rarely fatal.
There are several subtypes of papillary carcinoma. Of these, the follicular subtype
(also called mixed papillary -follicular variant ) occurs most oft en. The usual form
of papillary carcinoma and the follicular subtype have the same good outlook
(prognosis) when found early, and they are treated the same way. Other subtypes
of papillary carcinoma (columnar, tall cell, insular, and diffuse sclerosing) ar e not
as common and tend to grow and spread more quickly.
Follicular carcinoma: Follicular carcinoma, also called follicular cancer or
follicular adenocarcinoma , is the next most common type, making up about 1 out
of 10 thyroid cancers. It is more common in countries where people don’t get
enough iodine in their diet. These cancers usually do not spread to lymph nodes,
but they can spread to other parts of the bo dy, such as the lungs or bones. The
outlook (prognosis) for follicular carcinoma is not quite as good as that of papillary
carcinoma, although it is still very good in most cases.
Hürthle (Hurthle) cell carcinoma, also known as oxyphil cell carcinoma , is actually
a variant of follicular carcinoma. It accounts for about 3% of thyroid cancers. The
prognosis may not be as good as that of typical follicular carcinoma because this
type is harder to find and treat. This is because it is less likely to absorb ra dioactive
iodine, which is used both for treatment and to look for the spread of differentiated
thyroid cancer.
Other types of thyroid cancers
These thyroid cancers occur less often than differentiated thyroid cancers.
Medullary thyroid carcinoma: Med ullary thyroid carcinoma (MTC) accounts for
about 4% of thyroid cancers. It develops from the C cells of the thyroid gland,
which normally make calcitonin, a hormone that helps control the amount of
calcium in blood. Sometimes this cancer can spread to lym ph nodes, the lungs, or
liver even before a thyroid nodule is discovered.

60 Medullary thyroid cancers often release too much calcitonin and a protein called
carcinoembryonic antigen (CEA) into the blood. These substances can be detected
with blood tests.
Because MTC does not absorb or take up radioactive iodine (used for treatment
and to find metastases of differentiated thyroid cancer), the prognosis (outlook) is
not quite as good as that for differentiated thyroid cancers. There are 2 types of
MTC:
Sporadic MTC, which accounts for about 8 out of 10 cases of MTC, is not inherited
(meaning it does not run in families). It occurs mostly in older adults and affects
only one thyroid lobe.
Familial MTC is inherited and can occur in each generation of a f amily. These
cancers often develop during childhood or early adulthood and can spread early.
Patients usually have cancer in several areas of both lobes. Familial MTC is often
linked with an increased risk of other types of tumors. This is described in mor e
detail in the section “What are the risk factors for thyroid cancer?”
Anaplastic carcinoma: Anaplastic carcinoma (also called undifferentiated
carcinoma ) is a rare form of thyroid cancer, making up about 2% of all thyroid
cancers. It is thought to somet imes develop from an existing papillary or follicular
cancer. This cancer is called undifferentiated because the cancer cells do not look
very much like normal thyroid cells under the microscope. This cancer often
spreads quickly into the neck and to other parts of the body, and is very hard to
treat.
Thyroid lymphoma: Lymphoma is very uncommon in the thyroid gland.
Lymphomas are cancers that develop from lymphocytes, the main cell type of the
immune system. Most lymphocytes are found in lymph nodes, whic h are pea -sized
collections of immune cells scattered throughout the body (including the thyroid
gland). Lymphomas are discussed in our separate document, Non-Hodgkin
Lymphoma .
Thyroid sarcoma: These rare cancers start in the supporting cells of the thyro id.
They are often aggressive and hard to treat. Sarcomas are discussed in our separate
document, Sarcoma: Adult Soft Tissue Cancer .

61
risk factors for thyroid cancer:
Gender and age
For unclear reasons thyroid cancers (like almost all diseases of the th yroid) occur
about 3 times more often in women than in men.
Thyroid cancer can occur at any age, but the risk peaks earlier for women (who are
most often in their 40s or 50s when diagnosed) than for men (who are usually in
their 60s or 70s).
A diet low in iodine
Follicular thyroid cancers are more common in areas of the world where people’s
diets are low in iodine. In the United States, most people get enough iodine in their
diet because it is added to table salt and other foods. A diet low in iodine m ay also
increase the risk of papillary cancer if the person also is exposed to radioactivity.
Radiation
Exposure to radiation is a proven risk factor for thyroid cancer. Sources of such
radiation include certain medical treatments and radiation fallout f rom power plant
accidents or nuclear weapons.
Hereditary conditions and family history
Several inherited conditions have been linked to different types of thyroid cancer,
as has family history. Still, most people who develop thyroid cancer do not have
an inherited condition or a family history of the disease.
Medullary thyroid cancer
About 1 out of 3 medullary thyroid carcinomas (MTCs) result from inheriting an
abnormal gene. These cases are known as familial medullary thyroid carcinoma
(FMTC). FMTC can occur alone, or it can be seen along with other tumors.
The combination of FMTC and tumors of other endocrine glands is called multiple
endocrine neoplasia type 2 (MEN 2). There are 2 subtypes, MEN 2a and MEN 2b,
both of which are caused by mutations (de fects) in a gene called RET.

