Endocrine Abstracts

Introduction: Gitelman syndrome(GS) is a salt-wasting tubulopathy characterized by renal potassium wasting, hypokalemia, metabolic alkalosis, hypomagnesemia, hypocalciuria and hyperreninemic hyperaldosteronism. It is caused by the mutation of genes encoding sodium chloride (NCCT) and magnesium transporters in the thiazide-sensitive segments of the distal nephron (SLC12A3 and TRMP6 gene). GS is a rare autosomal recessive disease with a prevalence of only 25 cases per one million population.

Case report: A 23-year-old girl diagnosed with Hashimoto thyroiditis with hypothyroidism, polycystic ovarian syndrome, short stature due to SGA (2000 g at 38 wks, twin pregnancy), treated with recombinant GH during childhood, presented for paresthesias of the hands, nausea, dizziness, and acne. Her clinical features were short stature (T= 154 cm) and low BMI (15.61 kg/mp). The biological assessment revealed persistent hypokalemia (< 2.9 mmol/l), hypomagnesemia (<1.34 mg/dl), hypochloremia with a normal sodium and bicarbonate level, normocalcemia (9.13 mg/dl) with hypocalciuria (43 mg/24 h). Hormonal profile: normal thyroid function tests with levothyroxine replacement, hyperreninemic (281 uUI/ml, normal values: 2.8-39), hyperaldosteronism (35.2 ng/dl, normal values 1.76-23.2). The hepatic and renal functions were normal; she was also normoglycemic. The suspicion for Gitelman Syndrome was confirmed by the genetic testing, which showed heterozygosity for SCL12A3 gene mutation. Due to the absence of symptoms, her potassium and magnesium serum levels were not assessed periodically during childhood, and the diagnosis was raised at about 16 years. Her twin sister has average stature and no potassium or magnesium imbalance. Supplementation with oral potassium chloride of two grams per day and oral magnesium chloride 500 mg per day was started but with a slow improvement of biological parameters. Spironolactone treatment does not ameliorate potassium levels as in others hypopotasemia disorders but was mentained due to associated acne.

Discussion: Gitelman syndrome is a condition that may remain asymptomatic or present with mild or nonspecific symptoms. Phenotypic variability and potential severity are also seen in genetically confirmed GS patients, but many patients are not tested, with genetic testing that is not widely available and expensive. The primary differential diagnosis of GS is with Bartter syndrome, especially type III. Treatment is symptomatic and life-long to prevent cardiac arrhythmias and dehydration; it includes supplementation with potassium chloride (with better absorption) and magnesium replacement (organic salts are preferred). Magnesium replacement should be considered first because the repletion of magnesium will facilitate potassium repletion.