Thyroid gland

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The Thyroid Gland

Anatomy

The thyroid gland is a butterfly-shaped endocrine organ located in the anterior neck, lying deep to the sternohyoid, sternothyroid, and omohyoid muscles. It consists of two lateral lobes connected by a thin isthmus, which crosses the anterior surfaces of the 2nd and 3rd tracheal cartilages. The lateral lobes cover the anterolateral surfaces of the trachea, the cricoid cartilage, and the lower thyroid cartilage. The gland sits in the visceral compartment of the neck, surrounded by the pretracheal fascia alongside the pharynx, trachea, and esophagus. - Gray's Anatomy for Students, p. 1157

Fig. 8.181 - Thyroid gland in the anterior triangle of the neck (Gray's Anatomy for Students)

Arterial Supply

Two major arteries supply the thyroid:

Superior thyroid artery - the first branch of the external carotid artery; descends to the superior pole and divides into anterior and posterior glandular branches
Inferior thyroid artery - a branch of the thyrocervical trunk (from the 1st part of the subclavian artery); supplies the inferior pole and anastomoses with the superior thyroid artery

Venous Drainage

Three pairs of veins drain the thyroid:

Superior thyroid vein - drains into the internal jugular vein
Middle thyroid vein - drains into the internal jugular vein
Inferior thyroid vein - drains into the brachiocephalic vein

Important Relationships

Recurrent laryngeal nerve - runs posteriorly and is at risk during thyroid surgery
Parathyroid glands - four in number, embedded in the posterior surface of the thyroid lobes
External branch of the superior laryngeal nerve - runs close to the superior thyroid artery and can be injured during ligation

Embryology

The thyroid arises as a median outgrowth from the pharyngeal floor near the base of the tongue (foramen cecum). It migrates down via the thyroglossal duct to its final position in the anterior neck. The duct normally disappears but remnants can persist as:

Thyroglossal duct cyst (most common neck mass in children)
Lingual thyroid (ectopic thyroid at base of tongue)
Pyramidal lobe (upward extension along the duct path) - Robbins Pathologic Basis of Disease, p. 995

Histology

The thyroid is the only endocrine gland that stores its secretory product outside cells - in the colloid. It is divided by fibrous septa into lobules, each containing 20-40 follicles.

Anatomy and microscopic structure of the thyroid gland showing follicles, cuboidal epithelium, colloid, C cells, and capillaries

Figure 77.1 - Anatomy and microscopic structure of the thyroid gland (Guyton & Hall Medical Physiology)

Two Cell Types

Feature	Follicular cells (Thyrocytes)	Parafollicular cells (C cells)
Location	Line the follicle	In/between follicles
Size	Smaller, darker staining	Larger, pale staining
Shape	Squamous to low columnar (varies with activity)	Constant in size
Product	T3, T4	Calcitonin
Regulation	TSH from anterior pituitary	Serum Ca²+

Activity reflects cell shape: Active glands show low columnar epithelium; hypoactive glands show squamous follicular cells. - Junqueira's Basic Histology, p. 1034

Follicular colloid: Contains the large glycoprotein thyroglobulin (660 kDa), the precursor for thyroid hormones. There is sufficient hormone stored in the follicles to supply the body for up to 3 months without additional synthesis.

The thyroid is extremely well vascularized - blood flow is about five times the weight of the gland per minute, comparable only to the adrenal cortex. - Guyton & Hall, p. 930

Hormone Synthesis

The HPT (hypothalamus-pituitary-thyroid) axis controls hormone synthesis:

Hypothalamus-pituitary-thyroid axis and mechanism of action of thyroid hormones via TSH receptor, G-protein, cAMP, and nuclear receptors

Fig. 24.8 - Hypothalamus-pituitary-thyroid axis and mechanism of action (Robbins Pathologic Basis of Disease)

Steps of Thyroid Hormone Synthesis

Thyroid cell - iodine transport via NIS and pendrin, thyroglobulin synthesis, iodination, pinocytosis, and secretion of T3/T4

Figure 77.2 - Thyroid cellular mechanisms (Guyton & Hall Medical Physiology)

