title: Premature ovarian failure in patients with autoimmune Addison's disease: clinical, genetic, and immunological evaluation.
abstract: METHODS
  The design of the study was to investigate the prevalence of the following: 1) premature ovarian failure (POF) in patients with autoimmune Addison's disease (AD); 2) steroid-producing cell antibodies (StCA) and steroidogenic enzymes (17α-hydroxylase autoantibodies and P450 side-chain cleavage enzyme autoantibodies) in patients with or without POF; and 3) the value of these autoantibodies to predict POF.
  
  
  METHODS
  The study included 258 women: 163 with autoimmune polyendocrine syndrome type 2 (APS-2), 49 with APS-1, 18 with APS-4, and 28 with isolated AD.
  
  
  METHODS
  StCA were measured by an immunofluorescence technique and 17α-hydroxylase autoantibodies and P450 side-chain cleavage enzyme autoantibodies by immunoprecipitation assays.
  
  
  RESULTS
  Fifty-two of 258 women with AD (20.2%) had POF. POF was diagnosed in 20 of 49 (40.8%) with APS-1, six of 18 (33.3%) with APS-4, 26 of 163 (16%) with APS-2, and none of 28 with isolated AD. In patients with APS-1 and APS-4, POF developed after AD, whereas it preceded AD in patients with APS-2. StCA were detected in 31 of 43 with POF (72%) and 51 of 198 without POF (25.7%). StCA were present in 22 of 38 with APS-1 (57.9%) (11 of 13 with POF); in five of 13 with APS-4 (38.5%) (three of four with POF); in 53 of 162 with APS-2 (32.7%) (17 of 26 with POF), and in one of 28 isolated AD patients (3.6%). Twelve of 13 patients with POF with a duration less than 5 yr (92.3%) and 18 of 25 with duration longer than 5 yr (72%) were StCA positive. Twenty-eight of 31 with POF (90.3%) were positive for at least one steroidogenic antibody. Forty-one women with AD less than 40 yr were followed up for a mean period of 9 yr. Eight of 21 women (38%) positive or seroconverted for steroidogenic autoantibodies developed POF at a mean age of 23 yr (six with APS-1, one with APS-2, and one with APS-4), and none of the 20 patients negative for steroidogenic autoantibodies developed POF.
  
  
  CONCLUSIONS
  This study indicates that AD is frequently associated with POF and that steroidogenic antibodies are markers of patients with POF. Steroidogenic autoantibodies are predictive markers of POF in patients with AD.
authors.affiliation: Endocrine Unit, Department of Medical and Surgical Sciences, University of Padua School of Medicin, Padua; Italy.
authors.forename: G
authors.initials: G
authors.lastname: Reato
authors.forename: L
authors.initials: L
authors.lastname: Morlin
authors.forename: S
authors.initials: S
authors.lastname: Chen
authors.forename: J
authors.initials: J
authors.lastname: Furmaniak
authors.forename: B Rees
authors.initials: BR
authors.lastname: Smith
authors.forename: S
authors.initials: S
authors.lastname: Masiero
authors.forename: M P
authors.initials: MP
authors.lastname: Albergoni
authors.forename: S
authors.initials: S
authors.lastname: Cervato
authors.forename: R
authors.initials: R
authors.lastname: Zanchetta
authors.forename: C
authors.initials: C
authors.lastname: Betterle
mesh_terms: D000224:Addison Disease / Q000453:epidemiology / Q000235:genetics / Q000276:immunology; D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000097:blood; D002648:Child; D002675:Child, Preschool; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000276:immunology; D005260:Female; D005500:Follow-Up Studies; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D006801:Humans; D008875:Middle Aged; D016884:Polyendocrinopathies, Autoimmune / Q000453:epidemiology / Q000235:genetics / Q000276:immunology; D011237:Predictive Value of Tests; D015995:Prevalence; D016649:Primary Ovarian Insufficiency / Q000453:epidemiology / Q000235:genetics / Q000276:immunology; D013254:Steroid 17-alpha-Hydroxylase / Q000276:immunology; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D013254:Steroid 17-alpha-Hydroxylase; D002786:Cholesterol Side-Chain Cleavage Enzyme