Cardiovascular Health in Children and Adolescents With Congenital Adrenal Hyperplasia Due to 21-Hydroxilase Deficiency

Abstract

Increasing evidence indicates that adults with Congenital Adrenal Hyperplasia (CAH) may have a cluster of cardiovascular (CV) risk factors. In addition, ongoing research has highlighted that children and adolescents with CAH are also prone to developing unfavorable metabolic changes, such as obesity, hypertension, insulin resistance, and increased intima-media thickness, which places them at a higher risk of developing CV disease in adulthood. Moreover, CAH adolescents may exhibit subclinical left ventricular diastolic dysfunction and impaired exercise performance, with possible negative consequences on their quality of life. The therapeutic management of patients with CAH remains a challenge and current treatment regimens do not always allow optimal biochemical control. Indeed, overexposure to glucocorticoids and mineralocorticoids, as well as to androgen excess, may contribute to the development of unfavorable metabolic and CV abnormalities. Long-term prospective studies on large cohorts of patients will help to clarify the pathophysiology of metabolic alterations associated with CAH. Meanwhile, further efforts should be made to optimize treatment and identify new therapeutic approaches to prevent metabolic derangement and improve long-term health outcomes of CAH patients.

Cardiovascular dysfunction risk in young adults with congenital adrenal hyperplasia caused by 21‐hydroxylase enzyme deficiency

“…1 However, the long-term consequences of glucocorticoid therapy become increasingly important, 3 especially when some studies have revealed an increased risk for cardiovascular dysfunction in patients with CAH. [4][5][6][7][8][9][10][11][12] Myocardial hypertrophy, left ventricular (LV) and aortic diameter (AoD) dilation, and subclinical vascular diseases are potential indicators of cardiovascular dysfunction. The quantification of cardiac chamber size, ventricular mass and function are among the most clinically important and frequently requested echocardiography tasks.…”

Metabolic Perspectives for Non-classical Congenital Adrenal Hyperplasia With Relation to the Classical Form of the Disease

“…Namely, it was observed an increased hypertension rate in young patients with classical CAH on fludrocortisone therapy (64). Available studies on CAH patients of different age showed similar prevalence of hypertension between males and females with CAH (18, 40, 63) with few exceptions showing more deteriorated BP in younger females likely to be related to androgen excess (50).…”

“…Clinical studies based on dual x-ray absorptiometry (DXA) showed that either males or females with classic CAH exhibit higher total fat mass and reduced lean body mass than controls. In respect to therapy used, a week correlation was found for cumulative glucocorticoid dose and total fat mass in females only (50). However, there was no observed differences between males and females for body composition or obesity in either classical CAH or NC-CAH (18, 40, 47, 51) (Supplementary Table 1).…”

“…In respect to the therapy used, different studies analyzing patients with classical CAH showed variation in prevalence of obesity from 16.8 to 35% on hydrocortisone doses ranging from 13.3 to 15 mg/m 2 /day while only one study reported prevalence of obesity of 60.7% on the dose of 19.5 mg/m 2 /day (50). As meta-analyses was not performed yet, it could not be suggested a linear correlation between the prevalence of obesity and increasing doses of hydrocortisone as a frequently used therapeutic modality.…”

“…This could be partly explained with CAH studies analyzing patients younger than 50 as age group that is not typical for development of diabetes (4). In respect to glucocorticosteroids used, a few reports on classical CAH patients are giving opposite results with elevated insulin resistance index (HOMA-IR) in 18 and 44.4% on hydrocortisone doses of 19.5 and 11.2 mg/m 2 /day, respectively (50).…”