Addison's disease Study Guide

📖 Core Concepts Primary adrenal insufficiency (Addison’s disease) – loss of both cortisol and aldosterone production because the adrenal cortex is damaged. Cortisol: “stress hormone,” maintains glucose, blood pressure, immune balance. Aldosterone: mineralocorticoid that retains sodium and excretes potassium → controls fluid balance. ACTH‑stim test: gives synthetic ACTH (tetracosactide) → measures cortisol rise; failure → adrenal insufficiency. Hyperpigmentation: excess ACTH is cleaved to α‑MSH → melanin ↑; occurs only in primary disease because ACTH is high. Adrenal crisis: acute, life‑threatening glucocorticoid shortage precipitated by stress (infection, surgery, vomiting, etc.). 📌 Must Remember Epidemiology – 9‑14 per 100 000 in developed nations; 70 % autoimmune in the U.S. Autoimmune adrenalitis – 68 %–94 % of cases in industrialized countries; target = 21‑hydroxylase. ACTH‑stim short test: cortisol > 170 nmol/L baseline and increase ≥ 330 nmol/L to reach ≥ 690 nmol/L → normal. Failure = adrenal insufficiency. Lab hallmark – hyponatremia & hyperkalemia (aldosterone loss); hypoglycemia (cortisol loss). Hyperpigmentation = primary only (absent in secondary/tertiary). Stress dosing – double‑to‑triple usual hydrocortisone dose for fever, infection, surgery, or trauma. Fludrocortisone needed when aldosterone deficient; not required in secondary insufficiency. 🔄 Key Processes Short ACTH Stimulation Test Draw baseline cortisol. Inject 250 µg tetracosactide IM/IV. Draw cortisol at 60 min. Interpretation ≥ 690 nmol/L → normal adrenal reserve. < 690 nmol/L (or rise < 330 nmol/L) → adrenal insufficiency. Long ACTH Stimulation Test (if short abnormal) Give 1 mg tetracosactide. Measure cortisol at 1, 4, 8, 24 h. Pattern Primary: low cortisol at all times. Secondary: delayed rise, may reach normal later. Acute Adrenal Crisis Management IV hydrocortisone 100 mg bolus, then 200 mg/24 h (continuous or q6h). IV isotonic saline 1–2 L rapidly + 5 % dextrose if hypoglycemia. If no IV access → IM hydrocortisone 100 mg. Treat precipitating cause (antibiotics, surgery, etc.). Routine Hormone Replacement Hydrocortisone 15–25 mg/day divided (≈ morning 10 mg, midday 5 mg, afternoon 5 mg). Prednisone/Prednisolone ≈ ¼ the hydrocortisone dose for equivalent glucocorticoid effect. Fludrocortisone 0.05–0.2 mg daily if renin ↑ & K⁺ high. 🔍 Key Comparisons Primary vs. Secondary AI ACTH ↑ → hyperpigmentation vs ACTH low/normal → no pigment. Aldosterone ↓ → hyponatremia and hyperkalemia vs aldosterone usually preserved → only hyponatremia. Autoimmune vs. Infectious Etiology Autoimmune: anti‑21‑hydroxylase antibodies, common in developed world. Infectious (TB, histoplasmosis, etc.): more frequent in developing regions, often with adrenal calcifications. Short vs. Long ACTH Test Short: screening, single 1‑h cortisol. Long: distinguishes primary from secondary when short is abnormal. Hydrocortisone vs. Prednisone Hydrocortisone ≈ 4× the glucocorticoid potency of prednisone (i.e., 5 mg prednisone ≈ 20 mg hydrocortisone). ⚠️ Common Misunderstandings “Adrenal fatigue” is not a recognized medical condition; true insufficiency involves measurable hormone deficits. Hyperpigmentation does not occur in secondary/tertiary AI because ACTH is not elevated. Low potassium does not rule out AI; primary AI gives high K⁺, secondary may have normal K⁺. “Stress dosing” is not a one‑size‑dose; severity of stress dictates 2–3× usual hydrocortisone. 🧠 Mental Models / Intuition Two‑hormone engine: Think of the adrenal cortex as a dual‑engine car—cortisol = “fuel gauge” (energy), aldosterone = “oil pump” (salt balance). Loss of both stalls the car (fatigue, hypotension). ACTH → pigment pipeline: ↑ACTH → α‑MSH → melanin → hyperpigmentation → a visual clue that the problem is upstream (primary). Crisis cascade: Stress → vomiting/diarrhea → ↓ volume → ↓ BP → ↓ perfusion → hypoglycemia → emergency → replace cortisol + fluid. 🚩 Exceptions & Edge Cases Secondary AI: normal K⁺, no hyperpigmentation, but may still have hyponatremia from cortisol loss alone. Autoimmune polyendocrine syndrome Type 1: candidiasis + hypoparathyroidism + adrenalitis. Type 2: adrenalitis + autoimmune thyroid disease or type 1 DM. Long ACTH test required when patient is on chronic steroids (may blunt short test response). 📍 When to Use Which Initial diagnosis → short ACTH stimulation test. Abnormal short test → long ACTH test to differentiate primary vs. secondary. Acute crisis → IV hydrocortisone + saline; IM if IV unavailable. Routine replacement → hydrocortisone (physiologic) or prednisone (convenient) + fludrocortisone when aldosterone low. Stress dosing → double dose for mild illness, triple for surgery/major infection. 👀 Patterns to Recognize Triad: chronic fatigue + hyperpigmentation + hyponatremia / hyperkalemia → primary AI. Crisis trigger: any acute stress (infection, vomiting, surgery) + sudden hypotension, vomiting, hypoglycemia. Associated autoimmune diseases: thyroiditis, type 1 DM, vitiligo → consider polyendocrine syndrome. 🗂️ Exam Traps “Hyperpigmentation occurs in secondary AI.” – Wrong; only primary has excess ACTH. Cortisol > 690 nmol/L after ACTH = diagnostic of primary AI. – Misleading; that value indicates a normal response, not disease. Prednisone dose equal to hydrocortisone dose. – Incorrect; prednisone is roughly ¼ the hydrocortisone potency. Fludrocortisone needed in all adrenal insufficiency. – False; only when aldosterone is deficient (primary). Hyponatremia alone rules out adrenal insufficiency. – Not true; secondary AI can have hyponatremia without hyperkalemia. --- Keep this sheet handy; the bullet format makes quick scanning before the exam painless and effective.