Thyroid Gland: Embryology, Anatomy and Physiology

Thyroid Gland
Embryology, Anatomy and Physiology
Dr. Mahmoud W. Qandeel

Outlines
• Embryology
– Thyroglossal cyst
– Lingual thyroid
– Ectopic thyroid
– Pyramidal lobe
• Anatomy
– Triangles of the neck
– Neck fascia and compartments
– Strap muscles
– Thyroid gland and relations
– Blood supply
– Nerves
– Cervical lymph nodes
• Physiology

Embryology
• Out pouching of primitive foregut at third week
• Descend from the base of the tongue at foremen cecum
• Thyroglossal duct
• Median thyroid anlage ( follicular cells ); endoderm cells in the floor of the pharyngeal
anlage thicken to form the medial thyroid anlage
• Paired lateral thyroid anlage ( C – cells ) ; originate from the fourth branchial pouch and
fuse with the median anlage at approximately the fifth week of gestation.
– Neuroectodermal in origin and provide the calcitonin producing parafollicular or C cells.
• Thyroid follicles are initially apparent by 8 weeks, and colloid formation begins by the
eleventh week of gestation.

Thyroglossal duct cyst and sinus
• Obliteration start at 5 and end at 8 week of gestation age.

• 80% at juxtaposition to the hyoid bone
• Usually asymptomatic, on examination?
• The cyst it lined by pseudo stratified ciliated columnar epithelium and squamous
epithelium with some thyroid tissues in about 20%
• Thyroid imaging is not necessary but ?
• Sistrunk operation
• 1% of it contain cancer and 80% papillary type
• Total thyroidectomy in this is controversial
• Medullary thyroid cancer (MTC) are not found, why?

Lingual thyroid
• Failure of median anlage to descend

• May be the only thyroid tissue
• Surgery if obstructive symptoms
• TSH suppression therapy
• RAI ablation therapy

Ectopic thyroid tissue
• Any where in the central neck and upper mediastinum

• Also can be seen around the heart
• Lateral aberrant thyroid ?

Pyramidal lobe
• Remaining of the duct as a fibrous band

• 50% of individuals
• Just to the left or right
• It is not palpable unless ?

Thyroid Anatomy

Triangles of the Neck

Fascia and Compartments of the Neck

Strap Muscles

Strap Muscles

Strap Muscles
Innervation

Relations of the thyroid

Tubercle of Zuckerkandil

Blood Supply of Thyroid

8 7
6
4
5
3 2
Branches of
External
Carotid Artery

Arterial supply
• Two major arteries supply the thyroid gland.
1. Superior thyroid artery.

• The superior thyroid artery is the first branch of the external carotid artery.
• It descends , passing along the lateral margin of the thyrohyoid muscle, to

reach the superior pole of the lateral lobe of the gland where it divides into
anterior and posterior glandular branches.

2. Inferior thyroid artery.
• The inferior thyroid artery is a branch of the thyrocervical trunk, which arises
from the first part of the subclavian artery.
• It ascends along the medial edge of the anterior scalene muscle, passes
posteriorly to the carotid sheath, and reaches the inferior pole of the lateral
lobe of the thyroid gland
• At the thyroid gland the inferior thyroid artery divides into an:
– Inferior branch, which supplies the lower part of the thyroid gland and anastomoses
with the posterior branch of the superior thyroid artery, and
– An ascending branch , which supplies the parathyroid glands.

• Occasionally, a small thyroid ima artery arises from the brachiocephalic
trunk or the arch of the aorta and ascends on the anterior surface of
the trachea to supply the thyroid gland.

Venous drainage
Three veins drain the thyroid gland :

• The superior thyroid vein primarily drains the area supplied by the
superior thyroid artery.
• The middle and inferior thyroid veins drain the rest of the thyroid gland.
• The superior and middle thyroid veins drain into the internal jugular
vein, and the inferior thyroid veins empty into the right and left
brachiocephalic veins, respectively.

