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

Abstract

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.

Trial registration: ClinicalTrials.gov NCT00250159.

Keywords: androgen; congenital adrenal hyperplasia; glucocorticoid; metabolic syndrome; mineralocorticoid.

Published by Oxford University Press on behalf of the Endocrine Society 2021.

Figures

Figure 1.

Cohort of patients with classic congenital adrenal hyperplasia. (A) Duration of follow-up per patient and (B) age distribution at visits are shown.

Figure 2.

Metabolic outcomes across age categories in a cohort of patients with classic congenital adrenal hyperplasia. Shown are (A) obesity, defined as BMI ≥ 85th percentile for 2 for ≥18 years; (B) hypertension (stage 1 and 2) based on the American Academy of Pediatrics’s 2017 guidelines for children and the American College of Cardiology/American Heart Association 2017 Task Force for Adults (11,12); (C) insulin resistance based on HOMA-IR: ≥2.5 in adults or ≥3.16 in adolescents (≥12 years) (13,14); (D) fasting hyperglycemia (blood glucose ≥100); (E) dyslipidemia (based on NHANES percentiles for age and sex in children and specific targets for adults based on sex) (17,18).

Figure 3.

Fludrocortisone dose (mcg/day) in relation to age group among patients with and without hypertension.