Endocrine Pharmacology: Thyroid, Bone & Mineral Therapies

Endocrine Pharmacology Study Roadmap

🔹 1. Thyroid Physiology & Pathophysiology

🔸 Physiology

• TRH (hypothalamus) → stimulates TSH (anterior pituitary) → stimulates T3/T4 release (thyroid)

• T3 = active, T4 = prohormone

• Feedback loop: T3/T4 inhibit TRH and TSH

• T3/T4 actions:

  • ↑ Metabolic rate, heart rate, cardiac output

  • ↑ Oxygen consumption, lipolysis, glucose metabolism

  • CNS effects (mood), reproductive effects

🔸 Synthesis

• Iodide uptake → oxidation to iodine → binds to thyroglobulin → forms MIT/DIT → forms T3/T4

🔸 Disorders

• Hypothyroidism: Hashimoto's thyroiditis, iodine deficiency, thyroidectomy, myxedema coma

• Hyperthyroidism: Graves' disease, toxic adenoma, thyroid storm

🔹 2. Thyroid Pharmacology

🔸 For Hypothyroidism

• Levothyroxine (T4): DOC, stable; converted to T3 in the body

• Liothyronine (T3): Rapid onset; used in myxedema coma or when rapid replacement is required

• T4–T3 combination: For select patients (post-thyroidectomy or poor T4 response)

🔸 For Hyperthyroidism

1. Inhibitors of Iodine Uptake – Perchlorate salts
   ⮕ MOA: Compete with iodide for the sodium/iodide symporter (NIS) → ↓ thyroid hormone synthesis

2. Thionamides – Methimazole, PTU (propylthiouracil)
   ⮕ MOA: Block iodine oxidation and inhibit T4 → T3 peripheral conversion
   ⮕ Adverse effects: Rash, agranulocytosis, hepatotoxicity (PTU preferred in the first trimester of pregnancy)

3. Iodides (SSKI, Lugol's solution)
   ⮕ MOA: Inhibits thyroid hormone release (Wolff–Chaikoff effect)
   ⮕ Use: Pre-thyroidectomy preparation, thyroid storm

4. Beta Blockers (Propranolol, Atenolol)
   ⮕ Block thyroid hormone effects at β-receptors and reduce peripheral T4 → T3 conversion
   ⮕ Contraindications: Asthma, bradycardia

🔹 3. Bone Mineral Homeostasis

🔸 Hormonal Regulation

• PTH (parathyroid hormone) – ↑ Calcium reabsorption (kidney and GI), ↑ bone resorption

• Calcitonin – ↓ bone resorption

• Vitamin D (Calcitriol) – ↑ Calcium and phosphate intestinal absorption, ↑ bone turnover

🔹 4. Disorders of Bone Metabolism

🔸 Osteoporosis

• ↓ Bone mass = ↑ fracture risk

• Risk factors: Age, chronic steroid use, smoking, alcohol, menopause

🔸 Secondary Hyperparathyroidism

• ↑ PTH due to chronic kidney disease → ↑ bone turnover, hyperphosphatemia

🔹 5. Pharmacology of Bone Disorders

🔸 Anti-Resorptive Agents

🔸 Anabolic Agents

🔸 Secondary Hyperparathyroidism Treatment

🔸 Supplements

• Calcium: <= 2000 mg/day total intake

• Vitamin D3 (preferred): 600–800 IU/day

• Adverse effects: Kidney stones, drug interactions (iron, levothyroxine)