Successful Use of Fluconazole for Hypercalcemia in the Setting of Granulomatous Disease

Introduction: Hypercalcemia is typically managed with intravenous fluids (IVF), bisphosphonates, calcitonin, denosumab, glucocorticoids, and treatment of the underlying cause. In a small trial, off-label fluconazole showed benefit in patients with elevated 1,25(OH)2D. We present a case of hypercalcemia secondary to granulomatous disease successfully treated with fluconazole. Case Description: A 62-year-old woman with insulin-dependent diabetes, cirrhosis, and hepatitis C presented with weakness, hypercalcemia, and acute kidney injury. She was initially treated with IVF and calcitonin. Workup revealed elevated 1,25(OH)2D, mildly elevated PTHrP, and suppressed PTH and ionized calcium. Serum ACE was normal. SPEP showed non-specific bands; IFE and kappa/lambda ratio were unremarkable. Despite IV fluids and two doses of zoledronic acid, hypercalcemia persisted. Ketoconazole was initiated due to suspected granulomatous disease. Her calcium levels improved shortly after. Infectious workup revealed a weakly positive QuantiFERON, negative sputum AFB smears, and a negative MTB PCR. Chest CT showed no active pulmonary TB. PET-CT revealed colonic and peritoneal findings suspicious for malignancy. Colonoscopy identified two masses (image 1); biopsy showed granulomatous inflammation with MTB DNA. She was seen by medical oncology who felt the FDG uptake around the liver was likely related to SBP. Paracentesis confirmed peritoneal TB and was started on anti-TB therapy. Ketoconazole was continued temporarily and was associated with sustained resolution of hypercalcemia. Discussion: Hypercalcemia is a potentially life-threatening condition that requires prompt general management to improve clinical outcomes. In cases associated with elevated 1,25(OH)2D, fluconazole may serve as an effective interim therapy while further diagnostic evaluation is underway or until the underlying cause can be definitively treated.Ascending colon mass