Delineating the psychiatric morbidity spectrum in congenital adrenal hyperplasia: a population-based registry study

Clinical studies of psychiatric morbidity in patients with congenital adrenal hyperplasia (CAH) imply impaired mental health. To delineate psychiatric morbidity in a national CAH cohort by using complete data on psychiatric diagnoses from all Danish hospitals between 1977-2018 and on all psychiatric medication prescribed between 1995-2018. A registry-based cohort study. A public uniform healthcare system. Four-hundred-forty-eight patients (females: n=215) with CAH, hereof 410 with 21-hydroxylase deficiency (21-OHD) (females: n=255) and 44,527 age- and sex-matched general population controls. Diagnoses were analyzed by negative binomial regression yielding incidence rate ratios (IRR). Medication were analyzed by Cox regression yielding hazard ratios (HR). 21-OHD was associated with an increased risk of any psychiatric diagnosis; females: IRR=2.32 (confidence interval (CI) (1.48-3.64), males: IRR=2.74 (CI 1.31-5.71) as well as of medication related to psychiatric disorders; females: HR=1.74 (CI 1.42-2.13), males: HR=1.74 (CI1.30-2.33). Both females and males with 21-OHD had a significantly increased risk of alcohol use, stress- and adjustment disorders, and of suicidal behavior. For patients with more rare forms of CAH (n=24), the risk of any psychiatric diagnosis was significantly increased for males, IRR=12.85 (CI 1.78-92.87), but not for females, IRR=0.54 (CI 0.10-3.00). The risk of being prescribed psychiatric medication was not increased for neither females, HR=1.05 (CI 0.39-2.84), or males, HR=0.72 (CI 0.10-5.13), with rare forms of CAH. 21-OHD is associated with a significantly increased psychiatric morbidity. This study underlines a need for awareness of mental health in patients with 21-OHD.