L8 Thyroid and Parathyroid

I. Anatomy of the Thyroid Gland

• Structure:

  • Butterfly-shaped with 2 lobes connected by an isthmus.

  • Located in the anterior neck, surrounding the larynx and trachea.

  • Dimensions: Each lobe ~5x3 cm, isthmus >1 cm.

  • Weight: 20-60 g (largest endocrine gland in adults).

• Microscopic Anatomy:

  • Follicles: Functional units filled with colloid (contains thyroglobulin, Tg).

    • Follicular cells: Produce Tg and thyroid hormones (T₃, T₄).

    • C cells (parafollicular cells): Secrete calcitonin (regulates calcium).

  • Rich blood supply: Supports hormone synthesis and release.

II. Thyroid Hormone Synthesis

1. Iodine Uptake

• Dietary iodine (as iodide, I⁻) is actively transported into follicular cells via Na⁺/I⁻ symporter(stimulated by TSH).

• Concentrated 30x in follicles.

2. Hormone Synthesis Steps:

1. Iodination:

   • Thyroperoxidase (TPO) oxidizes I⁻ to reactive iodine.

   • Iodine binds to tyrosine residues on Tg → forms MIT (monoiodotyrosine) and DIT (diiodotyrosine).

2. Coupling:

   • MIT + DIT → T₃ (triiodothyronine).

   • DIT + DIT → T₄ (thyroxine).

3. Storage: Hormones stored in colloid as part of Tg.

4. Release:

   • Tg is endocytosed, cleaved by lysosomes → free T₃/T₄ secreted into blood.

3. Key Enzymes/Proteins:

• TPO: Critical for iodination (target in autoimmune thyroiditis).

• Pendrin: Exchanges I⁻ for Cl⁻ at follicular membrane.

• Megalin: Binds iodinated Tg for endocytosis.

III. Thyroid Hormones (T₃ and T₄)

• T₄ (Thyroxine):

  • Primary secretory product (~70-90 µg/day).

  • Pro-hormone: Converted to active T₃ in peripheral tissues (liver, kidney) via deiodinases:

    • Type I: Liver/kidney (80% of T₃ production).

    • Type II: CNS/pituitary (regulates TSH feedback).

    • Type III: Inactivates T₄ to reverse T₃ (rT₃).

• T₃ (Triiodothyronine):

  • More biologically active (10x affinity for nuclear receptors).

  • 20% from thyroid, 80% from peripheral conversion.

  • Daily production 15-30 µg/day.

Transport in Blood:

• >99% bound to carrier proteins:

  • Thyroxine-binding globulin (TBG): 75% of T₄.

  • Transthyretin (TTR): 10-15% of T₄.

  • Albumin: 7% (low affinity, high capacity).

• Free hormone hypothesis: Only unbound (0.03% T₄, 0.3% T₃) is biologically active.

IV. Regulation of Thyroid Function

• Hypothalamus-Pituitary-Thyroid Axis:

  1. TRH (Thyrotropin-Releasing Hormone) from hypothalamus → stimulates TSH release.

  2. TSH (Thyroid-Stimulating Hormone) → stimulates thyroid hormone synthesis/secretion.

  3. Negative feedback: High T₃/T₄ inhibits TRH/TSH.

V. Thyroid Disorders

A. Hypothyroidism

• Causes:

  • Primary: Thyroid destruction (e.g., Hashimoto’s thyroiditis—autoimmune anti-TPO antibodies).

  • Secondary: Pituitary dysfunction (low TSH).

  • Tertiary: Hypothalamic dysfunction.

• Symptoms:

  • Fatigue, weight gain, cold intolerance, bradycardia, dry skin, myxedema (severe hypothyroidism).

• Lab Findings:

  • High TSH, low T₃/T₄ (primary).

  • Low TSH/T₃/T₄ (secondary/tertiary).

B. Hyperthyroidism

• Causes:

  • Graves’ disease (most common): Autoantibodies activate TSH receptors → excess hormone production.

  • Thyroid nodules, thyroiditis.

• Symptoms:

  • Weight loss, tachycardia, heat intolerance, exophthalmos (Graves’), tremors.

• Lab Findings:

  • Low TSH, high T₃/T₄.

VI. Parathyroid Glands and Calcium Homeostasis

1. Anatomy:

• 4 small glands on posterior thyroid.

• Cell Types:

  • Chief cells: Secrete PTH (parathyroid hormone).

  • Oxyphil cells: Function unknown.

2. Parathyroid Hormone (PTH):

• Function: Raises blood calcium via:

  1. Bone: Stimulates osteoclasts → releases Ca²⁺.

  2. Kidneys: Reduces Ca²⁺ excretion, activates vitamin D.

  3. Intestines: Vitamin D enhances Ca²⁺ absorption.

• Regulation:

  • Low Ca²⁺ → ↑ PTH.

  • High Ca²⁺ → ↓ PTH (via calcium-sensing receptor, CaSR).

3. Calcitonin (from thyroid C cells):

• Lowers blood Ca²⁺ (opposes PTH):

  • Inhibits osteoclasts, promotes Ca²⁺ deposition in bone.

  • Minor role in adults; more important in children.

4. Vitamin D:

• Activated by PTH in kidneys → enhances intestinal Ca²⁺ absorption.

VII. Parathyroid Disorders

A. Hyperparathyroidism

• Cause: PTH overproduction (adenoma, hyperplasia).

• Effects:

  • Hypercalcemia, kidney stones, bone pain, osteoporosis.

• Treatment: Surgical removal of gland(s).

B. Hypoparathyroidism

• Cause: PTH deficiency (surgery, autoimmune).

• Effects:

  • Hypocalcemia → Convulsions, Aarrythmias, Tetany, Spasm (mnemonic: CATS).

• Treatment: Calcium/Vitamin D supplements.

VIII. Clinical Pearls

• Myxedema coma: Life-threatening severe hypothyroidism.

• Iodine pills in nuclear accidents: Block radioactive iodine uptake by thyroid.

• Postpartum thyroiditis: Autoimmune thyroid inflammation after childbirth.

• DiGeorge syndrome: Congenital absence of parathyroids (hypocalcemia).

• Levothyroxine: Synthetic T₄ for hypothyroidism treatment.