Cardiovascular Disease Risk Factors and Metabolic Morbidity in a Longitudinal Study of Congenital Adrenal Hyperplasia.

CONTEXT Patients with congenital adrenal hyperplasia (CAH) are exposed to hyperandrogenism and supraphysiologic glucocorticoids, both can increase risk of metabolic morbidity. OBJECTIVE Our aim was to evaluate cardiovascular and metabolic morbidity risk in a longitudinal study of patients with CAH spanning both childhood and adulthood. DESIGN AND SETTING Patients with classic CAH followed for a minimum of 5 years during both childhood and adulthood (n=57) at the National Institutes of Health were included and compared with the U.S. general population using NHANES data. MAIN OUTCOME MEASURES Obesity, hypertension, insulin resistance, fasting hyperglycemia and dyslipidemia. RESULTS Compared to the U.S. population, patients with CAH had higher (P<0.001) prevalence of obesity, hypertension, insulin resistance, fasting hyperglycemia and low HDL during childhood and obesity (P=0.024), hypertension (P<0.001) and insulin resistance (P<0.001) during adulthood. In our cohort, obesity, hypertension, fasting hyperglycemia, and hypertriglyceridemia began prior to age 10. During childhood, increased mineralocorticoid dose was associated with hypertension (P=0.0015) and low HDL (P=0.0021). During adulthood, suppressed androstenedione was associated with hypertension (P=0.002), and high LDL (P=0.0039); while suppressed testosterone (P=0.003) was associated with insulin resistance. Elevated 17-hydroxyprogesterone, possibly reflecting poor disease control, was protective against high cholesterol (P=0.0049) in children. Children whose mothers were obese (maternal obesity) had increased risk of obesity during adulthood (P=0.0021). Obesity in turn contributed to the development of hypertension, insulin resistance, and hypertriglyceridemia in adulthood. CONCLUSION Patients with CAH develop metabolic morbidity at a young age associated with treatment-related and familial factors. Judicious use of glucocorticoid and mineralocorticoid is warranted.