Thyroid hormones play a crucial role in metabolism, growth, and development.
Pharmacological manipulation of these hormones is essential in treating various thyroid disorders.
Thyroid Hormones: T3 (Triiodothyronine) and T4 (Thyroxine)
Synthesis:
Iodide uptake by thyroid follicular cells.
Iodination of tyrosine residues on thyroglobulin (organification).
Coupling of iodotyrosines (MIT & DIT) to form T3 and T4.
Proteolysis of thyroglobulin to release T3 and T4 into circulation.
Regulation:
TSH from the pituitary stimulates thyroid hormone synthesis.
Negative feedback by circulating T3/T4 regulates secretion.
Thyroid Hormone Analogues
Levothyroxine (Synthetic T4):
Uses: Primary treatment for hypothyroidism.
Mechanism: Replaces deficient T4, converted to active T3 in peripheral tissues.
Adverse Effects: Symptoms of hyperthyroidism if overdosed (e.g., tachycardia, weight loss).
Liothyronine (Synthetic T3):
Uses: Rapid thyroid hormone action (e.g., myxedema coma).
Adverse Effects: Higher risk of cardiac side effects.
Desiccated Thyroid Extracts:
Uses: Contains both T4 and T3, less commonly used.
Thyroid Hormone Inhibitors
Thionamides:
Methimazole and Propylthiouracil (PTU):
Uses: First-line treatments for hyperthyroidism (e.g., Graves' disease).
Mechanism: Inhibit thyroid peroxidase, blocking iodine incorporation and coupling. PTU also inhibits peripheral T4 to T3 conversion.
Adverse Effects: Rash, agranulocytosis, hepatotoxicity (rare).
Iodine Solutions (Potassium Iodide):
Uses: Acute hyperthyroidism management (e.g., thyroid storm) and pre-surgical preparation.
Mechanism: Temporarily inhibits hormone release and synthesis (Wolff–Chaikoff effect).
Adverse Effects: Hypersensitivity, metallic taste, salivary gland swelling.
Radioactive Iodine (I-131):
Uses: Definitive hyperthyroidism treatment by destroying thyroid tissue.
Adverse Effects: Hypothyroidism post-treatment, radiation thyroiditis.
Beta-Blockers (e.g., Propranolol):
Uses: Symptomatic control (e.g., tachycardia, tremor) and blocks peripheral T4 to T3 conversion.
Adverse Effects: Bradycardia, fatigue.
Clinical Applications
Hypothyroidism: Treated with levothyroxine or liothyronine to restore normal function.
Hyperthyroidism: Managed with thionamides, iodine solutions, radioactive iodine, or beta-blockers.
Thyroid Cancer: Treated with thyroid hormone analogues to suppress TSH or radioactive iodine for ablation.
Side Effects Overview
Thionamides: Agranulocytosis, hepatotoxicity, teratogenicity (methimazole).
Levothyroxine: Hyperthyroidism symptoms if overdosed (e.g., palpitations, anxiety).
Radioactive Iodine: Hypothyroidism post-treatment, radiation thyroiditis.