Primary hyperparathyroidism (PHPT) may occur as part of a complex syndrome or as an isolated (non-syndromic) disorder, and both of these forms can occur as hereditary (i.e. familial) or non-familial (i.e. sporadic) diseases. Syndromic forms of PHPT include multiple endocrine neoplasia (MEN) types 14 (MEN1MEN4), and the hyperparathyroidismjaw tumour (HPTJT) syndrome. MEN1 is characterised by the combined occurrence of parathyroid tumours, pancreatic neuroendocrine tumours (NETS), anterior pituitary tumours, adrenal tumours and gastro-intestinal NETS; MEN2a is characterised by the occurrence of medullary thyroid carcinoma (MTC), phaeochromocytomas, and parathyroid tumours; MEN2b, also called MEN3, is characterised by occurrence of MTC and phaeochromotyomas in association with a marfanoid habitus, mucosal neuromas, medullated corneal fibers and intestinal autonomic ganglion dysfunction; MEN4 may be associated with tumours of the parathyroids, anterior pituitary, adrenals and gonads; and the HPTJT syndrome is associated with parathyroid tumours, which in 15% of patients are carcinomas, fibro-osseous jaw tumours, renal tumours and uterine tumours. MEN1 is caused by abnormalities of the MEN1 gene which encodes a tumour suppressor; MEN2 and MEN3 are due to mutations of the rearranged during transfection (RET) proto-oncogene, which encodes a tyrosine kinase receptor; MEN4 is due to mutations of a cyclin-dependent-kinase inhibitor (CDNK1B); and HPTJT is due to mutations of cell division cycle 73 (CDC73) which encodes parafibromin. Non-syndromic PHPT, which may be familial and referred to as familial isolated hyperparathyroidism (FIHP), may also be due to mutations of the MEN1, CDC73, or calcium-sensing receptor (CASR) genes. In addition, ~10% of patients presenting below the age of 45 years with non-syndromic (sporadic) PHPT may have MEN1, CDC73 or CASR mutations, and overall more than 10% of patients with PHPT will have a mutation in one of 11 genes.
17 May 2014 - 20 May 2014