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Endocrine Findings in Tuberculosis — Full Details (MD Exam, 15 Marks)

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Introduction

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1. ADRENAL TUBERCULOSIS — Most Important Endocrine Manifestation

Pathology

• TB is historically the most common cause of primary adrenal insufficiency (Addison's disease) worldwide, though autoimmune adrenalitis now predominates in developed countries
• Bilateral adrenal involvement occurs via hematogenous spread
• Caseous necrosis → fibrosis → calcification → destruction of cortex (>90% of cortex must be destroyed before insufficiency manifests)
• Both glucocorticoid and mineralocorticoid secretion are lost (primary adrenal insufficiency)

Clinical Features

Diagnosis

• Serum cortisol (8 AM): <3 µg/dL = diagnostic; <18 µg/dL on stimulation = abnormal
• Short Synacthen (ACTH stimulation) test: Gold standard — 250 µg cosyntropin IV/IM; measure cortisol at 0, 30, 60 min; peak <18 µg/dL = primary adrenal insufficiency
• Plasma ACTH: Elevated (>2× upper limit) in primary AI
• Serum electrolytes: Hyponatremia, hyperkalemia
• CT abdomen: Bilateral adrenal enlargement (active TB) → later bilateral calcification (pathognomonic of old TB)
• Adrenal biopsy (if needed): Caseating granulomas, AFB

Treatment — Adrenal TB

Note: Rifampicin significantly induces CYP3A4 and accelerates cortisol metabolism — hydrocortisone dose may need to be increased by 2–3× during rifampicin therapy.

• Minor illness/fever: Double glucocorticoid dose
• Major illness/surgery: Hydrocortisone 50–100 mg IV/IM q6–8h (stress dosing)
• Adrenal crisis: Hydrocortisone 100 mg IV bolus → 50–100 mg IV q6–8h + IV normal saline 1L in 1st hour + glucose

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2. SIADH (Syndrome of Inappropriate ADH Secretion)

Mechanism

• Pulmonary TB → ectopic ADH production from lung tissue or hypothalamic stimulation
• Tuberculous meningitis → direct hypothalamic/pituitary involvement
• Result: Free water retention → dilutional hyponatremia (euvolemic)

Features

• Hyponatremia (Na⁺ <135 mEq/L), serum hypo-osmolality (<275 mOsm/kg)
• Urine Na⁺ >20 mEq/L, urine osmolality >100 mOsm/kg (inappropriately concentrated)
• Normal/expanded plasma volume (no edema, no dehydration)
• Neurological symptoms: headache, confusion, seizures (if Na⁺ <120 mEq/L)

Treatment

• Treat underlying TB (ATT as above) — SIADH resolves with treatment
• Fluid restriction: 800–1000 mL/day (first-line for mild-moderate SIADH)
• For severe/symptomatic hyponatremia (Na⁺ <120 or seizures): Hypertonic saline (3% NaCl) IV — correct Na⁺ at rate ≤8–10 mEq/L per 24 hours (to prevent osmotic demyelination syndrome)
• Demeclocycline 300–600 mg BD (blocks ADH at collecting duct) — if fluid restriction fails

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3. HYPERCALCEMIA

Mechanism

• Activated macrophages in TB granulomas express 1-α hydroxylase (CYP27B1) → converts 25-OH vitamin D to 1,25-(OH)₂ vitamin D (calcitriol) in an unregulated fashion (not subject to normal feedback)
• ↑ Calcitriol → ↑ intestinal calcium absorption + ↑ bone resorption → hypercalcemia
• Granulomatous hypercalcemia: seen in ~10% of TB patients; hypercalciuria more common

Features

• "Bones, stones, groans, psychic moans" (hypercalcemia symptoms)
• Polyuria, polydipsia (nephrogenic DI from hypercalcemia)
• Nephrolithiasis, nephrocalcinosis
• Low PTH (suppressed), elevated calcitriol

Treatment

• ATT (primary treatment — resolves hypercalcemia as granulomas heal)
• Hydration: IV normal saline 200–300 mL/hour
• Glucocorticoids: Prednisolone 40–60 mg/day (inhibit macrophage 1-α hydroxylase) — highly effective in granulomatous hypercalcemia
• Avoid: Calcium supplements, vitamin D, thiazide diuretics, sunlight exposure (all worsen hypercalcemia)
• Bisphosphonates if refractory

