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Inactivating Mutations of Calcium-Sensing Receptor Results in Parathyroid Lipohyperplasia

Fukumoto, Seiji M.D.; Chikatsu, Noriko M.D.; Okazaki, Ryo M.D.; Takeuchi, Yasuhiro M.D.; Tamura, Yasuhiro M.D.; Murakami, Toshikazu M.D.; Obara, Takao M.D.; Fujita, Toshiro M.D.

Diagnostic Molecular Pathology: December 2001 - Volume 10 - Issue 4 - pp 242-247
Original Articles

Familial hypocalciuric hypercalcemia (FHH) is an autosomal dominant disease characterized by mild hypercalcemia, an inappropriately high parathyroid hormone level, and absence of hypercalciuria. Heterozygous inactivating mutations of calcium-sensing receptor (CaSR) are found in about two thirds of patients with FHH. Histologic examination of parathyroid glands in FHH is reported to show normal histology or chief cell hyperplasia. Thus, histologic features of the parathyroid glands in FHH vary, and there is no clear histologic criterion that indicates FHH. The authors have encountered three hypercalcemic patients with characteristic histologic features of enlarged parathyroid glands. Clusters of parenchymal cells were mixed with fat cells, and the area of fat cells was 33% to 49% of the total area. These features are similar to those described as parathyroid lipohyperplasia. Postoperative evaluation showed that fractional excretion of calcium was low in these patients. Direct sequencing of the polymerase chain reaction product showed that the first patient was heterozygous for an already reported inactivating mutation of CaSR (P55L). The second patient was also heterozygous for a novel inactivating mutation (R220W). The third was homozygous for an inactivating mutation (Q27R). These results indicate that histologic features of parathyroid lipohyperplasia suggest the presence of inactivating mutations of CaSR.

From the Departments of Laboratory Medicine (S.F., T.M.) and Internal Medicine (N.C., Y. Takeuchi, Y. Tamura, T.F.), University of Tokyo Branch Hospital, Tokyo, Japan; Third Department of Medicine, Teikyo University School of Medicine, Chiba, Japan (R.O.); and Department of Endocrine Surgery, Tokyo Women's Medical University, Tokyo, Japan (T.O.)

Supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture, Ministry of Health and Welfare, a grant from Research Society for Metabolic Bone Diseases, and a grant from Araki Memorial Foundation for Biochemical Research, Japan.

Address correspondence and reprint requests to Dr. Seiji Fukumoto, Department of Laboratory Medicine, University of Tokyo Branch Hospital, 3-28-6 Mejirodai, Bunkyo-ku Tokyo 112-8688, Japan (e-mail:

© 2001 Lippincott Williams & Wilkins, Inc.