Challenges in treatment of patients with non-classic congenital adrenal hyperplasia

Abstract

Congenital adrenal hyperplasia (CAH) due to 21α-hydroxylase deficiency (21OHD) or 11β-hydroxylase deficiency (11OHD) are congenital conditions with affected adrenal steroidogenesis. Patients with classic 21OHD and 11OHD have a (nearly) complete enzyme deficiency resulting in impaired cortisol synthesis. Elevated precursor steroids are shunted into the unaffected adrenal androgen synthesis pathway leading to elevated adrenal androgen concentrations in these patients. Classic patients are treated with glucocorticoid substitution to compensate for the low cortisol levels and to decrease elevated adrenal androgens levels via negative feedback on the pituitary gland. On the contrary, non-classic CAH (NCCAH) patients have more residual enzymatic activity and do generally not suffer from clinically relevant glucocorticoid deficiency. However, these patients may develop symptoms due to elevated adrenal androgen levels, which are most often less elevated compared to classic patients. Although glucocorticoid treatment can lower adrenal androgen production, the supraphysiological dosages also may have a negative impact on the cardiovascular system and bone health. Therefore, the benefit of glucocorticoid treatment is questionable. An individualized treatment plan is desirable as patients can present with various symptoms or may be asymptomatic. In this review, we discuss the advantages and disadvantages of different treatment options used in patients with NCCAH due to 21OHD and 11OHD.

Hiperplasia Adrenal Congênita

“…A hiperplasia adrenal congênita é uma doença autossômica recessiva, emergente de mutações de genes para enzimas, que levam às etapas bioquímicas de produção de glicocorticóides, mineralocorticóides ou esteróides sexuais, a partir do colesterol, pelas glândulas adrenais. A maioria dessas doenças envolve uma alteração na produção, excessiva ou deficiente, de esteróides sexuais, podendo levar a alterações das características sexuais primárias ou secundárias em alguns bebês, crianças ou adultos afetados (ADRIAANSEN BPH, et al, 2022;PODGÓRSKI R, et al, 2018).…”

Nonclassical congenital adrenal hyperplasia: Metabolic and hormonal profile

“…1 Decreased cortisol levels lead to enhanced production of adrenocorticotropic hormone (ACTH) along with adrenal hyperplasia. 2 In most cases, CAH is caused by a 21a-hydroxylase deficiency (21OHD), whereas, NCCAH typically has 20%-50% residual 21OH enzyme activity, leading to androgen excess. 3 Most women with NCCAH present with mild symptoms such as acne, irregular menstruation and hirsutism.…”

“…9 It is explained by the vicious circle in which hyperandrogenism leads to insulin resistance and, consequently hyperinsulinemia, which in turn leads to an aggravation of hyperandrogenism. 2 Furthermore, hyperandrogenism can alter lipid metabolism and plasma lipid levels. 10 Current knowledge evaluating the metabolic profile of women with CAH is limited to classic CAH.…”

“…NCCAH is a type of congenital adrenal hyperplasia (CAH)—a group of diseases where affected adrenal steroidogenesis is responsible for impaired cortisol synthesis 1 . Decreased cortisol levels lead to enhanced production of adrenocorticotropic hormone (ACTH) along with adrenal hyperplasia 2 . In most cases, CAH is caused by a 21a‐hydroxylase deficiency (21OHD), whereas, NCCAH typically has 20%–50% residual 21OH enzyme activity, leading to androgen excess 3 …”

“…The androgen excess may also contribute to metabolic consequences 9 . It is explained by the vicious circle in which hyperandrogenism leads to insulin resistance and, consequently hyperinsulinemia, which in turn leads to an aggravation of hyperandrogenism 2 . Furthermore, hyperandrogenism can alter lipid metabolism and plasma lipid levels 10 .…”