Iodide trapping - The sodium-iodide symporter (NIS) on the basolateral membrane co-transports 1 I⁻ with 2 Na⁺ into the cell (using Na⁺-K⁺-ATPase-driven gradient). Concentration ratio is normally ~30x blood, rising to 250x when maximally active.
Iodide transport to follicle - Iodide is moved across the apical membrane into the follicular lumen by pendrin (chloride-iodide counter-transporter).
Oxidation of iodide - Thyroid peroxidase (using H₂O₂) oxidizes iodide (I⁻) to active iodine (I₀ or I₃⁻) at the apical membrane.
Organification - Oxidized iodine binds tyrosine residues on thyroglobulin. Iodination of one tyrosine produces monoiodotyrosine (MIT); two iodines produces diiodotyrosine (DIT).
Coupling - MIT + DIT → T3 (triiodothyronine); DIT + DIT → T4 (thyroxine). Both remain within the thyroglobulin molecule until secretion.
Storage - Thyroid hormones are stored as part of thyroglobulin in the follicular colloid.
Secretion - TSH stimulates thyrocytes to pinocytose colloid droplets. Proteases cleave thyroglobulin to release free T3 and T4 into the bloodstream. MIT and DIT are deiodinated intracellularly, and iodide is recycled.

Iodine requirement: ~50 mg/year (~1 mg/week) of dietary iodine. Table salt is iodized at 1 part sodium iodide per 100,000 parts NaCl to prevent deficiency. - Guyton & Hall, p. 930-931

Circulating Hormones and Peripheral Conversion

Most secreted hormone is T4 (85%), with smaller amounts of T3 (15%)
In plasma, hormones are bound to thyroxine-binding globulin (TBG), transthyretin, and albumin - these act as a buffer maintaining stable free hormone levels
In peripheral tissues, ~80% of T4 is deiodinated to T3 (the active form)
T3 binds nuclear thyroid hormone receptors with 10-fold greater affinity than T4 and has proportionately greater biological activity
T3 acts on the nucleus as a heterodimer with retinoid X receptor (RXR) at thyroid hormone response elements, activating or suppressing gene transcription - Robbins, p. 995

Kinetics of Action

Hormone	Latent Period	Peak Effect	Half-life
T4 (thyroxine)	2-3 days	10-12 days	~15 days
T3 (triiodothyronine)	6-12 hours	2-3 days	~1 day

Physiological Actions of Thyroid Hormones

Thyroid hormones activate nuclear transcription of many genes and increase the functional activity of virtually every cell in the body:

System	Effect
Metabolism	Increases basal metabolic rate (BMR); stimulates carbohydrate and lipid catabolism; increases protein synthesis
Cardiovascular	Increases heart rate, cardiac output, and blood flow
Nervous system	Critical for fetal and neonatal brain development; maintains alertness and reflexes in adults
Growth	Promotes normal growth and skeletal maturation
Thermogenesis	Increases heat production (uncouples oxidative phosphorylation)
GI	Increases gut motility

Calcitonin (C cells)

C cells (parafollicular cells) secrete calcitonin, a polypeptide hormone that:

Is released in response to elevated serum calcium
Lowers plasma calcium by inhibiting osteoclast activity (reducing bone resorption)
Acts as a physiological antagonist to parathyroid hormone (PTH)
Has clinical use as a marker for medullary thyroid carcinoma - Junqueira's Basic Histology, p. 1035; Guyton & Hall, p. 930

HPT Axis and Feedback Regulation

Hypothalamus releases thyrotropin-releasing hormone (TRH)
Anterior pituitary responds with thyroid-stimulating hormone (TSH/thyrotropin)
TSH binds the TSH receptor on follicular cells → activates Gs protein → increases cAMP → stimulates thyroid hormone synthesis and release AND thyroid gland growth
Elevated T3/T4 feeds back negatively to inhibit both TRH and TSH secretion

Mutations in thyroid hormone receptors:

THRB (TR-beta) mutations → resistance to thyroid hormone, elevated T3/T4 levels (impaired feedback)
THRA (TR-alpha) mutations → different phenotype with mildly low T4 but elevated T3/T4 ratio - Robbins, p. 995-996

Sources:

Gray's Anatomy for Students (pp. 1157-1158) - Anatomy, blood supply, embryology
Guyton & Hall Textbook of Medical Physiology (pp. 930-934) - Physiology, hormone synthesis
Robbins & Cotran Pathologic Basis of Disease (pp. 995-996) - Pathology, HPT axis
Junqueira's Basic Histology (pp. 1034-1036) - Histology, cell types, calcitonin

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