Recurrent laryngeal nerves
• The thyroid gland is closely related to the recurrent laryngeal nerves.
• After branching from the vagus nerve [X] and looping around the
subclavian artery on the right and the arch of the aorta on the left, the
recurrent laryngeal nerves ascend in a groove between the trachea and
esophagus.
• They pass deep to the posteromedial surface of the lateral lobes of the
thyroid gland and enter the larynx by passing deep to the lower margin
of the inferior constrictor of the pharynx.

• Identification of the nerves or their branches often necessitates
mobilization of the most lateral and posterior extent of the thyroid gland,
the tubercle of Zuckerkandl, at the level of the cricoid cartilage.
• Branches of the nerve may traverse the ligament of Berry in 25% of

individuals and are particularly vulnerable to injury at this junction.
• The RLNs terminate by entering the larynx posterior to the cricothyroid

muscle.

• The right RLN may be nonrecurrent in 0.5% to 1% of individuals
and often is associated with a vascular anomaly ( Aberrant Rt.
subclavian artery).
• Nonrecurrent left RLNs are rare but have been reported in

patients with situs inversus and a right-sided aortic arch.

• The RLNs innervate all the intrinsic muscles of the larynx, except the
cricothyroid muscles, which are innervated by the external laryngeal
nerves.
• Injury to one RLN leads to paralysis of the ipsilateral vocal cord, which
comes to lie in the paramedian or the abducted position.
– The paramedian position results in a normal but weak voice, whereas the
abducted position leads to a hoarse voice and an ineffective cough.
• Bilateral RLN injury may lead to airway obstruction, necessitating

emergency tracheostomy, or loss of voice.

Superior laryngeal nerves
• The superior laryngeal nerves also arise from the vagus nerves.
• After their origin at the base of the skull, these nerves travel along the
internal carotid artery and divide into two branches at the level of the
hyoid bone.
• The internal branch of the superior laryngeal nerve is sensory to the

supraglottic larynx.
• Injury to this nerve is rare in thyroid surgery, but its occurrence may
result in aspiration.

• The external branch of the superior laryngeal nerve lies on the inferior
pharyngeal constrictor muscle and descends alongside the superior
thyroid vessels before innervating the cricothyroid muscle.
• Injury to this nerve leads to inability to tense the ipsilateral vocal cord
and hence difficulty “hitting high notes,” difficulty projecting the voice,
and voice fatigue during prolonged speech.

Relations
between
Arteries
and Nerves

Parathyroid glands and RLN

Parathyroid glands and RLN

Ectopic Parathyroids

• Lymphatic drainage of the thyroid gland is to nodes beside the
trachea (paratracheal nodes) and to deep cervical nodes
inferior to the omohyoid muscle along the internal jugular
vein.

Neck Lymph nodes

Thyroid Gland Physiology

Thyroid Follicles
• The thyroid gland weighs 10 to 20 g in normal adults and is responsible for the production
of three metabolic hormones: thyroxine (T4), triiodothyronine (T3), and calcitonin.
• Thyroid follicular unit is the important site of thyroid hormone production.
• The follicular unit is composed of a single layer of cuboidal follicular cells that encompass a
central depository of colloid filled mostly with thyroglobulin (Tg), the protein in which T4
and T3 are synthesized and stored.
• In between these units are parafollicular cells, or C cells, that generate calcitonin.

Iodine Metabolism
• Iodine is essential for the production of thyroid hormones.

• The average daily iodine requirement is 0.1 mg
• Dietary sources of iodine include dairy products, eggs, iodized table salt, saltwater fish,
shellfish, soy products, and multivitamins.
• Iodine is efficiently absorbed from the gastrointestinal tract in the form of inorganic
iodide and rapidly enters the extracellular iodide pool.
• The thyroid gland is responsible for storing 90% of total body iodide at any given time.
• Iodide is stored in the thyroid as preformed thyroid hormone or as an iodinated AA.

