Parathyroid glands and the multiple endocrine neoplasia syndromes and familial hypocalciuric hypercalcemia

Hypercalcemia is a variable feature of inherited endocrine disorders. In the multiple endocrine neoplasia (MEN) syndromes, generalized hyperparathyroidism is a common feature. It occurs much more frequently in patients with MEN type 1 as compared to patients with MEN type 2A. Unlike the MEN syndromes, patients with familial hypocalciuric hypercalcemia (FHH) have only hypercalcemia with no associated endocrinopathies. The hyperparathyroidism in patients with either of the MEN syndromes is managed by parathyroidectomy, whereas patients with FHH are managed nonoperatively. The specific genetic defects associated with MEN type 2 syndromes and FHH have been identified. They explain, in part, the clinical and pathophysiologic features of these diseases. The genetic defect causative of MEN type 1 will doubtless soon be found and thereby provide further insights into the molecular basis of calcium homeostasis. We will review the clinical presentation and the management of patients with these disorders. We will also review the recent molecular discoveries in MEN 2A, MEN 2B, and FHH, and define how they have altered the management of patients who have these syndromes.