medwireNews: Children with congenital adrenal hyperplasia (CAH) have an increased propensity to develop cardiometabolic risk factors in childhood, research shows.
“The median age of onset was under 10 years emphasizing the importance of intervention at young ages”, write the researchers in The Journal of Clinical Endocrinology & Metabolism.
For their study, Deborah Merke (The Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland, USA) and colleagues assessed data from a median 18.6 years of follow-up of 57 patients with CAH (61.4% male, 84.2% Caucasian). Of these patients, 68.4% had classic salt-wasting CAH.
During childhood, rates of obesity were significantly higher in patients with CAH than in the general population, ascertained from NHANES data, at 56.1% versus 15.9%. The CAH patients also had significantly higher rates of hypertension, at 87.7% versus 5.5%, insulin resistance, at 71.9% versus 33.1%, and elevated fasting blood glucose, at 75.4% versus 27.0%. They were also more likely to have low levels of high-density lipoprotein cholesterol, at 42.1% versus 3.9%.
The significantly increased rates of obesity, hypertension and insulin resistance persisted into adulthood.
Cardiometabolic risk factors appeared at a young age, say the researchers, ranging from a median of 5.7 years for hypertension to 9.3 years for dyslipidaemia. Insulin resistance was detected at a median age of 13.4 years, but this was not evaluated before age 12 years due to lack of a reference range.
The prevalence of obesity declined as patients grew older, whereas insulin resistance and dyslipidaemia became more common. Elevated fasting glucose became more common as childhood progressed, but then declined in frequency with the onset of adulthood.
Hypertension often appeared at a very young age (<2 years); its prevalence fell during later childhood before rising again in adulthood.
In multivariate analysis, the only factors significantly associated with cardiometabolic risk in childhood were increasing fludrocortisone dose and older age, which were associated with a respective increased and decreased risk of hypertension, and obesity, which was linked to a higher risk of insulin resistance.
Finally, the researchers report that androstenedione and 17-hydroxyprogesterone levels were within their target ranges only around 28% of the time, “demonstrating the challenges of attaining optimal disease control in CAH, especially in adolescents and young adults.”
Merke and team observe that although obesity was probably responsible for some of the increased cardiometabolic risk in these patients with CAH, “glucocorticoid and mineralocorticoid effects likely play an important role”.
“Lifestyle assessment, evaluating family history and careful monitoring and screening for risk factors are important to limit the development of metabolic comorbidities”, they advise.
The team adds that monitoring for excessive glucocorticoid and mineralocorticoid dosing and adjusting accordingly may help to minimise cardiometabolic risk, but caution that “this needs to be weighed against the risk of using lower dose therapy, which has been associated with increased rates of adrenal crisis, tumor formation and infertility.”
By Eleanor McDermid
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J Clin Endocrinol Metab 2021; doi:10.1210/clinem/dgab133