title: Hormonal evaluation in relation to phenotype and genotype in 286 patients with a disorder of sex development from Indonesia.
abstract: The objective of this study was to determine the aetiological spectrum of disorders of sex development (DSD) in a large cohort of underprivileged and undiagnosed patients from Indonesia.
  
  
  
  A total of 286 patients with atypical external and/or internal genitalia were evaluated using clinical, hormonal, molecular genetic and histological parameters.
  
  
  
  The age (years) at presentation was 0-0·5 in 41 (14·3%), >0·5-12 in 181 (63·3%) and >12 in 64 cases (22·4%). 46,XY DSD was most common (68·2%, n = 195), 46,XX DSD was found in 23·4% (n = 67) and sex chromosomal DSD in 8·4% (n = 24). In 61·2% of 46,XX DSD patients, 17·9% of 46,XY DSD patients and all sex chromosome DSD patients (29·4% in total), a final diagnosis was reached based on genetic or histological gonadal tissue evaluation. 17-hydroxyprogesterone and androstenedione levels were the most distinctive parameters in 46,XX DSD patients. In 46,XY DSD, diagnostic groups were identified based on the external masculinization score: androgen action disorder (AAD), unknown male undermasculinization (UMU), and gonadal dysgenesis (GD). LH, FSH and testosterone levels were most informative especially in the older age group. HCG tests were of no additional value as no patients with androgen synthesis disorders were found. Hormonal profiles of patients with sex chromosome DSD and a Y-chromosome sequence containing karyotype showed high levels of LH and FSH, and low levels of AMH, inhibin B and testosterone compared with the normal male range. Gene mutations were found in all patients with CAH, but in only 24·5% and 1·8% of patients with AAD and UMU. In 32% of 46,XY GD patients, copy number variants of different genes were found.
  
  
  
  A stepwise diagnostic approach led to a molecularly or histologically proven final diagnosis in 29·4% of the patients. The most informative parameters were serum levels of 17-hydroxyprogesterone and androstenedione in 46,XX DSD patients, and serum LH, FSH and testosterone levels in 46,XY DSD patients.
authors.affiliation: Division of Human Genetics, Center for Biomedical Research Faculty of Medicine Diponegoro University (FMDU), Semarang, Indonesia.
authors.forename: A Zulfa
authors.initials: AZ
authors.lastname: Juniarto
authors.affiliation: Department of Paediatrics, Division of Endocrinology, Sophia Children's Hospital, Erasmus University Medical Centre, Rotterdam, The Netherlands.|Department of Pathology, Josephine Nefkens Institute, Erasmus University Medical Centre, Rotterdam, The Netherlands.
authors.forename: Yvonne G
authors.initials: YG
authors.lastname: van der Zwan
authors.affiliation: Department of Urology, Dr Kariadi Hospital, Semarang, Indonesia.
authors.forename: Ardy
authors.initials: A
authors.lastname: Santosa
authors.affiliation: Division of Human Genetics, Center for Biomedical Research Faculty of Medicine Diponegoro University (FMDU), Semarang, Indonesia.
authors.forename: Mahayu Dewi
authors.initials: MD
authors.lastname: Ariani
authors.affiliation: Murdoch Children's Research Institute, Royal Children's Hospital and Department of Paediatrics, University of Melbourne, Melbourne, Australia.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Eggers
authors.affiliation: Department of Pathology, Josephine Nefkens Institute, Erasmus University Medical Centre, Rotterdam, The Netherlands.
authors.forename: Remko
authors.initials: R
authors.lastname: Hersmus
authors.affiliation: Department of Internal Medicine, Section of Endocrinology, Erasmus University Medical Centre, Rotterdam, The Netherlands.
authors.forename: Axel P N
authors.initials: AP
authors.lastname: Themmen
authors.affiliation: Department of Clinical Genetics, Erasmus University Medical Centre, Rotterdam, The Netherlands.
authors.forename: Hennie T
authors.initials: HT
authors.lastname: Bruggenwirth
authors.affiliation: Department of Paediatric Urology, Erasmus University Medical Centre, Rotterdam, The Netherlands.
authors.forename: Katja P
authors.initials: KP
authors.lastname: Wolffenbuttel
authors.affiliation: Murdoch Children's Research Institute, Royal Children's Hospital and Department of Paediatrics, University of Melbourne, Melbourne, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Sinclair
authors.affiliation: Centre for Genetic Diseases, MIMR-PHI Institute of Medical Research, Monash University, Clayton, Australia.
authors.forename: Stefan J
authors.initials: SJ
authors.lastname: White
authors.affiliation: Department of Pathology, Josephine Nefkens Institute, Erasmus University Medical Centre, Rotterdam, The Netherlands.
authors.forename: Leendert H J
authors.initials: LH
authors.lastname: Looijenga
authors.affiliation: Division of Human Genetics, Center for Biomedical Research Faculty of Medicine Diponegoro University (FMDU), Semarang, Indonesia.
authors.forename: Frank H
authors.initials: FH
authors.lastname: de Jong
authors.affiliation: Division of Human Genetics, Center for Biomedical Research Faculty of Medicine Diponegoro University (FMDU), Semarang, Indonesia.
authors.forename: Sultana M H
authors.initials: SM
authors.lastname: Faradz
authors.affiliation: Department of Paediatrics, Division of Endocrinology, Sophia Children's Hospital, Erasmus University Medical Centre, Rotterdam, The Netherlands.
authors.forename: Stenvert L S
authors.initials: SL
authors.lastname: Drop
mesh_terms: D019326:17-alpha-Hydroxyprogesterone / Q000097:blood; D000293:Adolescent; D000367:Age Factors; D000735:Androstenedione / Q000097:blood; D002648:Child; D002675:Child, Preschool; D012734:Disorders of Sex Development / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D005838:Genotype; D006061:Gonadal Dysgenesis, 46,XY; D006728:Hormones / Q000097:blood*; D006801:Humans; D007214:Indonesia; D007223:Infant; D007231:Infant, Newborn; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D010641:Phenotype; D012730:Sex Chromosomes / Q000235:genetics; D013739:Testosterone / Q000097:blood
chemical_list: D006728:Hormones; D013739:Testosterone; D000735:Androstenedione; D019326:17-alpha-Hydroxyprogesterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone