Background: PTHrP-mediated hypercalcemia is a rare complication of disseminated coccidioidomycosis. Hypercalcemia in coccidioidomycosis is more commonly driven by granulomatous disease, which increases bone resorption and alters vitamin D metabolism through α-hydroxylase overexpression. In contrast, PTHrP-mediated hypercalcemia is typically associated with suppressed 1,25-dihydroxyvitamin D levels. We report a case of disseminated coccidioidomycosis with PTHrP-mediated hypercalcemia. Clinical
Case: A 57-year-old man with type 2 diabetes mellitus and hypertension presented with acute chest pain and dyspnea. He was COVID-19 positive and afebrile, normotensive, tachycardic, tachypneic, and hypoxic. CT chest revealed a right tension pneumothorax and multiple right lung cavitary lesions, the largest measuring 8.8 cm. He denied sick contacts, animal exposure, and substance use but reported travel to Mexico three months prior. A chest tube was placed, and broad-spectrum antibiotics were initiated. Initial infectious workup was negative; coccidioides serologies later returned positive. He was treated with liposomal amphotericin B followed by fluconazole. Pleural biopsy showed necrotizing pneumonia, with cultures positive for Coccidioides and no evidence of malignancy. His hospital course was complicated by bronchopleural fistula, acute hypoxic respiratory failure requiring intubation and tracheostomy, severe malnutrition requiring PEG-J placement, and prolonged ICU stay. He developed hypercalcemia with total calcium 11.2 mg/dL (8.6–10.6 mg/dL), albumin 2.9 g/dL, and corrected calcium 12.2 mg/dL, with suppressed PTH 5.5 pg/mL (12.0–88.0 pg/mL). Despite IV hydration, calcium increased to 13.3 mg/dL, with ionized calcium 6.7 mg/dL (4.5–5.3 mg/dL), while renal function remained stable. Evaluation for non–PTH-mediated hypercalcemia showed a negative pleural biopsy and whole-body imaging for malignancy. Vitamin D and vitamin A toxicity were excluded, with low 25-hydroxyvitamin D < 13 ng/mL (30–80 ng/mL), and normal vitamin A 0.2 mg/L. PTHrP was elevated at 9.2 pmol/L (0.0–2.3 pmol/L) with low1,25-dihydroxyvitamin D 10.8 pg/mL(19.9–79.3 pg/mL). Hypercalcemia persisted despite IV fluids and calcitonin. A single dose of IV zoledronic acid normalized calcium within four days, and vitamin D supplementation was initiated.
Conclusion: This case highlights an uncommon PTHrP-mediated mechanism of hypercalcemia in disseminated coccidioidomycosis, likely related to high granuloma burden. Recognition of this pathway is important, as bisphosphonates can effectively control hypercalcemia by inhibiting osteoclastic bone resorption.
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