Calcium infusion suggests a “set-point” abnormality of parathyroid gland function in familial benign hypercalcemia and more complex disturbances in primary hyperparathyroidism

PTH clearly plays a role in maintaining the hypercalcemia of familial benign hypercalcemia (FBH or familial hypocalciuric hypocalcemia). To better define the abnormalities of parathyroid function in FBH and primary hyperparathyroidism (1 ° HPT), we used a two-site immunochemiluminometric assay for intact PTH to examine PTH suppressibility in normal individuals and patients having FBH or 1 ° HPT. Twelve normal, 11 FBH, and 7 1 ° HPT subjects were given calcium (Ca) iv with frequent sampling for ionized Ca and intact PTH. In normal and FBH subjects, plasma PTH levels decreased essentially identically in response to iv Ca. In the 1 ° HPT group, PTH was not normally suppressible. However, there was a spectrum of responsiveness in 1 ° HPT patients, with a significant correlation between tumor mass and ° of PTH nonsuppressibility (r = 0.87, P = 0.01). Analysis of the relationship between plasma PTH and ionized Ca values in the three groups demonstrated a shift to the right in the FBH curve, with no difference of slope, consistent with the notion of a simple “set-point” error in FBH. In contrast, the curve in 1 ° HPT was not only shifted to the right but also differed from normal in slope (normal, -8.92; 1 ° HPT, -3.92, P = 0.04). Thus, we propose that the parathyroid functional abnormality in FBH represents a simple set-point error, whereas the defect in 1 ° HPT consists of a set-point error combined with varying °s of Ca nonsuppressible PTH secretion that may be related to tumor mass.