62 In MEN 2a, MTC occurs along with pheochromocytomas (tumors that make
adrenaline) and with parathyroid gland tumors.
In MEN 2b, MTC is associated with pheochromocytomas and with benign growths
of nerve tissue on the tongue an d elsewhere called neuromas . This subtype is much
less common than MEN 2a.
In these inherited forms of MTC, the cancers often develop during childhood or
early adulthood and can spread early. MTC is most aggressive in the MEN 2b
syndrome. If MEN 2a, MEN 2 b, or isolated FMTC runs in your family, you may
be at very high risk of developing MTC. Ask your doctor about having regular
blood tests or ultrasound exams to look for problems and the possibility of genetic
testing.
Other thyroid cancers
People with c ertain inherited medical conditions have a higher risk of more
common forms of thyroid cancer. Higher rates of thyroid cancer occur among
people with uncommon genetic conditions such as:
Familial adenomatous polyposis (FAP): People with this syndrome dev elop many
colon polyps and have a very high risk of colon cancer. They also have an increased
risk of some other cancers, including papillary thyroid cancer. Gardner syndrome
is a subtype of FAP in which patients also get certain benign tumors. Both Gardne r
syndrome and FAP are caused by defects in the gene APC .
Cowden disease: People with this syndrome have an increased risk of thyroid
problems and certain benign growths (including some called hamartomas). They
also have an increased risk of cancers of th e thyroid, uterus, breast, as well as some
others. The thyroid cancers tend to be either the papillary or follicular type. This
syndrome is most often caused by defects in the gene PTEN . It is also known as
Multiple Hamartoma Syndrome and PTEN Hamartoma Tu mor Syndrome
Carney complex, type I: People with this syndrome may develop a number of
benign tumors and hormone problems. They also have an increased risk of
papillary and follicular thyroid cancers. This syndrome is caused by defects in the
gene PRKAR1A .
Familial nonmedullary thyroid carcinoma: Thyroid cancer occurs more often in
some families, and is often seen at an earlier age. The papillary type of thyroid

63 cancer most often runs in families. Genes on chromosome 19 and chromosome 1
are suspected of c ausing these familial cancers.
If you suspect you might have a familial condition, talk with your doctor, who
might recommend genetic counseling if your medical history warrants it.
Family history: Having a first -degree relative (parent, brother, sister, or child) with
thyroid cancer, even without a known inherited syndrome in the family, increases
your risk of thyroid cancer. The genetic basis for these cancers is not totally clear.
causes thyroid cancer:
Thyroid cancer is linked with a number of inherited conditions (described in the
section “What are the risk factors for thyroid cancer?”), but the exact cause of most
thyroid cancers is not yet known.
Certain changes in a person’s DNA can cause thyroid cells to become cancerous.
DNA is the chemical in each of our cells that makes up our genes – the instructions
for how our cells function. We usually look like our parents because they are the
source of our DNA. But DNA affects more t han just how we look. It also can
influence our risk for developing certain diseases, including some kinds of cancer.
Some genes contain instructions for controlling when our cells grow and divide
into new cells. Certain genes that help cells grow and div ide or make them live
longer than they should are called oncogenes . Other genes that slow down cell
division or make cells die at the right time are called tumor suppressor genes .
Cancers can be caused by DNA changes that turn on oncogenes or turn off tumo r
suppressor genes.
People inherit 2 copies of each gene – one from each parent. We can inherit
damaged DNA from one or both parents. Most cancers, though, are not caused by
inherited gene changes. In these cases, the genes change during a person’s life.
They may occur when a cell’s DNA is damaged by something in the environment,
like radiation, or they may just be random events that sometimes happen inside a
cell, without an outside cause.
Papillary thyroid cancer
Several DNA mutations (changes) have be en found in papillary thyroid cancer.
Many of these cancers have changes in specific parts of the RET gene. The altered

64 form of this gene, known as the PTC oncogene, is found in about 10% to 30% of
papillary thyroid cancers overall, and in a larger percent age of these cancers in
children and/or linked with radiation exposure. These RET mutations usually are
acquired during a person’s lifetime rather than being inherited. They are found only
in cancer cells and are not passed on to the patient’s children.
Many papillary thyroid cancers have a mutated BRAF gene. The BRAF mutation is
less common in thyroid cancers in children and in those thought to develop from
exposure to radiation. Cancers with BRAF changes tend to grow and spread to other
parts of the bod y more quickly.
Both BRAF and RET/PTC changes are thought to make cells grow and divide. It is
extremely rare for papillary cancers to have changes in both the BRAF and
RET/PTC genes. Some doctors now advise testing thyroid biopsy samples for these
gene mutations, as they can help diagnose cancer and may also affect the patient’s
outlook (see “How is thyroid cancer diagnosed?”).
Changes in other genes have also been tied to papillary thyroid cancer, including
those in the NTRK1 gene and the MET gene.
Follicular thyroid cancer
Acquired changes in the RAS oncogene have a role in causing some follicular
thyroid cancers.
Anaplastic thyroid cancer
These cancers tend to have some of the mutations described above and often have
changes in the TP53 tumor supp ressor gene and the CTNNB1 oncogene as well.
Medullary thyroid cancer
People who have medullary thyroid carcinoma (MTC) have mutations in different
parts of the RET gene compared with papillary carcinoma patients. Nearly all
patients with the inherited form of MTC and about 1 of every 10 with the sporadic
(non-inherited) form of MTC have a mutation in the RET gene. Most patients with
sporadic MTC have gene mutations only in their cancer cells. Those with familial
MTC and MEN 2 inherit the RET mutation from a parent. These mutations are in
every cell of the patient’s body and can be detected by testing the DNA of blood
cells.

