A 45-year-old non-smoker woman with bilateral hilar lymphadenopathy, elevated serum ACE, hypercalcemia, and erythema nodosum undergoes transbronchial biopsy showing non-caseating epithelioid granulomas with Schaumann bodies and asteroid bodies. The mechanism of hypercalcemia in this condition is:
- A PTHrP secretion by activated lymphocytes
- B Osteoclast activation by TNF-alpha from granulomas
- C Granuloma macrophages produce 1-alpha-hydroxylase, converting 25-OH vitamin D to active 1,25-(OH)2 vitamin D ✓
- D Impaired renal clearance of calcium due to interstitial nephritis
Explanation
In sarcoidosis, activated macrophages and epithelioid cells within granulomas express CYP27B1 (1-alpha-hydroxylase), converting 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D (calcitriol) in an unregulated manner — unlike renal 1-alpha-hydroxylase, which is feedback-regulated by PTH and calcium. Elevated calcitriol increases intestinal calcium absorption and promotes osteoclast activity, causing hypercalcemia (and hypercalciuria). Treatment with glucocorticoids inhibits granuloma macrophage CYP27B1 activity, correcting hypercalcemia. This mechanism also occurs in other granulomatous diseases (TB, histoplasmosis).
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.