Gitelmans Syndrome (GS) is a rare autosomal recessive salt-losing tubulopathy of young adults, characterized by secondary hyperaldosteronism, hypokalemia, hypomagnesemia, hypocalciuria and metabolic alkalosis. It is caused by mutations in SLC12A3 gene. Hypercalcemia due to hypocalciuria in these patients is extremely rare and requires further evaluation.
A 25-year-old normotensive female was referred to Endocrinology clinic for evaluation of persistent hypokalemia. She presented history of malaise, fatigue, myalgias, cramps and paresthesia. She denied diarrhea, recent treatment with diuretics or laxatives. Her physical exam was normal. Laboratory workout revealed: aldosterone 47.1 ng/mL (r.v. 431), active renin 374.7 μUI/ml (r.v. 4.446.1), K+2.7 mEq/l (r.v. 3.55.1), 24 h urinary K+84.7 mEq/24 h (r.v. 25125), Mg2+0.71 mg/dl (r.v. 1.62.6), 24 h urinary Mg2+143.1 mg/24 h (r.v. 73122), Ca2+12 mg/dl (r.v. 8.410.2) and 24 h urinary Ca2+133 mg/24 h (r.v. 100300). GS was diagnosed and she was treated with spironolactone, oral K+ and Mg2+ supplementation. Further investigation confirmed hypercalcemia due to primary hyperparathyroidism (parathyroid hormone (PTH) 107.3 pg/ml (r.v. 14.883.1)) caused by a large single parathyroid adenoma. Following parathyroidectomy calcium profile normalized. The sequencing of SLC12A3 gene detected the variant c.60216G>A and the mutation c.2221G>A (p.Gly741Arg), both in heterozygosity. In this context genetic study of the progenitors was required. The father presents the variant c.60216G>A and the mother the mutation c.2221G>A (p.Gly741Arg), in SLC12A3 gene.
The assotiation of hypokalemia, hypomagnesemia and hypercalcemia is uncommon but potentially lethal. Current knowledge favors that hypomagnesemia in GSs patients protects them from hypercalcemia. In this context of multiple electrolyte imbalances, correction of hypomagnesemia is a challenge and should be done carefully. Like in our patient hypercalcemias etiology should be prompt diagnosed and reversed.
20 - 23 May 2017
European Society of Endocrinology