Familial hypocalciuric hypercalcemia. The relation to primary parathyroid hyperplasia

In familial hypocalciuric hypercalcemia, the parathyroid and kidney may be insensitive to extracellular calcium ions. Evidence of such insensitivity in the mechanisms that control hormone secretion and cell proliferation in the parathyroid glands is summarized. Data on renal function can also be explained by insensitivity to extracellular calcium. Beck et al. showed that in hypoparathyroid rats the response of urinary cyclic AMP to the administration of parathyroid hormone was diminished at progressively higher concentrations of serum calcium. The exaggerated response of cyclic AMP to parathyroid hormone in familial hypocalciuric hypercalcemia may similarly reflect renal insensitivity to the inhibitory effects of hypercalcemia. The conservation of urine-concentrating ability by the kidney in familial hypocalciuric hypercalcemia may show an insensitivity to the nephrotoxic effects of chronic hypercalcemia. Furthermore, the avid tubular resorption of calcium, which persists even when parathyroidectomy has led to otherwise typical features of hypoparathyroidism, also indicates a disturbance in the ability of renal cells to recognize or transport calcium. The explanation of the underlying mechanism, however, remains incomplete. Dysfunction of a single metabolic pathway should account for the defect in calcium metabolism in the parathyroid and kidney in familial hypocalciuric hypercalcemia. The fact that the degree of hypercalcemia is different in selected families and the fact that certain persons may carry related genes without even expressing hypercalcemia suggests that there is a series of related mutations.