Ectopic production of 1,25-dihydroxyvitamin D in high-grade intranasal non-intestinal-type adenocarcinoma induced hypercalcemic crisis: a case report with review of literature.

Abstract

Hypercalcemia is an oncologic metabolic emergency in cancer patients, primarily caused by local osteolytic hypercalcemia and humoral hypercalcemia of malignancy. Hormones associated with oncologic metabolic emergency include parathyroid hormone and parathyroid hormone-related peptide (PTHrP), but 1,25-dihydroxyvitamin D (1,25(OH)₂D) is rarely the cause. We report the case of an 87-year-old man with hypercalcemic crisis owing to 1,25(OH)₂D overproduction from a high-grade intranasal non-intestinal-type adenocarcinoma. 1,25(OH)₂D and corrected Ca levels normalized after tumor resection and did not re-elevate subsequently. Serum PTH was suppressed and PTHrP not detected, suggesting the hypercalcemia was not due to the PTH pathway. Immunohistochemistry for CYP27B1, a key enzyme that converts 25-hydroxyvitamin D (25(OH)D) to 1,25(OH)₂D, showed positivity in the cytosol of about 20% of tumor cells, but only about 1% of the macrophages. On the other hand, CYP24A1, a 1,25(OH)₂D-degrading enzyme, was diffusely expressed in the cytosol of about 80% of tumor cells. These findings may suggest overproduction of CYP27B1 mRNA. The balance between synthesis and degradation of 1,25(OH)₂D in tumor tissue is thought to be implicated in the development of 1,25(OH)₂D-producing solid tumors. Further case accumulation and studies will be needed to confirm this hypothesis. Nonetheless, in diagnosing 1,25(OH)₂D-producing solid tumors, it is important to evaluate not only CYP27B1 expression but also CYP24A1.