Management challenges and therapeutic advances in congenital adrenal hyperplasia

Abstract

Treatment for congenital adrenal hyperplasia (CAH) was introduced in the 1950s following the discovery of the structure and function of adrenocortical hormones. Although major advances in molecular biology have delineated steroidogenic mechanisms and the genetics of CAH, management and treatment of this condition continue to present challenges. Management is complicated by a combination of comorbidities that arise from disease-related hormonal derangements and treatment-related adverse effects. The clinical outcomes of CAH can include life-threatening adrenal crises, altered growth and early puberty, and adverse effects on metabolic, cardiovascular, bone and reproductive health. Standard-of-care glucocorticoid formulations fall short of replicating the circadian rhythm of cortisol and controlling efficient adrenocorticotrophic hormone-driven adrenal androgen production. Adrenal-derived 11-oxygenated androgens have emerged as potential new biomarkers for CAH, as traditional biomarkers are subject to variability and are not adrenal-specific, contributing to management challenges. Multiple alternative treatment approaches are being developed with the aim of tailoring therapy for improved patient outcomes. This Review focuses on challenges and advances in the management and treatment of CAH due to 21-hydroxylase deficiency, the most common type of CAH. Furthermore, we examine new therapeutic developments, including treatments designed to replace cortisol in a physiological manner and adjunct agents intended to control excess androgens and thereby enable reductions in glucocorticoid doses.

Toward Improving the Transition of Patients With Congenital Adrenal Hyperplasia From Pediatrics to Adult Healthcare in Japan

“…Multiple alternative treatment approaches are being developed with the aim of tailoring therapy for improved long-term outcomes for patients with 21-OHD, including treatments designed to replace cortisol in a physiological manner and treatments with adjunct agents intended to control excess levels of androgen, which thereby enables reduction in glucocorticoid doses, e.g., modified-release hydrocortisone, continuous subcutaneous hydrocortisone infusion pump, 17-hydroxylase inhibitor, hypothalamic–pituitary–adrenal axis suppressors, and cell-based or gene-based therapies ( 33 ). These advances in treatment may shed more light on the significance and necessity of healthcare transition.…”

Diagnosis and Management of Adrenal Crisis in 46XX Congenital Adrenal Hyperplasia Infant

“…Children with classic CAH who had predicted adult height two standard deviations below their MPH treated with GH alone or in combination with a GnRH analog achieved taller adult height compared with their predicted height at baseline (Mallappa & Merke 2022). Overall, there is limited evidence to support the benefits of GH therapy in adults, with or without a GnRH analog.…”

Prevalence of CAH-X Syndrome in Italian Patients with Congenital Adrenal Hyperplasia (CAH) Due to 21-Hydroxylase Deficiency

“…On the other hand, the NC (mild) form, with a prevalence between 1:1000-1:500 live births, is caused by CYP21A2 variants that retain 20-50% of enzyme activity. This form is often asymptomatic and the diagnosis is made during biochemical evaluations performed for hirsutism and menstrual irregularities (8,9).…”