Introduction to Endocrine Pharmacology – Part I
The endocrine system uses hormones as chemical messengers to regulate metabolism, growth, reproduction, and homeostasis. This unit covers the pharmacology of Anterior Pituitary hormones (Growth Hormone, Prolactin, Gonadotropins), Thyroid and Antithyroid drugs, Calcium-regulating hormones (Parathormone, Calcitonin, Vitamin D), the vital Insulin/Oral Hypoglycemic drugs for Diabetes Mellitus, and the powerful ACTH/Corticosteroid system. Understanding when and how to use these drugs — and their significant adverse effects — is clinically paramount.
Syllabus & Topics
- 1Basic Concepts in Endocrine Pharmacology: Hormones are chemical messengers secreted by endocrine glands into the bloodstream. Hormone replacement (hypothyroidism → thyroxine), Hormone suppression (hyperthyroidism → antithyroid drugs), Hormone analogues (synthetic insulin), Hormone antagonists (anti-estrogens). Feedback loops: Hypothalamus → Anterior Pituitary → Target gland → Negative feedback.
- 2Anterior Pituitary Hormones – Growth Hormone (GH/Somatotropin): Stimulates linear growth, protein synthesis, lipolysis, and blood glucose elevation. Recombinant GH (Somatropin) – used for GH-deficient dwarfism, Turner syndrome. Excess → Gigantism (children), Acromegaly (adults). GH inhibitors: Octreotide (somatostatin analogue – inhibits GH release, used in acromegaly).
- 3Anterior Pituitary – Other Hormones: Prolactin (stimulates lactation. Excess → hyperprolactinemia. Treatment: Bromocriptine, Cabergoline – dopamine D₂ agonists → ↓prolactin). Gonadotropins: FSH + LH (regulate reproductive function. Used for infertility treatment). ACTH (stimulates adrenal cortex → cortisol). Oxytocin and Vasopressin from Posterior Pituitary.
- 4Thyroid Hormones – Physiology: Thyroid gland produces T₄ (thyroxine, prohormone) and T₃ (triiodothyronine, active form – 3-5x more potent). Synthesis: Iodide uptake → Oxidation → Organification → Coupling (MIT + DIT = T₃; DIT + DIT = T₄). Actions: ↑BMR, ↑heat production, growth & development, cardiac stimulation.
- 5Thyroid Hormones – Drugs: Levothyroxine (synthetic T₄ – drug of choice for hypothyroidism, long t½ ~7 days, once daily). Liothyronine (synthetic T₃ – rapid onset, used for myxedema coma). Hypothyroidism causes: fatigue, weight gain, cold intolerance, constipation, bradycardia, myxedema.
- 6Antithyroid Drugs: Thioureylenes: Propylthiouracil (PTU – inhibits thyroid peroxidase + blocks peripheral T₄→T₃ conversion), Methimazole/Carbimazole (inhibits TPO only, more potent, longer duration, preferred for Graves’ disease). ADRs: agranulocytosis (rare but serious). Radioactive Iodine (¹³¹I) – destroys thyroid tissue (definitive treatment for Graves’). Iodides (Lugol’s solution – pre-surgery, ↓vascularity of thyroid gland).
- 7Calcium-Regulating Hormones – Parathormone (PTH): Secreted by parathyroid glands when plasma Ca²⁺ ↓. Actions: ↑Ca²⁺ reabsorption (kidney), ↑Ca²⁺ release from bone (osteoclast activation), ↑Vitamin D activation (1,25-DHCC). Teriparatide (recombinant PTH 1-34): paradoxically, intermittent low-dose → anabolic (builds bone) → used for severe osteoporosis.
- 8Calcium – Calcitonin & Vitamin D: Calcitonin (from thyroid C-cells): opposes PTH → ↓plasma Ca²⁺ by inhibiting osteoclasts (↓bone resorption). Salmon calcitonin (Miacalcin nasal spray) – used for Paget’s disease, osteoporosis. Vitamin D (Cholecalciferol D₃): activated in liver (25-OH) → kidney (1,25-dihydroxycholecalciferol = Calcitriol – active form). ↑Ca²⁺ absorption from gut. Deficiency → Rickets (children), Osteomalacia (adults).
- 9Bisphosphonates: Alendronate, Risedronate, Zoledronic acid – pyrophosphate analogues that bind to hydroxyapatite on bone surface. Inhibit osteoclast-mediated bone resorption → ↓bone loss. First-line for osteoporosis. ADR: esophageal ulceration (must take upright with full glass of water), osteonecrosis of jaw (rare).
- 10Insulin – Physiology & Preparations: Secreted by β-cells of pancreatic islets. Actions: ↓blood glucose by (1) ↑glucose uptake into muscle/fat (GLUT4), (2) ↑glycogenesis, (3) ↓gluconeogenesis, (4) ↑protein/fat synthesis. Preparations: Rapid-acting (Lispro, Aspart – 15 min onset), Short-acting (Regular insulin – 30 min), Intermediate (NPH/Isophane – 1-2 hr), Long-acting (Glargine – 24 hr peakless basal, Detemir).
