Familial isolated hyperparathyroidism caused by single adenoma: a distinct entity different from multiple endocrine neoplasia

Endocr J. 1998 Oct;45(5):637-46. doi: 10.1507/endocrj.45.637.


Familial hyperparathyroidism (FHPT) is a hereditary disease where hyperparathyroidism (HPT) is transmitted in an autosomal dominant fashion. FHPT consists of a variety of diseases such as multiple endocrine neoplasia type1 (MEN 1) and type2 (MEN 2), familial isolated hyperparathyroidism (FIHPT) with single adenoma and with multiple adenomas (or hyperplasia), and FHPT with jaw-tumor (FHPT-JT). Isolation of the genes responsible for MEN1, and 2, i.e. MEN1 and RET, respectively, makes it possible to examine the relations among disorders constituting FHPT. We studied germ-line mutations in these 2 genes in a family of FHPT with single parathyroid adenoma. The disorder in this family was proved to be an entity different from MEN1 because no germ-line mutations in MEN1 gene were found in the affected members. The loss of heterozygosity (LOH) at MEN1 gene and PYGM were not found in the abnormal parathyroid in this family, supporting the above conclusion. No mutations in exons 10, and 11 of RET proto-oncogene was found in germ-line DNA of the affected member of the family, suggesting no relation to MEN2A. Linkage study excluded the possibility of FHPT-JT syndrome. PRAD1 was not overexpressed in the parathyroid tumors in this family. The relation of this disorder to FIHPT with multiple enlarged parathyroid glands remains to be clarified. A search for the gene(s) predisposing to FIHPT is needed.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Adenoma / genetics*
  • Adult
  • Drosophila Proteins*
  • Female
  • Genetic Markers
  • Germ-Line Mutation
  • Haplotypes
  • Humans
  • Hyperparathyroidism / genetics*
  • Male
  • Middle Aged
  • Multiple Endocrine Neoplasia Type 1 / genetics
  • Parathyroid Neoplasms / genetics*
  • Parathyroid Neoplasms / pathology
  • Pedigree
  • Polymerase Chain Reaction
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins c-ret
  • Receptor Protein-Tyrosine Kinases / genetics


  • Drosophila Proteins
  • Genetic Markers
  • MAS1 protein, human
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-ret
  • Receptor Protein-Tyrosine Kinases
  • Ret protein, Drosophila