Please use this identifier to cite or link to this item: https://hdl.handle.net/11499/46661
Title: Catch-up Growth and Discontinuation of Fludrocortisone Treatment in Aldosterone Synthase Deficiency
Authors: Tosun, Busra Gurpinar
Demirkol, Yasemin Kendir
Menevse, Tuba Seven
Kaygusuz, Sare Betul
Ozbek, Mehmet Nuri
Altincik, Selda Ayca
Mammadova, Jamala
Cayir, Atilla
Doger, Esra
Bayramoglu, Elvan
Nalbantoglu, Ozlem
Mutlu, Gul Yesiltepe
Aghayev, AghaRza
Turan, Serap
Bereket, Abdullah
Guran, Tulay
Keywords: aldosterone synthase deficiency
hypoaldosteronism
catch-up growth
steroid hormone profile
follow-up
children
Congenital Adrenal-Hyperplasia
Sequence Variants
Disorders
Mutation
Cyp11b2
Biosynthesis
Association
Mechanisms
Balance
Type-1
Publisher: Endocrine Soc
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.
URI: https://doi.org/10.1210/clinem/dgab619
https://hdl.handle.net/11499/46661
ISSN: 0021-972X
1945-7197
Appears in Collections:Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
Tıp Fakültesi Koleksiyonu
WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection

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