Hypercalcemia in Disseminated Coccidioidomycosis

Abstract

Abstract Introduction: Hypercalcemia is associated with various granulomatous diseases, most commonly sarcoidosis and tuberculosis, less frequently fungal disease. We present a rare case of hypercalcemia associated with disseminated coccidioidomycosis. Clinical Case: A 44-year-old man with ESRD s/p DDRT on immunosuppression presented with fever and cough. His physical exam was significant for tender scattered cutaneous nodules. His labs revealed non-PTH mediated hypercalcemia: calcium 12 mg/dL (normal 8.5–10.1 mg/dL), albumin 2.2 g/dL (normal 3.6–5.1 g/dL) and PTH 41 pg/mL (normal 14–72 pg/mL). Further hypercalcemia work-up was unremarkable: PTHrP 16 pg/mL (normal 14–27 pg/mL); 25-hydroxyvitamin D 33 ng/mL (normal 30–100 ng/mL); 1,25-hydroxyvitamin D 62 pg/mL (normal 20–79 pg/mL); serum electrophoresis was indeterminate; and immunofixation did not detect monoclonal proteins. His highest calcium level was 12.8 mg/dL with albumin 1.9 g/dL. He underwent additional tests that explained his presentation: sputum culture grew Coccidioides immitis; CT scan showed miliary pulmonary nodules, and bilateral deep cervical and mediastinal lymph node enlargement; lumbar puncture revealed elevated protein and cell counts; and a biopsy of a nodule on his thigh revealed Coccidioides immitis. He was treated with amphotericin for disseminated coccidioidomycosis with pulmonary, cutaneous and possible CSF involvement. He received IV fluids, furosemide and pamidronate for treatment of hypercalcemia. Based on his presentation, evaluation and complete resolution without recurrence of hypercalcemia after treatment of disseminated coccidioidomycosis, the most likely cause of hypercalcemia was disseminated coccidioidomycosis. Hypercalcemia is associated with various granulomatous diseases. It is a rare complication of disseminated coccidioidomycosis that is important to recognize as Coccidioides is endemic in the United States. The pathology of the disease is pyogenic granuloma. In contrast to sarcoidosis, our case and previous case studies of hypercalcemia in coccidioidomycosis did not show an elevation of 1,25 dihydroxyvitamin D. Various potential inducers have been implicated including PTHrP, lipopolysaccharide, prostaglandin E, interleukin 1 and transforming growth factor β. It has been demonstrated that granulomas produce PTHrP; however, not all patients with granulomas develop hypercalcemia. One theory is that hypercalcemia may be a sequelae in cases with a greater number and extent of lesions making PTHrP as seen in disseminated disease. Conclusion: Hypercalcemia is a rare complication of disseminated coccidioidomycosis that is important to recognize as coccidioidomycosis is endemic in the United States. The mechanism of hypercalcemia is poorly understood; in contrast to other granulomatous disease, it appears to be unrelated to 1,25-hydroxyvitamin D.