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

Abstract

Non-classical congenital adrenal hyperplasia (NC-CAH) represents mild form of CAH with the prevalence of 0. 6 to 9% in women with androgen excess. Clinical and hormonal findings in females with NC-CAH are overlapping with other hyperandrogenic entities such as polycystic ovary syndrome hence causing difficulties in diagnostic approach. Metabolic consequences in subjects with NC-CAH are relatively unknown. We are lacking longitudinal follow of these patients regarding natural course of the disease or the therapeutic effects of the different drug regiments. Patients with NC-CAH similarly to those with classical form are characterized with deteriorated cardiovascular risk factors that are probably translated into cardiometabolic diseases and events. An increased preponderance of obesity and insulin resistance in patients with NC-CAH begin at young age could result in increased rates of metabolic sequelae and cardiovascular disease later during adulthood in both sexes. On the other hand, growth disorder was not proven in patients with NC-CAH in comparison to CAH patients of both gender characterized with reduced final adult height. Similarly, decreased bone mineral density and osteoporosis are not constant findings in patients with NC-CAH and could depend on the sex, and type or dose of corticosteroids applied. It could be concluded that NC-CAH represent a particular form of CAH that is characterized with specificities in clinical presentation, diagnosis, therapeutic approach and metabolic outcomes.

Clinical outcomes and characteristics of P30L mutations in congenital adrenal hyperplasia due to 21-hydroxylase deficiency

“…Its frequency is between 0 and 46% in different populations (Table 1) [14,16,18,19,23,37,45,55,62,63,[66][67][68][69][70][71][72][73][74][75][76][77][78]. Interestingly, P30L mutation occur more frequently in Central and Southeast Europe, including Balkans, and Mexico [39,62,63,68,74,79,80].…”

“…In patients with NC CAH predominant signs are those of mild androgen excess. Therefore, in females the diagnosis is made mostly in late childhood, adolescence, or young adulthood due to symptoms as premature pubarche, acne, hirsutism, male-pattern alopecia, polycystic ovary syndrome (PCOS), and subfertility [ 11 , 65 , 79 ]. However, there are females with minimal or no symptoms, even after a long life [ 83 ].…”

“…Long-term glucocorticoid replacement may cause abdominal obesity and hypertension with an onset even in youngsters [ 131 , 167 – 169 ]. Obesity is frequently associated with high CRP levels, hypercholesterolemia, hyperlipidemia, insulin resistance, diabetes, high leptin, and low adiponectin levels causing a common metabolic syndrome in ~20% of patients with a cardiovascular risk independent of mutations [ 79 , 123 , 167 , 170 ]. Very few studies analyzed cardiovascular outcomes according to the genotype [ 111 , 123 ].…”

Congenital Adrenal Hyperplasia: Diagnostic Features in a Limited Resource Country, Senegal

“…It was a boy and a girl, all revealed by a pseudo precocious puberty. These forms, more common in girls with hyperandrogenism, vary from 0.6% to 9% of CAH [19].…”

Quality of Life in Children Diagnosed With Non-classic Congenital Adrenal Hyperplasia

“…NC-CAH is more prevalent than the classic form, estimated to affect 0.1-0.2% of the population [ 11 ]. It is also more frequently observed in females, as males with NC-CAH have less recognized signs of androgen excess [ 12 ]. Androgen excess in NC-CAH patients can lead to premature pubarche in children and ovarian hyperandrogenism in adolescence.…”