A 38-year-old man from rural India presents with a 6-month history of progressive fatigue, weight loss, and hyperpigmentation. Investigations reveal low cortisol, elevated ACTH, and hyponatremia. CT abdomen shows bilateral adrenal enlargement with calcification. What is the most common cause of his primary adrenal insufficiency?

## Clinical Diagnosis: TB-Related Addison Disease ### Case Analysis **Key Point:** The clinical presentation and imaging findings are pathognomonic for tuberculosis of the adrenal gland: 1. **Geographic context:** Rural India (high TB prevalence) 2. **Imaging hallmark:** Bilateral adrenal enlargement + calcification (not atrophy) 3. **Biochemistry:** Low cortisol, elevated ACTH (primary insufficiency) 4. **Systemic features:** Fatigue, weight loss, hyperpigmentation (classic Addison triad) ### Distinguishing TB from Autoimmune Adrenalitis | Feature | TB Adrenalitis | Autoimmune Adrenalitis | |---------|---|---| | **Adrenal size on imaging** | Bilateral enlargement | Bilateral atrophy | | **Calcification** | Present (pathognomonic) | Absent | | **Onset** | Subacute to chronic (weeks to months) | Insidious (months to years) | | **Associated autoimmune disease** | Rare | Common (thyroiditis, vitiligo, pernicious anemia) | | **Autoantibodies** | Absent | Anti-21-OH, anti-17-OH present | | **Extrapulmonary TB findings** | Often present (lymph nodes, ascites) | Absent | | **TB contact history** | Often positive | Absent | | **Geographic prevalence** | High in endemic regions | High in developed nations | **Clinical Pearl:** Bilateral adrenal calcification on CT is virtually diagnostic of TB-related Addison disease. This finding is rare in autoimmune disease and should always prompt TB investigation (sputum AFB, TB-IGRA, chest imaging). ### Why TB is Most Likely in This Case ```mermaid flowchart TD A[Primary adrenal insufficiency<br/>Bilateral adrenal enlargement + calcification]:::outcome --> B{Geographic risk?}:::decision B -->|High TB burden region<br/>Rural India| C[TB adrenalitis likely]:::action B -->|Developed nation| D[Consider autoimmune first]:::action A --> E{Imaging pattern?}:::decision E -->|Enlargement + calcification| F[TB]:::action E -->|Atrophy, no calcification| G[Autoimmune]:::action A --> H{Autoimmune markers?}:::decision H -->|Anti-21-OH positive| I[Autoimmune adrenalitis]:::action H -->|Negative| J[TB or infection]:::action ``` **High-Yield:** The combination of: - **Bilateral adrenal enlargement** (not atrophy) - **Calcification** (pathognomonic for TB) - **Rural India** (high TB prevalence) - **No mention of autoimmune antibodies** ...makes TB the only defensible answer. ### Diagnostic Confirmation 1. **Sputum AFB smear microscopy** (if pulmonary TB suspected) 2. **TB-IGRA (QuantiFERON-Gold)** or tuberculin skin test 3. **Chest X-ray** (may show old TB scars, hilar lymphadenopathy) 4. **Adrenal biopsy** (rarely needed; shows caseating granulomas if done) 5. **Serum and urine cortisol** (confirm insufficiency) **Mnemonic:** **CALCIFY** — TB Adrenalitis findings: - **C**alcification on CT - **A**drenomegaly (bilateral enlargement) - **L**ow cortisol, high ACTH - **C**aseating granulomas on biopsy - **I**ncreased TB risk (endemic region, immunocompromised) - **F**atigue, weight loss, hyperpigmentation - **Y**ield positive TB investigations [cite:Harrison 21e Ch 375; Park 26e Ch 7]