Congenital adrenal hyperplasia (CAH) is lethal in its most severe forms if not treated with glucocorticoids. However, glucocorticoids may increase the cardiovascular and metabolic morbidity. The long term outcome in CAH was studied using the Swedish national CAH registry, 588 patients 335 females and 253 males, >80% with known severity of CAH; were compared with 100 controls per patient matched for sex, and year and place of birth. Information on mortalty, cause of death, morbidity, and psykosocial factors were derived through linkage of national population-based registers. Subgroup analyses were performed regarding sex, clinical severity (salt-wasting, simple virilising, non-classic), CYP21A2 genotype (null, I2 splice, I172N, P30L) and before and after the introduction of neonatal screening.
Results: The mean age of death was lower (41.2±26.9 vs 47.7±27.7 years (P<0.001). The hazard ratio of death was 2.3 (1.24.3) in males and 3.5 (2.06.0) in females. The causes of death were adrenal crisis (42%), cardiovascular (32%), cancer (16%), and suicide (10%). Metabolic disorders (OR 3.9), and cardiovascular disease (OR 2.7) were increased. Both men and women had more disability pension (OR 1.5) and sick leave (OR 1.7). The men more often had long lasting employment (OR 3.1). Men were more often (OR 1.6) while women were less often married (OR 0.7). Patients had children less often (OR 0.3). Women with salt-wasting (SW) CAH had completed primary education less often (OR 0.3), this was not explained by neonatal salt-crisis or hypoglycemia since the men did not differ from controls. Men and women in the less severe I172N genotype group were more likely to have an academic education (OR 1.8) and SW women were more likely to have an income in the top 20 percentile (OR 2.0). Both males and females had an increased psychiatric morbidity. In particular, the risk of substance misuse was increased with OR 2.8 in females and 1.9 in males and appeared most common among the girls and women with the most severe null genotype (OR 5.5). The risk of stress and adjustment disorders was doubled (OR 2.1).
Conclusions: CAH was associated with excess mortality due to adrenal crisis despite diagnosis and treatment. The salt-wasting phenotype seemed to have a worse outcome not only before the introduction of neonatal screening. Our studies show important outcome differences regarding education, employment, marriage and fertility depending on sex and severity of CAH. The mechanisms behind this and the increased risk for sick leave or disability pension in both men and women should be identified to improve medical and psychological care. Late diagnosis may explain some of the findings. Those born before the introduction of neonatal screening were more affected, which may be explained by the higher age.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology