Adrenal Tuberculosis — Complete 15-Mark MD Exam Answer

INTRODUCTION

EPIDEMIOLOGY & ETIOLOGY

• Adrenal TB constitutes ~7–10% of extrapulmonary TB cases.
• Worldwide (especially in developing countries including India), TB remains the commonest cause of primary adrenal insufficiency.
• In developed countries, autoimmune adrenalitis has surpassed TB as the leading cause.
• Occurs predominantly in adults; males slightly more affected.
• Associated with active TB elsewhere — lungs (most common), genitourinary tract, lymph nodes.

• Haematogenous spread from a primary pulmonary or other focus (most common route)
• Direct extension from retroperitoneal lymph nodes (rare)
• Reactivation of dormant bacilli within the adrenal gland

Clinical insufficiency manifests only when >90% of the adrenal cortex is destroyed — both adrenals are almost always involved bilaterally.

PATHOLOGY

Gross Pathology

• Early/active disease: Bilateral adrenal enlargement — glands replaced by caseous necrotic material, sometimes with abscess formation. On imaging, bilateral adrenal enlargement is seen in ~91% of cases of acute adrenal TB.
• Late/healed disease: Adrenals become fibrotic, shrunken, and densely calcified. Calcification is seen in up to 50–59% of cases and is the radiological hallmark of healed adrenal TB.

Histopathology

• Classic caseating epithelioid granulomas with Langhans giant cells — identical to TB at other sites.
• Central caseous necrosis surrounded by epithelioid histiocytes, Langhans giant cells, and a peripheral cuff of lymphocytes.
• The adrenal architecture is effaced by granulomatous inflammation.
• As the disease heals: fibrosis, dystrophic calcification, and glandular atrophy supervene.
• AFB staining (Ziehl-Neelsen): positive in 25–50% of cases on tissue sections; culture positivity is higher.
• Both cortex and medulla may be destroyed, though the cortex is the primary target.

CLINICAL FEATURES

A. Chronic Primary Adrenal Insufficiency (Classical Addison's Disease)

B. Adrenal Crisis (Addisonian Crisis)

• Infection, surgery, trauma, dehydration, or sudden steroid withdrawal

INVESTIGATIONS

1. Hormonal Assays (Confirmatory)

• 8 AM serum cortisol: Low (<3 μg/dL = diagnostic; >18 μg/dL rules out insufficiency)
• ACTH stimulation (Synacthen/Cosyntropin) test (Gold standard):
  • 250 μg synthetic ACTH IV/IM → cortisol measured at 0, 30, 60 min
  • Normal: cortisol rises to >18–20 μg/dL
  • Primary adrenal insufficiency (TB): Blunted/absent cortisol response
• Plasma ACTH level: Markedly elevated (>200 pg/mL) in primary adrenal insufficiency (distinguishes from secondary)
• Serum aldosterone: Low (primary); Normal (secondary)
• Plasma renin activity: Elevated (primary)
• Serum electrolytes: Hyponatremia, hyperkalemia
• Blood glucose: Hypoglycemia
• CBC: Eosinophilia, normocytic anaemia

2. Imaging

• T1: Heterogeneous signal; central hypointensity (necrosis)
• T2: Central hyperintensity (fluid/necrosis), peripheral hypointensity (fibrosis)
• Post-contrast: Peripheral rim enhancement (granuloma), non-enhancing central necrosis
• Calcification better seen on CT than MRI

Key radiological clue: Bilateral adrenal enlargement + calcification in a TB-endemic patient with features of adrenal insufficiency = adrenal TB until proven otherwise.

3. Microbiological & Immunological

• Mantoux test / IGRA (Interferon Gamma Release Assay): Positive (supporting evidence)
• Sputum/urine AFB smear and culture: May reveal systemic TB
• CT/USG-guided Fine Needle Aspiration Cytology (FNAC) or core biopsy: Caseating granulomas; AFB staining and culture from adrenal tissue
• GeneXpert MTB/RIF on adrenal tissue: Rapid molecular confirmation
• Adrenal tissue culture (BACTEC/Lowenstein-Jensen): Positive for Mycobacterium tuberculosis (gold standard for adrenal TB)
• Anti-21-hydroxylase antibodies: Absent in TB (helps distinguish from autoimmune adrenalitis where these are positive in ~90%)

DIAGNOSIS

1. Proven primary adrenal insufficiency (low cortisol + blunted ACTH stimulation test + elevated ACTH)
2. Bilateral adrenal pathology on imaging (enlarged ± calcified)
3. Microbiological/histological confirmation of TB (AFB/culture/GeneXpert/histopathology showing caseating granulomas)
4. Supporting evidence: active TB elsewhere, positive IGRA/Mantoux, response to ATT

DIFFERENTIAL DIAGNOSIS

TREATMENT

A. Antituberculosis Treatment (ATT)

• Some guidelines recommend extending to 9–12 months for adrenal TB given the limited vascularity of caseous lesions.
• Response to ATT: In 88% of cases with acute adrenal TB, enlarged glands decrease in size or normalize after successful treatment; adrenal function may partially recover if treatment is initiated early.

B. Hormone Replacement Therapy

• Hydrocortisone 15–20 mg/day in divided doses:
  • Morning dose: 10 mg (two-thirds of daily dose)
  • Afternoon dose: 5–10 mg (one-third)
• Alternatively: Prednisolone 5–7.5 mg/day

• Minor illness/fever: Double the dose
• Major surgery/critical illness: IV hydrocortisone 50–100 mg 6-hourly

• Fludrocortisone 100–150 μg/day orally
• Monitor: BP sitting vs. standing (postural drop = hypovolemia); serum electrolytes; plasma renin activity

Important: Before starting ATT, initiate glucocorticoid replacement first (or simultaneously), because Rifampicin induces CYP450 enzymes and accelerates cortisol metabolism — can precipitate acute adrenal crisis. Hydrocortisone dose may need upward adjustment (up to 50%) when on Rifampicin.

C. Management of Addisonian Crisis (Emergency)

• Immediate IV access — draw blood for cortisol/ACTH before treatment
• IV Normal Saline (0.9%): 1 litre over 30–60 min → correct volume depletion
• IV Hydrocortisone: 100 mg bolus immediately, then 50–100 mg every 6–8 hours
• Dextrose (10–20%): For hypoglycemia
• Treat precipitating cause (antibiotics for infection, etc.)
• Taper to oral hydrocortisone as patient improves; add fludrocortisone once oral intake is established

PROGNOSIS

• Adrenal function recovery: Partial recovery of cortisol production is possible with early ATT initiation (when <90% gland destroyed). Most patients, however, require lifelong hormone replacement.
• Adrenal calcification on imaging after healing does not predict functional recovery.
• Prognosis of TB itself depends on drug sensitivity, extent of disease, and HIV status.
• Patients on lifelong steroids need TB preventive therapy consideration.

SUMMARY TABLE — Key Points for Exam