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 of which 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 US general population using NHANES data. Main outcome measures: Obesity, hypertension, insulin resistance, fasting hyperglycemia, and dyslipidemia. Results: Compared to the US population, patients with CAH had higher (P < 0.001) prevalence of obesity, hypertension, insulin resistance, fasting hyperglycemia, and low high-density lipoprotein (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 low-density lipoprotein (P = 0.0039) whereas 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.

Automated summary

Patients with CAH have a higher prevalence of obesity, hypertension, insulin resistance, fasting hyperglycemia, and dyslipidemia during childhood and adulthood compared to the general US population, indicating an early onset of metabolic morbidity in this population. Treatment-related and familial factors play a role in the development of these metabolic conditions.