title: Aetiological diagnosis of male sex ambiguity: a collaborative study.
abstract: A collaborative study, supported by the Biomed2 Programme of the European Community, was initiated to optimise the aetiological diagnosis in genetic or gonadal males with intersex disorders, a total of 67 patients with external sexual ambiguity, testicular tissue and/or a XY karyotype. In patients with gonadal dysgenesis or true hermaphroditism, the incidence of vaginal development was 100%, a uterus was present in 60%; uni or bilateral cryptorchidism was seen in nearly all cases of testicular dysgenesis (99%) but in only 57% of true hermaphrodites. Mean serum levels of anti-mullerian hormone and of serum testosterone response to chorionic gonadotropin stimulation were significantly decreased in both conditions, by comparison with patients with unexplained male pseudohermaphroditism or partial androgen insensitivity (PAIS). Mutations in the androgen receptor, 90% within exons 2-8, were detected in patients with PAIS. Clinically, a vaginal pouch was present in 90%, cryptorchidism in 36%. In 52% of cases, no diagnosis could be reached, despite an exhaustive clinical and laboratory work-up, including routine sequencing of exons 2-8 of the androgen receptor. By comparison with PAIS, unexplained male pseudohermaphroditism was characterised by a lower incidence of vaginal pouch (55%) and cryptorchidism (22%) but a high incidence of prematurity/intrauterine growth retardation (30%) or mild malformations (14%).
  
  
  CONCLUSIONS
  reaching an aetiological diagnosis in cases of male intersex is difficult because of the variability of individual cases. Hormonal tests may help to discriminate between partial androgen insensitivity and gonadal dysgenesis/true hermaphroditism but are of less use for differentiating from unexplained male pseudohermaphroditism. Sequencing of exons 2-8 of the androgen receptor after study of testosterone precursors following human chorionic gonadotrophin stimulation is recommended when gonadal dysgenesis and true hermaphroditism can be excluded.
authors.affiliation: Unité de Recherches sur la Pathologie Hormonale Moléculaire (INSERM), Hôpital Debrousse, Lyon, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Morel
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Rey
authors.forename: Cécile
authors.initials: C
authors.lastname: Teinturier
authors.forename: Marc
authors.initials: M
authors.lastname: Nicolino
authors.forename: Laurence
authors.initials: L
authors.lastname: Michel-Calemard
authors.forename: Irène
authors.initials: I
authors.lastname: Mowszowicz
authors.forename: Francis
authors.initials: F
authors.lastname: Jaubert
authors.forename: Marc
authors.initials: M
authors.lastname: Fellous
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Chaussain
authors.forename: Pierre
authors.initials: P
authors.lastname: Chatelain
authors.forename: Michel
authors.initials: M
authors.lastname: David
authors.forename: Claire
authors.initials: C
authors.lastname: Nihoul-Fékété
authors.forename: Maguelone G
authors.initials: MG
authors.lastname: Forest
authors.forename: Nathalie
authors.initials: N
authors.lastname: Josso
mesh_terms: D054304:Anti-Mullerian Hormone; D006063:Chorionic Gonadotropin; D003456:Cryptorchidism / Q000235:genetics; D003937:Diagnosis, Differential; D012734:Disorders of Sex Development / Q000097:blood / Q000209:etiology* / Q000235:genetics; D005060:Europe; D006023:Glycoproteins; D006059:Gonadal Dysgenesis / Q000097:blood / Q000209:etiology / Q000235:genetics; D006131:Growth Inhibitors / Q000097:blood; D006801:Humans; D007223:Infant; D007621:Karyotyping; D008297:Male; D011944:Receptors, Androgen / Q000235:genetics; D013735:Testicular Hormones / Q000097:blood; D013737:Testis / Q000002:abnormalities; D013739:Testosterone / Q000097:blood
chemical_list: D006063:Chorionic Gonadotropin; D006023:Glycoproteins; D006131:Growth Inhibitors; D011944:Receptors, Androgen; D013735:Testicular Hormones; D013739:Testosterone; D054304:Anti-Mullerian Hormone