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Somatic Mutations of the MEN1 Gene and Microsatellite Instability in a Case of Tertiary Hyperparathyroidism Occurring during High Phosphate Therapy for Acquired, Hypophosphatemic Osteomalacia

Departments of Medicine (K.S., K.N., A.Y., T.Y., Y.K., K.T.) and Surgery (T.O., K.Y., M.K.), Institute of Clinical Endocrinology, and Department of Surgical Pathology (T.N.), Tokyo Women’s Medical University, Tokyo 162-8666, Japan

Address all correspondence and requests for reprints to: Dr. Kanji Sato, Institute of Clinical Endocrinology, Tokyo Women’s Medical University, Kawada-cho 8-1, Shinjuku-ku, Tokyo, Japan 162-8666. E-mail: satokan{at}attglobal.net

Abstract

Somatic mutations of the MEN type 1 (MEN1) gene were recently shown to be responsible for tumorigenesis in 13–26% of sporadic, nonfamilial primary hyperparathyroidism. However, it is unknown whether these mutations are also involved in tumorigenesis of parathyroid glands occurring during high phosphate therapy for hypophosphatemic rickets or osteomalacia. A male patient with adult-onset, hypophosphatemic osteomalacia had been treated with 1-OHD₃ and oral phosphate for 13 yr when tertiary hyperparathyroidism developed. After total resection of four enlarged parathyroid glands and autotransplantation of a hyperplastic gland, the patient has continued to do well for the last 2 yr. Sequence analysis of the coding exons of MEN1 gene revealed a 36-bp deletion with a 2-bp insertion (exon 2) in the right upper parathyroid gland accompanied with loss of heterozygosity at 11q13 locus and a heterozygous mutation of 2-bp deletion (AG) in exon 10 in the right lower gland, in which microsatellite instability was also found. No MEN1 gene mutation was detected in the other two hyperplastic parathyroid glands or in the peripheral blood. These findings indicate that MEN1 gene mutations contributed to tumorigenesis of the right upper parathyroid gland in this case of phosphate-induced tertiary hyperparathyroidism. Very recently a bone tumor was found in the right femoral neck, and the tumor (chondroblastoma) was resected.

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				S. M. Mallya, J. J. Gallagher, and A. Arnold Analysis of Microsatellite Instability in Sporadic Parathyroid Adenomas J. Clin. Endocrinol. Metab., March 1, 2003; 88(3): 1248 - 1251. [Abstract] [Full Text] [PDF]