Thyroid Hormone synthesis

Steps
• Iodide trapping
• Oxidation of iodide to iodine
• Iodination of tyrosine residues on Tg to form MIT & DIT
• Coupling
• Thyroglobulin hydrolyzed to release T3,T4
• Deiodination to release iodide

Thyroid Hormone synthesis
• Once organic iodide is oxidized and bound, it couples to Tg with tyrosine moieties to form
iodotyrosines in a single conformation (monoiodotyrosine [MIT]) or a coupled conformation
(diiodotyrosine [DIT]).
• The formation of DIT and MIT depends on an important intracellular catalytic agent, thyroid
peroxidase, which is an integral part of the initial process of organification and storage of
inorganic iodide.
• This enzyme, along with Tg, is remarkably specific to the thyroid follicular cells, making
both important in the diagnosis and management of autoimmune thyroid disease and the
follow-up of DTC.

• MIT and DIT are biologically inert.
• T4 is formed by the coupling of two molecules of DIT, whereas T3 is formed by the coupling
of one molecule of MIT with one molecule of DIT. (form 3,5,3′-triiodothyronine (T3) or 3,3′,5′-
triiodothyronine reverse (rT3). )
• In normal circumstances, formation of T4 predominates.
• T3 and T4 are bound to Tg and stored in the colloid in the center of the follicular unit, which
allows quicker secretion of the hormones than if they had to be synthesized de novo.

• After synthesis of the thyroid hormones has run its course, each thyroglobulin
molecule contains up to 30 thyroxine molecules and a few triiodothyronine
molecules.
• In this form, the thyroid hormones are stored in the follicles in an amount sufficient
to supply the body with its normal requirements of thyroid hormones for 2 to 3
months.
• Most thyroid hormone released from the thyroid gland is T4, which is deiodinated
in peripheral tissues and converted to T3.

• Release of T4 and T3 is regulated at the follicular cell apical membrane via
lysosomal hydrolysis of the colloid that contains the Tg-bound hormones.
• The apical membrane of the thyroid cell forms multiple pseudopodia and
incorporates Tg into small vesicles, which are brought into the cell apparatus.
• Within the vesicles, lysosomal hydrolysis results in the reduction of the

disulfide bonds, and T3 and T4 are then free to pass through the basement
membrane and be absorbed into the circulation, where more than 99% of
each hormone is bound to serum protein.

• This metabolic process is efficient in releasing T3 and T4, while maintaining
the storage components, Tg and colloid, within the follicular apparatus.
• Although sensitive assays of peripheral blood can measure Tg, peripheral Tg

represents an extremely small fraction of total body stores.
• Residual iodotyrosines undergo peripheral breakdown, deiodination, and

recycling and can be added to the recently absorbed iodide stores and
become available for the synthesis of new thyroid hormone.

• Of circulating T3 and T4, 80% is bound
to thyroxine-binding globulin (TBG) in
the periphery.
• Numerous medications and clinical

scenarios alter serum levels of TBG or
the affinity of TBG or circulating
thyroid hormone .
• T4 also is bound to albumin and

prealbumin.

• Most T3 and T4 are bound to the extent that free T4 constitutes less than 1% of
peripheral hormone.
• Most T3 is peripherally derived from the deiodination of T4, which takes place
largely in the plasma and liver.
• Peripheral conversion of T4 to T3 can be impaired in many clinical circumstances,

such as overwhelming sepsis and malnutrition, thionamide (propylthiouracil
[PTU]) use, high-dose corticosteroids, beta blockers, iodinated contrast agents,
and amiodarone use resulting in thyroid imbalance

• The half-life of T3 is approximately 8 to 12 hours, and free levels disappear
rapidly from the peripheral circulation.
• In adults, the half-life of T4 is approximately 7 days because of the efficient

and significant degree of binding to carrier proteins.
• Thyroid hormones generally have a slow turnover time in the peripheral

circulation, and the body is ensured of at least a 7- to 10-day supply of T4
available for peripheral metabolism.

