Bartter syndrome is a group of rare autosomal-recessive renal disorders characterized by hypokalemic hypochloremic metabolic alkalosis associated with severe growth failure; the exact causes for growth retardation are unclear. GH deficiency (GHD) has been reported in a few cases of Bartter syndrome. The aim of our study was to determine the prevalence of GHD in children with antenatal Bartter syndrome and to assess their response to GH therapy.
Ten patients aged 1.5–14.5 years and diagnosed with antenatal Bartter syndrome were enrolled. Seven children with short stature underwent GH stimulation tests.
Common presenting symptoms were failure to thrive and polyuria. The mean patient height at study entry was −2.7 standard deviation (SD) (range 0.89 to −5.95) and mean weight (SD) was −1.7 (range 1.89 to −4.11). A decline in height and weight (SD) was observed over the years. GHD was diagnosed in four children and GH therapy was started in all of them. Two patients responded very well and gained >1 SD in height, one patient stopped therapy due to non-adherence and one had a poor response.
In addition to other important causes for poor growth in antenatal Bartter syndrome, our findings suggest that GHD should also be considered as a cause of growth retardation and therefore, clinical assessment of the GH axis is recommended. GH therapy has a role in the treatment of growth failure in some individuals with Bartter syndrome.
We are grateful to the Pediatric Endocrine Team for fruitful collaboration. We thank Camille Vainstein for professional language editing and Naama Schwartz for the statistical analysis. Thanks to the patients and their families for participating in the study.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted article and approved submission.
Research funding: This study was supported by a grant from the Academic Committee of Ha’Emek Medical Center.
Employment or leadership: None declared.
Honorarium: None declared.
Competing of interest: The funding organization played no role in the study design, in the collection, analysis or interpretation of data, in the writing of the report, or in the decision to submit the report for publication.
1. Jeck N, Schlingmann KP, Reinalter SC, Kömhoff M, Peters M, et al. Salt handling in the distal nephron: lessons learned from inherited human disorders. Am J Physiol Regul Integr Comp Physiol 2005;288:R782–95. Search in Google Scholar
2. Proesmans W. Bartter syndrome and its neonatal variant. Eur J Pediatr 1997;156:669–79. Search in Google Scholar
3. Peters M, Jeck N, Reinalter S, Leonhardt A, Tönshoff B, et al. Clinical presentation of genetically defined patients with hypokalemic salt-losing tubulopathies. Am J Med 2002;112:183–90. Search in Google Scholar
4. Flyvbjerg A, Dørup I, Everts ME, Orskov H. Evidence that potassium deficiency induces growth retardation through reduced circulating levels of growth hormone and insulin-like growth factor I. Metabolism 1991;40:769–75. Search in Google Scholar
5. Gil-Peña H, Mejia N, Alvarez-Garcia O, Loredo V, Santos F. Longitudinal growth in chronic hypokalemic disorders. Pediatr Nephrol 2010;25:733–7. Search in Google Scholar
6. Bettinelli A, Borsa N, Bellantuono R, Syrèn ML, Calabrese R, et al. Patients with biallelic mutations in the chloride channel gene CLCNKB: long-term management and outcome. Am J Kidney Dis 2007;49:91–8. Search in Google Scholar
7. Buyukcelik M, Keskin M, Kilic BD, Kor Y, Balat A. Bartter syndrome and growth hormone deficiency: three cases. Pediatr Nephrol 2012;27:2145–8. Search in Google Scholar
8. Lefebvre J, Racadot A, Dequiedt P, Linquette M. [Exchangeable electrolytes, glycoregulation and growth hormone in one case of Bartter’s syndrome (author’s transl.)]. Ann Endocrinol (Paris) 1977;38:385–6. Search in Google Scholar
9. Boer LA, Zoppi G. Bartter’s syndrome with impairment of growth hormone secretion. Lancet 1992;340:860. Search in Google Scholar
