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The Thyroid Gland: Anatomy & Physiology

Gross Anatomy

The thyroid is a butterfly-shaped, highly vascular endocrine gland located in the anterior neck, below and lateral to the thyroid cartilage. It has two lateral lobes connected by a narrow isthmus, which crosses the anterior surfaces of the 2nd and 3rd tracheal cartilages. The lobes cover the anterolateral surfaces of the trachea, cricoid cartilage, and the lower thyroid cartilage.

The gland lies deep to the sternohyoid, sternothyroid, and omohyoid muscles, enclosed within the pretracheal layer of cervical fascia (the visceral compartment of the neck).

Thyroid gland in the anterior triangle of the neck - anterior view, transverse section, ultrasound, and nuclear medicine scan

A pyramidal lobe may extend upward from the isthmus (usually on the left side) along the path of the thyroglossal duct.

Embryology & Development

The thyroid develops as a midline outgrowth (evagination) of the pharyngeal epithelium (foregut endoderm) near the base of the developing tongue, at the site known as the foramen cecum. It descends via the thyroglossal duct to its adult position anterior to the trachea in the root of the neck.

The thyroglossal duct usually disappears early in development
Remnants can persist as a thyroglossal duct cyst (presents as a midline neck swelling) or fistula
Arrest along the descent can produce ectopic thyroid tissue, including a lingual thyroid at the tongue base

(Gray's Anatomy for Students, p. 1157)

Blood Supply

Arterial

Artery	Origin	Supplies
Superior thyroid artery	First branch of the external carotid artery	Superior pole; anterior branch anastomoses across isthmus; posterior branch may meet inferior thyroid artery
Inferior thyroid artery	Thyrocervical trunk (from 1st part of subclavian artery)	Lower pole; ascending branch supplies parathyroid glands
Thyroid ima artery (occasional)	Brachiocephalic trunk or aortic arch	Anterior surface of trachea/isthmus

Venous Drainage

Three veins drain the thyroid:

Superior thyroid vein → internal jugular vein
Middle thyroid vein → internal jugular vein
Inferior thyroid veins → right and left brachiocephalic veins respectively

(Gray's Anatomy for Students, p. 1158-1159)

Lymphatic Drainage

Lymphatics drain to paratracheal nodes beside the trachea and to deep cervical nodes (inferior to the omohyoid muscle along the internal jugular vein). This is clinically important in thyroid cancer staging.

Nerve Supply & Key Surgical Relations

The thyroid has an intimate relationship with the recurrent laryngeal nerves (RLN), branches of the vagus nerve [CN X]:

The right RLN loops around the right subclavian artery
The left RLN loops around the arch of the aorta
Both ascend in the tracheo-esophageal groove and pass deep to the posteromedial surface of the lateral thyroid lobes before entering the larynx

The RLN runs near the inferior thyroid artery and may pass through Berry's ligament (the ligament of Gruber), which binds the thyroid to the trachea and cricoid cartilage. Damage to the RLN during thyroid surgery causes hoarseness (unilateral) or potentially fatal airway compromise (bilateral).

(Gray's Anatomy for Students, p. 1159-1160)

Histology

The thyroid is the only endocrine gland that stores its secretory product extracellularly - and in large quantities (enough for up to 3 months without further synthesis).

Low-power H&E micrograph of thyroid gland showing capsule (C), septa (S), and colloid-filled follicles

Structural organisation:

Covered by a fibrous capsule; septa extend inward dividing the parenchyma into lobules carrying blood vessels, nerves, and lymphatics
Each lobule contains 20-40 follicles

Thyroid follicle - the functional unit:

A spherical structure lined by simple follicular epithelium (thyrocytes)
Central lumen densely filled with colloid - a gelatinous, acidophilic material containing thyroglobulin (a 660 kDa glycoprotein), the precursor to thyroid hormones
Thyrocytes range from squamous (hypoactive gland) to low columnar (active gland) - their height is a direct indicator of functional activity
Thyrocytes are rich in rough ER basally, and have Golgi complexes, secretory granules, lysosomes, and microvilli apically (facing the colloid)

