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Etiologies of parathyroid gland dysfunction in primary hyperparathyroidism
Author(s) -
Marx Stephen J.
Publication year - 1991
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.5650061408
Subject(s) - primary hyperparathyroidism , hyperparathyroidism , endocrinology , medicine , parathyroid hormone , parathyroid gland , multiple endocrine neoplasia , biology , cancer research , gene , genetics , calcium
Primary hyperparathyroidism is caused by defects in the parathyroid gland. Investigations have implicated three interesting genes whose mutation can cause primary hyperparathyroidism. Familial hypocalciuric hypercalcemia is believed to be an atypical form of primary hyperparathyroidism with an inherited defect in calcium recognition expressed not only in all parathyroid chief cells (thus a polyclonal defect) but in some renal tubular cells as well. In typical primary hyperparathyroidism a monoclonal parathyroid tumor is usually the central cause. Either of two apparently different genes on the long arm of chromosome 11 has been implicated in development of a parathyroid tumor clone. One gene (D11S287) was shown to have undergone a rearrangement with the parathyroid hormone gene on the short arm of the same chromosome (pericentro‐meric inversion) in a small fraction of tumors; the D11S287 locus may encode a growth stimulator. Another gene, the locus for familial multiple endocrine neoplasia type 1 (FMEN1), is likely to encode a growth inhibitor. Inactivation of this gene or another nearby gene by somatic mutation has been indirectly implicated in one‐quarter of sporadic parathyroid adenomas and in more than half of parathyroid tumors in FMEN1. In conclusion, studies have suggested three different mechanisms for parathyroid gland dysfunction in primary hyperparathyroidism: (1) a defect in calcium recognition, (2) a monoclonal tumor from overexpression of a growth stimulator, or (3) a monoclonal tumor from inactivation of a growth inhibitor.