7082 Hypercalcemia Due To Tumoral Production Of Calcitriol By Seminoma In A Patient With Pre-existing Primary Hyperparathyroidism

Abstract Disclosure: E. Naous: None. A. Jain: None. M. ElNajjar: None. A. Sabet: None. Background: Malignant hypercalcemia due to seminoma is extremely rare and has been reported in association with tumoral parathyroid-related protein (PTHrP) and/or calcitriol production. We present a unique case of a patient with seminoma and paraneoplastic calcitriol-induced hypercalcemia with co-existing primary hyperparathyroidism. Case Presentation: A 67-year-old male patient presented in May 2023 with obstructive uropathy and was diagnosed with a metastatic left testicular seminomatous germ-cell tumor with involvement of retroperitoneal soft tissue. At the time of diagnosis, the patient exhibited severe hypercalcemia with an albumin-corrected serum calcium level 14.1 mg/dL [8.6-10.3], phosphorus 3.0 mg/dL [2.5-4.5], intact parathyroid hormone (PTH) 20 pg/ml [15-65], PTHrP <2 pmol/L, 25-hydroxyvitamin-D 32 ng/ml [>30], and normal serum protein electrophoresis. 1,25-hydroxyvitamin-D was elevated at 132 pg/mL [24.8-81.5]. Review of prior records showed that the patient had a history of mild, chronic hypercalcemia (albumin-corrected serum calcium 10.5 mg/dL in August 2021, stable in 2022). His calcium level increased to 11.8 mg/dl in March 2023 and 14.1 mg/dl on presentation in May 2023. Given history of chronic mild hypercalcemia and presentation with severe hypercalcemia and “inappropriately normal” intact PTH, he was initially considered to have hypercalcemia solely due to primary hyperparathyroidism, a condition where elevated calcitriol levels are expected. However, the patient’s hypercalcemia was out of proportion to his intact PTH level, raising concern that tumoral calcitriol was contributory. He underwent left orchiectomy in May 2023 and completed chemotherapy cycles, including bleomycin, etoposide, and cisplatin, in September 2023. For hypercalcemia, he received IV saline, 48 hours of SC calcitonin, and prednisone 20 mg daily for 1 week followed by a rapid taper in addition to cinacalcet 30 mg daily. His serum calcium normalized within 48 hours of prednisone treatment. The patient remained on cinacalcet for a month, and his calcium levels remained normal more than a month after cinacalcet discontinuation. Clinical lesson: Severe hypercalcemia may be multifactorial. Our patient exhibited incompletely suppressed intact PTH and low-normal serum phosphorus, consistent with primary hyperparathyroidism. However, the abrupt onset of severe hypercalcemia, disproportionate to intact PTH, in a patient with seminoma and elevated calcitriol, suggested paraneoplastic hypercalcemia. The rapid response to corticosteroids and cancer chemotherapy, along with sustained normal calcium levels post-cinacalcet discontinuation, supported this diagnosis. Despite primary hyperparathyroidism being common, its presence in patients with severe hypercalcemia and malignancy does not rule out the possibility of co-existing hypercalcemia of malignancy. Presentation: 6/2/2024