Evidence for disturbed regulation of calciotropic hormone metabolism in gitelman syndrome.

Abstract

Little attention has been paid to interactions between circulating levels of calcium, PTH, and 1,25-dihydroxycholecalciferol [1,25(OH)2D] and bone mineral density in primary renal magnesium deficiency. Plasma and urinary electrolytes, and circulating levels of calciotropic hormones were studied in 13 untreated patients with primary renal tubular hypokalemic alkalosis with hypocalciuria and magnesium deficiency. The blood ionized calcium concentration was significantly lower in patients than in controls. Despite this fact, PTH and 1,25-(OH)2D levels were similar in both groups of subjects. The negative linear relationships between PTH and ionized calcium, which significantly differed between Gitelman patients and healthy subjects in terms of intercept; the negative relationship between ionized calcium and 1,25-(OH)2D, which was comparable in both groups; and the positive relationship between 1,25-(OH)2D and PTH, which was identical in both groups, point both to a blunted secretion of PTH induced by magnesium depletion and to the lack of interference of the latter with the activation of 1 alpha-hydroxylase by PTH. The similar bone mineral density at the lumbar spine by dual energy x-ray absorptiometry in 11 patients and 11 healthy subjects argues against chronically sustained negative calcium balance.

Renal Genetic Disorders Related to K+ and Mg2+

“…Mg 2+ wasting accounts for many of the symptoms (97) and for relative PTH resistance with low serum Ca 2+ levels. In contrast, the plasma 1,25-(OH)2-D 3 levels and bone density appear to be normal (106).…”

Parathyroid hormone and phosphate homeostasis in patients with Bartter and Gitelman syndrome: an international cross-sectional study

“…This latter response is suggested to result from intracellular disinhibition of G-protein signalling downstream from the calcium-sensing receptor, precluding PTH release [ 29 ]. Accordingly, decreased PTH secretion and decreased responsiveness of PTH to ionized calcium have been suggested in small cohorts of patients with Gitelman syndrome [ 30 , 31 , 32 ]. In agreement with these data, we observed a significant correlation between PTH and serum magnesium in patients with Gitelman syndrome, suggesting that low serum magnesium might be, at least in part, responsible for hypoparathyroidism.…”

A Case of Gitelman Syndrome with Hypercalcemia Secondary to Primary Hyperparathyroidism

“…This includes the function of parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D [1,25 (OH) 2 D], resulting in decreased intestinal absorption of calcium. Lack of magnesium hinders the activation of 1 alpha-hydroxylase by PTH, leading to a decreased level of 1,25 (OH) 2 D. In addition, the negative relationship between circulating calcium levels and PTH is blunted in patients with Gitelman syndrome [ 6 ].…”