A 52-year-old man with a 2-year history of Addison disease (autoimmune adrenalitis) is being counselled on long-term management. He is currently on hydrocortisone 15 mg daily and fludrocortisone 0.1 mg daily. Which of the following statements about Addison disease management and associated conditions is NOT correct?

Explanation

## Addison Disease: Management Principles and Associated Conditions ### Overview of Replacement Therapy Addison disease requires lifelong glucocorticoid and mineralocorticoid replacement. The goal is to restore physiological hormone levels while avoiding both insufficiency and iatrogenic excess. ### Glucocorticoid Replacement **Key Point:** Hydrocortisone is the **gold standard** for maintenance glucocorticoid replacement in Addison disease. - **Dose:** 15–20 mg daily in divided doses (mimics physiological cortisol secretion: ~10 mg in morning, 5 mg in afternoon) - **Rationale:** Hydrocortisone has both glucocorticoid and mineralocorticoid activity, closely mimicking endogenous cortisol - **Why NOT dexamethasone?** Dexamethasone is a long-acting synthetic glucocorticoid (36–72 hour half-life) that: - Cannot be titrated to physiological levels - Causes iatrogenic Cushing syndrome (moon facies, central obesity, hypertension, osteoporosis) - Is reserved for acute adrenal crisis or diagnostic suppression testing, not maintenance **High-Yield:** The statement claiming dexamethasone is preferred for maintenance is **incorrect**. Hydrocortisone is the standard; dexamethasone causes Cushing-like side effects and is unsuitable for long-term replacement. ### Mineralocorticoid Replacement **Key Point:** Fludrocortisone (a synthetic mineralocorticoid) is **essential** in primary adrenal insufficiency. - **Dose:** 0.05–0.2 mg daily (typical: 0.1 mg) - **Mechanism:** Activates aldosterone receptors in the collecting duct to promote Na⁺ reabsorption and K⁺ excretion - **Why hydrocortisone alone is insufficient:** Although hydrocortisone has some mineralocorticoid activity, it is insufficient to correct the severe hyponatraemia and hyperkalaemia of Addison disease - **Monitoring:** Titrate based on blood pressure, Na⁺, and K⁺ levels (target: Na⁺ > 135 mEq/L, K⁺ 4–5 mEq/L) ### Stress-Dose Steroids **Clinical Pearl:** During acute illness, surgery, infection, or trauma, patients with Addison disease require **stress-dose glucocorticoids** to prevent adrenal crisis. ```mermaid flowchart TD A[Addison patient with acute stressor]:::outcome --> B{Type of stressor?}:::decision B -->|Minor illness, fever| C[Double usual dose for 2-3 days]:::action B -->|Moderate stress: minor surgery| D[50-75 mg hydrocortisone IV/IM at induction,<br/>then 25-50 mg every 6-8 hrs for 24 hrs]:::action B -->|Major stress: major surgery,<br/>sepsis, trauma| E[100 mg hydrocortisone IV/IM every 6-8 hrs<br/>for 24-48 hrs, then taper]:::action C --> F[Prevent adrenal crisis]:::outcome D --> F E --> F ``` **High-Yield:** Failure to provide stress-dose steroids in an Addison patient undergoing surgery or acute illness can precipitate **adrenal crisis** (shock, hypoglycaemia, hyperkalaemia, hyponatraemia, death). ### Associated Autoimmune Conditions **Key Point:** Autoimmune Addison disease is part of the **autoimmune polyendocrine syndrome (APS)**. Patients have increased risk of: - **Autoimmune thyroiditis** (Hashimoto disease) — 50–70% of Addison patients - **Type 1 diabetes mellitus** — 10–15% of Addison patients - **Hypogonadism** (primary ovarian or testicular failure) — 5–10% - **Pernicious anaemia** (vitamin B₁₂ deficiency) — 5–10% - **Coeliac disease** — 5–10% **Mnemonic:** **APECED** (Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy) — a rare monogenic form of APS with Addison disease, hypoparathyroidism, and chronic mucocutaneous candidiasis. ### Summary: Correct vs. Incorrect Statements | Statement | Correct? | Explanation | |-----------|----------|-------------| | Fludrocortisone is essential | ✓ YES | Hydrocortisone alone cannot correct mineralocorticoid deficiency | | Autoimmune Addison → ↑ risk of thyroiditis & T1DM | ✓ YES | Part of autoimmune polyendocrine syndrome | | Stress-dose steroids in acute illness | ✓ YES | Standard of care to prevent adrenal crisis | | Dexamethasone preferred for maintenance | ✗ **NO** | Hydrocortisone is gold standard; dexamethasone causes Cushing syndrome | **Warning:** A common trap in exams is confusing the role of dexamethasone (diagnostic/acute use) with hydrocortisone (maintenance use). Always remember: **hydrocortisone for replacement, dexamethasone for testing or acute crisis.**