L8 Thyroid and Parathyroid

I. Anatomy of the Thyroid Gland

• Structure:

  • Butterfly-shaped:

    • Consisting of two lobes.

    • Connected by the isthmus.

  • Location:

    • Situated in the anterior neck.

    • Surrounds the larynx and trachea.

• Microscopic Anatomy:

  • Follicles:

    • Functional units of the thyroid.

    • Filled with colloid.

      • Colloid contains thyroglobulin (Tg).

  • Follicular cells:

    • Produce thyroglobulin (Tg).

    • Synthesize thyroid hormones (T₃, T₄).

  • C cells (parafollicular cells):

    • Secrete calcitonin.

    • Regulate calcium levels in the blood.

  • Rich Blood Supply:

    • Essential for hormone synthesis.

    • Facilitates hormone release.

II. Thyroid Hormone Synthesis

1. Iodine Uptake

• Dietary iodine (I⁻):

  • Actively transported into follicular cells.

  • Via Na⁺/I⁻ symporter.

    • Stimulated by TSH (Thyroid-Stimulating Hormone).

  • Concentrated significantly:

    • Approximately 30 times higher in follicles compared to blood.

2. Hormone Synthesis Steps:

• Iodination:

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

  • Iodine binds to tyrosine residues on Tg.

    • Forms monoiodotyrosine (MIT) and diiodotyrosine (DIT).

• Coupling:

  • MIT + DIT → T₃ (triiodothyronine).

  • DIT + DIT → T₄ (thyroxine).

• Storage:

  • Hormones stored in the colloid.

  • Stored as part of thyroglobulin (Tg).

• Release:

  • Thyroglobulin (Tg) is endocytosed.

  • Cleaved by lysosomes.

    • Results in the release of free T₃ and T₄.

  • Hormones are secreted into the bloodstream.

3. Key Enzymes/Proteins:

• Thyroperoxidase (TPO):

  • Critical for iodination.

  • Target in autoimmune thyroiditis.

• Pendrin:

  • Exchanges I⁻ for Cl⁻ at the follicular membrane.

• Megalin:

  • Binds iodinated Tg for endocytosis.

III. Thyroid Hormones (T₃ and T₄)

• T₄ (Thyroxine):

  • Primary secretory product.

    • Approximately 70-90 µg/day.

  • Pro-hormone:

    • Converted to active T₃ in peripheral tissues.

      • Liver, kidney.

    • Conversion via deiodinases:

      • Type I:

        • Found in liver/kidney.

        • Responsible for approximately 80% of T₃ production.

      • Type II:

        • Found in CNS/pituitary.

        • Regulates TSH feedback.

      • Type III:

        • Inactivates T₄ to reverse T₃ (rT₃).

• T₃ (Triiodothyronine):

  • More biologically active.

    • Has 10x affinity for nuclear receptors compared to T₄.

  • Production:

    • 20% from the thyroid gland.

    • 80% from peripheral conversion.

  • Daily production: 15-30 µg/day.

Transport in Blood:

• Highly bound to carrier proteins:

  • Approximately >99% bound.

  • Thyroxine-binding globulin (TBG):

    • Carries approximately 75% of T₄.

  • Transthyretin (TTR):

    • Carries approximately 10-15% of T₄.

  • Albumin:

    • Carries approximately 7%.

    • Low affinity but high capacity.

• Free hormone hypothesis:

  • Only the unbound hormone is biologically active.

    • Approximately 0.03% of T₄ and 0.3% of T₃.

IV. Regulation of Thyroid Function

• Hypothalamus-Pituitary-Thyroid Axis:

  • TRH (Thyrotropin-Releasing Hormone):

    • Released from the hypothalamus.

    • Stimulates TSH release from the pituitary.

  • TSH (Thyroid-Stimulating Hormone):

    • Stimulates thyroid hormone synthesis and secretion.

  • Negative feedback:

    • High levels of T₃/T₄ inhibit TRH and TSH release.

V. Thyroid Disorders

A. Hypothyroidism

• Causes:

  • Primary:

    • Thyroid destruction.

      • Hashimoto’s thyroiditis: autoimmune anti-TPO antibodies.

  • Secondary:

    • Pituitary dysfunction.

      • Results in low TSH.

  • Tertiary:

    • Hypothalamic dysfunction.

• Symptoms:

  • Fatigue.

  • Weight gain.

  • Cold intolerance.

  • Bradycardia.

  • Dry skin.

  • Myxedema (severe hypothyroidism).

• Lab Findings:

  • Primary:

    • High TSH, low T₃/T₄.

  • Secondary/Tertiary:

    • Low TSH/T₃/T₄.

B. Hyperthyroidism

• Causes:

  • Graves’ disease:

    • Autoantibodies activate TSH receptors.

      • Leads to 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:

• Four small glands:

  • Located on the posterior side of the thyroid.

• Cell Types:

  • Chief cells:

    • Secrete PTH (parathyroid hormone).

  • Oxyphil cells:

    • Function is currently unknown.

2. Parathyroid Hormone (PTH):

• Function:

  • Raises blood calcium levels via:

    • Bone:

      • Stimulates osteoclasts.

      • Results in the release of Ca²⁺.

    • Kidneys:

      • Reduces Ca²⁺ excretion.

      • Activates vitamin D.

    • Intestines:

      • Vitamin D enhances Ca²⁺ absorption.

• Regulation:

  • Low Ca²⁺ stimulates PTH release.

  • High Ca²⁺ inhibits PTH release.

    • Via calcium-sensing receptor (CaSR).

3. Calcitonin (from thyroid C cells):

• Lowers blood Ca²⁺:

  • Opposes PTH.

  • Inhibits osteoclasts.

  • Promotes Ca²⁺ deposition in bone.

  • Role:

    • 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 the affected gland(s).

B. Hypoparathyroidism

• Cause:

  • PTH deficiency (surgery, autoimmune).

• Effects:

  • Hypocalcemia.

  • Convulsions, Aarrythmias, Tetany, Spasm (CATS).

• Treatment:

  • Calcium/Vitamin D supplements.