MANAGEMENT OF ENDOCRINE DISEASE: Congenital adrenal hyperplasia due to 21-hydroxylase deficiency: update on the management of adult patients and prenatal treatment

Abstract

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is characterized by cortisol and in some cases aldosterone deficiency associated with androgen excess. Goals of treatment are to replace deficient hormones and control androgen excess, while avoiding the adverse effects of exogenous glucocorticoid. Over the last 5 years, cohorts of adults with CAH due to 21-hydroxylase deficiency from Europe and the United States have been described, allowing us to have a better knowledge of long-term complications of the disease and its treatment. Patients with CAH have increased mortality, morbidity and risk for infertility and metabolic disorders. These comorbidities are due in part to the drawbacks of the currently available glucocorticoid therapy. Consequently, novel therapies are being developed and studied in an attempt to improve patient outcomes. New management strategies in the care of pregnancies at risk for congenital adrenal hyperplasia using fetal sex determination and dexamethasone have also been described, but remain a subject of debate. We focused the present overview on the data published in the last 5 years, concentrating on studies dealing with cardiovascular risk, fertility, treatment and prenatal management in adults with classic CAH to provide the reader with an updated review on this rapidly evolving field of knowledge.

Clitoromegaly in Childhood and Adolescence: Behind One Clinical Sign, a Clinical Sea

“…CAH is divided into a classic form, characterized by salt-wasting and/or simple virilization, and late-onset or non-classic CAH (NCCAH), where isolated clitoromegaly is more frequent. Fetal exposure to abnormal androgen levels causes masculinization of female genitalia, with a spectrum of abnormalities that include clitoromegaly [Bachelot et al, 2017]. Isolated clitoromegaly has been described both in CAH and NCCAH [Siddiqui et al, 2013;Moura-Massari et al, 2016].…”

Complex Association of Sex Hormones on Left Ventricular Systolic Function: Insight into Sexual Dimorphism

“…CAH corresponds to a group of inherited autosomal recessive disorders that arises from defective steroidogenesis and results from a deficiency in one or several of the enzymes of cortisol biosynthesis. [20] Deficiency of the 21-hydroxylase enzyme is the most common form of CAH and is characterized by cortisol and in some cases aldosterone deficiency associated with adrenal androgen excess and renin increase ( Figure 1). [20] Cortisol deficiency results in the ACTH-induced accumulation of substrate precursors such as 17OH-progesterone and progesterone, and to increased secretion of adrenal androgens.…”

“…[20] Deficiency of the 21-hydroxylase enzyme is the most common form of CAH and is characterized by cortisol and in some cases aldosterone deficiency associated with adrenal androgen excess and renin increase ( Figure 1). [20] Cortisol deficiency results in the ACTH-induced accumulation of substrate precursors such as 17OH-progesterone and progesterone, and to increased secretion of adrenal androgens. [20] Goals of treatment are to replace deficient hormones by glucocorticoids and in some cases mineralocorticoids, and control adrenal androgen excess.…”

“…[20] Cortisol deficiency results in the ACTH-induced accumulation of substrate precursors such as 17OH-progesterone and progesterone, and to increased secretion of adrenal androgens. [20] Goals of treatment are to replace deficient hormones by glucocorticoids and in some cases mineralocorticoids, and control adrenal androgen excess. The optimal dose of glucocorticoid is that which fails to fully suppress 17hydroxy(OH)-progesterone and maintains androgens in the mid-normal range.…”

“…The optimal dose of glucocorticoid is that which fails to fully suppress 17hydroxy(OH)-progesterone and maintains androgens in the mid-normal range. [20] There is variability in ACTH suppression by this supplementation, leading to inter-individual variability in residual secretion of adrenal androgen and ultimately testosterone levels. In some patients, this leads to insufficient control of their disease, resulting in high levels of progesterone and adrenal androgens, disturbing gonadal axis with low LH and FSH release by the pituitary gland.…”