65 In people with inherited mutations of RET, one RET gene is usually normal and
one is mutated. Because every person has 2 RET genes but passes only one of them
to a child (the child’s other RET gene comes from the other parent), the odds that
a person with familial MTC will pass a mutated gene on to a child are 1 in 2 (or
50%).
Signs and symptoms of thyroid cancer
Prompt attention to signs and symptoms is the best way to diagnose most thyroid
cancers early. Thyroid cancer can cause any of the following signs or symptoms:
A lump in the neck, sometimes growing quickly
Swelling in the neck
Pain in the front of the neck, s ometimes going up to the ears
Hoarseness or other voice changes that do not go away
Trouble swallowing
Trouble breathing
A constant cough that is not due to a cold
If you have any of these signs or symptoms, talk to your doctor right away. Many
of th ese symptoms can also be caused by non -cancerous conditions or even other
cancers of the neck area. Lumps in the thyroid are common and are usually benign.
Still, if you have any of these symptoms, it’s important to see your doctor right
away so the cause can be found and treated, if needed.
Diagnosis:
Thyroid cancer may be diagnosed after a person goes to a doctor because of
symptoms, or it might be found during a routine physical exam or other tests. If
there is a reason to suspect you might have thyroid cancer, your doctor will use one
or more tests t o find out. Signs and symptoms might suggest you have thyroid
cancer, but you will need tests to confirm the diagnosis.
Medical history and physical exam
If you have any signs or symptoms that suggest you might have thyroid cancer,
your health care profe ssional will want to know your complete medical history.

66 You will be asked questions about your possible risk factors, symptoms, and any
other health problems or concerns. If someone in your family has had thyroid
cancer (especially medullary thyroid cance r) or tumors called pheochromocytomas ,
it is important to tell your doctor, as you might be at high risk for this disease.
Your doctor will examine you to get more information about possible signs of
thyroid cancer and other health problems. During the ex am, the doctor will pay
special attention to the size and firmness of your thyroid and any enlarged lymph
nodes in your neck.
Biopsy
The actual diagnosis of thyroid cancer is made with a biopsy, in which cells from
the suspicious area are removed and loo ked at under a microscope. However, this
might not be the first test done if you have a suspicious lump in your neck. The
doctor might order other tests first, such as blood tests, an ultrasound exam, or a
radioiodine scan to get a better sense of whether you might have thyroid
cancer.biopsy is done by fine needle aspiration (FNA).
Imaging tests
Imaging tests may be done for a number of reasons, including to help find
suspicious areas that might be cancer, to learn how far cancer may have spread,
and to h elp determine if treatment is working.
People who have or may have thyroid cancer will get one or more of these tests.
Ultrasound
Ultrasound uses sound waves to create images of parts of your body. For this test,
a small, wand -like instrument called a transducer is placed on the skin in front of
your thyroid gland. It gives off sound waves and picks up the echoes as they bounce
off the thyroid. The echoes are converted by a computer into a black and white
image on a computer screen. You are not exposed to radiation during this test.
This test can help determine if a thyroid nodule is solid or filled with fluid. (Solid
nodules are more likely to be cancerous.) It can also be used to check the number
and size of thyroid nodules. How a nodule looks on ult rasound can sometimes
suggest if it is likely to be a cancer, but ultrasound can’t tell for sure.

