No abstract

The calcium-sensing receptor (CaSR) has been detected in human antral gastrin-secreting cells, where, upon calcium and/or amino acid allosteric activation, it stimulates gastrin secretion. Patients with absorptive hypercalciuria (AH) display an enhanced gastric acid output; therefore, we evaluated the secretion of gastrin in subjects with AH (30 subjects vs. 30 healthy female controls, all postmenopausal) after oral calcium administration (1 g calcium gluconate) and, on a separate occasion, after peptone loading test (protein hydrolyzed, 10 g). Gastrin and monomeric calcitonin responses were higher in AH after both oral calcium administration (P < 0.01) and peptone loading (P < 0.01). Because the activation of CaSR by oral calcium and peptones directly induces gastrin release, the higher gastrin responses to these stimuli suggest an increased sensitivity of gastrin-secreting cells CaSR in patients with AH. A similar alteration in thyroid C cells might explain the enhanced calcitonin responses to both calcium and peptones. If the same alterations should in addition be present in the distal tubule (where CaSR is expressed as well), then a possible explanation for amino acid-induced hypercalciuria in AH would have been identified.

We analyzed gastrin, PTH, and calcitonin responses to oral calcium and peptones in hypocalciuric hypercalcemia, mild primary hyperparathyroidism, and normal controls. We observed diverse hormonal responses that may help in the differential diagnosis of these conditions. Introduction: Hypocalciuric hypercalcemia (HH) is consequent to calcium-sensing receptor (CaSR) genetic mutations or anti-CaSR antibodies. CaSR is expressed in parathyroid tissue, thyroid C cells, and gastrinsecreting cells, where it has been suggested that on calcium and/or amino acid allosteric activation, promotes gastrin secretion. Materials and Methods:We evaluated gastrin, PTH, and calcitonin responses to oral calcium (1 g) and peptones (10 g) in 10 patients with HH (mean age, 58.5 ± 10.3 years; F/M ‫ס‬ 9/1), 15 patients with primary hyperparathyroidism (PH; mean age, 60.4 ± 8.3 years; F/M ‫ס‬ 11/4), and 30 healthy controls (mean age, 60.3 ± 8.1 years). Statistical analyses for differences during oral loading tests were calculated with ANOVA for repeated measurements and comparisons between two groups were performed with Student's t-test. Results: PTH response to peptones was markedly increased in patients with PH compared with flat responses in controls and HH patients (p < 0.05). Gastrin increase after oral calcium was absent in HH and PH subjects (p < 0.05 versus controls), and gastrin responses to peptones were blunted in HH and PH subjects compared with controls (p < 0.05). PTH drop and calcitonin increase after calcium load observed in controls were absent in HH and PH subjects (p < 0.05). Conclusions:The marked difference in PTH response elicited by peptones observed in PH compared with subjects with HH may help in the differential diagnosis of these conditions without genetic studies. Peptones may stimulate CaSR-controlled hormones as an allosteric regulatory pathway. CaSR abnormalities may help to explain the different calcium-and peptones-induced hormonal responses observed in PH and HH compared with normal subjects.

Although nonsteroidal anti-inflammatory drugs are effective in improving pain and disability in OA patients, to date it has been unclear to what extent these drugs could affect joint metabolism and hence joint structure. Patients with flare-up of their osteoarthritis disease process exhibit enhanced levels of markers of joint inflammation and cartilage collagen breakdown, which were markedly decreased by nimesulide but not by ibuprofen.