title: One hundred years of congenital adrenal hyperplasia in Sweden: a retrospective, population-based cohort study.
abstract: BACKGROUND
  Congenital adrenal hyperplasia due to 21-hydroxylase deficiency results in cortisol and aldosterone deficiency and is, in its most severe form, lethal. We aimed to assess the effect of historical medical improvements in the care of patients with this disorder over time and to assess the effects of neonatal screening in Sweden.
  
  
  METHODS
  For this retrospective, population-based cohort study, we collected data for all known patients with congenital adrenal hyperplasia in Sweden between 1910 and 2011 [corrected]. Data sources included the registry at the Swedish national screening laboratory, patients identified via the Swedish neonatal screening programme, late-diagnosed patients reported to the laboratory, and patients who underwent genetic diagnostics or became known to us through clinical contacts. All known patients were included in a population-based cohort study of the distribution of clinical severity, genotype, sex, and the effect of nationwide neonatal screening.
  
  
  RESULTS
  We identified 606 patients with the disorder, born between 1915 and 2011. The CYP21A2 genotype (conferring deficiency of 21-hydroxylase) was known in 490 patients (81%). The female-to-male ratio was 1·25 in the whole cohort, but close to 1 in patients detected by the screening. We noted a sharp increase in the number of patients diagnosed in the 1960s and 1970s, and after the introduction of neonatal screening in 1986 the proportion of patients with the salt-wasting form of congenital adrenal hyperplasia increased in both sexes, from 114 (47%) of 242 individuals between 1950 and 1985 to 165 (57%) of 292 individuals between 1986 and 2011 (p=0·038). On average, five to ten children were missed every year before 1970. The non-classic form of the disorder was diagnosed more often in women than in men, which accounts for the female preponderance in our cohort.
  
  
  CONCLUSIONS
  Our findings suggest that, contrary to current belief, boys and girls with salt-wasting congenital adrenal hyperplasia were equally missed clinically. Neonatal screening improved detection of the salt-wasting form in girls as well as boys, saving lives in both sexes. The non-classic form was diagnosed more often in women than it was in men, leading to the female preponderance in this cohort.
  
  
  BACKGROUND
  The Swedish Research Council, the Centre of Gender Medicine at Karolinska Institutet, the Stockholm County Council, the Sällskapet Barnavård Foundation, the Stiftelsen Samariten Foundation, the Stiftelsen Frimurare Barnhuset Foundation, and the Novo Nordisk Foundation.
authors.affiliation: Department of Molecular Medicine and Surgery, Centre for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Obstetrics and Gynaecology, Karolinska University Hospital Huddinge, Stockholm, Sweden. Electronic address: sebastian.gidlof@karolinska.se.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Gidlöf
authors.affiliation: Department of Molecular Medicine and Surgery, Centre for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital Solna, Stockholm, Sweden.
authors.forename: Henrik
authors.initials: H
authors.lastname: Falhammar
authors.affiliation: Department of Paediatrics, Jönköping Hospital, Jönköping, Sweden.
authors.forename: Astrid
authors.initials: A
authors.lastname: Thilén
authors.affiliation: Centre for Inherited Metabolic Diseases, Karolinska University Hospital Solna, Stockholm, Sweden.
authors.forename: Ulrika
authors.initials: U
authors.lastname: von Döbeln
authors.affiliation: Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Martin
authors.initials: M
authors.lastname: Ritzén
authors.affiliation: Department of Molecular Medicine and Surgery, Centre for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden; Centre for Inherited Metabolic Diseases, Karolinska University Hospital Solna, Stockholm, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Wedell
authors.affiliation: Department of Molecular Medicine and Surgery, Centre for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden; Paediatric Endocrinology, Karolinska University Hospital Solna, Stockholm, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Nordenström
mesh_terms: D000293:Adolescent; D000312:Adrenal Hyperplasia, Congenital / Q000453:epidemiology* / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011159:Population Surveillance / Q000379:methods*; D012189:Retrospective Studies; D013255:Steroid 21-Hydroxylase / Q000235:genetics; D013548:Sweden / Q000453:epidemiology; D013997:Time Factors; D055815:Young Adult
chemical_list: C531510:CYP21A2 protein, human; D013255:Steroid 21-Hydroxylase