67 For thyroid nodules that are too small to feel, this test can be used to guide a biopsy
needle into the nodule to obtain a sample. Even when a nodule is lar ge enough to
feel, most doctors prefer to use ultrasound to guide the needle.
Ultrasound can also help determine if any nearby lymph nodes are enlarged
because the thyroid cancer has spread. Many thyroid specialists recommend
ultrasound for all patients with thyroid nodules large enough to be felt.
Radioiodine scan
Radioiodine scans can be used to help determine if someone with a lump in the
neck might have thyroid cancer. They are also often used in people who have
already been diagnosed with different iated (papillary, follicular, or Hürthle cell)
thyroid cancer to help show if it has spread. Because medullary thyroid cancer cells
do not absorb iodine, radioiodine scans are not used for this cancer.
For this test, a small amount of radioactive iodine (called I-131) is swallowed
(usually as a pill) or injected into a vein. Over time, the iodine is absorbed by the
thyroid gland (or thyroid cells anywhere in the body). A special camera is used
several hours later to see where the radioactivity is.
For a thyroid scan , the camera is placed in front of your neck to measure the amount
of radiation in the gland. Abnormal areas of the thyroid that have less radioactivity
than the surrounding tissue are called cold nodules , and areas that take up more
radiation are called hot nodules . Hot nodules are usually not cancerous, but cold
nodules can be benign or cancerous. Because both benign and cancerous nodules
can appear cold, this test by itself can’t diagnose thyroid cancer.
After surgery for thyroid cancer, w hole-body radioiodine scans are useful to look
for possible spread throughout the body. These scans become even more sensitive
if the entire thyroid gland has been removed by surgery because more of the
radioactive iodine is picked up by any remaining thyr oid cancer cells.
Radioiodine scans work best if patients have high blood levels of thyroid –
stimulating hormone (TSH, or thyrotropin). For people whose thyroid has been
removed, TSH levels can be increased by stopping thyroid hormone pills for a few
week s before the test. This leads to low thyroid hormone levels (hypothyroidism)
and causes the pituitary gland to release more TSH, which in turn stimulates any
thyroid cancer cells to take up the radioactive iodine. A downside of this is that it

68 can cause th e symptoms of hypothyroidism, including tiredness, depression,
weight gain, sleepiness, constipation, muscle aches, and reduced concentration.
Another way to raise TSH levels for a scan is to give an injectable form of
thyrotropin (Thyrogen®) before the sc an, which does not require withholding
thyroid hormone.
Because any iodine already in the body can affect this test, people are usually told
not to ingest foods or medicines that contain iodine in the days before the scan.
Radioactive iodine can also be used to treat differentiated thyroid cancer, but it is
given in much higher doses. This type of treatment is described in the section
“Radioactive iodine (radioiodine) therapy.”
Chest x -ray
If you have been diagnosed with thyroid cancer (especially folli cular thyroid
cancer), a plain x -ray of your chest may be done to see if cancer has spread to your
lungs.
Computed tomography (CT) scan
The CT scan is an x -ray test that produces detailed cross -sectional images of your
body. It can help determine the lo cation and size of thyroid cancers and whether
they have spread to nearby areas, although ultrasound is usually the test of choice.
A CT scan can also be used to look for spread into distant organs such as the lungs.
A CT scanner has been described as a large donut, with a narrow table in the middle
opening. You will need to lie still on the table while the scan is being done. CT
scans take longer than regular x -rays, and you might feel a bit confined by the ring
while the pictures are being taken.
Instead of taking one picture, like a regular x -ray, a CT scanner takes many pictures
as it rotates around you while you lie on the table. A computer then combines these
pictures into images of slices of the part of your body being studied. A CT scan
creates m ore detailed images of the soft tissues in the body than a standard x -ray.
Before the test, you may be asked to drink a contrast solution or receive an IV
(intravenous) line through which a different contrast dye is injected. This helps
better outline str uctures in your body. The injection may cause some flushing (a
feeling of warmth, especially in the face). Some people are allergic and get hives.

69 Rarely, more serious reactions like trouble breathing or low blood pressure can
occur. Be sure to tell the do ctor if you have any allergies or have ever had a reaction
to any contrast material used for x -rays.
In some cases, a CT scan can be used to guide a biopsy needle precisely into a
suspected area of cancer spread. For a CT -guided needle biopsy, you remain on the
CT scanning table, while the doctor advances a biopsy needle through the skin and
toward the ma ss. CT scans are repeated until the doctor can see that the needle is
within the mass. A biopsy sample is then removed and looked at under a
microscope.
One problem with using CT scans for differentiated thyroid cancer is that the CT
contrast dye contains iodine, which interferes with radioiodine scans. For this
reason, many doctors prefer MRI scans instead of CT scans.
Magnetic resonance imaging (MRI) scan
Like CT scans, MRI scans can be used to look for cancer in the thyroid, or cancer
that has spread to nearby or distant parts of the body. But ultrasound is usually the
first choice for looking at the thyroid. MRI can provide very detailed images of soft
tissues such as the thyroid gland. MRI scans are also very helpful in looking at the
brain and spina l cord.
MRI scans use radio waves and strong magnets instead of x -rays. The energy from
the radio waves is absorbed and then released in a pattern formed by the type of
body tissue and by certain diseases. A computer translates the pattern into a very
detailed image of parts of the body. A contrast material called gadolinium is often
injected into a vein before the scan to better show details.
MRI scans take longer than CT scans – often up to an hour. You may have to lie
inside a narrow tube, which can u pset people with a fear of enclosed spaces. Newer,
more open MRI machines can sometimes be used instead. The machine also makes
buzzing and clicking noises, so some centers provide earplugs to block this noise
out.
Positron emission tomography (PET) scan
For a PET scan, a radioactive substance (usually a type of sugar related to glucose,
known as FDG ) is injected into the blood. The amount of radioactivity used is very
low. Because cancer cells in the body grow quickly, they absorb more of the sugar

