SUN-773 - A Tale Of Two Pathways: Parathyroid Related Peptide And Calcitriol-Mediated Hypercalcemia In Seminoma

Hypercalcemia as a paraneoplastic manifestation of seminoma is rare, and its underlying mechanisms remain poorly understood. Reported cases typically involve a single humoral pathway. We describe an unusual case of severe hypercalcemia mediated by dual mechanisms in a patient with recurrent seminoma.

A 34-year-old man with a history of seminoma status post orchiectomy two years prior presented with several weeks of fatigue, weight loss, tachycardia, abdominal pain, nausea, and constipation. Surveillance imaging one year earlier had demonstrated progressive left para-aortic lymphadenopathy; however, the patient declined chemotherapy at that time. On presentation, laboratory evaluation revealed severe hypercalcemia with a serum calcium of 17.0 mg/dL (reference 8.2–10.2 mg/dL). Imaging demonstrated a 26-cm left upper quadrant mass encasing the aorta without evidence of osseous metastases. Biochemical evaluation showed suppressed parathyroid hormone (PTH) at 14 pg/mL (reference 15–65 pg/mL), elevated 1,25-dihydroxyvitamin D at 106 pg/mL (reference 20–79 pg/mL), elevated PTH-related peptide (PTHrP) at 43 pmol/L (reference 11–20 pmol/L), low 25-hydroxyvitamin D at 12 ng/mL (reference >20 ng/mL), and normal phosphorus at 2.9 mg/dL (reference 2.5–4.5 mg/dL).

The patient was treated with aggressive intravenous fluids, four doses of calcitonin, and zoledronic acid 5 mg. Dexamethasone was initiated at 10 mg daily and tapered to 8 mg after two days, concurrent with cisplatin and etoposide chemotherapy. Serum calcium normalized within five days but subsequently declined to persistent hypocalcemia ( < 7.0 mg/dL), necessitating frequent intravenous calcium repletion. Follow-up testing demonstrated normalization of 1,25-dihydroxyvitamin D levels. The patient ultimately required ongoing oral calcium and calcitriol supplementation.

This case illustrates a rare instance of seminoma-associated hypercalcemia mediated by both PTHrP secretion and increased 1,25-dihydroxyvitamin D production. It also highlights the potential for profound and prolonged hypocalcemia following treatment with bisphosphonates, glucocorticoids, and chemotherapy. Awareness of dual mechanisms of hypercalcemia and subsequent calcium derangements is critical for optimal management of affected patients.

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