A paper recently published in Endocrine Reviews takes a look at the cardiometabolic risk in patients with congenital adrenal hyperplasia (CAH), since patients with CAH who are being treated still face numerous complications and increased mortality.
The authors of the review (Krysiak et al) write that the aim of their article is to create an authoritative and balanced review concerning the cardiometabolic risk in patients with CAH. For this paper, the authors searched all major databases and reviewed and scanned reference lists of all potentially eligible articles to find eligible articles published between January 1966 and October 2023 and compared the cardiometabolic risk in CAH to controls and other forms of adrenal insufficiency.
“The reviewed articles, most of which were published recently, provided conflicting results, which can be partially explained by differences in the inclusion criteria and treatment, small sample sizes and gene-environmental interactions,” the authors write. “However, many studies showed that the presence of CAH is associated with an increased risk of weight gain, worsening of insulin sensitivity, high blood pressure, endothelial dysfunction, early atherosclerotic changes in the vascular wall, and left ventricular diastolic dysfunction.”
The authors make the distinction between classic CAH (C-CAH) and non-classic CAH (NC-CAH) and point out that the complications listed above were more consistently reported in patients with C-CAH. The authors start by concluding that analysis of the reviewed articles does show an association between CAH and cardiometabolic complications.
The authors go on to write that CAH is associated with an increased risk of developing overweight and obesity. Patients with CAH also have reduced insulin sensitivity, which, according to the authors, can only partially be explained by increased body weight. “They are also determined by the degree of 21OH deficiency, are partially related to imperfections of the glucocorticoid replacement and may improve after treatment with insulin-sensitizing drugs,” the authors write. “Some subjects with CAH may, however, develop morning, nocturnal and maybe also exercise-induced hypoglycemia, with potential negative cardiovascular consequence.”
The review covers a lot, from the complex relationship between CAH and blood pressure, inconsistent results in prior studies related to adipose tissue hormones, CAH’s effect on the heart itself, advances in treatment, and more. The authors conclude the paper by stating that the increased cardiovascular risk in patients with CAH is likely multifactorial: glucocorticoid overtreatment, imperfect adrenal hormone replacement therapy, androgen excess and adrenomedullary failure.
For example, the authors write that excess cardiovascular and metabolic morbidity in CAH could be explained by “a U-shaped relationship between cardiovascular complications and androgen concentrations, which means that both low and high concentrations of these hormones predispose to increased cardiometabolic risk.”
The authors end by calling for future studies in middle-aged and older adults with CAH (since the risk of cardiovascular complications increases with age), studies related to the cardiometabolic aspects of NC-CAH, and for partially updating the current recommendations of the Endocrine Society.
“The guidelines ‘suggest introducing counseling regarding healthy lifestyle choices at an early age to maintain BMI within the normal range to avoid metabolic syndrome and related sequelae (point 6.10),’ as well as ‘recommend against routine evaluation for cardiac and metabolic disease in patients with CAH beyond that recommended for the general population (point 6.14),’” the authors write. “In our opinion, routine counseling concerning lifestyle choices should be part of the follow-up of each patient with CAH. All necessary questions should be discussed with the parents, and with the affected child when able to comply. Moreover, we advise that all individuals with C-CAH require metabolic and cardiovascular follow-up.”
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