SUN-797 Management of Hypercalcemia in an Infant With Fungemia and Its Challenges

Abstract Disclosure: S. Muneer: None. M. Munoz: None. J. Iyer: None. D.R. Weber: None. S.M. Willi: None. Background: Hypercalcemia in infants is rare but potentially serious. While often asymptomatic, it may present with failure to thrive, constipation, dehydration, poor feeding, and in severe cases, hypotonia or seizures. Differential diagnosis includes hypervitaminosis, malignancy, endocrinopathies, granulomatous disease, and fat necrosis. Case: A full-term male infant with congenital lymphatic malformation and neonatal chylothorax developed candidal fungemia on day of life (DOL) 30. Before this diagnosis, he had been noted to have hypercalcemia, 11.5mg/dL (ref 7.8-11.3) on DOL 28. His fungemia was treated with amphotericin B on DOL 32-35 and then fluconazole DOL 36-47. During this time his Ca remained elevated and did not improve. Initial evaluation for hypercalcemia commenced on DOL 48 which showed hypercalcemia 12.7mg/dL, normal 25-OH Vitamin D, low 1,25-dihydroxy Vitamin D, appropriately suppressed PTH, and elevated urinary Ca/creatinine. Bone turnover markers, including c-telopeptide and bone-specific alkaline phosphatase, were normal. The patient initially responded to hyperhydration and removal of calcium from feeds, but hypercalcemia recurred. On DOL 63, he required calcitonin at 2 IU/kg BID. Calcitonin was discontinued after 17 days as calcium normalized, and 1,25-dihydroxy Vitamin D returned to normal. Discussion: Infant hypercalcemia is rare, and its association with fungemia is even more unusual. Hypercalcemia secondary to fungemia is suspected to result from extra-renal 1,25OHD2 production by activated macrophages expressing CYP27B1 (1-alpha hydroxylase). Excess 1,25OHD2 causes hypercalcemia via increased intestinal absorption and increased bone resorption of calcium. In this case, hypercalcemia in the setting of elevated 1,25OHD2 and suppressed PTH is consistent with extra-renal production by activated macrophages. Fluconazole is an inhibitor of CYP27B1, and therefore exerts a beneficial effect on hypercalcemia by reducing 1,25OHD2 synthesis, in addition to treating the fungemia. Calcitonin, an inhibitor of osteoclast activity, is effective in the acute management of hypercalcemia driven in whole or in part by excess bone resorption. Steroids are also an effective treatment of hypercalcemia secondary to activated macrophages, however, are typically not an option with a fungal infection because of the risk of reactivating a systemic infection. This case adds to the limited literature on hypercalcemia secondary to systemic infections in infants. It was noted that the patient started to develop hypercalcemia shortly after the diagnosis of the fungemia and failed to improve while receiving fluconazole. Calcitonin proved effective in rapidly reducing serum Ca levels, highlighting its utility in acute management. Further studies are warranted to understand the pathophysiological mechanisms linking infection and hypercalcemia in infants. Presentation: Sunday, July 13, 2025