A 54-yr-old man with a left adrenal pheochromocytoma showed mild hypercalcemia and elevated nephrogenous cAMP. Serum levels of PTH and 1,25-dihydroxyvitamin D3 were not elevated. Postoperatively, serum calcium and nephrogenous cAMP declined to normal ranges. Pathologically, the tumor was a benign pheochromocytoma. The clinical findings resembled those of humoral hypercalcemia of malignancy (HHM), and PTH-related protein (PTHrP) immunoreactivity was detected in the tumor extract at a concentration of 80.7 pmol/g wet wt, which is high compared to levels in malignant tumors causing HHM. Production of PTHrP was further confirmed by the demonstration of PTHrP mRNA with Northern blot hybridization analysis. Gel filtration of the extract revealed the presence of at least two different molecules with both immunological and biological activities. One of the peaks appeared close to PTHrP-(1-34), and the other between cytochrome-c and BSA. The latter showed a higher bioactivity to immunoreactivity ratio. These data indicate the multiplicity of PTHrP molecules in pheochromocytoma and support the idea that PTHrP produced by pheochromocytoma causes hypercalcemia in a similar fashion as HHM.
We report a case of a 32-year-old male, an asymptomatic carrier of human T-cell leukemia virus type 1 (HTLV-1), who underwent a renal transplantation and developed adult T-cell leukemia (ATL) during the course of posttransplant immunosuppressive treatment. He was treated with combination chemotherapies consisting of cyclophosphamide, vincristine, doxorubicin, prednisolone, cisplatin, cytosine arabinoside, etoposide, and methyl-prednisolone, without any improvement. Bestrabucil (KM2210), a conjugate of chlorambucil and estradiol, was administered as an alternative therapy; this therapy successfully suppressed his leukemic cell growth, and partial remission was achieved. Posttransplant immunosuppressive therapy with prednisolone, mizoribine, and cyclosporin A might have been the predominant cause of the transition from an asymptomatic HTLV-1 infection to overt ATL. A careful approach is required with HTLV-1 asymptomatic carriers who need organ transplantation followed by immunosuppressive treatment.
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