SUN-775 - Non-PTH Mediated Hypercalcemia Due to Cryptococcus Infection in an Immunocompromised Patient

Introduction: There are a limited number of reported cases of hypercalcemia secondary to fungal infection. We report a case of hypercalcemia due to Cryptococcus infection (CI) in a patient with acquired immunodeficiency syndrome (AIDS).

Case:
A 64-year-old woman with chronic obstructive pulmonary disease, hypertension, polysubstance abuse, human immunodeficiency virus with AIDS and pulmonary cryptococcus presented with dyspnea, fatigue and pleuritic chest pain for two weeks. She was admitted for sepsis due to pneumonia. On exam, she was cachectic. Vitals were notable for tachycardia (126 heart rate), tachypneic (44 respiratory rate), and hypoxic on room air. Initial lab work reported lactate 5.3 mmol/L (.5-2.2), WBC 13.7 10*3/uL (4-10), sodium of 129 mEq/L (135-145), creatinine 1.4 mg/dL (0.6-1.2), CD 4 50/uL (359-1519) and a corrected calcium 14.7 mg/dL (9.2-11.0). She is started on vancomycin, cefepime, trimethoprim-sulfamethoxazole, amphotericin B, and flucytosine. She was recently discharged a month prior for pulmonary cryptococcosis, which was treated with amphotericin B and flucytosine followed by fluconazole. Further work up showed a positive serum cryptococcal antigen of 1:1280 (normal: negative), parathyroid hormone (PTH) 8 pg/mL (15-65), PTH related protein (PTHrP) < 2.0 pmol/L ( < 2.5), 25 hydroxy-vitamin-D (25(OH)-D) 39 ng/mL (30.0-96.0), total 1,25-dihydroxy vitamin D (1,25 (OH)2-D) 74 pg/mL (18-78), and negative serum protein electrophoresis. With borderline high vitamin D 1,25 and the rest of results negative, hypercalcemia was attributed to CI. Intravenous normal saline was given with down trending calcium, pamidronate was considered if levels persisted high. Due to worsening respiratory status, she was intubated 3 days later and had a cardiac arrest the next week and passed.

Discussion:
Hypercalcemia is most commonly caused by excess PTH or malignancy, with fungal infection being a rare source with only a handful of cases described in medical literature. Diagnostic workup for our patient indicated CI as the cause of hypercalcemia. Cryptococcus are known to induce granulomatous response, although exact mechanism is unclear, it has been proposed that macrophages in the granulomas produce the enzyme 1-alpha-hydroxylase, that converts 25(OH)-D to 1,25 (OH)2-D with subsequent increase intestinal absorption of calcium. On admission, labs reported severe hypercalcemia with patient’s symptoms ranging from fatigue to abdominal pain. Treatment includes intravenous fluids, bisphosphonates and calcitonin, with definitive management targeting the underlying fungal infection.

Conclusion:
Fungal infection should be considered in the differential diagnosis of unexplained hypercalcemia, particularly in immunocompromised patients such as in this case.

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