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4. THYROID INVOLVEMENT

Mechanisms & Types

Diagnosis

• TFTs: TSH, Free T3, Free T4
• Thyroid ultrasound/FNAC: Caseating granulomas, AFB on ZN stain
• Cold nodule on scintigraphy

Treatment

• ATT is primary treatment for tuberculous thyroiditis
• Transient thyrotoxicosis: Beta-blocker (propranolol 40–80 mg TDS) for symptom relief; antithyroid drugs NOT effective (no hypersynthesis)
• PAS-induced hypothyroidism: Levothyroxine 25–50 µg/day titrated up; stop PAS if feasible

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5. PITUITARY AND HYPOTHALAMIC TB

Pathology

• Hematogenous seeding or extension from tuberculous meningitis
• Tuberculoma in sella turcica or suprasellar region
• Basal meningitis → infundibular involvement

Clinical Features

Treatment

• ATT (6–12 months; extend to 12 months for CNS TB)
• Central DI: Desmopressin (DDAVP):
  • Intranasal: 10–40 µg/day in 1–2 divided doses
  • Oral: 0.05–1.2 mg/day
  • IV/SC: 1–4 µg/day
• Hormone replacement: Replace each deficient axis individually (as above)
• Corticosteroids for CNS TB: Dexamethasone 0.4 mg/kg/day for 2 weeks, then tapered over 4 weeks (WHO recommended for TB meningitis)
• Surgical decompression if visual compromise persists despite ATT

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6. HYPOGONADISM IN TB

Mechanism

• Systemic illness effect: Chronic inflammation suppresses GnRH → hypogonadotropic hypogonadism
• Direct testicular/ovarian involvement: Rare; miliary TB
• Malnutrition in TB → hypothalamic amenorrhea

Features

• Oligomenorrhea/amenorrhea in women
• Reduced testosterone, libido, spermatogenesis in men
• Infertility

Treatment

• Primarily resolves with ATT and nutritional rehabilitation
• Hormone replacement if persistent after TB treatment

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7. PANCREATIC TB AND GLUCOSE DYSREGULATION

TB and Diabetes Mellitus — Bidirectional Relationship

• DM triples the risk of TB (impaired macrophage function, reduced T-cell immunity)
• TB worsens glycemic control (cytokine-mediated insulin resistance, catabolic state)
• Pancreatic TB (rare): caseous granulomas → pancreatic insufficiency

TB Drug Effects on Glucose

Management

• Optimize glycemic control (target HbA1c <7–8% in TB-DM)
• Insulin preferred during intensive phase of ATT
• Monitor sulfonylurea/OHA efficacy if rifampicin used

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8. ELECTROLYTE AND METABOLIC DISTURBANCES SUMMARY

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Standard ATT Regimen — Quick Reference Card

First-Line Drugs (Daily Doses — Adult)

Regimen Duration by Site

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Key Points for MD Exam

1. Adrenal TB is the most important endocrine manifestation; TB was historically the leading cause of Addison's disease worldwide.
2. Bilateral adrenal calcification on CT is pathognomonic of healed adrenal TB.
3. Rifampicin accelerates cortisol metabolism via CYP3A4 — hydrocortisone dose must be increased during ATT.
4. SIADH occurs in pulmonary TB and TB meningitis — hyponatremia is the most common electrolyte abnormality.
5. Hypercalcemia in TB is granulomatous — low PTH, elevated calcitriol, responds dramatically to steroids and ATT.
6. Central DI is the most common pituitary axis affected in hypothalamic-pituitary TB.
7. Sick euthyroid syndrome (low T3) is common in severe TB — does not require treatment; resolves with ATT.
8. DM and TB have a bidirectional relationship; rifampicin reduces OHA efficacy.
9. Pyridoxine (25 mg/day) must be co-administered with isoniazid to prevent peripheral neuropathy.
10. Fludrocortisone is always needed in primary adrenal insufficiency (adrenal TB) — not in secondary (pituitary TB).

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