Thyroid Gland: Complete Anatomy and Physiology

1. Embryology

Embryology: path of descent of the thyroid (median bud) and parathyroids from pharyngeal pouches. IPG = inferior parathyroid; SPG = superior parathyroid; UBB = ultimobranchial body. - Bailey & Love's Surgery, 28th Ed.

• The initially hollow thyroglossal duct migrates caudally, passing through or near the developing hyoid cartilage
• By week 7, the thyroid has assumed its definitive shape and position anterior to the trachea
• The thyroid lobes amalgamate with structures from the 4th pharyngeal pouch (superior parathyroid gland and ultimobranchial body)
• Parafollicular C cells (calcitonin-secreting) originate from neural crest cells and reach the thyroid via the ultimobranchial body
• Parathyroid glands develop from the 3rd (inferior) and 4th (superior) pharyngeal pouches
• The thyroglossal duct normally involutes; its remnant may persist as a pyramidal lobe (~50% of individuals) or cause pathology (thyroglossal duct cysts)

• Lingual thyroid: failure to descend, leaving gland at base of tongue
• Thyroglossal duct cysts: cystic remnants along the descent path, lined by pseudostratified ciliated columnar epithelium; treated by Sistrunk operation (en bloc cystectomy + central hyoid bone excision)

2. Gross Anatomy

Position and Shape

Full anatomical relationships of the thyroid gland and surrounding structures - anterior view (Netter illustration, from Rosen's Emergency Medicine)

Lobes and Isthmus

• Two lobes (right and left), connected by an isthmus located just inferior to the cricoid cartilage
• Each lobe extends from the midthyroid cartilage superiorly, lying adjacent to the carotid sheaths and sternocleidomastoid muscles laterally
• Pyramidal lobe: present in ~50% of people, projects upward from the isthmus, just left or right of midline - becomes enlarged and palpable in Graves' disease or thyroiditis

Fascial Relations

• Enveloped by a loose fascia derived from the deep cervical fascia (anterior and posterior divisions)
• The true capsule is a thin, densely adherent fibrous layer that sends septa inward, forming pseudolobules
• The capsule condenses posteriorly into Berry's ligament (posterior suspensory ligament) near the cricoid and upper tracheal rings - this ligament anchors the thyroid to the trachea, causing the gland to move with swallowing

Strap Muscles (anterior)

3. Blood Supply

Thyroid gland from behind showing parathyroid glands, recurrent laryngeal nerves, vessels - Bailey & Love's Surgery, 28th Ed.

Arteries

Veins

• Superior thyroid veins - drain into the internal jugular vein
• Middle thyroid veins - drain into the internal jugular vein
• Inferior thyroid veins - drain into the brachiocephalic veins (right and left)

4. Nerve Supply

Recurrent Laryngeal Nerve (RLN)

• A branch of the vagus nerve (CN X)
• Left RLN: recurs around the arch of the aorta - has more distance to travel, runs in a more medial plane in the tracheo-oesophageal groove
• Right RLN: recurs around the subclavian artery - has less distance, runs more obliquely to reach the groove
• ~2% of right nerves are non-recurrent (enter larynx from above) - associated with an aberrant right subclavian artery
• The nerve runs posterior to the thyroid and enters the larynx at the cricothyroid joint
• Critical relation: the RLN crosses the inferior thyroid artery; the superior parathyroid is characteristically dorsal to the nerve plane, the inferior parathyroid is ventral
• Injury → hoarseness (unilateral) or respiratory distress (bilateral)

Superior Laryngeal Nerve (SLN)

• Also a branch of the vagus
• External branch runs near the superior thyroid vessels and controls the cricothyroid muscle (voice pitch)
• Injury during superior pole dissection → monotone voice, difficulty singing high notes

5. Lymphatic Drainage

• Subcapsular plexus drains principally to:
  • Central compartment (level VI): juxtathyroid "Delphian" nodes, paratracheal nodes, and nodes on superior and inferior thyroid veins
• Then onwards to:
  • Deep cervical nodes (levels II, III, IV, V)
  • Mediastinal nodes (level VII)

6. Histology (Microscopic Anatomy)

Histology of the normal thyroid gland (H&E stain) showing multiple follicles filled with colloid, lined by cuboidal epithelium - Bailey & Love's Surgery, 28th Ed.