• Epinephrine and human chorionic gonadotropin hormones stimulate
thyroid hormone production.
• Thus, elevated thyroid hormone levels are found in pregnancy and
gynecologic malignancies such as hydatidiform mole.
• In contrast, glucocorticoids inhibit thyroid hormone production.
• In severely ill patients, peripheral thyroid hormones may be reduced,

without a compensatory increase in TSH levels, giving rise to the euthyroid
sick syndrome.

• Although TSH is the primary regulator of thyroid hormone synthesis,
there also are intrinsic autoregulatory mechanisms whereby the thyroid
can control intraglandular stores of thyroid hormones.
• In areas in which dietary iodide is excessive, the thyroid gland has an

autoregulated process that inhibits the uptake of iodide into follicular
cells. The reverse is true in iodide deficiency.
• Excessively large doses of iodide have complex effects, including an

increase in organification followed by cessation of production, a
syndrome known as the Wolff-Chaikoff effect.


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Thyroid Gland

Embryology, Anatomy and Physiology

Dr. Mahmoud W. Qandeel

Dr. Mahmoud W. Qandeel

Dr. Mahmoud W. Qandeel

• Obliteration start at 5 and end at 8 week of gestation age.

Dr. Mahmoud W. Qandeel

• Failure of median anlage to descend

Dr. Mahmoud W. Qandeel

• Any where in the central neck and upper mediastinum

Dr. Mahmoud W. Qandeel

• Remaining of the duct as a fibrous band

Dr. Mahmoud W. Qandeel

Dr. Mahmoud W. Qandeel

Dr. Mahmoud W. Qandeel

Dr. Mahmoud W. Qandeel

Dr. Mahmoud W. Qandeel

Dr. Mahmoud W. Qandeel

Dr. Mahmoud W. Qandeel

Dr. Mahmoud W. Qandeel

Dr. Mahmoud W. Qandeel

Dr. Mahmoud W. Qandeel

Dr. Mahmoud W. Qandeel

• Two major arteries supply the thyroid gland.

1. Superior thyroid artery.

• It descends , passing along the lateral margin of the thyrohyoid muscle, to

Dr. Mahmoud W. Qandeel

Dr. Mahmoud W. Qandeel

Dr. Mahmoud W. Qandeel

Three veins drain the thyroid gland :

Dr. Mahmoud W. Qandeel

• The thyroid gland is closely related to the recurrent laryngeal nerves.

Dr. Mahmoud W. Qandeel

• Branches of the nerve may traverse the ligament of Berry in 25% of

• The RLNs terminate by entering the larynx posterior to the cricothyroid

Dr. Mahmoud W. Qandeel

• Nonrecurrent left RLNs are rare but have been reported in

Dr. Mahmoud W. Qandeel

• Bilateral RLN injury may lead to airway obstruction, necessitating

Dr. Mahmoud W. Qandeel

• The internal branch of the superior laryngeal nerve is sensory to the

Dr. Mahmoud W. Qandeel

Dr. Mahmoud W. Qandeel

Dr. Mahmoud W. Qandeel

Dr. Mahmoud W. Qandeel

Dr. Mahmoud W. Qandeel

Dr. Mahmoud W. Qandeel

Dr. Mahmoud W. Qandeel

Dr. Mahmoud W. Qandeel

Dr. Mahmoud W. Qandeel

• Thyroid follicular unit is the important site of thyroid hormone production.

Dr. Mahmoud W. Qandeel

• Iodine is essential for the production of thyroid hormones.

Dr. Mahmoud W. Qandeel

Dr. Mahmoud W. Qandeel

• Oxidation of iodide to iodine

• Iodination of tyrosine residues on Tg to form MIT & DIT

• Thyroglobulin hydrolyzed to release T3,T4