70 than normal cells. After waiting about an hour, you lie on a table in the PET scanner
for about 30 minutes while a special camera creates a picture of areas of
radioactivity in the body.
This test can be very useful if your thyroid cancer is one that doesn’t take up
radioactive iodine. In this situation, the PET scan may be able to tell whether the
cancer has spread.
PET scan images are not finely detailed like CT or MRI images, but a PET scan
can look for possible areas of cancer spread in all areas of the body at once. Some
newer machines are able to do both a PET and CT scan at the same time (PET/CT
scan). This lets the doctor compare an abnormal area on the PET scan with its
detailed appearance on the CT.
Blood tests
Blood tests alone can’t tell if a th yroid nodule is cancerous. But they can help show
if the thyroid is working normally, which may help the doctor decide what other
tests may be needed.
Thyroid -stimulating hormone (TSH)
Tests of blood levels of thyroid -stimulating hormone (TSH or thyrotr opin) may be
used to check the overall activity of your thyroid gland. Levels of TSH, which is
made by the pituitary gland, may be high if the thyroid is not making enough
hormones. This information can be used to help choose which imaging tests (such
as ultrasound or radioiodine scans) to use to look at a thyroid nodule. The TSH
level is usually normal in thyroid cancer.
T3 and T4 (thyroid hormones)
These are the main hormones made by the thyroid gland. Levels of these hormones
may also be measured to ge t a sense of thyroid gland function. The T3 and T4
levels are usually normal in thyroid cancer.
Thyroglobulin
Thyroglobulin is a protein made by the thyroid gland. Measuring the thyroglobulin
level in the blood can’t be used to diagnose thyroid cancer, b ut it can be helpful
after treatment. A common way to treat thyroid cancer is to remove most of the
thyroid by surgery and then use radioactive iodine to destroy any remaining thyroid

71 cells. These treatments should lead to a very low level of thyroglobulin in the blood
within several weeks. If it is not low, this might mean that there are still thyroid
cancer cells in the body. If the level rises again after being low, it is a sign that the
cancer could be coming back.
Calcitonin
Calcitonin is a hormone t hat helps control how the body uses calcium. It is made
by C cells in the thyroid, the cells that can develop into medullary thyroid cancer
(MTC). If MTC is suspected or if you have a family history of the disease, blood
tests of calcitonin levels can help look for MTC. This test is also used to look for
the possible recurrence of MTC after treatment. Because calcitonin can affect blood
calcium levels, these may be checked as well.
Carcinoembryonic antigen (CEA)
People with MTC often have high blood leve ls of a protein called
carcinoembryonic antigen (CEA). Tests for CEA can sometimes help find this
cancer.
Other blood tests
You might have other blood tests as well. For example, if you are scheduled for
surgery, tests will be done to check your blood ce ll counts, to look for bleeding
disorders, and to check your liver and kidney function.
Medullary thyroid carcinoma (MTC) can be due to a genetic syndrome that also
causes a tumor called pheochromocytoma, which can cause problems during
surgery under anes thesia. This is why patients with MTC who will have surgery
are often tested to see if they have pheochromocytoma, as well. This can involve
blood tests for epinephrine (adrenaline) and a related hormone called
norepinephrine, and/or urine tests for their breakdown products (called
metanephrines).
Other tests
Vocal cord exam (laryngoscopy)
Thyroid tumors can sometimes affect the vocal cords. If you are going to have
surgery to treat thyroid cancer, a procedure called a laryngoscopy will probably be
done first to see if the vocal cords are moving normally. For this exam, the doctor

72 looks down the throat at the larynx (voice box) with special mirrors or with a
laryngoscope, a thin tube with a light and a lens on the end for viewing.
How is thyroid cancer treated?
This information represents the views of the doctors and nurses serving on the
American Cancer Society’s Cancer Information Database Editorial Board. These
views are based on their interpretation of studies published in medical journals, as
well as their o wn professional experience.
The treatment information in this document is not official policy of the Society and
is not intended as medical advice to replace the expertise and judgment of your
cancer care team. It is intended to help you and your family m ake informed
decisions, together with your doctor.
Your doctor may have reasons for suggesting a treatment plan different from these
general treatment options. Don’t hesitate to ask him or her questions about your
treatment options.
Making treatment deci sions
Depending on the type and stage of thyroid cancer, you may need more than one
type of treatment.
.Surgery
Radioactive iodine treatment
Thyroid hormone therapy
External beam radiation therapy
Chemotherapy
Targeted therapy
Often 2 or more of these are combined.
Most thyroid cancers can be cured, especially if they have not spread to distant
parts of the body. If the cancer can’t be cured, the goal of treatment may be to
remove or destroy as much of the cancer as possible and to keep it from g rowing,
spreading, or returning for as long as possible. Sometimes treatment is aimed at

