Hypercalcemia related to Granulomatous Disease

Hypercalcemia is defined as a serum calcium level above the reference range. The reference range for serum calcium is based on the data derived from healthy subjects and is dependent on age, vitamin D status, and analytical methods.

Over 90% of patients with hypercalcemia have either primary hyperparathyroidism (in the clinic, incidental finding) or malignancy (hospitalization with hypercalcemic symptoms). Either of infectious or non-infectious origin, Granulomatous diseases can result in hypercalcemia.

Mechanisms of hypercalcemia in granulomatous disease

How does sarcoidosis and tuberculosis cause hypercalcemia

  • Increased 1α-hydroxylase activity, decreased degradation of 1,25-OHD3 (active vitamin D) , secretion of PTH-related peptide (PTHrP) and cytokines like IL-6 by granulomatous lesions.

Treatment of hypercalcemia of granulomatous disease

  • Treatment includes glucocorticoids (prednisolone 0.5–1 mg/kg/day) and specific therapy for the underlying disease.
  • Glucocorticoids inhibit 1α-hydroxylase activity and decrease the secretion of cytokines from the granulomatous lesions

Granulomatous diseases

Noninfectious causesInfectious causes
Crohn's diseaseTuberculosis
Granulomatosis with polyangiitisCoccidioidomycosis
Eosinophilic granulomaPneumocystis carinii pneumonia (HIV/AIDS)


Lemann J Jr, Gray RW. Calcitriol, calcium, and granulomatous disease. N Engl J Med. 1984 Oct 25;311(17):1115-7. 

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