FAMILIAL ISOLATED PRIMARY HYPERPARATHYROIDISM

Familial primary hyperparathyroidism (PHPT) is usually encountered in the context of multiple endocrine neoplasia (MEN) syndromes. Few families have been reported in the literature where PHPT was the only abnormality. However, in these families no long-term follow-up data were reported and no genetic linkage studies were performed. OBJECTIVE We investigated a large family with a familiar primary hyperparathyroidism for biochemical and genetic markers of multiple endocrine neoplasia syndromes. DESIGN A family screening study. PATIENTS Thirty-seven family members participated in this study including 7 patients who had been previously operated upon for PHPT. MEASUREMENTS Serum calcium (albumin adjusted), was measured in all family members. Hypercalcaemic subjects and patients who had been operated upon for PHPT were assessed for biochemical markers of MEN syndromes (serum gastrin, prolactin, calcitonin, fasting plasma glucose and 24-hours urinary excretion of adrenaline, noradrenaline and vanillylmandelic acid (VMA)). Genetic linkage analysis was performed using DNA markers linked to chromosome 11q13, the presumed MEN type 1 (MEN-1) locus. RESULTS Four new patients with PHPT and two with probable PHPT were discovered. No clinical or biochemical evidence of MEN syndromes could be detected. DNA marker pMS51(D11S97) was informative, maximum two-point lodscore of 2.12 at a recombination fraction of 0.05 confirming linkage to chromosome 11q13. CONCLUSIONS Familial PHPT can exist as a separate clinical entity. Isolated familiar PHPT is caused by mutation in a gene located in the MEN-1 region on chromosome 11q13, possibly the MEN-1 locus.