- 11Oral Hypoglycemics – Sulfonylureas & Biguanides: Sulfonylureas (Glibenclamide, Glipizide, Glimepiride – close K⁺-ATP channels on β-cells → insulin secretion. ADR: hypoglycemia, weight gain). Biguanides: Metformin – first-line for Type 2 DM. Activates AMPK → ↓hepatic gluconeogenesis, ↑insulin sensitivity. No hypoglycemia, weight neutral/loss. ADR: lactic acidosis (rare, contraindicated in renal failure).
- 12Oral Hypoglycemics – Other Classes: Thiazolidinediones (Pioglitazone – PPARγ agonist → ↑insulin sensitivity. ADR: weight gain, edema, hepatotoxicity). Meglitinides (Repaglinide – rapid-acting insulin secretagogue, pre-meal). α-Glucosidase inhibitors (Acarbose, Voglibose – delay carbohydrate digestion → ↓postprandial glucose). DPP-4 inhibitors (Sitagliptin – ↑incretin levels → ↑insulin secretion). GLP-1 agonists (Exenatide – injectable, weight loss). SGLT2 inhibitors (Dapagliflozin – ↑urinary glucose excretion).
- 13Glucagon: Secreted by α-cells of pancreatic islets. Actions: oppose insulin → ↑blood glucose (↑glycogenolysis, ↑gluconeogenesis). Used IV/IM for severe hypoglycemia (when patient is unconscious and cannot take oral glucose). Also used in β-blocker overdose (↑cardiac contractility via non-adrenergic pathway).
- 14ACTH & Corticosteroids – Physiology: ACTH from anterior pituitary → stimulates adrenal cortex. Cortisol (glucocorticoid): anti-inflammatory, immunosuppressive, metabolic (↑blood glucose, protein catabolism, fat redistribution). Aldosterone (mineralocorticoid): Na⁺/water retention, K⁺ excretion.
- 15Corticosteroids – Drugs & ADRs: Hydrocortisone (replacement therapy), Prednisolone (4x potent, less mineralocorticoid), Dexamethasone (30x potent, no mineralocorticoid, diagnostic use – Dexamethasone suppression test for Cushing’s). ADRs (chronic use): Cushing’s syndrome (moon face, buffalo hump, central obesity), diabetes, osteoporosis, peptic ulcer, immunosuppression, adrenal suppression (abrupt withdrawal → Addisonian crisis), skin thinning, cataracts, growth retardation in children.
Learning Objectives
Frequently Asked Questions (FAQs)
Q1. Why Is Metformin the First-Line Drug for Type 2 Diabetes?
Metformin is considered first-line therapy for Type 2 Diabetes Mellitus because it lowers blood glucose without stimulating insulin secretion, making hypoglycemia uncommon. It also promotes weight neutrality or modest weight loss, improves insulin sensitivity, and reduces hepatic glucose production by activating the AMPK pathway. Clinical trials such as the UKPDS trial demonstrated that metformin can reduce cardiovascular complications, further supporting its use as initial therapy.
Q2. What Is Addisonian Crisis and Why Does It Occur?
Addisonian crisis is a life-threatening condition that occurs when long-term corticosteroid therapy is suddenly discontinued. Chronic steroid use suppresses the hypothalamic–pituitary–adrenal (HPA) axis through negative feedback, causing adrenal gland atrophy. If therapy is abruptly stopped, the adrenal glands cannot rapidly produce sufficient cortisol, leading to severe hypotension, hypoglycemia, electrolyte disturbances, and possible shock. To prevent this, corticosteroid therapy must be gradually tapered.
Q3. How Does Radioactive Iodine Treat Graves’ Disease?
Iodine-131 is used to treat Graves disease because the thyroid gland naturally concentrates iodine. Once inside thyroid follicular cells, iodine-131 emits beta radiation that selectively destroys overactive thyroid tissue. Over several weeks, this reduces thyroid hormone production. Many patients eventually develop hypothyroidism and require lifelong thyroid hormone replacement with Levothyroxine.
Q4. What Is the Difference Between Insulin Glargine and Regular Insulin?
Regular insulin has an onset of about 30 minutes, peaks within 2–4 hours, and lasts approximately 6–8 hours, so it is typically administered before meals to control postprandial glucose. Insulin glargine has a slow onset (about 1–2 hours), no pronounced peak, and a duration of around 24 hours. It provides continuous basal insulin levels because it forms microprecipitates at the injection site, releasing insulin gradually.
Q5. Why Is PTU Preferred Over Methimazole in Thyroid Storm?
Propylthiouracil and Methimazole both inhibit thyroid peroxidase, preventing synthesis of new thyroid hormones. However, propylthiouracil also inhibits peripheral conversion of T4 to the more active T3 by blocking type 1 deiodinase. Because rapid reduction of circulating T3 levels is essential in severe thyrotoxicosis such as Thyroid storm, PTU is often preferred in this emergency situation.