Somatic mutations of the MEN1 gene and microsatellite instability in a case of tertiary hyperparathyroidism occurring during high phosphate therapy for acquired, hypophosphatemic osteomalacia.
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 1alpha-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.
Sato
K
K
Department of Medicine, Institute of Clinical Endocrinology, Tokyo Women's Medical University, Tokyo 162-8666, Japan. satokan@attglobal.net
Obara
T
T
Yamazaki
K
K
Kanbe
M
M
Nakajima
K
K
Yamada
A
A
Yanagisawa
T
T
Kato
Y
Y
Nishikawa
T
T
Takano
K
K
D000328:Adult; D000595:Amino Acid Sequence; D001842:Bone and Bones / Q000000981:diagnostic imaging; D002117:Calcitriol / Q000008:administration & dosage / Q000627:therapeutic use; D002118:Calcium / Q000627:therapeutic use; D005260:Female; D017353:Gene Deletion; D006801:Humans; D006961:Hyperparathyroidism / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D006965:Hyperplasia; D017674:Hypophosphatemia / Q000188:drug therapy* / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D018761:Multiple Endocrine Neoplasia Type 1 / Q000235:genetics*; D010018:Osteomalacia / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000235:genetics*; D010280:Parathyroid Glands / Q000473:pathology; D010281:Parathyroid Hormone / Q000097:blood; D010710:Phosphates / Q000009:adverse effects / Q000627:therapeutic use*; D011877:Radionuclide Imaging; D020133:Reverse Transcriptase Polymerase Chain Reaction
D010281:Parathyroid Hormone; D010710:Phosphates; D002117:Calcitriol; D002118:Calcium