Cardiovascular health, growth and gonadal function in children and adolescents with congenital adrenal hyperplasia

Abstract

After the introduction of replacement therapy with glucocorticoids and mineralocorticoids in the 1950s, congenital adrenal hyperplasia (CAH) is no longer a life-limiting condition. However, due to the successful introduction of medical steroid hormone replacement, CAH has become a chronic condition, with associated comorbidities and long-term health implications. The aim of treatment is the replacement of mineralocorticoids and glucocorticoids and the normalisation of elevated androgen concentrations. Long-term consequences of the condition and current treatment regimens include unfavourable changes in the cardiovascular risk profile, impaired growth, testicular adrenal rest tumours (TART) in male and subfertility in both male and female patients with CAH. Optimising replacement therapy in patients with CAH remains challenging. On one hand, treatment with supraphysiological doses of glucocorticoids might be required to normalise androgen concentrations and decrease size or presence of TARTs. On the other hand, treatment with supraphysiological doses of glucocorticoids is associated with an increased prevalence of unfavourable cardiovascular and metabolic risk profiles as well as impaired longitudinal growth and gonadal function. Therefore, treatment of children and adults with CAH requires an individualised approach. Careful monitoring for early signs of complications is already warranted during paediatric healthcare provision to prevent and reduce the impact of comorbidities in later life.

Bone mineral density and body composition in children with congenital adrenal hyperplasia

“…The effects of adrenal sex steroids and glucocorticoids on measures of body composition, such as visceral adipose tissue (VAT) and the Android:Gynoid (A:G) ratio, have not been well studied in children with CAH. This area of investigation is important given that children and adults with CAH may have higher risk for cardiovascular disease compared to the general population . VAT is associated with increased cardiometabolic risk, while the A:G ratio is associated with elevated triglyceride levels and lower HDL levels and is a better predictor of cardiovascular risk than BMI .…”

“…This area of investigation is important given that children and adults with CAH may have higher risk for cardiovascular disease compared to the general population. 19 VAT is associated with increased cardiometabolic risk, 20 while the A:G ratio is associated with elevated triglyceride levels and lower HDL levels and is a better predictor of cardiovascular risk than BMI. 21 Although the A:G ratio can be calculated from dual-energy X-ray absorptiometry (DXA) measures, 22 data quantitating VAT in children with CAH are limited, and no studies have examined VAT using DXA.…”

Cardiac function in paediatric patients with congenital adrenal hyperplasia due to 21 hydroxylase deficiency

“…Both androgen excess and treatment with supraphysiological doses of glucocorticoids are associated with an unfavourable cardiovascular and metabolic risk profile in patients with CAH . Several studies performed in adult and paediatric patients with CAH showed that they indeed cluster a number of cardiovascular risk factors: obesity, increased fat mass, insulin resistance and high blood pressure .…”

Miscarriages in families with an offspring that have classic congenital adrenal hyperplasia and 21-hydroxylase deficiency

“…Recently, this finding was also reported in men with classic CAH [ 21 ]. In women, the causes were assigned to factors such as adrenal overproduction of androgens and progestins, neuroendocrine factors, genital surgery and/or psychosocial factors [ 22 ]. However, at this point, one should not confuse the terms fertility and fecundity.…”