73 palliating (relieving) symptoms such as pain or problems with breathing and
swallowing.
If you have any concerns about your treatment plan, if time permits it is oft en a
good idea to get a second opinion. In fact, many doctors encourage this. A second
opinion can provide more information and help you feel confident about the
treatment plan you choose.
Some treatments for thyroid cancer might affect your ability to h ave children later
in life. If this might be a concern for you, talk to your doctor about it before you
decide on treatment. For more information, see Fertility and Women With Cancer
or Fertility and Men With Cancer .
The next few sections describe the typ es of treatment used for thyroid cancers. This
is followed by a description of the most common approaches based on the type and
stage of the cancer.
Surgery for thyroid cancer
Surgery is the main treatment in nearly every case of thyroid cancer, except f or
some anaplastic thyroid cancers. If thyroid cancer is diagnosed by a fine needle
aspiration (FNA) biopsy, surgery to remove the tumor and all or part of the
remaining thyroid gland is usually recommended.
Lobectomy
This operation is sometimes used to treat differentiated (papillary or follicular)
thyroid cancers that are small and show no signs of spread beyond the thyroid
gland. It is also sometimes used to diagnose thyroid cancer if an FNA biopsy result
doesn’t pro vide a clear diagnosis (see “How is thyroid cancer diagnosed?”).
First, the surgeon makes an incision (cut) a few inches long across the front of the
neck and exposes the thyroid. The lobe containing the cancer is then removed,
usually along with the ist hmus (the small piece of the gland that acts as a bridge
between the left and right lobes).
An advantage of this surgery, if it can be done, is that some patients might not need
to take thyroid hormone pills afterward because it leaves part of the gland behind.
But having some thyroid left can interfere with some tests that look for cancer
recurrence after treatment, such as radioiodine scans and thyroglobulin blood tests.

74 Thyroidectomy
Thyroidectomy is surgery to remove the thyroid gland. As with lobec tomy, this is
typically done through an incision a few inches long across the front of the neck.
This is the most common surgery for thyroid cancer. If the entire thyroid gland is
removed, it is called a total thyroidectomy . Sometimes the surgeon may not be able
to remove the entire thyroid. If nearly all of the gland is removed, it is called a
near-total thyroidectomy . If most of the gland is removed, it is called a subtotal
thyroidectomy .
After a thyroidectomy (and possibly radioactive iodine [radioiod ine] therapy), you
will need to take daily thyroid hormone (levothyroxine) pills. But one advantage
of this surgery over lobectomy is that your doctor can most often watch you for
disease recurrence afterward using radioiodine scans and thyroglobulin blood tests.
Lymph node removal
If cancer has spread to nearby lymph nodes in the neck, these will be removed at
the same time surgery is done on the thyroid. This is especially important for
treatment of medullary thyroid cancer and for anaplastic cancer (wh en surgery is
an option).
For papillary or follicular cancer where only 1 or 2 enlarged lymph nodes are
thought to contain cancer, the enlarged nodes may be removed and any small
deposits of cancer cells that may be left are then treated with radioactive iodine
(see the section about radioactive iodine [radioiodine] therapy). More often, several
lymph nodes near the thyroid are removed in an operation called a central
compartment neck dissection . Removal of even more lymph nodes, including those
on the sid e of the neck, is called a modified radical neck dissection .
Radioactive iodine (radioiodine) therapy for thyroid cancer
Your thyroid gland absorbs nearly all of the iodine in your body. When radioactive
iodine (RAI), also known as I -131, is taken into the body in liquid or capsule form,
it concentrates in thyroid cells. The radiation can destroy the thyroid gland and any
other thyroid cells (including cancer cells) that take up iodine, with little effect on
the rest of your body. (The radiation dose used here is much stronger than the one
used in radioiodine scans, which were described in “How is thyroid cancer
diagnosed?”)

75 This treatment can be used to ablate (destroy) any thyroid tissue not removed by
surgery or to treat some types of thyroid cancer that have spread to lymph nodes
and other parts of the body.
Radioactive iodine therapy improves the survival rate of pati ents with papillary or
follicular thyroid cancer (differentiated thyroid cancer) that has spread to the neck
or other body parts, and this treatment is now standard practice in such cases. But
the benefits of RAI therapy are less clear for patients with sm all cancers of the
thyroid gland that do not seem to have spread, which can often be removed
completely with surgery. Discuss your risks and benefits of RAI therapy with your
doctor. Radioactive iodine therapy cannot be used to treat anaplastic
(undifferen tiated) and medullary thyroid carcinomas because these types of cancer
do not take up iodine.
For RAI therapy to be most effective, patients must have high levels of thyroid –
stimulating hormone (TSH or thyrotropin) in the blood. This substance stimulates
thyroid tissue (and cancer cells) to take up radioactive iodine. If the thyroid has
been removed, one way to raise TSH levels is to not take thyroid hormone pills for
several weeks. This causes very low thyroid hormone levels (a condition known as
hypothyr oidism ), which in turn causes the pituitary gland to release more TSH.
This intentional hypothyroidism is temporary, but it often causes symptoms like
tiredness, depression, weight gain, constipation, muscle aches, and reduced
concentration. Another way to raise TSH levels before RAI therapy is to give an
injectable form of thyrotropin (Thyrogen), which can make withholding thyroid
hormone for a long period of time unnecessary. This drug is given daily for 2 days,
with the RAI on the 3rd day.
Most doctors also recommend that the patient follow a low iodine diet for 1 or 2
weeks before treatment. This means avoiding foods that contain iodized salt and
red dye #3, as well as dairy products, eggs, seafood, and soy.
Thyroid hormone therapy
Taking daily pills of thyroid hormone (thyroid hormone therapy) can serve 2
purposes:
It can help maintain the body’s normal metabolism (by replacing missing thyroid
hormone after surgery).

