Gitelman syndrome and primary hyperparathyroidism: a rare association

Abstract

Gitelman syndrome(GS) is a rare autosomal recessive salt-losing tubulopathy of young adults, characterised by hypokalaemia, hypomagnesaemia, hypocalciuria and secondary hyperaldosteronism. Hypercalcaemia due to hypocalciuria in these patients is extremely rare.A 25-year-old healthy woman was referred to the Endocrinology clinic for evaluation of persistent hypokalaemia. She presented with fatigue, myalgias, cramps and paraesthesia. Her physical examination was normal. Laboratory workup revealed: K+ 2.7 mEq/L (r.v.3.5–5.1), 24 hours urinary K+ 84.7 mEq/24 hours (r.v.25–125), Mg2+ 0.71 mg/dL (r.v.1.6–2.6), 24 hours urinary Mg2+ 143.1 mg/24 hours (r.v.73–122), Ca2+ 12 mg/dL (r.v.8.4–10.2), aldosterone 47.1 ng/mL (r.v. 4–31) and active renin 374.7 uUI/mL (r.v.4.4–46.1). She was diagnosed with GS and was treated with spironolactone, oral K+ and Mg2+ supplementation. Further investigation confirmed hypercalcaemia due to primary hyperparathyroidism owing to a single parathyroid adenoma. Following parathyroidectomy serum calcium normalised.Current knowledge favours that hypomagnesaemia in patients with GS protects them from hypercalcaemia. In this context of multiple electrolyte imbalances, correction of hypomagnesaemia is a challenge and should be done carefully. Like in our patient, aetiology of hypercalcaemia should be promptly diagnosed and reversed.

Bilateral hamstring origin calcification: rare presentation of Gitelman syndrome

“…Bianchetti et al reported the blunted relationship between calcium ions, parathyroid hormone (PTH) and calcitriol in patients with GS 6. Moreover, the typical urinary excretion and blood levels of phosphate indicate normal parathyroid function 1. Some patients with GS may not show hypomagnesaemia or hypocalciuria 3…”

“…Gitelman syndrome (GS) is a salt-losing disorder affecting the distal convoluted tubule of the nephron. It is an autosomal recessive disorder with a prevalence of 1/40 000 1. GS represents the clinical manifestations of inactivation of the Slc12a3 genes encoding the thiazide-sensitive sodium chloride cotransporter and the Trpm6-Mg genes encoding the magnesium transporters in the distal convoluted tubule 2.…”

“…Serum calcium and phosphate levels are usually unaffected in GS unless associated with hyperparathyroidism or other reversible aetiologies 1. Mild hypercalcaemia can occur in patients with GS because of dehydration-induced hyperproteinaemia.…”

Concomitance of Familial Mediterranean Fever and Gitelman syndrome in an adolescent

“…In a recent study, the variant c.602-16G>A and the variant c.2221G>A, both in heterozygosity, were detected in SLC12A3 gene, in a patient with GS and primary hyperparathyroidism. 14 In another study, nine splice site mutations, including c.602-16G>A as a novel splice site mutation, were identified and predicted to lead to a frameshift and premature stopcodon. 15 The variant c.602-16G>A is described on the database of HGMD, as a disease-causing mutation.…”

“…15 Furthermore, it is described in dbSNP and ExAC databases, and it's frequency is reported as 0.0016%. 14 The functional analysis of mutations in SLC12A3 gene were performed for a limited number of mutations. Rego et al 14 reported that the variant c.602-16G>A is considered of undetermined significance due to lack of functional analysis confirming the splicing effect.…”