Molecular pathogenesis of primary hyperparathyroidism

J Endocrinol Invest. 2011 Jul;34(7 Suppl):35-9.


Primary hyperparathyroidism (PHPT) is a common endocrinopathy, mostly caused by a monoclonal parathyroid adenoma. The hereditary syndromes include multiple endocrine neoplasia types 1 (MEN 1) and 2A (MEN 2A), hereditary hyperparathyroidism-jaw tumor (HPTJT), familial isolated hyperparathyroidism (FIHP), familial hypocalciuric hypercalcemia (FHH) and neonatal severe hyperparathyroidism (NSHPT). Mutations of MEN1 and CDKN1B genes are responsible for MEN 1 in 70-80% and about 2% of cases, respectively. MEN1 and CDKN1B genes have also a role in the pathogenesis of sporadic parathyroid adenomas. HRPT2/CDC73 gene mutations are responsible for HPT-JT and sporadic parathyroid carcinoma. MEN1 and HRPT2/CDC73 genes mutations have also been found in a subset of FIHP families. FHH and NSHPT represent the mildest and severest variants of PHPT, caused by heterozygous and homozygous mutations in the calcium sensing receptor (CASR) gene, respectively.

Publication types

  • Review

MeSH terms

  • Animals
  • Cyclin-Dependent Kinase Inhibitor p27 / genetics
  • Humans
  • Hyperparathyroidism / genetics
  • Hyperparathyroidism, Primary / genetics*
  • Multiple Endocrine Neoplasia Type 1 / genetics
  • Multiple Endocrine Neoplasia Type 2a / genetics
  • Parathyroid Neoplasms / genetics
  • Proto-Oncogene Proteins / genetics
  • Receptors, Calcium-Sensing / genetics


  • CASR protein, human
  • CDKN1B protein, human
  • MEN1 protein, human
  • Proto-Oncogene Proteins
  • Receptors, Calcium-Sensing
  • Cyclin-Dependent Kinase Inhibitor p27