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The Thyroid

Mr. Peter Wellington


Outline

• Basic Anatomy and Embryology


• Physiology
• Pathology
• Clinical Bits and Pieces
Goitre
Hypothyroidism
THYROID EMBRYOLOGY
Earliest
Endocrine
4th week
Thyro Foramen caecum
glossal
duct
cyst/ Pyramidal
fistulae lobe

Ectopic thyroid tissue


Thyroid Embryology
• First Endocrine to • First hollow , then
develop....day 24 solid , the thyroid
diverticulum descends
• Starts as endodermal anterior to hyoid and
pharynx
bud, between copula and
tuberculum
impar( tongue • Connected to tongue
structures) on mid initially....connection
pharyngeal floor obliterates..remnants
persist as Thyroglossal
• Thyroid originates duct....pyramidal lobe
between 1st & 2nd
pouch • During descent thyroid
gets its adult form..2
lateral lobes connected
by isthmus
Going Down
Parafollicular cells
• C cells arise ex • C cells secrete calcitonin
ultimobranchial body. to regulate Ca++, along
with PTH
• Ultimobranchial body
(4th or 5th pouch) • ( Fifth pouch disputed..
invaded by neural crest may actually be ventral
cells wing of 4th pouch )

• UB body is incorporated • Medullary Carcinoma


& diffuse into thyroid develop ex C cells
tissue
• calcitonin➡serum Ca++
levels
Neural Crest

• Totipotential migratory
cells of ectodermal
roots

• Originate ex dorsal
neural tube

• Form varied structures


eg neural ganglia; adrenal
medulla; melanocytes;
craniofacial cartilage &
bone
thyroid descent
Adult anatomy
• ++Vascular ant neck • Innervated by
gland, ex C5 -T1 ANS..sympathetic on
blood vessels;
• 2 elongated lateral Parasympathetic via
vagus N
lobes joined by median
isthmus (which overlies
2-4 tracheal rings) • Regulation of secretion
may be by perfusion
• Weighs 25-30 gm; lat rates
eral lobes 5cm long;
heavier in F; in
pregnant
Thyroid structure
• Gland has thin capsule , • Follicular unit is colloid
encased by deep cervical filled structure lined by
fascia single layer of epithelial
cells
• Extensions of Capsule
into substance of gland • Colloid is a
forms lobes & lobules glycoprotein, iodo-
thyroglobulin which is a
• Lobules are composed precursor thyroid
hormone
of follicles
Follicle
lateral thyroid ligament of Berry

• Attaches posterior
fascia thy to cricoid /
tracheal rings

• condensation of pre
tracheal fascia attaching
thyroid to larynx

• RLN always lateral to lig

• Thyroid moves on
swallowing because of
ligament of Berry
Why no upward growth?
Note extension down into
mediastinum
Thyroid Development
• Thyroid diverticulum • Thyroglossal duct runs
descends anterior to through Hyoid bone
foregut
• Sistrunks op...middle of
• First hollow ,then solid , hyoid bone excised
then obliterated

• If obliteration fails the


remnant is a thyroglossal
duct or cyst
US thyroglossal duct cyst..R
The embryonic hyoid
bone forms around the
thyroglossal duct.

It is important to remove
the body of the hyoid
along with the
thyroglossal duct and
follow it to the foramen
caecum at the base of
the tongue (Sistrunk
procedure)
Paramedian thyroglossal duct cyst...Left

This lesion not in the midline, but the


key finding this lesion is cystic and embedded in the strap musculature
Demonstrating
the duct
A radio-opaque dye is
injected into the opening
of the thyroglossal duct.

The course of the


thyroglossal duct from
the lower neck, to the
region of the hyoid is
seen
Pyramidal Lobe
Anatomy
• Develops from the base
of Tongue (Foramen
Caecum)

• Migrates caudally,
anterior to foregut.

