Eur J Endocrinol 2009 Aug 01;1612:275-83. doi: 10.1530/EJE-09-0271.

Coexistence of normotensive primary aldosteronism in two patients with Gitelman's syndrome and novel thiazide-sensitive Na-Cl cotransporter mutations.

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BACKGROUND: Primary aldosteronism (PA) is the most common form of secondary hypertension, while Gitelman's syndrome (GS) is the most common inherited renal tubular disease. However, coexistence of these two diseases has never been previously reported. AIM AND SUBJECTS: The aim of our study was to describe the association of GS and PA in two unrelated patients and compare their clinical presentation with a group of patients with GS. METHODS: Ten subjects suspected to have only GS were assigned to the control group. Saline infusion test was used to confirm the diagnosis of PA. GS was confirmed by sequencing of the causal genes (SLC12A3 and CLCNKB) and functional analyses in Xenopus laevis oocytes. RESULTS: Confirmatory tests, gene analysis, and functional studies demonstrated the coexistence of GS and PA in both patients. In total, nine novel SLC12A3 gene variants, including seven missense mutations, one splice mutation, and one frameshift deletion, were found in 12 subjects. Four mutations (p.T60M, p.T304M, p.T465P, and p.N611T) harbored by the two patients with both PA and GS were revealed to be loss-of-function variants. Although both patients were normotensive, neither of them had normal nocturnal dip. CONCLUSIONS: Two rare diseases GS and PA may occasionally coexist in one subject. In these patients, salt depletion and volume constriction might explain the absence of hypertension normally seen in PA patients. However, the protective mechanism against hypertension via down-regulation of renal sodium handling was probably not sufficient in those patients, since their normal circadian rhythm of blood pressure was disrupted.

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Species referenced: Xenopus laevis
Genes referenced: slc12a3