76 It can help stop any remaining cancer cells from growing (by lowering TSH levels) .
After a thyroidectomy, the body can no longer make the thyroid hormone it needs,
so patients must take thyroid hormone (levothyroxine) pills to replace the loss of
the natural hormone.
Taking thyroid hormone may also help prevent some thyroid cancers from
returning. Normal thyroid function is regulated by the pituitary gland. The pituitary
makes a hormone called TSH that causes the thyroid gland to make thyroid
hormone for the body. TSH also promotes growth of the thyroid gland and probably
of thyroid cancer cells. The level of TSH, in turn, is regulated by how much thyroid
hormone is in the blood. If the level of thyroid hormone is low, the pituitary makes
more TSH. If the level of thyroid hormone is high, not as much TSH is needed, so
the pituitary ma kes less of it.
Doctors have learned that by giving higher than normal doses of thyroid hormone,
TSH levels can be kept very low. This may slow the growth of any remaining
cancer cells and lower the chance of some thyroid cancers (especially high -risk
cancers) coming back.
Possible side effects
Taking higher than normal levels of thyroid hormone seems to have few short -term
side effects, but some doctors have expressed concerns about taking them for long
periods of time. High levels of thyroid hormone c an lead to problems with a rapid
or irregular heartbeat.
Over the long run, high doses of thyroid hormone can lead to weak bones
(osteoporosis). Because of this, high doses of thyroid hormone may be reserved for
people with differentiated thyroid cancers who are at high risk of recurrence.
External beam radiation therapy for thyroid cancer
External beam radiation therapy uses high -energy rays (or particles) to destroy
cancer cells or slow their growth. A carefully focused beam of radiation is delivered
from a machine outside the body. Generally, this type of radiation treatment is not
used for cancers that take up iodine (that is, most differentiated thyroid cancers),
which are better treated with radioiodine therapy. It is more often used as part of
the treatment for medullary thyroid cancer and anaplastic thyroid cancer.

77 When a cancer that does not take up iodine has spread beyond the thyroid, external
radiation treatment may help treat the cancer or reduce the chance of the disease
coming back in the n eck after surgery. If a cancer does not respond to radioiodine
therapy, external radiation therapy may be used to treat local neck recurrence or
distant metastases that are causing pain or other symptoms.
External beam radiation therapy is usually given 5 days a week for several weeks.
Before your treatments start, the medical team will take careful measurements to
find the correct angles for aiming the radiation beams and the proper dose of
radiation. The treatment itself is painless and much like getting a regular x -ray.
Each treatment lasts only a few minutes, although the setup time — getting you
into place for treatment — usually takes longer.
Possible side effects
The main drawback of this treatment is that the radiation can destroy nearby
healthy t issue along with the cancer cells. Some patients get skin changes similar
to a sunburn, but this slowly fades away. Trouble swallowing, dry mouth,
hoarseness, and fatigue are also potential side effects of external beam radiation
therapy aimed at or near t he thyroid.
To reduce the risk of side effects, doctors carefully figure out the exact dose needed
and aim the beam as accurately as they can to hit the target.
For more information about radiation therapy, see the “Radiation Therapy” section
of our we bsite, or Understanding Radiation Therapy: A Guide for Patients and
Families .
Chemotherapy for thyroid cancer
Chemotherapy (chemo) uses anti -cancer drugs that are injected into a vein or
muscle, or are taken by mouth. Chemotherapy is systemic therapy, wh ich means
that the drug enters the bloodstream and travels throughout the body to reach and
destroy cancer cells.
Chemotherapy is seldom helpful for most types of thyroid cancer, but fortunately
it is not needed in most cases. It is combined with external beam radiation therapy
for anaplastic thyroid cancer and is sometimes used for other advanced cancers that
no longer respond to other treatments.