10. Ruvalcaba RH, Martinez FE. Case report: familial growth hormone deficiency associated with Bartter’s syndrome. Am J Med Sci 1992;303:411–4. Search in Google Scholar
11. Akil I, Ozen S, Kandiloglu AR, Ersoy B. A patient with Bartter syndrome accompanying severe growth hormone deficiency and focal segmental glomerulosclerosis. Clin Exp Nephrol 2010;14:278–82. Search in Google Scholar
12. Adachi M, Tajima T, Muroya K, Asakura Y. Classic Bartter syndrome complicated with profound growth hormone deficiency: a case report. J Med Case Rep 2013;30:283. Search in Google Scholar
13. Krysiak R, Gdula-Dymek A, Bednarska-Czerwiñska A, Okopieñ B. Growth hormone therapy in children and adults. Pharmacol Rep 2007;59:500–16. Search in Google Scholar
14. Kuczmarski RJ, Ogden CL, Grummer-Strawn LM, Flegal KM, Guo SS, et al. CDC growth charts: United States. Advance Data 2000;314:1–27. Search in Google Scholar
15. Greulich WW, Pyle SI. Radiograph atlas of skeletal development of the hand and wrist, 2nd ed. Stanford, CA, USA: Stanford University Press, 1959. Search in Google Scholar
16. Puricelli E, Bettinelli A, Borsa N, Sironi F, Mattiello C, et al. Long-term follow-up of patients with Bartter syndrome type I and II. Nephrol Dial Transplant 2010;25:2976–81. Search in Google Scholar
17. Bettinelli A, Rusconi R, Ciarmatori S, Righini V, Zammarchi E, et al. Gitelman disease associated with growth hormone deficiency, disturbances in vasopressin secretion and empty sella: a new hereditary renal tubular-pituitary syndrome? Pediatr Res 1999;46:232–8. Search in Google Scholar
18. Dunn MJ. Prostaglandins and Bartter’s syndrome. Kidney Int 1981;19:86–102. Search in Google Scholar
19. Hertelendy F. Studies on growth hormone secretion. II. Stimulation by prostaglandins in vitro. Acta Endocrinol 1971;68:355–62. Search in Google Scholar
20. MacLeod RM, Lehmeyer JE. Release of pituitary growth hormone by prostaglandins and dibutyryl adenosine cyclic 3′:5′-monophosphate in the absence of protein synthesis. Proc Natl Acad Sci USA 1970;67:1172–9. Search in Google Scholar
21. Cooper RH, Mcpherson M, Schofield JG. The effect of prostaglandins on ox pituitary content of adenosine 3′: 5′-cyclic monophosphate and the release of growth hormone. Biochem J 1972;127:143–54. Search in Google Scholar
22. Dray F, Kouznetzova B, Harris D, Brazeau P. Role of prostaglandins on growth hormone secretion: PGE2 a physiological stimulator. Adv Prostaglandin Thromboxane Res 1980;8:1321–8. Search in Google Scholar
23. Drouin J, Labrie F. Specificity of the stimulatory effect of prostaglandins on hormone release in rat anterior pituitary cells in culture. Prostaglandins 1976;11:355–65. Search in Google Scholar
24. Vierhapper H, Bratusch-Marrain P, Waldhäusl W. Effect of i.v. prostaglandin E2 on the secretion of pituitary hormones in healthy men. Exp Clin Endocrinol 1983;82:372–5. Search in Google Scholar
25. Mourani CC, Sanjad SA, Akatcherian CY. Bartter syndrome in a neonate: early treatment with indomethacin. Pediatr Nephrol 2000;14:143–5. Search in Google Scholar
26. Haas NA, Nossal R, Schneider CH, Lewin MA, Ocker V, et al. Successful management of an extreme example of neonatal hyperprostaglandin-E syndrome (Bartter’s syndrome) with the new cyclooxygenase-2 inhibitor rofecoxib. Pediatr Crit Care Med 2003;4:249–51. Search in Google Scholar
27. Vaisbich MH, Fujimura MD, Koch VH. Bartter syndrome: benefits and side effects of long-term treatment. Pediatr Nephrol 2004;19:858–63. Search in Google Scholar
28. Seyberth HW, Schlingmann KP. Bartter-and Gitelman-like syndromes: salt-losing tubulopathies with loop or DCT defects. Pediatr Nephrol 2011;10:1789–802. Search in Google Scholar
29. Nascimento CL, Garcia CL, Schvartsman BG, Vaisbich MH. Treatment of Bartter syndrome. Unsolved issue. Pediatr (Rio J) 2014;90:512–7. Search in Google Scholar
30. Kleta R, Basoglu C, Kuwertz-Bröking E. New treatment options for Bartter’s syndrome. N Engl J Med 2000;343: 661–2. Search in Google Scholar
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