학술논문
Steroid Hormone Profiles and Molecular Diagnostic Tools in Pediatric Patients With non-CAH Primary Adrenal Insufficiency.
Document Type
Academic Journal
Author
Seven Menevse T; Department of Pediatric Endocrinology and Diabetes, Marmara University, School of Medicine, 34899, Ustkaynarca/Pendik Istanbul, Turkey.; Kendir Demirkol Y; Department of Pediatric Genetics, Umraniye Research and Training Hospital, University of Health Sciences, 34764 Istanbul, Turkey.; Gurpinar Tosun B; Department of Pediatric Endocrinology and Diabetes, Marmara University, School of Medicine, 34899, Ustkaynarca/Pendik Istanbul, Turkey.; Bayramoglu E; Department of Pediatric Endocrinology, Haseki Training and Research Hospital, 34096 Istanbul, Turkey.; Yildiz M; Department of Pediatric Endocrinology and Diabetes, Istanbul University, School of Medicine, 34093 Istanbul, Turkey.; Acar S; Department of Pediatric Endocrinology and Diabetes, Behcet Uz Education and Research Hospital, 35210 Izmir, Turkey.; Erisen Karaca S; Department of Pediatric Pediatrics, Duzce University, School of Medicine, 81620 Bolu, Turkey.; Orbak Z; Department of Pediatric Endocrinology and Diabetes, Ataturk University, School of Medicine, 25030 Erzurum, Turkey.; Onder A; Department of Pediatric Endocrinology and Diabetes, Medeniyet University, School of Medicine, 34722 Istanbul, Turkey.; Sobu E; Department of Pediatric Endocrinology, Kartal Training and Research Hospital, 34865 Istanbul, Turkey.; Anık A; Department of Pediatric Endocrinology, Aydin Adnan Menderes University, School of Medicine, 09010 Aydin, Turkey.; Atay Z; Department of Pediatric Endocrinology and Diabetes, Istanbul Medipol University, School of Medicine, 34810 Istanbul, Turkey.; Bugrul F; Department of Pediatric Endocrinology and Diabetes, Selcuk University, School of Medicine, 42250 Konya, Turkey.; Derya Bulus A; Department of Pediatric Endocrinology and Diabetes, Ankara Kecioren Research and Training Hospital, University of Health Sciences, 06000 Ankara, Turkey.; Demir K; Department of Pediatric Endocrinology and Diabetes, Dokuz Eylul University, School of Medicine, 35340 Izmir, Turkey.; Dogan D; Department of Pediatric Endocrinology and Diabetes, Onsekiz Mart University, School of Medicine, 17110 Canakkale, Turkey.; Cihan Emeksiz H; Department of Pediatric Endocrinology and Diabetes, Medeniyet University, School of Medicine, 34722 Istanbul, Turkey.; Kirmizibekmez H; Department of Pediatric Endocrinology and Diabetes, Umraniye Research and Training Hospital, University of Health Sciences, 34764 Istanbul, Turkey.; Ozcan Murat N; Department of Pediatric Endocrinology and Diabetes, Derince Research and Training Hospital, 41900 Kocaeli, Turkey.; Yaman A; Department of Pediatrics, Gungoren Hospital, 34164 Istanbul, Turkey.; Turan S; Department of Pediatric Endocrinology and Diabetes, Marmara University, School of Medicine, 34899, Ustkaynarca/Pendik Istanbul, Turkey.; Bereket A; Department of Pediatric Endocrinology and Diabetes, Marmara University, School of Medicine, 34899, Ustkaynarca/Pendik Istanbul, Turkey.; Guran T; Department of Pediatric Endocrinology and Diabetes, Marmara University, School of Medicine, 34899, Ustkaynarca/Pendik 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
Context: There is a significant challenge of attributing specific diagnoses to patients with primary adrenal insufficiency of unknown etiology other than congenital adrenal hyperplasia (non-CAH PAI). Specific diagnoses per se may guide personalized treatment or may illuminate pathophysiology.
Objective: This work aimed to investigate the efficacy of steroid hormone profiles and high-throughput sequencing methods in establishing the etiology in non-CAH PAI of unknown origin.
Methods: Pediatric patients with non-CAH PAI whose etiology could not be established by clinical and biochemical characteristics were enrolled. Genetic analysis was performed using targeted-gene panel sequencing (TPS) and whole-exome sequencing (WES). Plasma adrenal steroids were quantified by liquid chromatography-mass spectrometry and compared to that of controls. This study comprised 18 pediatric endocrinology clinics with 41 patients (17 girls, median age: 3 mo, range: 0-8 y) with non-CAH PAI of unknown etiology.
Results: A genetic diagnosis was obtained in 29 (70.7%) patients by TPS. Further molecular diagnosis could not be achieved by WES. Compared to a healthy control group, patients showed lower steroid concentrations, most statistically significantly in cortisone, cortisol, and corticosterone (P < .0001, area under the receiver operating characteristic curve: .96, .88, and .87, respectively). Plasma cortisol of less than 4 ng/mL, cortisone of less than 11 ng/mL, and corticosterone of less than 0.11 ng/mL had a greater than 95% specificity to ensure the diagnosis of non-CAH PAI of unknown etiology.
Conclusion: Steroid hormone profiles are highly sensitive for the diagnosis of non-CAH PAI of unknown etiology, but they are unlikely to point to a specific molecular diagnosis. TPS is an optimal approach in the molecular diagnosis of these patients with high efficacy, whereas little additional benefit is expected from WES.
(© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Objective: This work aimed to investigate the efficacy of steroid hormone profiles and high-throughput sequencing methods in establishing the etiology in non-CAH PAI of unknown origin.
Methods: Pediatric patients with non-CAH PAI whose etiology could not be established by clinical and biochemical characteristics were enrolled. Genetic analysis was performed using targeted-gene panel sequencing (TPS) and whole-exome sequencing (WES). Plasma adrenal steroids were quantified by liquid chromatography-mass spectrometry and compared to that of controls. This study comprised 18 pediatric endocrinology clinics with 41 patients (17 girls, median age: 3 mo, range: 0-8 y) with non-CAH PAI of unknown etiology.
Results: A genetic diagnosis was obtained in 29 (70.7%) patients by TPS. Further molecular diagnosis could not be achieved by WES. Compared to a healthy control group, patients showed lower steroid concentrations, most statistically significantly in cortisone, cortisol, and corticosterone (P < .0001, area under the receiver operating characteristic curve: .96, .88, and .87, respectively). Plasma cortisol of less than 4 ng/mL, cortisone of less than 11 ng/mL, and corticosterone of less than 0.11 ng/mL had a greater than 95% specificity to ensure the diagnosis of non-CAH PAI of unknown etiology.
Conclusion: Steroid hormone profiles are highly sensitive for the diagnosis of non-CAH PAI of unknown etiology, but they are unlikely to point to a specific molecular diagnosis. TPS is an optimal approach in the molecular diagnosis of these patients with high efficacy, whereas little additional benefit is expected from WES.
(© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)