78 Possible side effects
Chemo drugs attack cells that are dividing quickly, which is why they work against
cancer cells. But other cells in the body, such as those in the bone marrow, the
lining of the mouth and intestines, and the hair follicles, also divide quickly. These
cells are also likely to be affected by chemotherapy, which can lead to side effects.
The side effects of chemotherapy depend on the type and dose of drugs given and
the length of time they are taken. Common side effects of chemo include:
Hair loss
Mouth sores
Loss of appetite
Nausea and vomiting
Diarrhea
Increased chance of infection s (from too few white blood cells)
Easy bruising or bleeding (from too few low blood platelets)
Fatigue (from too few low red blood cells)
These side effects are usually short -term and go away after treatment is finished.
There are often ways to lessen these side effects. For example, drugs can be given
to help prevent or reduce nausea and vomiting.
Some chemotherapy drugs may have other specific side effects that require
monitoring. For example, doxorubicin (one of the most common chemo drugs used
in thyroid cancer) can affect heart function. Therefore a patient taking doxorubicin
will get regular heart function tests like echocardiograms.
For more information about chemotherapy, see the “Chemotherapy” section on our
website, or A Guide to Chemotherap y.
Targeted therapy for thyroid cancer
Researchers have begun to develop newer drugs that specifically target the changes
inside cells that cause them to become cancerous. Unlike standard chemotherapy

79 drugs, which work by attacking rapidly growing cells in general (including cancer
cells), these drugs attack one or more specific targets on cancer cells.
Targeted drugs for medullary thyroid cancer
Doctors have been especially interested in finding targeted drugs to treat medullary
thyroid cancer (MTC) b ecause thyroid hormone -based treatments (including
radioactive iodine therapy) are not effective against these cancers.
Vandetanib (Caprelsa®) is a targeted drug taken as a pill once a day. In patients
with advanced MTC, vandetanib stops cancers from grow ing for an average of
about 6 months, although it is not yet clear if it can help people live longer.
Some common side effects of vandetanib include diarrhea, rash, nausea, high blood
pressure, headache, fatigue, decreased appetite, and belly (abdominal) pain. Rarely,
it can also cause serious problems with heart rhythm and infection that can lead to
death. Because of its potential side effects, doctors must get special training before
they are allowed to prescribe this drug.
Cabozantinib (Cometriq®) is another targeted drug used to treat MTC. It is taken
in pill form once a day. In MTC patients, cabozantinib has been shown to help stop
cancers from growing for about 7 months longer than a sugar pill. So far, though,
it has not been shown to help patient s live longer.
Common side effects include diarrhea, constipation, belly pain, mouth sores,
decreased appetite, nausea, weight loss, fatigue, high blood pressure, loss of hair
color, and hand -foot syndrome (redness, pain, and swelling of the hands and fe et).
Rarely, this drug can also cause serious side effects, such as severe bleeding and
holes in the intestine.
Several other targeted drugs have shown promising early results against MTC as
well. Some of these, such as sorafenib (Nexavar®) and sunitinib (Sutent®) are
already used to treat other types of cancer. Doctors may try giving these drugs if
other treatments, including vandetanib and cabozantinib, aren’t helpful.
Targeted drugs for papillary or follicular thyroid cancer
Fortunately, most of these cancers can be treated effectively with surgery and
radioactive iodine therapy, so there is less need for other drugs to treat them. But
for cancers in which these treatments aren’t effective, targeted drugs can be helpful.

80 Sorafenib (Nexavar®) and lenva tinib (Lenvima®) are both the type of targeted drug
known as kinase inhibitors. They work in 2 ways. They helps block tumors from
forming new blood vessels, which the tumors need to grow. These drugs also target
some of the proteins made by cancer cells th at normally help them grow.
These drugs can help stop cancer growth for a time when given to patients with
differentiated thyroid cancer (papillary, follicular, and poorly differentiated thyroid
cancers) whose cancers no longer respond to treatment with radioactive iodine. It
isn’t yet clear if these drugs help patients live longer.
Both of these drugs are taken by mouth.
Common side effects include fatigue, rash, loss of appetite, diarrhea, nausea, high
blood pressure, and hand foot syndrome (redness, pain, swelling, or blisters on the
palms of the hands or soles of the feet). Other side effects can also occur, some of
which can be serious. Ask your doctor what you can expect.
Other targeted drugs, such as such as, sunitinib (Sutent®), pazopanib (Votr ient®),
and vandetanib are not approved to treat papillary and follicular thyroid cancer, but
have shown some early promise and may be helpful for some patients.
For general information about targeted therapy, see Targeted Therapy .

81 Conclusion :
 Benign thyroid nodules account >90%
 Malignant account 6 %
 Knowing that most of thyroid nodules is benign is helpful for the diagnosis and treatment
 Thyroid nodules in women (6.4%)is more prevalent than in men(1.5%)
 Cysts can be benign and also malignant

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88 Declaration

I hereby declare that the diploma thesis entitled " Thyroid Nodules &Multi -Nodular
Goiter , " is written by me and has not been presented before at another college or
institution of higher education in the country or abroad. Also, I declare that all sources
used, including the Internet sources, are indicated in the paper, considering the rules fo r
avoiding plagiarism: – all text fragments are reproduced exactly, even the proper
translations from other languages are written in quotes and have detailed reference
source; – paraphrasing in own words of text written by other authors has detailed
refere nce; – summary of the ideas of other authors has a detailed reference to the original
text.

Date 11.05.2015.

Name and surname of studen t Abu Riya Razy