Vitamin D-mediated hypercalcemia and Cushing syndrome as manifestations of malignant pleural mesothelioma.

Objective: To report a case of coincident hypercalcemia and Cushing syndrome arising from mesothelioma.

Methods: We describe the clinical, laboratory, imaging, and pathologic findings of a patient with malignant pleural mesothelioma and elucidate the underlying biologic mechanisms resulting in concurrent overexpression of steroid and polypeptide hormones.

Results: A 62-year-old woman presented with chest discomfort and cough. Radiologic imaging revealed a diffuse pleural-based mass encasing the right lung. There was no invasion into the chest wall, diaphragm, or mediastinum, and there was no distant disease. Laboratory analyses documented hypercalcemia and Cushing syndrome, which were due to ectopic overproduction of 1,25-dihydroxyvitamin D (1,25[OH](2)D) and corticotropin. Surgical resection resulted in normocalcemia with normalization of serum 1,25(OH)(2)D and reduction in hypercortisolemia. The extrapleural pneumonectomy specimen revealed overexpression of the 1,25(OH)(2)D synthetic enzyme 25-hydroxyvitamin-D-1alpha-hydroxylase (1alpha-hydroxylase) and underexpression of the 1,25(OH)(2)D catabolic enzyme 24-hydroxylase. Immunohistochemistry and electron microscopy demonstrated corticotropin and secretory granules in the tumor tissue.

Conclusion: These findings support the evidence for a paracrine role of vitamin D in the resistance of the human host to antigen.