Normomagnesemic Gitelman Syndrome Patients Exhibit A Stronger Reaction to Thiazide than Hypomagnesemic Patients

Abstract

In recent decades, the thiazide test has been introduced to aid the diagnosis of Gitelman syndrome (GS), but the effect of thiazide in normomagnesemic GS patients is currently unknown. This study was conducted to compare the thiazide test results of normomagnesemic and hypomagnesemic GS patients. Seventeen GS patients with SLC12A3 gene mutations were enrolled, five of whom did not have a history of hypomagnesemia. The clinical data were documented, and SLC12A3 gene screening was performed. The thiazide test was performed in all of the patients and 20 healthy controls. A receiver operating characteristic curve was used to evaluate the sensitivity and specificity of the thiazide test in the diagnosis of GS. A 7-fold increase in sodium and chloride excretion was observed after thiazide application in healthy controls, and an approximately 2-fold increase was found in the 5 normomagnesemic GS patients; however, there was no change in the 12 hypomagnesemic GS patients. A weaker reaction to thiazide was observed in hypomagnesemic compared with normomagnesemic GS patients. The clearance of chloride in 1 patient was overestimated because of chronic renal function insufficiency (CRI). When a reasonable cutoff value for chloride fractional excretion was selected, the thiazide test was 95% sensitive and 94.1% specific for the diagnosis of GS. Hypomagnesemic GS patients exhibited greater sodium-chloride cotransporter dysfunction than normomagnesemic GS patients. When CRI occurs, the chloride and sodium clearance rates, rather than the fractional excretion, should be used in the evaluation of the thiazide test results.