Parathyroid hormone and phosphate homeostasis in patients with Bartter and Gitelman syndrome: an international cross-sectional study

Abstract

Background Small cohort studies have reported high parathyroid hormone (PTH) levels in patients with Bartter syndrome and lower serum phosphate levels have anecdotally been reported in patients with Gitelman syndrome. In this cross-sectional study, we assessed PTH and phosphate homeostasis in a large cohort of patients with salt-losing tubulopathies. Methods Clinical and laboratory data of 589 patients with Bartter and Gitelman syndrome were provided by members of the European Rare Kidney Diseases Reference Network (ERKNet) and the European Society for Pediatric Nephrology (ESPN). Results 285 patients with Bartter syndrome and 304 patients with Gitelman syndrome were included for analysis. Patients with Bartter syndrome type I & II had the highest median PTH level (7.5 pmol/l) and 56% had hyperparathyroidism (PTH >7.0 pmol/l). Serum calcium was slightly lower in Bartter syndrome type I & II patients with hyperparathyroidism (2.42 vs. 2.49 mmol/l; p = 0.038) compared to those with normal PTH levels and correlated inversely with PTH (rs -0.253; p = 0.009). Serum phosphate and urinary phosphate excretion did not correlate with PTH. Overall, 22% of patients had low serum phosphate levels (phosphate – standard deviation score < -2), with the highest prevalence in patients with Bartter syndrome type III (32%). Serum phosphate correlated with TmP/GFR (rs 0.699; p < 0.001), suggesting renal phosphate wasting. Conclusions Hyperparathyroidism is frequent in patients with Bartter syndrome type I & II. Low serum phosphate is observed in a significant number of patients with Bartter and Gitelman syndrome and appears associated with renal phosphate wasting.

Recurrent transient severe hypocalcaemia in two siblings with type 1 Bartter syndrome

“…15 They also reported that there was no correlation between PTH levels and urinary calcium excretion, which is usually high in type 1 and type 2 BS patients. 15 In some papers, it is discussed that hypokalaemia and high prostaglandin E2 levels may contribute to PTH resistance. 13,16 However, the details of why patients with type 1 and type 2 BS exhibit PTH resistance are largely unknown.…”

“…In addition, Verploegen et al analysed biological data from hundreds of patients with BS and Gitelman syndrome. They found that patients with type 1 BS and type 2 BS had significantly higher PTH levels than those with other types of BS and Gitelman syndrome 15 . They also reported that there was no correlation between PTH levels and urinary calcium excretion, which is usually high in type 1 and type 2 BS patients 15 .…”

“…They found that patients with type 1 BS and type 2 BS had significantly higher PTH levels than those with other types of BS and Gitelman syndrome 15 . They also reported that there was no correlation between PTH levels and urinary calcium excretion, which is usually high in type 1 and type 2 BS patients 15 . In some papers, it is discussed that hypokalaemia and high prostaglandin E2 levels may contribute to PTH resistance 13,16 .…”

The genetic spectrum of Gitelman(-like) syndromes

“…In-depth phenotyping of Gitelman patients with SLC12A3 mutations has resulted in the identification of subclinical phenotypes [5,20 ▪ ]. In a large European cohort, 20% of patients with Gitelman syndrome had hypoparathyroidism [20 ▪ ].…”

“…In-depth phenotyping of Gitelman patients with SLC12A3 mutations has resulted in the identification of subclinical phenotypes [5,20 ▪ ]. In a large European cohort, 20% of patients with Gitelman syndrome had hypoparathyroidism [20 ▪ ]. As the parathyroid harmone (PTH) and magnesium concentrations were correlated in this cohort, it has been hypothesized that the hypoparathyroidism is explained by Mg 2+ -dependent regulation of the calcium-sensing receptor [21].…”