Molecular genetics of primary and secondary hyperparathyroidism

Hyperparathyroidism (HPT) can be caused by solitary parathyroid adenomas and carcinomas, and primary and secondary multiglandular parathyroid disease. Primary HPT is also a feature of several hereditary diseases e.g. multiple endocrine neoplasia type 1 and type 2A (MEN1 and 2A), familial hypocalciuric hyperparathyroidism (FHH), the HPT-jaw tumor syndrome (HPT-JT), and familial isolated HPT. Summarizing data from the literature and our own observations, various genetic abnormalities are observed in the pathogenesis of HPT. These include chromosomal deletions of the MEN1 locus on 11q in sporadic and MEN1 associated primary HPT, of RB1 on 13q in carcinomas, and of the FHH gene located on 3q in sporadic primary and secondary HPT. Genetic material is also lost from chromosomes 1p, 6q, 15q and X suggesting loss of yet unidentified tumor suppressor genes in these regions. In addition the HRPT2 gene on 1q, as well as the proto-oncogenes RET on 10q and PRAD1 on 11q are associated with a subset of parathyroid tumors.