• Comes to rest with


isthmus between 2nd
-4th tracheal ring
Goitre
• Lies lateral to thyroid
cartilage

• Encased by strap
muscles ( 4 infrahyoids)

• Sternothyroid;
sternohyoid;
thyrohyoid;omohyoid

• Strap nerve ,Ansa


cervicalis (C1-
C3)...thyrohyoid is
innervated by C1 only
Supra hyoids

• Digastric
• Myelohyoid
• Geniohyoid
• Stylohyoids
(elevate larynx)
THE
INFRAHYOIDS

• Sternohyoid

• Sternothyroid

• Thyro-hyoid

• Omohyoid
The Framework
Anatomy
• 2 Main Arteries -
Superior and Inferior
thyroid

• 3 Main Veins -
Superior, Mid, and Inferior

• sup & mid ➜ Inf Jug Vein

• R inf ➜brachiocephalic
vein..L or R

• L inf ➜ L brachiocephalic
vein..
Lymphatics
• Extensive &
multidirectional

• Periglandular➜prelaryng
eal➜pretracheal➜paratr
acheal➜RLN➜mediastin
um

• Mets can travel via


lymphatics; blood
bone ;direct spread
Blood Supply
Anatomy: Nerves
• Recurrent Laryngeal

• Superior Laryngeal
N...external branch
curves medially to
supply CRICOTHYROID.

• Internal
branch....pierces
thyrohyoid memb &
supplies all mucosa of
larynx above vocal
cords. irritation causes
uncontrollable coughing
RLN & Berry
RLN & Berrys ligament
• RLN enters cricothyroid
musc at level of Cricoid
cartilage

• RLN dorsal & lateral to


Lig of Berry

• LOB binds posterior


thyroid fascia to cricoid
& upper tracheal rings ;
thus thyroid moves with
swallowing
Arteries of the Thyroid
Superior Thyroid Art
• Superior Thyroid is 1st • Cephalad to Sup Pole , the
Ant Branch of Ext Carotid external Branch of Sup Lar
N runs with STA, before
• STA descends beside larynx curving medially to supply
Cricothyroid
covered by omohyoid and
Sternothyroid
• High Ligation of STA ...➜
• STA runs superficially on # ext br SLN ➼leads to
lat lobe sending a deep dysphonia ....inability to
branch , then anas with its reach high notes
counterpart on the isthmus
Inferior Thyroid irrigation
Inferior Thyroid Artery
• Branch of the • Most branches of ITA
Thyrocervical trunk penetrate postior
( Subclavian ) lateral aspect of gland

• ITA ascends vertically • ITA intimately and


and curves medially to variably related to
run in trach -eso groove Recurrent Laryngeal N
in a plane post to
carotid sheath

• ITA brings most blood


to thyroid (> STA)
Picture of the right recurrent laryngeal nerve passing in the
groove between the trachea and the esophagus (the
gutter), as it ascends toward the larynx.
Control of Thyroid
Hormone
• TSH ex anterior • (3)Thyroglobulin
pituitary ....influenced
by TRH ex hypothalamus • (4) also increase rate of
T4 release by raising
• TSH binds to thyroid rate of endocytosis of
cell receptors stimulate Thyroglobulin-T4
synthesis of...... complexes

• (1)Iodine Transporter

• (2)Thyroid peroxidase
Thyroxine synthesis
• Accumulation of raw materials....iodide and tyrosine

• Assembly ...put I- and Tyrosine together upon a


thyroglobulin scaffold

• Release of T4 from Thyroglobulin into Blood....

• Role of Enyzyme Thyroid peroxidase in all of the above


THYROXINE SYNTHESIS
Fabrication and Release
• The synthesis of T3 or
T4 from iodotyrosines
• Thyroid peroxidase eg Mit to Dit to T3 & T4
catalyses sequential
reactions ....

