Parathyroid expression of calcium-sensing receptor protein and in vivo parathyroid hormone-Ca2+ set-point in patients with primary hyperparathyroidism

A reduced expression of calcium-sensing receptor [CaR) messenger ribonuclei c acid and protein accompanied by abnormalities in parathyroid cell prolife ration and PTH secretion are present in primary hyperparathyroidism. We stu died the expression of CaR protein by immunohistochemistry in 36 sporadic p arathyroid adenomas and investigated the relationship between CaR expressio n and several preoperative clinical parameters, including the set-point of Ca2+ -regulated PTH secretion (measured in vivo). The adenomas were classif ied in 4 categories according to the intensity of immunohistochemical stain ing: 5 (14%) showed a CaR staining intensity similar to that of normal para thyroid(+ + +), 10 (27%) showed moderate staining(; +), 16 (45%) showed wea k staining (+), and 5 (14%) were negative (-). The intensity of CaR stainin g was not related to preoperative serum Ca2+, PTH levels or adenoma volume. Twenty-nine patients underwent preoperatively the calcium infusion test to evaluate the PTH-Ca2+ set-point. Individual values of PTH-Ca2+ set-point r anged from 1.38-1.93 mmol/L and were significantly correlated with basal Ca 2+ levels (r = 0.96; P = 0.0001) and adenoma volume (r = 0.5; P = 0.01). Th e mean PTH-Ca2+ set-point values were significantly different in the 4 grou ps of patients classified according to immunohistochemical staining intensi ty of their adenoma (P = 0.025; F = 3.78); the mean PTH-Ca2+ set-point was significantly higher in the groups classified as negative than in those cla ssified as weak or moderate. No correlation was observed between the PTH-Ca 2+ set-point and basal PTH levels or between the percent maximal PTH inhibi tion and adenoma volume and basal PTH or Ca2+ levels. In summary, our data suggest that there is a relationship between apparent CaR protein expressio n and PTH-Ca2+ set-point abnormality, suggesting that a reduced receptor co ntent might have an important role in the pathogenesis of primary hyperpara thyroidism.