MON-772 - A Rare Case of 1,25-Dihydroxyvitamin D-Mediated Hypercalcemia in Testicular Seminoma

Background: Testicular seminomas are the most common subtype of testicular germ cell tumors, predominantly affecting males aged 15-44 years. Hypercalcemia of malignancy occurs in approximately 20% of cancer patients, but only 12 cases have been reported with testicular seminomas. We report a case of recurrent seminoma presenting with hypercalcemia mediated by elevated levels of 1,25-dihydroxyvitamin D (1,25(OH)2D), highlighting an uncommon paraneoplastic manifestation of this tumor type.

Clinical

Case: A 49-year-old man with pT1 left testicular seminoma status post orchiectomy in 2023 was lost to oncologic follow-up and presented to the emergency department two years later with several months of lower back pain, bilateral lower extremity claudication, and a 30-lb unintentional weight loss. Computed tomography of the abdomen and pelvis demonstrated a large confluent left intra-abdominal mass measuring 11 x 17 x 26 cm with no evidence of bony metastasis. Laboratory evaluation revealed severe hypercalcemia (15.4 mg/dL; 8.4-10.2 mg/dL), acute kidney injury (creatinine 1.9 mg/dL; 0.6-1.3 mg/dL), and elevated alkaline phosphatase (217 U/L; 40-150 U/L). Parathyroid hormone was appropriately suppressed (11.6 pg/mL; 17.9-58.6 pg/mL), and parathyroid hormone-related protein (PTHrP) was within normal limits (1.4 pmol/L; ≤4.2 pmol/L). 25-hydroxyvitamin D (35.2 ng/mL; 20-90 ng/mL) and phosphorus (3.7 mg/dL; 2.3-4.7 mg/dL) were normal, while 1,25(OH)2D was elevated (98.8 pg/mL; 19.9-79.3 pg/mL), consistent with 1,25(OH)2D-mediated hypercalcemia. The patient was treated with aggressive intravenous fluids along with zoledronic acid and calcitonin, resulting in normalization of serum calcium and improvement in renal function.

Conclusion: With only 12 cases reported in the literature, five with documented calcitriol elevation, this case represents an exceedingly rare presentation of 1,25(OH)2D-mediated hypercalcemia associated with testicular seminoma. While PTHrP accounts for approximately 80% of malignancy-related hypercalcemia, 1,25(OH)2D-mediated mechanisms comprise less than 1%. Ectopic expression of 1-alpha-hydroxylase may underlie this process, though the pathophysiology in testicular seminoma remains unclear. This case underscores the importance of evaluating 1,25(OH)2D in malignancy-associated hypercalcemia beyond PTHrP.

References:
1. Sim J, Irvin J, Altorok N. 1,25-dihydroxyvitamin D mediated hypercalcemia in seminoma. Am J Med Sci. 2025;369(2):292-295.

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