CONTEXT: Congenital adrenal hyperplasia (CAH) is lethal in its most severe forms
if not treated with glucocorticoids. However, glucocorticoids may increase the
risk of cardiovascular and metabolic morbidity.
OBJECTIVE: This study aimed to
study cardiovascular and metabolic morbidity in CAH.
DESIGN, SETTING, AND PARTICIPANTS: Patients with CAH due to 21-hydroxylase deficiency (n = 588; >80%
with known CYP21A2 mutations) were compared with controls matched for sex, year,
and place of birth (n = 58 800). Data were obtained by linking national
population-based registers. Subgroup analyses were performed regarding sex,
clinical severity (salt wasting, simple virilizing, nonclassic), CYP21A2 genotype
(null, I2 splice, I172N, P30L), and stratified by the introduction of neonatal
screening, age groups, and nonobesity.
MAIN OUTCOME MEASURES: To study
cardiovascular and metabolic morbidity in CAH. RESULTS: In CAH, both any
cardiovascular and metabolic disorders (OR [odds ratio], 3.9; 95% CI [confidence
interval], 3.1-5.0), and cardiovascular disease (OR, 2.7; 95% CI, 1.9-3.9) were
increased. Separate analyses of the individual diseases showed higher frequencies
in CAH of hypertension, hyperlipidemia, atrial fibrillation, venous
thromboembolism, obesity, diabetes (mainly type 2), obstructive sleep disorder,
thyrotoxicosis, and hypothyroidism. Similar results were seen in the stratified
groups. On the subgroup level, females were generally more affected (especially
I172N and the nonclassic group), as were males with the null genotype.
CONCLUSIONS: CAH was associated with excess cardiovascular and metabolic
morbidity but the mechanism is not certain as the glucocorticoids were not
assessed. Hypothyroidism and obesity may be an effect of close observation.
However, more severe conditions were presumably detected equally in patients and
controls. Screening for diabetes and other metabolic disorders that increase
cardiovascular risk is important.Magn. Bergvalls FoundationKarolinska InstitutetStockholm County CouncilSwedish Research Council through the Swedish Initiative for Research on Microdata in the Social And Medical Sciences, SIMSAM 340-2013-5867Manuscrip
