1,25-dihydroxyvitamin D mediated hypercalcemia in seminoma

Hypercalcemia has rarely been associated with seminomas. Due to the limited data available, the pathophysiology of hypercalcemia in seminoma has not been established in literature. We present a case of a 59-year-old male who presented with weakness, abdominal fullness, fatigue, constipation, and a 14 lb unintentional weight loss. On initial presentation he was found to be hypercalcemia with calcium of 16.2 mg/dL (normal 8.6-10.3 mg/dL). Subsequently, a metastatic seminoma was discovered with no evidence of bony metastasis. 1,25-dihydroxyvitamin D was elevated at >200 pg/mL (reference 19.9-79.3 pg/mL). PTH was suppressed at 11 pg/mL (reference 12-88 pg/mL). PTHrP was normal at 1.0 pmol/L (reference ≤4.2 pmol/L), 25‑hydroxy vitamin D was low at 22.6 ng/mL (reference 30-100 ng/mL), and phosphorus was normal at 3.9 mg/dL (reference 2.4-4.9 mg/dL). These findings indicate 1,25-dihydroxyvitamin D mediated hypercalcemia of malignancy. Hypercalcemia in seminoma has been reported in 11 cases, that we review in this report. However, few cases present sufficient data to conclude the pathophysiology of hypercalcemia. In all four cases that presented 1,25-hydroxyvitamin D levels, the levels were elevated, suggesting seminomas are associated with 1,25-hydroxyvitamin D mediated hypercalcemia. Interestingly, one case was associated with increased 1,25-hydroxyvitamin D and increased PTHrP levels, suggesting there may be multiple mechanisms of hypercalcemia in seminomas.