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A Case of Pheochromocytoma Producing Parathyroid Hormone-Related Protein and Presenting with Hypercalcemia^*

Departments of Infectious Diseases and Applied Immunology (S.K., K.S.) and Surgery (Y.N., H.U.), Institute of Medical Science, University of Tokyo Tokyo, Japan
The Growth Factor Division, National Cancer Center Research Institute, (K. Y., K.N.) Tokyo, Japan

Address all correspondence and requests for reprints to: Dr. Satoshi Kimura, Department of Infectious Diseases and Applied Immunology, Institute of Medical Science, University of Tokyo, 4–6–1 Shirokanedai, Minato-ku, Tokyo 108, Japan.

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-(l–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.

^* This work was supported in part by Grants-in-Aid for Cancer Research 62–26 and 1–33 from the Ministry of Health and Welfare, Japan.

Received November 20, 1989.

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