Cardiovascular abnormalities and impaired exercise performance in adolescents with congenital adrenal hyperplasia

Context: Patients with classic Congenital Adrenal Hyperplasia (CAH) are treated with lifelong glucocorticoids (GCS). Cardiovascular (CV) and metabolic effects of such therapy in adolescents have never been quantified. Objective: To investigate left ventricular (LV) morphology, function and exercise performance in adolescents with CAH. Design and Setting: cross-sectional and controlled study conducted at a tertiary referral centre. Patients: Twenty patients with classic CAH (10 females) aged 13.6±2.5 years and 20 healthy controls comparable for sex and pubertal status were enrolled in the study and compared to a group of 18 patients without CAH receiving a similar dose of GCS for Juvenile Idiopathic Arthritis (JIA). Main Outcomes Measures: Echocardiographic assessment and symptom-limited exercise testing were performed. Anthropometric, hormonal and biochemical parameters were also measured. Results: Compared to healthy controls, patients with CAH exhibited an increased BMI (p<0.001), waist-to-height ratio (p<0.001), percentage of body fat (p<0.001) as well as higher insulin concentrations and HOMA index even after adjustment for BMI (p=0.03 and p=0.05, respectively). Moreover, CAH patients exhibited an impaired exercise capacity as shown by reduced peak workload (99±27 vs 126±27 W, p<0.01) and higher systolic blood pressure response at peak (156±18 vs 132±11 mmHg, p<0.01; Δ=45±24 vs 22±10 mmHg, p=0.05) with respect to healthy controls. CAH males displayed mild LV diastolic dysfunction as documented by significant prolongation of both isovolumic relaxation time (IRT) (118±18 vs 98±11ms, p<0.05) and mitral deceleration time (MDT) (138±25 vs 111±15 ms, p<0.01). No significant differences in CV function were found between CAH and JIA patients. Conclusion: Adolescents with CAH exhibit impaired exercise performance and enhanced systolic blood pressure response during exercise. In our population, such abnormalities appear related to GCS therapy rather than CAH per se. CAH males, but no females, present mild LV diastolic dysfunction that correlates with testosterone concentrations suggesting a sex hormone related difference.