• Oxidation of iodide to • Release of T3 & T4 from


iodine( I- to I) thyroglobulin by
lysosomes
• Iodination of tyrosine on
the thyroglobulin • Binding to transporter
scaffolding and ----- proteins for journey to
target cells
Chemistry of Thyroxine
• Poorly soluble in H2O.... • Carrier proteins allow a
99% bound to carrier stable pool from which
protein the active free hormone
is released for uptake by
• Thyroxine binding target cells
globulin(synthesized in
liver) is principal carrier

• Albumin &Transthyrein
are other key carriers
Iodination

Iodine Trap
Oxidation .....peroxidase
Iodination of
Tyrosine..MIT;DIT;TIT
Release of T4
Chemistry of Thyroxine
T4
Physiology of thyroid
hormones
• All cells are targets for T3
• BMR and Body heat increase
• Stimulates Metabolism CHO; Lipids and Proteins
• Stimulates Growth...along with growth hormone
• Stimulates Development
• Cardiovascular....cardiac contractility; output;
vasodilation
Thyroid Hormone receptors and
mechanism of action

• Receptors for T3 are • This binding to DNA


intracellular DNA modulates gene
binding proteins→ expression either by
stimulating or
• The hormone receptor
inhibiting
complex then interacts
with specific DNA transcription of
sequences in the specific genes
promoters on
responsive genes→
Physiology
• Thyroxine (T3) &
Triiodothyronine (T4)
Production

• T3 & T4 Regulation

• Thyroid Function Tests

• Thyroxine (Regulation of
Metabolism & Growth)
T3 & T4 Production
1. T4 made by Follicular Cells from free Tyrosine
& Tyrosine Residues of Thyroglobulin Protein
2. Iodine Trap by the H2O2 generated by TPO
enzymes ... and linked to 3' and 5' sites of
Tyrosine residues benzene ring on Tg & free
tyrosine.
T3 / T4 Production
3. TSH stimulates follicular cells to reabsorb
Thyroglobulin and cleave the Iodinated
Tyrosines from Tg, forming T4 and T3, and
releasing them into the blood.
4. Deiodinase enzymes convert T4 to T3.
5. Thyroid hormones that are secreted from
the gland is about 80-90% T4 and about
10-20% T3.
Regulation

• Negative feedback loop to hypothal-


pituitary axis
• Blood levels of T4 ➜Decreased ➡ TRH
production in hypothalamus➜ ➡TSH from
anterior pituitary
Pathology Normal
Thyroid

• Diffuse Enlargements

★ Graves’ Disease (Hyper-Thyroidism or


Thyotoxicosis)

★ Hypo-Thyroidism (Myxedema

• Goitres (Toxic / Nontoxic)

• Nodules (Single / Multiple)

• Cancers (Papillary, Follicular,


Anaplastic
Thyroid
Cancer...General Obs
• Relatively Uncommon.... • Medullary...C cells ..
Incidence Female 25%familial...MEN
>>>M( 3; 1)
• Anaplastic...aggressive
• Papillary...local <5% 10 yr. survival
nodes...>90% 10 yr
survival

• Follicular...vascular/
distant mets..>80% 10
yr. survival
Thyroid Cancer Treatment (PDQ®)

TNM Classification
Table 1. Primary Tumor (T)a,b
Last Modified: 08/13/2010

TX Primary tumor cannot be assessed.

T0 No evidence of primary tumor.

T1 Tumor !2 cm in greatest dimension limited to the thyroid.

T1a Tumor !1 cm, limited to the thyroid.

T1b Tumor >1 cm but !2 cm in greatest dimension, limited to the thyroid.

T2 Tumor >2 cm but !4 cm in greatest dimension, limited to the thyroid.

T3 Tumor >4 cm in greatest dimension limited to the thyroid or any tumor with minimal extrathyroid extension (e.g., extension to
sternothyroid muscle or perithyroid soft tissues).

T4a Moderately advanced disease.

Tumor of any size extending beyond the thyroid capsule to invade subcutaneous soft tissues, larynx, trachea, esophagus, or
recurrent laryngeal nerve.

T4b Very advanced disease.

Tumor invades prevertebral fascia or encases carotid artery or mediastinal vessels.

cT4a Intrathyroidal anaplastic carcinoma.

cT4b Anaplastic carcinoma with gross extrathyroid extension.

aReprintedwith permission from AJCC: Thyroid. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed.
New York, NY: Springer, 2010, pp 87–96.
bAll categories may be subdivided: (s) solitary tumor and (m) multifocal tumor (the largest determines the classification).
cAll anaplastic carcinomas are considered T4 tumors.
TNM Classification
Thyroid Cancer Treatment (PDQ®)

Last Modified: 08/13/2010

Table 2. Regional Lymph Nodes (N)a,b


Thyroid Cancer Treatment - National Cancer Institute 12/18/10 7:41 PM
NX Regional lymph nodes cannot be assessed.

