title: Steroid Metabolomic Disease Signature of Nonsyndromic Childhood Obesity.
abstract: The profile of urinary steroids as measured by gas chromatography-mass spectrometry defines a subject's "steroidal fingerprint."
  
  
  
  Here, we clustered steroidal fingerprints to characterize patients with nonsyndromic childhood obesity by "steroid metabolomic signatures."
  
  
  
  Nonsyndromic obesity is a symptom of different diseases and conditions, some of them will have their own signature.
  
  
  
  A total of 31 steroid metabolites were quantified by gas chromatography-mass spectrometry, and their excretion rates were z-transformed. Using MetaboAnalyst 3.0, we divided the subjects into 5 distinctive groups by k-means clustering. Steroidal fingerprints and clinical/biochemical data of patients in each cluster were analyzed.
  
  
  
  A total of 87 obese children (44 females), aged 8.5-17.9 years, were clinically characterized, and their 24-hour urine was collected.
  
  
  
  Cluster 1 (n = 39, 21 females) had normal steroid profile. Cluster 2 (n = 20, 11 females) showed mild, nonspecific elevation of C19 and C21 steroids, females' resistance to polycystic ovary morphology, and hirsutism. Cluster 3 (n = 7 female), with relative 21-hydroxylase insufficiency, was characterized by partial or full polycystic ovary syndrome. Cluster 4 (n = 4 males), showed markedly elevated C21 steroids and imbalance in the 11β-hydroxysteroid dehydrogenase system, higher insulin, increased frequency of glucose/insulin index more than 0.3, γ-glutamyl transpeptidase activity, systolic blood pressure, and tendency to liver steatosis. Cluster 5 (n = 17, 5 females) had elevated dehydroepiandrosterone and 17-OH-pregnenolone metabolites, suggesting 3β-hydroxysteroid dehydrogenase insufficiency but no clinically unique phenotype. Z-score body mass index values were not significantly different between the clusters.
  
  
  
  We defined a novel concept of disease-specific steroid metabolomic signature based on urinary steroidal gas chromatography-mass spectrometry. Clustering by software designed for metabolic data analysis reclassified childhood obesity into 5 groups with distinctive signatures; groups require further definition and may require cluster-specific therapeutic strategies.
authors: Department of Pediatrics, Pediatric Endocrinology and Diabetes (A.G., E.M.-T.), School of Medicine in Katowice, Medical University of Silesia, 40752 Katowice, Poland; Bioinformatics Knowledge Unit (M.S.), Lorry I. Lokey Interdisciplinary Center for Life Sciences and Engineering, Technion-Israel Institute of Technology, Haifa 31096, Israel; Steroid Research and Mass Spectrometry Unit (M.F.H., S.A.W.), Division of Pediatric Endocrinology and Diabetology, Center of Child and Adolescent Medicine, Justus Liebig University, 35392 Giessen, Germany; and Faculty of Medicine (Z.H.), Technion - Israel Institute of Technology, Haifa 31096, Israel.
authors: Aneta
authors: A
authors: Gawlik
authors: Department of Pediatrics, Pediatric Endocrinology and Diabetes (A.G., E.M.-T.), School of Medicine in Katowice, Medical University of Silesia, 40752 Katowice, Poland; Bioinformatics Knowledge Unit (M.S.), Lorry I. Lokey Interdisciplinary Center for Life Sciences and Engineering, Technion-Israel Institute of Technology, Haifa 31096, Israel; Steroid Research and Mass Spectrometry Unit (M.F.H., S.A.W.), Division of Pediatric Endocrinology and Diabetology, Center of Child and Adolescent Medicine, Justus Liebig University, 35392 Giessen, Germany; and Faculty of Medicine (Z.H.), Technion - Israel Institute of Technology, Haifa 31096, Israel.
authors: Michael
authors: M
authors: Shmoish
authors: Department of Pediatrics, Pediatric Endocrinology and Diabetes (A.G., E.M.-T.), School of Medicine in Katowice, Medical University of Silesia, 40752 Katowice, Poland; Bioinformatics Knowledge Unit (M.S.), Lorry I. Lokey Interdisciplinary Center for Life Sciences and Engineering, Technion-Israel Institute of Technology, Haifa 31096, Israel; Steroid Research and Mass Spectrometry Unit (M.F.H., S.A.W.), Division of Pediatric Endocrinology and Diabetology, Center of Child and Adolescent Medicine, Justus Liebig University, 35392 Giessen, Germany; and Faculty of Medicine (Z.H.), Technion - Israel Institute of Technology, Haifa 31096, Israel.
authors: Michaela F
authors: MF
authors: Hartmann
authors: Department of Pediatrics, Pediatric Endocrinology and Diabetes (A.G., E.M.-T.), School of Medicine in Katowice, Medical University of Silesia, 40752 Katowice, Poland; Bioinformatics Knowledge Unit (M.S.), Lorry I. Lokey Interdisciplinary Center for Life Sciences and Engineering, Technion-Israel Institute of Technology, Haifa 31096, Israel; Steroid Research and Mass Spectrometry Unit (M.F.H., S.A.W.), Division of Pediatric Endocrinology and Diabetology, Center of Child and Adolescent Medicine, Justus Liebig University, 35392 Giessen, Germany; and Faculty of Medicine (Z.H.), Technion - Israel Institute of Technology, Haifa 31096, Israel.
authors: Ewa
authors: E
authors: Malecka-Tendera
authors: Department of Pediatrics, Pediatric Endocrinology and Diabetes (A.G., E.M.-T.), School of Medicine in Katowice, Medical University of Silesia, 40752 Katowice, Poland; Bioinformatics Knowledge Unit (M.S.), Lorry I. Lokey Interdisciplinary Center for Life Sciences and Engineering, Technion-Israel Institute of Technology, Haifa 31096, Israel; Steroid Research and Mass Spectrometry Unit (M.F.H., S.A.W.), Division of Pediatric Endocrinology and Diabetology, Center of Child and Adolescent Medicine, Justus Liebig University, 35392 Giessen, Germany; and Faculty of Medicine (Z.H.), Technion - Israel Institute of Technology, Haifa 31096, Israel.
authors: Stefan A
authors: SA
authors: Wudy
authors: Department of Pediatrics, Pediatric Endocrinology and Diabetes (A.G., E.M.-T.), School of Medicine in Katowice, Medical University of Silesia, 40752 Katowice, Poland; Bioinformatics Knowledge Unit (M.S.), Lorry I. Lokey Interdisciplinary Center for Life Sciences and Engineering, Technion-Israel Institute of Technology, Haifa 31096, Israel; Steroid Research and Mass Spectrometry Unit (M.F.H., S.A.W.), Division of Pediatric Endocrinology and Diabetology, Center of Child and Adolescent Medicine, Justus Liebig University, 35392 Giessen, Germany; and Faculty of Medicine (Z.H.), Technion - Israel Institute of Technology, Haifa 31096, Israel.
authors: Ze'ev
authors: Z
authors: Hochberg
mesh_terms: D000293:Adolescent; D002648:Child; D005260:Female; D006801:Humans; D008297:Male; D055432:Metabolomics / Q000379:methods*; D063766:Pediatric Obesity / Q000145:classification / Q000652:urine*; D013256:Steroids / Q000652:urine*
chemical_list: D013256:Steroids