A 58-year-old man with chronic obstructive pulmonary disease (COPD) exacerbation is admitted to hospital. He is prescribed methylprednisolone 40 mg IV 6-hourly for 5 days, then switched to oral prednisolone 40 mg daily for 7 days, followed by abrupt discontinuation. On day 3 after stopping prednisolone, he develops severe fatigue, myalgia, fever (38.5°C), and hypotension (BP 100/65 mmHg). Serum sodium is 128 mEq/L (normal 135–145), potassium 5.8 mEq/L (normal 3.5–5.0), and cortisol is 2 µg/dL (normal 8–20 µg/dL at 8 AM). What is the MOST likely diagnosis?

Explanation

## Clinical Diagnosis: Acute Secondary Adrenal Insufficiency This patient has **acute adrenal crisis** precipitated by **abrupt withdrawal of glucocorticoids** after prolonged high-dose therapy. ## Pathophysiology of HPA Suppression **Key Point:** Exogenous glucocorticoids suppress the hypothalamic-pituitary-adrenal (HPA) axis by negative feedback. Doses >20 mg/day prednisolone (or equivalent) for >2 weeks cause significant suppression. The adrenal cortex may take **weeks to months** to recover endogenous cortisol production after discontinuation. **High-Yield:** Recovery of HPA axis function is dose- and duration-dependent: - High-dose (>40 mg prednisolone/day) for >2 weeks → expect 4–12 weeks suppression - Abrupt cessation → risk of acute adrenal crisis within 24–72 hours - Gradual taper (10% dose reduction every 3–7 days) → allows gradual HPA recovery ## Clinical Features of Acute Adrenal Insufficiency | Feature | Mechanism | |---------|----------| | **Hypotension** (100/65) | Loss of cortisol-mediated vasoconstriction and catecholamine sensitivity | | **Hyponatremia** (128 mEq/L) | Impaired free water excretion; loss of aldosterone (secondary) | | **Hyperkalemia** (5.8 mEq/L) | Loss of aldosterone-mediated K^+^ excretion | | **Low cortisol** (2 µg/dL) | Adrenal insufficiency; normal morning cortisol >8 µg/dL | | **Fever, myalgia, fatigue** | Inflammatory response to cortisol deficiency | **Clinical Pearl:** The **triad of hypotension + hyponatremia + hyperkalemia** in a patient recently exposed to high-dose glucocorticoids is pathognomonic for acute adrenal insufficiency. ## Management Algorithm ```mermaid flowchart TD A[Suspected acute adrenal insufficiency]:::outcome --> B{Hemodynamically unstable?}:::decision B -->|Yes| C["IV hydrocortisone 50-100 mg stat, then 50-100 mg Q6-8H"]:::urgent B -->|No| D["IV hydrocortisone 50 mg Q6H or oral prednisolone 15-20 mg TDS"]:::action C --> E["Concurrent IV saline 0.9% for hyponatremia"]:::action D --> E E --> F["Taper over 1-2 weeks as symptoms resolve"]:::action F --> G["Confirm HPA recovery before stopping (cosyntropin stimulation test)"]:::action ``` ## Why This Answer Is Correct 1. **Temporal relationship:** Symptoms began 3 days after abrupt prednisolone cessation — classic timing for acute adrenal crisis 2. **Clinical triad:** Hypotension + hyponatremia + hyperkalemia is diagnostic 3. **Low cortisol:** 2 µg/dL confirms adrenal insufficiency (normal ≥8 µg/dL) 4. **Immediate action:** This is a **medical emergency** requiring IV hydrocortisone within minutes to prevent cardiovascular collapse and death ## Prevention Strategy **Mnemonic — TAPER glucocorticoids:** **T**ime (gradual, not abrupt), **A**djust dose (10% reduction per week), **P**eripheral signs (monitor for adrenal insufficiency), **E**nsure HPA recovery (cosyntropin test if uncertain), **R**eplace if needed (hydrocortisone bridge). **High-Yield:** Any patient on ≥20 mg prednisolone (or equivalent) for ≥2 weeks MUST be tapered gradually (10% dose reduction every 3–7 days). Abrupt cessation is a medical error. [cite:Harrison 21e Ch 379; KD Tripathi 8e Ch 56]