Congenital adrenal hyperplasia (CAH) is a group of inherited disorders affecting the adrenal glands' ability to produce cortisol and, in most forms, aldosterone. It results from deficiency of one of the enzymes needed for cortisol synthesis. When cortisol production is impaired, the pituitary produces excess ACTH, causing the adrenal glands to enlarge (hyperplasia) and accumulate hormone precursors — some of which are converted to androgens.
The Most Common Form: 21-Hydroxylase Deficiency
Over 90% of CAH cases result from deficiency of the 21-hydroxylase enzyme, encoded by the CYP21A2 gene. Without 21-hydroxylase, the adrenal glands cannot make cortisol or aldosterone, and excess precursors are shunted into androgen production.
Clinical Presentations
- Classic CAH — Salt-Wasting Form (most severe): Both cortisol and aldosterone are deficient. Presents in newborns with adrenal crisis (salt wasting, vomiting, low blood pressure, potentially fatal without treatment). Females have ambiguous genitalia due to excess androgen exposure in the womb. Newborn screening in the U.S. identifies most cases.
- Classic CAH — Simple Virilizing Form: Cortisol deficient; aldosterone production is sufficient. Females have ambiguous genitalia; males appear normal at birth but have signs of early puberty in childhood.
- Non-Classic CAH (NCAH): The most common form; partial enzyme deficiency. Presents in adolescence or adulthood with acne, hirsutism, irregular periods, and signs of androgen excess similar to PCOS. Often discovered during workup for PCOS-like symptoms.
Diagnosis
The key diagnostic test is a morning 17-hydroxyprogesterone (17-OHP) level. Elevated 17-OHP is the hallmark of 21-hydroxylase deficiency. Genetic testing of the CYP21A2 gene confirms the diagnosis. For non-classic CAH, an ACTH stimulation test may be needed for confirmation.
Treatment
Treatment replaces the deficient hormones:
- Glucocorticoids (hydrocortisone in children; prednisone or dexamethasone in adults): Suppress excess ACTH and reduce androgen overproduction. Dosing must be carefully balanced — too little leads to androgen excess; too much causes Cushing's features and stunted growth.
- Mineralocorticoid replacement (fludrocortisone): Required in salt-wasting forms to prevent dangerous sodium and fluid loss
- Stress dosing: Like all adrenal insufficiency patients, CAH patients must increase their glucocorticoid dose during illness, surgery, or significant stress
- Newer treatments: Crinecerfont (Crenessity), a CRF1 receptor antagonist, was recently FDA-approved as an add-on therapy to reduce excess adrenal androgens while potentially allowing lower glucocorticoid doses
Key Takeaways
- CAH is an inherited enzyme deficiency causing cortisol deficiency and androgen excess
- Classic forms are diagnosed at birth through newborn screening; non-classic forms may be diagnosed in adulthood
- 17-OHP is the primary diagnostic test
- Lifelong glucocorticoid replacement is the cornerstone of treatment
- Emergency stress dosing is critical — all CAH patients should know their sick day rules and carry injectable hydrocortisone
Our Team Treats Adrenal Disorders
All five of our providers evaluate and manage adrenal and endocrine conditions. Book with any member of our team:
Book an Appointment → or call 832-968-7003