Update on Genetic and Clinical Aspects of Primary Hyperparathyroidism: Update on Genetic and Clinical Aspects of Primary Hyperparathyroidism

S. Miedlich, K. Krohn, R. Paschke


Clin Endocrinol. 2003;59(5) 

In This Article


The hallmarks of primary hyperparathyroidism are hypercalcaemia and hypersecretion of parathyroid hormone. In the majority of the patients with pHPT, sporadic solitary tumours within the parathyroids are detected. Inherited syndromes, mostly associated with multiglandular disease, can be found in a minority of patients with pHPT. These syndromes include multiple endocrine neoplasia type 1 and type 2a, familial hypocalciuric hypercalcaemia and neonatal severe pHPT, as well as hyperparathyroidism-jaw tumour syndrome. In sporadic parathyroid adenomas, two specific genetic defects have been further characterized. Inactivating mutations of the recently identified putative tumour suppressor, the MEN1 gene, have been described in more than 25% of parathyroid adenomas. Activation of the PRAD1/cyclinD1 oncogene, caused by a chromosomal rearrangement on chromosome 11, has been found in a small subset of parathyroid adenomas. The characteristic feature of pHPT is the impaired inhibition of PTH secretion in response to extracellular calcium. Whereas initially suspected as the primary defect for the development of pHPT, the downregulation of the CaR on the cell surface of parathyroid adenomas seems to be a secondary event in parathyroid tumourigenesis. Primary hyperparathyroidism predominantly occurs in postmenopausal women, which may point to a role of oestrogens in the pathogenesis of the disease. Previous neck irradiation, lithium therapy, calcium and vitamin D deficiency can promote parathyroid hyperplasia and should be considered as risk factors for the development of parathyroid neoplasia. There does not seem to be a single genetic polymorphism, which clearly represents a risk factor for the development or the progression of pHPT. Further work is needed to determine whether genetic polymorphisms are truly associated with the prevalence and clinical phenotype of pHPT. In view of an increasing percentage of oligo- and asymptomatic patients and a slow progression of pHPT in the majority of patients, oestrogens, bisphosphonates and possibly SERMs as well calcimimetics may be considered as alternative medical approaches to surgery.

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