Understanding Congenital Adrenal Hyperplasia (CAH), with Richard Auchus, M.D., Ph.D.

Congenital adrenal hyperplasia (CAH) is a genetic disorder affecting cortisol production in the adrenal glands. In an interview with The Educated Patient, Richard Auchus, M.D., Ph.D., explains that CAH results from enzyme deficiencies that disrupt cortisol synthesis. The body compensates by increasing adrenocorticotropic hormone (ACTH) production, leading to adrenal hyperplasia and an accumulation of steroid precursors. These precursors can overflow into androgen pathways, causing hormonal imbalances.

Auchus says the most common form of CAH is 21-hydroxylase deficiency, which can present in classic or nonclassic forms. Classic CAH is severe, leading to cortisol and aldosterone deficiencies, which can be life-threatening if untreated. Luckily, newborn screening programs in the U.S. identify this condition early, ensuring prompt cortisol and aldosterone replacement therapy. Excess androgens in classic CAH can cause early puberty, abnormal growth patterns, and fertility issues.

Nonclassic CAH is a milder form where individuals can still produce cortisol but steroid precursors accumulate, leading to excess androgens. This condition often manifests in childhood as early pubic hair growth, rapid height increase or body odor. In women, symptoms may include irregular periods, acne and excess facial hair.

Treatment involves glucocorticoid therapy, primarily hydrocortisone in children, to reduce androgen overproduction. Patients with classic CAH need lifelong cortisol replacement, similar to insulin therapy for type 1 diabetes. Managing CAH is a delicate balance — patients often need higher-than-normal glucocorticoid doses to control androgen levels, which can lead to long-term side effects including bone loss, obesity, hypertension and cardiovascular disease. Auchus notes that research conducted in the U.S., England and Sweden has shown that chronic high-dose glucocorticoid use can also impact mental health, increasing the risk of anxiety, depression and other mood disorders.

He says in children with classic CAH, excessive androgens can cause rapid growth and premature bone maturation, leading to shorter adult height. In adulthood, androgen excess can contribute to fertility problems and even tumor formation in the adrenal glands and gonads. Women with nonclassic CAH may continue glucocorticoid therapy to manage symptoms, while men often discontinue treatment.

Auchus emphasizes the importance of early diagnosis, personalized treatment plans and long-term monitoring to balance cortisol replacement while minimizing complications.