Endocrine Abstracts

Introduction: Bartter Syndrome types 3 and 4 (BS3/4) are rare tubulopathies, caused by CLCNKB and BSND mutations, which affect chloride channel function in the loop of Henle and distal convolute. Historically, with late presentation and poor disease control, patients had severe short stature. Multiple case reports have also found associations between BS3/4 and Growth Hormone deficiency (GHD). Our aim was to investigate growth and presence of GHD in a large contemporaneous BS3/4 cohort.

Method: Case notes were retrospectively reviewed for patients with BS3/4, seen by a UK paediatric nephrology service since 1984. Data collected included: anthropometry; endocrine testing and pituitary imaging results; GH treatment.

Results: 26 BS3/4 patients, seen as children, were identified (currently aged 2–35 years). 16 patients were not referred to endocrinology, 10 of whom are post-pubertal with heights between 9th and 91st centiles. Ten (38%) children were/are seen by an endocrinologist; 9 underwent GH stimulation testing. Of those with abnormal tests (N=6), 5 received GH treatment: 4 for GHD (peak GH 0.9–2.4 mcg/l), 1 with GH neurosecretory dysregulation. GH increased growth velocity for most, but all have current/final height below 25th centile. Another has possible GH dysregulation (peak GH>40 mcg/l). The remaining stimulation tests showed: borderline low (6.7 mcg/l), normal (8 mcg/l) and borderline high (16.2 mcg/l) GH peaks. 4 children had MRIs. 2 GHD children had pituitary stalk thickening/possible thickening (one with absent posterior pituitary); 2 children with possible GH dysregulation (1 taking GH) had small anterior pituitary glands (with absent pituitary bright spot/optic nerve enlargement).

Conclusion: We report a high prevalence (23%) of GH disorders in BS3/4, with 20% of the cohort prescribed GH to date. Conversely, BS3/4 per se does not seem to cause growth failure, with many attaining normal final height. The pathophysiology of GHD is unknown, but may relate to the severe electrolyte/acid-base abnormalities in BS3/4. GH dysregulation is a novel finding in BS3/4, and the heterogeneity of pituitary images is striking and not previously reported. These suggest possible abnormalities in pituitary development, GH production and/or regulation in BS3/4.