Metabolic syndrome and cardiovascular morbidity in patients with congenital adrenal hyperplasia

Abstract

Since the introduction of glucocorticoid (GC) replacement therapy, congenital adrenal hyperplasia (CAH) is no longer a fatal disease. The development of neonatal screening programs and the amelioration of GC treatment strategies have improved significantly life expectancy in CAH patients. Thanks to these achievements, CAH patients are now in their adulthood, but an increased incidence of cardiovascular risk factors has been reported compared to general population in this stage of life. The aim of CAH treatment is to both prevent adrenal insufficiency and suppress androgen excess; in this delicate balance, under- as well as overtreatment might be equally harmful to long-term cardiovascular health. This work examines the prevalence of metabolic features and cardiovascular events, their correlation with hormone levels and GC replacement regimen in CAH patients and focuses on precocious markers to early detect patients at higher risk and new potential treatment approaches.

Keywords: cardiovascular risk; congenital adrenal hyperplasia (CAH)–21-alpha hydroxylase deficiency; diabetes mellitus; glucocorticoid therapy; metabolic syndrome; obesity.

Figure 1

A schematic illustration of the metabolic and vascular complications caused by the difficult balance between glucocorticoid overtreatment and androgen excess in congenital adrenal hyperplasia. GC, glucocorticoid.

Figure 2

Major adrenal steroid synthesis pathways. Uncommon CAH forms include: - 11β-hydroxylase deficiency (11-OHD): block at CYP11B1 → ↓ cortisol; ↑ DOC, ↑ 17-hydroxyprogesterone, androgens, ↑ 11-deoxycortisol - 17α-hydroxylase deficiency (17-OHD): block at CYP17A1 → ↓ 17-hydroxyprogeserone, ↓ androgens; ↑ DOC, ↑ corticosterone - 3β-hydroxysteroid dehydrogenase type II deficiency (3β-HSD): block at 3β-HSD → ↓ aldosterone, ↓ androgens in male; ↑ 17hydroxypregnenolone, ↑ 17-hydroxyprogesterone, ↑ DHEA - Lipoid form (LCAH)→ block at StAR level → ↓ all steroids - P450 oxidoreductase deficiency (PORD): multiple partial blocks of CYP17A1 and CYP21A2→ ↓ androgens; ↑ progesterone, ↑ 17-hydroxyprogesterone, ↑ corticosterone (74). DOC, 11-deoxycorticosterone; DHEA, dehydroepiandrosterone; DHEAS, dehydroepiandrosterone sulfate.