A 30-year-old woman with bilateral hilar lymphadenopathy and noncaseating granulomas on transbronchial biopsy has corrected calcium of 11.8 mg/dL with a suppressed parathyroid hormone level. What mechanism accounts for the hypercalcemia?

• A Ectopic parathyroid hormone secretion by granulomas
• B Osteolytic cytokine release from bone marrow involvement
• C Increased renal tubular calcium reabsorption from volume depletion alone
• D Unregulated 1-alpha hydroxylase activity within granuloma macrophages generating excess calcitriol ✓

Explanation

Granuloma macrophages in sarcoidosis express 1-alpha hydroxylase outside feedback control of PTH, converting 25-hydroxyvitamin C to active 1,25-dihydroxyvitamin C, which increases intestinal calcium absorption and produces suppressed-PTH hypercalcemia with hypercalciuria. This also explains corticosteroid responsiveness, since steroids reduce calcitriol production. Granulomas do not secrete PTH, and bone marrow osteolysis is the mechanism of malignancy associated hypercalcemia.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.