N0 No regional lymph node metastasis.


In English | En español
N1 Regional lymph node metastasis.

N1a Metastases to Level VI (pretracheal, paratracheal, and prelaryngeal/Delphian lymph nodes).

N1b Metastases to unilateral, bilateral, or contralateral cervical (Levels I, II, III, IV, or V) or retropharyngeal or superior mediastinal lymph
nodes (Level VII).

a
Reprinted with permission from AJCC: Thyroid. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed.
Thyroid Cancer Treatment (PDQ®)
New York, NY: Springer, 2010, pp 87–96.
bRegional lymph nodes are the central compartment, lateral cervical, and upper mediastinal lymph nodes.

Last Modified: 08/13/2010

Table 3. Distant Metastasis (M)a


M0 NCI Home | metastasis.
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M1 Distant metastasis.
aReprinted A Service of the National Cancer Institute
with permission from AJCC: Thyroid. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed.
New York, NY: Springer, 2010, pp 87–96.
Papillary/Follicular Ca
Stage I&2

• Surgery....Total • Consider because of


Thyroidectomy multicentricity/dediff. of
residual tumor to
• Surgery ...Lobectomy anaplastic

• Surgery... Tot Thy plus • Post op I131 ablative


Node Excision....? therapy decreases
recurrence
• Thyroidectomy plus
Neck Disection...? • Post op suppression
with L-thyroxine
Papillary Ca

• Etio....genetic mutation; • Spreads more by lymph


early exposure to than blood
radiation
• About 74 % of thy ca
• Earlier, RT was used to
Rx all things ..ex acne to
tonsillitis!

• Papillary ca has good


prognosis...younger pts
fare better than old
Papillary Follicular...didfferentiated
Follicular Carcinoma
PAPILLARY/FOLL. CA.
STAGE 3
• Total Thyroidectomy/ • Younger Pts better
node excision/ prognosis

• Total Thyroidectomy • Hypoparathyroidism


with post op I131 ablation
• Post op suppression
• Total Thyroidectomy with L thyroxine
with post op external
beam irrad....if no I 131
uptake
Papillary Carcinoma
• Most common Thy Ca • Post op thyrx...lifetime

• lymphatic invasion • Follow up... serum


frequent thyroglob ↑ means
recurrence↑↑
• Vascular invasion
low...lung/bone • Path....Psammoma
bodies; Orphan Annie
• Good prognosis...10yr nuclei
surv> 85%

• Sx...Total thyroidectomy
followed by RaI
Psammoma Body

Rounded bodies of calcium ie calcified papillae or calcified


thrombae seen in papillary cancer
Orphan Annie Nuclei

Clear nuclei...like orphan annie eyes...assoc with papillary


cancers
Stage 4

I131 radioactive ablation...if there is


uptake

External Beam Irradiation

L-Thyroxine Suppression

Experimental....Chemotherapy
Thyroiditis
Lymphoid follicle

• Hashimotos...large
gland...antibodies...high
TSH....low T4...hypothyroidism

• DeQuervains...pain/fever...rapid
swelling...low TSH....high T4... few
or no antibodies...may have viral
etio; self limiting. Hyperthy→ Askanazy cells
hypo→Euthy

• Reidels Fibrosing Struma..rare ..


60% antibodies..involves
perithyroid tissues...compressive
symptoms...looks like anaplastic
Ca.