Parafollicular cells (C cells):

Located in or between follicles, within the basement membrane but not touching the colloid
Larger, paler-staining than thyrocytes
Secrete calcitonin - a polypeptide involved in calcium metabolism (lowers serum calcium by inhibiting osteoclasts)
Derived from neural crest cells (not from foregut endoderm like thyrocytes)
Origin of medullary thyroid carcinoma

(Junqueira's Basic Histology, p. 1034-1036)

Physiology: Hormone Synthesis & the HPT Axis

The thyroid produces two main hormones: T4 (thyroxine / tetraiodothyronine) and T3 (triiodothyronine), and regulates a third: calcitonin.

Hypothalamus-Pituitary-Thyroid (HPT) Axis

HPT axis and mechanism of action of thyroid hormones - TRH → TSH → cAMP → T3/T4 → nuclear receptor activation

Hypothalamus releases TRH (thyrotropin-releasing hormone)
TRH stimulates anterior pituitary thyrotrophs to release TSH (thyroid-stimulating hormone / thyrotropin)
TSH binds to the TSH receptor on thyroid follicular cells - a Gs protein-coupled receptor
Gs protein activation → ↑ cAMP → activates cAMP-dependent protein kinases
This stimulates thyroid growth and T3/T4 synthesis and release
Rising T3/T4 provide negative feedback to both the hypothalamus and pituitary

T3/T4 Synthesis Steps (in follicular cells)

Iodide uptake from blood via the sodium-iodide symporter (NIS) at the basolateral membrane
Iodide is oxidised to iodine by thyroid peroxidase (TPO) at the apical surface
Thyroglobulin (synthesised in follicular cells) is secreted into the colloid
Organification: iodine is attached to tyrosine residues on thyroglobulin to form MIT (monoiodotyrosine) and DIT (diiodotyrosine)
Coupling: MIT + DIT → T3; DIT + DIT → T4
On TSH stimulation, follicular cells endocytose colloid droplets (pseudopodia extend into the lumen)
Lysosomes digest thyroglobulin, releasing T3 and T4 into the bloodstream

Transport & Peripheral Conversion

Most circulating T3 and T4 are bound to thyroxine-binding globulin (TBG), transthyretin, and albumin
Only free (unbound) hormone is biologically active
In peripheral tissues, the majority of free T4 is deiodinated to T3
T3 binds thyroid hormone nuclear receptors (TR-alpha, TR-beta) with 10-fold greater affinity than T4 - it is the more potent form
TR forms a heterodimer with RXR and binds thyroid response elements (TREs) in target gene promoters → gene expression

Physiological Effects of Thyroid Hormones

System	Effect
Metabolism	↑ basal metabolic rate; stimulates carbohydrate and lipid catabolism; promotes protein synthesis
Cardiovascular	↑ heart rate and cardiac output; sensitises heart to catecholamines
Nervous system	Critical for fetal and neonatal brain development (deficiency causes cretinism/intellectual disability)
Bone	Normal linear growth and skeletal maturation
Thermogenesis	↑ heat production (calorigenic effect)

(Robbins, Cotran & Kumar Pathologic Basis of Disease, p. 993-995)

Receptor Mutations & Clinical Correlations

THRB gene mutations (TR-beta): tissue resistance to thyroid hormone → elevated T3/T4 levels with ineffective feedback inhibition of hypothalamus/pituitary
THRA gene mutations (TR-alpha): mildly low T4, elevated T3/T4 ratio, skeletal abnormalities
Thyroglossal duct cyst: midline neck mass, moves up on tongue protrusion; treated by Sistrunk procedure (removal of cyst + mid-portion of hyoid bone)

Sources:

Gray's Anatomy for Students (Gray's, p. 1157-1160)
Junqueira's Basic Histology, 17th ed. (p. 1034-1036)
Robbins, Cotran & Kumar Pathologic Basis of Disease (p. 993-995)

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