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.

Findings: 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.

Interpretation: 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.

Funding: 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.