Hormone Regulation of Urine Formation. Antidiuretic Hormone ( ADH)
Classic Bartter syndrome complicated with profound growth hormone deficiency
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POSTER PRESENTATION Open Access Classic Bartter syndrome complicated with profound growth hormone deficiency Masanori Adachi 1* , Toshihiro Tajima 2 , Koji Muroya 1 , Yumi Asakura 1 From 7th APPES Biennial Scientific Meeting Nusa Dua, Bali. 14-17 November 2012 Case history A Japanese boy was born at 41 weeks of gestational age by spontaneous cephalic delivery, with birth weight 3,680g. Family history was remarkable for his elderly sister suffer- ing from classic Bartter syndrome. He also was diagnosed as classic Bartter syndrome, based on the findings such as failure to thrive, metabolic alkalosis with hypokalemia, and the activated renin-aldosterone system. The diagnosis was later confirmed by CLCNKB gene analysis which revealed compound heterozygous mutations: deletion of the exon 1 - 3 (derived from his mother) and ΔL130 (derived from the father). Treatment with spironolactone, indomethacin, sodium chloride, and potassium supplementation was commenced at 8 months of age. However, his serum potassium level failed to normalize, and tended to be around 2 - 3mEq/L. He had mild intellectual impairment, and needed specialized education. When he was 11 years old, through the investigation for macrohematuria, renal stones with nephrocalcinosis were detected. This compli- cation resolved following the amelioration of hypokalemia, which was achieved by vigorous potassium fortification. Because his growth rate was consistently subnormal and he was very short (-4.7SD), scrutiny for growth hormone (GH) secretion was conducted at his 14 years of age. Results Profound GH deficiency was evident. Serum IGF-1 level was 80ng/mL (norm, 178-686), with IGFBP-3 1.92μg/mL (2.69-4.16). Pharmacologically stimulated GH levels were 0.15 and 0.39 ng/mL, after insulin and arginine adminis- tration, respectively. His bone age was 11.4 years old (TW2-RUS for Japanese). MR imaging detected no abnormality within hypothalamic-pituitary region. Clinical course GH treatment with 0.15-0.19mg/kg/week resulted in growth rate as much as 11.7cm during the first 12-months, followed by 10.8cm during the subsequent 12 months. Although his pubertal stage progressed from Tanner stage 1 to stage 2 during 2 years, Δ bone age / Δ chronological age was 1.02. No significant change in serum potassium level was observed. Discussion In literature, GH deficiency in Bartter syndrome and Gitelman syndrome has been anecdotally reported, with diverse severity among patients. At present, its precise pathogenesis, as well as its prevalence, is unknown. Classic Bartter syndrome complicated with profound GH deficiency, as seen in this case, is rare. The sister of the case, who also suffered from classic Bartter syn- drome, is 145 cm tall (-2.0SD) now and seemed not to be GH deficient. Her potassium level had been managed rather better than this case. It may be tempting to spec- ulate that long-term hypokalemia may be harmful for somatotrophs to produce GH. Authors’ details 1 Kanagawa Children’s Medical Center, Japan. 2 Hokkaido University School of Medicine, Japan. Published: 3 October 2013 doi:10.1186/1687-9856-2013-S1-P40 Cite this article as: Adachi et al.: Classic Bartter syndrome complicated with profound growth hormone deficiency. International Journal of Pediatric Endocrinology 2013 2013(Suppl 1):P40. 1 Kanagawa Children’s Medical Center, Japan Full list of author information is available at the end of the article Adachi et al. International Journal of Pediatric Endocrinology 2013, 2013(Suppl 1):P40 http://www.ijpeonline.com/content/2013/S1/P40 © 2013 Adachi et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Transcript of Classic Bartter syndrome complicated with profound growth hormone deficiency
POSTER PRESENTATION Open Access
Classic Bartter syndrome complicated withprofound growth hormone deficiencyMasanori Adachi1*, Toshihiro Tajima2, Koji Muroya1, Yumi Asakura1
From 7th APPES Biennial Scientific MeetingNusa Dua, Bali. 14-17 November 2012
Case historyA Japanese boy was born at 41 weeks of gestational age byspontaneous cephalic delivery, with birth weight 3,680g.Family history was remarkable for his elderly sister suffer-ing from classic Bartter syndrome. He also was diagnosedas classic Bartter syndrome, based on the findings such asfailure to thrive, metabolic alkalosis with hypokalemia, andthe activated renin-aldosterone system. The diagnosis waslater confirmed by CLCNKB gene analysis which revealedcompound heterozygous mutations: deletion of the exon1 - 3 (derived from his mother) and ΔL130 (derived fromthe father). Treatment with spironolactone, indomethacin,sodium chloride, and potassium supplementation wascommenced at 8 months of age. However, his serumpotassium level failed to normalize, and tended to bearound 2 - 3mEq/L. He had mild intellectual impairment,and needed specialized education. When he was 11 yearsold, through the investigation for macrohematuria, renalstones with nephrocalcinosis were detected. This compli-cation resolved following the amelioration of hypokalemia,which was achieved by vigorous potassium fortification.Because his growth rate was consistently subnormal andhe was very short (-4.7SD), scrutiny for growth hormone(GH) secretion was conducted at his 14 years of age.
ResultsProfound GH deficiency was evident. Serum IGF-1 levelwas 80ng/mL (norm, 178-686), with IGFBP-3 1.92μg/mL(2.69-4.16). Pharmacologically stimulated GH levels were0.15 and 0.39 ng/mL, after insulin and arginine adminis-tration, respectively. His bone age was 11.4 years old(TW2-RUS for Japanese). MR imaging detected noabnormality within hypothalamic-pituitary region.
Clinical courseGH treatment with 0.15-0.19mg/kg/week resulted ingrowth rate as much as 11.7cm during the first 12-months,followed by 10.8cm during the subsequent 12 months.Although his pubertal stage progressed from Tanner stage1 to stage 2 during 2 years, Δ bone age / Δ chronologicalage was 1.02. No significant change in serum potassiumlevel was observed.
DiscussionIn literature, GH deficiency in Bartter syndrome andGitelman syndrome has been anecdotally reported, withdiverse severity among patients. At present, its precisepathogenesis, as well as its prevalence, is unknown.Classic Bartter syndrome complicated with profoundGH deficiency, as seen in this case, is rare. The sister ofthe case, who also suffered from classic Bartter syn-drome, is 145 cm tall (-2.0SD) now and seemed not tobe GH deficient. Her potassium level had been managedrather better than this case. It may be tempting to spec-ulate that long-term hypokalemia may be harmful forsomatotrophs to produce GH.
Authors’ details1Kanagawa Children’s Medical Center, Japan. 2Hokkaido University School ofMedicine, Japan.
Published: 3 October 2013
doi:10.1186/1687-9856-2013-S1-P40Cite this article as: Adachi et al.: Classic Bartter syndrome complicatedwith profound growth hormone deficiency. International Journal ofPediatric Endocrinology 2013 2013(Suppl 1):P40.
1Kanagawa Children’s Medical Center, JapanFull list of author information is available at the end of the article
Adachi et al. International Journal of Pediatric Endocrinology 2013, 2013(Suppl 1):P40http://www.ijpeonline.com/content/2013/S1/P40
© 2013 Adachi et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative CommonsAttribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction inany medium, provided the original work is properly cited.