• Infectious..Viral ; Bacterial
Hashimotos (1912)
• Destruction of Thyroid • May have gradual onset
cells by cell and antibody with myriad symptoms
mediated autoimmune ex depression to
processes. mania;ex hyperlipidemia
to hair loss
• Antibodies...anti-
thyroglobulin; anti- • Rx thyroxine
peroxidase enzyme and
anti-TSH receptors • Sx

• Commonest cause of
hypothyroidism in West
Hashimoto Hamuru

Born 1881 Died 1934


De Quervains
• Viral ...Sub Acute • Epithelial cell damage ➞ T4;
granulomatous..transient Thyroglobulin to leak into
painful inflammation of blood ➞TSH suppression
Thyroid ➞no new hormone
production
• Human Leucocyte Antigen
35 (HLA 35) on • The process is self limiting
Macrophages binds to virus, and not self perpetrating as
excites T lymphocytes which in Hashimotos
destroy thyroid epithelial
cells. • As healing occurs, and
inflation subsides thyroid
Cells regenerate and Thy
hormone synthesis resume
Toxic Goitre
Def. Goiter with thyrotoxicosis.
PRIMARY SECONDARY

GRAVES’ Disease Second to SNG


(Exophthalmos Goiter) (Toxic nodular goiter)

Etiology:Unknown (Autoimmune’LATS)
Toxic Goitre

Marked epithelial hyperplasia with many Diffuse fleshy vascular enlargement


papillae of thyroid gland
Graves
Graves Disease
• Autoimmune • Pretibial myxedema(infilt
Thyrotoxicosis rative dermopathy) non
pitting
• low TSH & high T3/T4
• Antibodies to TSH
• Opthalmopathy receptors→↑ T3/
←inflammation of extra T4→Thyrotoxicosis.
occular muscles; orbital
fat and connective • 3keyimunglobs ,,,,.
tiss→bulging eyes; 1.TSI ...slow chr
corneal irritation; stimulator (LATS)...
diplopia; periorbital 2.TGI→↑Follice growth
edema 3.TBII →stops TSH
binding to receptors
Graves Disease
• First described by • Exopthalmos ;
Persian Al -jurani in 12 extraoccular muscles &
th century:Graves /von TSH receptors share a
Basedow in 1830’s similar antigen which is
attacked by the
• Root cause; occupation antibodies
of TSH receptor sites by
antibodies. These
antibodies stimulate
continuous T3&T4
production; negative
feedback causes low
blood tsh
• Cardiac

• Skin

• Eye

• Nervous

• Muscular
Cancer Goitre

Nodules Dif. Enlargements


Goitre

Dif. Enlargements
(Graves’ Disease)
Nodules

Thyroid Cancer
Thyroid Surgery
Thyroid Surgery...Goals

• Safety...preservation of the integrity of the


recurrent laryngeal nerve and of the
external branch of superior laryngeal nerve
• Preservation of blood supply to the
Parathyroids
• Cosmesis
Clinical Algos
• History
• Clinical Examination / Bed side maneuvers
• Investigations (Histopathology Imaging,
Biochemistry,)
• Choosing Treatment Modalities..Drugs;
RAI; Sx; Ext beam..Lin Ac..combinations
• Surveillance
Laryngeal Innervation
The superior laryngeal nerve
divides into two branches, the
internal laryngeal branch that
enters the larynx in the thyrohyoid
membrane.

Internal laryngeal N supplies


mucosa above vocal cords

The second branch, the external


laryngeal, supplies the cricothyroid
muscles.
Clinical Anecdotes
• Post-operatively:
• Stridor←RLN
• Hoarseness←Neuropraxaia RLN
• Haematoma
• Inability to hit high notes while
singing←SLN

• Hypocalcemia←Parathyroids
Vocal Cord Paralysis

Source: http://www.entusa.com/
Clinical Anecdotes
• Decide Who needs Surgery
• In Preparing the Patient for Surgery...DL,
FNAC..Render Euthyroid ( ?Lugols ➡
bleeding)
• Intra-operative ... protect the
RLN,SLN,Parathyroids
• Leave a clean Trachea behind
• Be Meticulous in Hemostasis
Common Indications for
Thyroid Sx
• Non Toxic Nodular Goitre
• Toxic Nodular Goitre
• Single Cold Nodules
• Carcinoma
• Cosmesis
• Graves Disease
Q&A

Thank You ...