• Each lobule (supplied by a single arteriole) contains 24-40 follicles
• Each follicle measures 200-300 µm in diameter
• Lined by a single layer of cuboidal follicular epithelial cells (become columnar when active, flat when inactive)
• The cells have a basal membrane facing the blood and an apical membrane facing the follicular lumen
• The lumen contains colloid - a viscous material composed of thyroglobulin (TG) with attached thyroid hormones
• Between follicles lie parafollicular cells (C cells) - larger, pale cells that secrete calcitonin (lowers blood calcium)

7. Thyroid Hormone Synthesis (Step-by-Step)

The 8 Steps

• Inhibited by: perchlorate, thiocyanate

• Inhibited by: propylthiouracil (PTU), methimazole

• 1 iodine + tyrosine = monoiodotyrosine (MIT)
• 2 iodines + tyrosine = diiodotyrosine (DIT)
• High iodine levels block this step = Wolff-Chaikoff effect

• DIT + DIT = T₄ (thyroxine/tetraiodothyronine) - 4 iodine atoms
• DIT + MIT = T₃ (triiodothyronine) - 3 iodine atoms
• MIT + MIT = T₂ (inactive)

8. Transport in Blood

• >99% of circulating thyroid hormones are bound to plasma proteins:
  • Thyroxine-binding globulin (TBG) - primary carrier
  • Transthyretin (T₄-binding prealbumin)
  • Albumin
• <1% circulates as free (unbound) hormone - this is the biologically active fraction
• The bound pool serves as a large reservoir that buffers free hormone levels
• T₄ has a plasma half-life of ~7 days; T₃ ~1 day

9. Peripheral Conversion

• T₄ is the dominant secretory product but is the pro-hormone
• Target tissues (liver, kidney, brain, skeletal muscle, gut) convert T₄ → T₃ by 5'-deiodinase (removes one iodine) - this accounts for ~80% of circulating T₃
• Reverse T₃ (rT₃) - inactive isomer formed by deiodination at a different position; increases in illness/starvation (sick euthyroid syndrome)

10. Regulation: The HPT Axis

Negative feedback loop of thyroid hormone regulation - hypothalamic-pituitary-thyroid axis. TRH stimulates TSH; TSH stimulates T₄/T₃ release; T₄ and T₃ feed back negatively at both levels.

The Axis

1. Hypothalamus releases TRH (thyrotropin-releasing hormone, a tripeptide) → stimulates anterior pituitary
2. Anterior pituitary thyrotroph cells release TSH (thyroid-stimulating hormone, a glycoprotein) → binds receptors on follicular cells
3. TSH actions on thyroid:
   • Increases iodide uptake
   • Stimulates all steps of hormone synthesis
   • Stimulates endocytosis and secretion of T₃/T₄
   • Promotes thyroid cell growth (hypertrophy and hyperplasia)
4. Negative feedback: elevated T₃/T₄ suppresses both TRH (hypothalamus) and TSH (pituitary), completing the loop

Other regulators

• Iodine excess directly suppresses thyroid hormone synthesis (Wolff-Chaikoff effect) - used in preoperative preparation (Lugol's iodine)
• Dopamine and glucocorticoids suppress TSH secretion

11. Actions of Thyroid Hormones

Metabolic Actions

• Primary driver of basal metabolic rate (BMR)
• Stimulates mitochondrial ATP production, oxygen consumption, and glucose oxidation (calorigenic effect - generates heat)
• Increases lipid and carbohydrate metabolism
• Stimulates gluconeogenesis and lipolysis

Cardiovascular

• Increases cardiac output, heart rate, and stroke volume
• Causes peripheral vasodilation
• Synergistic with catecholamines via β-adrenergic receptors (explains why propranolol reduces symptoms of hyperthyroidism)

Growth and Development

• Essential for normal in utero and childhood growth (bone maturation, linear growth)
• Critical for CNS maturation in the perinatal period - neonatal hypothyroidism causes irreversible cretinism (mental retardation, growth failure) if untreated → mandates newborn screening
• In adults, hypothyroidism causes slowed cognition, lethargy, somnolence

Reproductive Function

• Normal reproductive function depends on adequate thyroid hormone
• Both hypo- and hyperthyroidism cause menstrual irregularities and subfertility

12. Calcitonin (C Cell Function)

• Secreted by parafollicular (C) cells in response to hypercalcemia
• Lowers blood calcium by inhibiting osteoclast activity and promoting renal calcium excretion
• Less important in adult calcium homeostasis than PTH
• Clinically significant as a tumor marker for medullary thyroid carcinoma (MTC)

13. Quick Pathophysiology Summary