학술논문
Catch-up Growth and Discontinuation of Fludrocortisone Treatment in Aldosterone Synthase Deficiency.
Document Type
Academic Journal
Author
Gurpinar Tosun B; Department of Pediatric Endocrinology and Diabetes, Marmara University, School of Medicine, Istanbul, Turkey.; Kendir Demirkol Y; Department of Pediatric Genetics, Umraniye Research and Training Hospital, University of Health Sciences, Istanbul, Turkey.; Seven Menevse T; Department of Pediatric Endocrinology and Diabetes, Marmara University, School of Medicine, Istanbul, Turkey.; Kaygusuz SB; Department of Pediatric Endocrinology and Diabetes, Marmara University, School of Medicine, Istanbul, Turkey.; Ozbek MN; Department of Pediatric Endocrinology and Diabetes, Gazi Yasargil Education and Research Hospital, Diyarbakir, Turkey.; Altincik SA; Department of Pediatric Endocrinology and Diabetes, Pamukkale University, Denizli, Turkey.; Mammadova J; Department of Pediatric Endocrinology and Diabetes, Ondokuz Mayis University, Samsun, Turkey.; Cayir A; Department of Pediatric Endocrinology and Diabetes, Erzurum Education and Research Hospital, Erzurum, Turkey.; Doger E; Department of Pediatric Endocrinology, Gazi University, Faculty of Medicine, Ankara, Turkey.; Bayramoglu E; Department of Pediatric Endocrinology, Haseki Training and Research Hospital, Istanbul, Turkey.; Nalbantoglu O; Department of Pediatric Endocrinology, Dr. Behcet Uz Children's Hospital, Izmir, Turkey.; Yesiltepe Mutlu G; Department of Pediatric Endocrinology and Diabetes, Koç University Hospital, Istanbul, Turkey.; Aghayev A; Medical Genetics Department, National Hematology and Transfusiology Center, Baku, Azerbaijan.; Turan S; Department of Pediatric Endocrinology and Diabetes, Marmara University, School of Medicine, Istanbul, Turkey.; Bereket A; Department of Pediatric Endocrinology and Diabetes, Marmara University, School of Medicine, Istanbul, Turkey.; Guran T; Department of Pediatric Endocrinology and Diabetes, Marmara University, School of Medicine, Istanbul, Turkey.
Source
Publisher: Oxford University Press Country of Publication: United States NLM ID: 0375362 Publication Model: Print Cited Medium: Internet ISSN: 1945-7197 (Electronic) Linking ISSN: 0021972X NLM ISO Abbreviation: J Clin Endocrinol Metab Subsets: MEDLINE
Subject
Language
English
Abstract
Background: Aldosterone synthase deficiency (ASD) caused by mutations in the CYP11B2 gene is characterized by isolated mineralocorticoid deficiency. Data are scarce regarding clinical and biochemical outcomes of the disease in the follow-up.
Objective: Assessment of the growth and steroid profiles of patients with ASD at the time of diagnosis and after discontinuation of treatment.
Design and Method: Children with clinical diagnosis of ASD were included in a multicenter study. Growth and treatment characteristics were recorded. Plasma adrenal steroids were measured using liquid chromatography-mass spectrometry. Genetic diagnosis was confirmed by CYP11B2 gene sequencing and in silico analyses.
Results: Sixteen patients from 12 families were included (8 females; median age at presentation: 3.1 months, range: 0.4 to 8.1). The most common symptom was poor weight gain (56.3%). Median age of onset of fludrocortisone treatment was 3.6 months (range: 0.9 to 8.3). Catch-up growth was achieved at median 2 months (range: 0.5 to 14.5) after treatment. Fludrocortisone could be stopped in 5 patients at a median age of 6.0 years (range: 2.2 to 7.6). Plasma steroid profiles revealed reduced aldosterone synthase activity both at diagnosis and after discontinuation of treatment compared to age-matched controls. We identified 6 novel (p.Y195H, c.1200 + 1G > A, p.F130L, p.E198del, c.1122-18G > A, p.I339_E343del) and 4 previously described CYP11B2 variants. The most common variant (40%) was p.T185I.
Conclusions: Fludrocortisone treatment is associated with a rapid catch-up growth and control of electrolyte imbalances in ASD. Decreased mineralocorticoid requirement over time can be explained by the development of physiological adaptation mechanisms rather than improved aldosterone synthase activity. As complete biochemical remission cannot be achieved, a long-term surveillance of these patients is required.
(© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Objective: Assessment of the growth and steroid profiles of patients with ASD at the time of diagnosis and after discontinuation of treatment.
Design and Method: Children with clinical diagnosis of ASD were included in a multicenter study. Growth and treatment characteristics were recorded. Plasma adrenal steroids were measured using liquid chromatography-mass spectrometry. Genetic diagnosis was confirmed by CYP11B2 gene sequencing and in silico analyses.
Results: Sixteen patients from 12 families were included (8 females; median age at presentation: 3.1 months, range: 0.4 to 8.1). The most common symptom was poor weight gain (56.3%). Median age of onset of fludrocortisone treatment was 3.6 months (range: 0.9 to 8.3). Catch-up growth was achieved at median 2 months (range: 0.5 to 14.5) after treatment. Fludrocortisone could be stopped in 5 patients at a median age of 6.0 years (range: 2.2 to 7.6). Plasma steroid profiles revealed reduced aldosterone synthase activity both at diagnosis and after discontinuation of treatment compared to age-matched controls. We identified 6 novel (p.Y195H, c.1200 + 1G > A, p.F130L, p.E198del, c.1122-18G > A, p.I339_E343del) and 4 previously described CYP11B2 variants. The most common variant (40%) was p.T185I.
Conclusions: Fludrocortisone treatment is associated with a rapid catch-up growth and control of electrolyte imbalances in ASD. Decreased mineralocorticoid requirement over time can be explained by the development of physiological adaptation mechanisms rather than improved aldosterone synthase activity. As complete biochemical remission cannot be achieved, a long-term surveillance of these patients is required.
(© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)