What is the treatment for Congenital Adrenal Hyperplasia (CAH)?

From the Guidelines

The treatment of Congenital Adrenal Hyperplasia (CAH) primarily involves glucocorticoid replacement therapy to suppress excess androgen production and replace deficient hormones, with hydrocortisone being the preferred glucocorticoid, as evidenced by general principles of steroid replacement in adrenal insufficiency 1. When considering the management of CAH, several key points must be addressed to prioritize morbidity, mortality, and quality of life.

• Glucocorticoid replacement is crucial, with hydrocortisone typically dosed at 10-15 mg/m²/day divided into 2-3 doses for children, and for adults, prednisone (3-5 mg/day) or dexamethasone (0.25-0.5 mg/day) may be used.
• Mineralocorticoid replacement with fludrocortisone (0.05-0.2 mg daily) is necessary for salt-wasting forms of CAH to maintain electrolyte balance, similar to the principles outlined for primary adrenal insufficiency 1.
• Infants with salt-wasting CAH also require sodium chloride supplements (1-2 g daily) to compensate for increased renal loss, aligning with the need for increased intake of sodium chloride in patients with primary adrenal insufficiency 1.
• Treatment must be lifelong and requires regular monitoring of hormone levels, growth parameters, and bone health, with dose adjustments needed during periods of stress, illness, or surgery, typically by doubling or tripling the glucocorticoid dose, emphasizing the importance of patient education on managing steroid doses during concurrent illnesses or injury 1.
• Patients should carry emergency medical identification and have injectable hydrocortisone available for adrenal crisis, highlighting the critical need for prompt administration of hydrocortisone in emergency situations to prevent fatal outcomes 1.
• The goal of therapy is to suppress excess androgen production while minimizing glucocorticoid side effects, maintaining normal growth in children, and allowing normal reproductive function, all of which are crucial for optimizing quality of life in patients with CAH.
• Regular follow-up with an endocrinologist is essential for optimal management, ensuring that patients receive the necessary care and adjustments to their treatment plan to manage their condition effectively and improve their quality of life.

From the FDA Drug Label

INDICATIONS AND USAGE PredniSONE Tablets are indicated in the following conditions: 1 Endocrine Disorders Primary or secondary adrenocortical insufficiency (hydrocortisone or cortisone is the first choice; synthetic analogs may be used in conjunction with mineralocorticoids where applicable; in infancy mineralocorticoid supplementation is of particular importance) Congenital adrenal hyperplasia

The treatment of Congenital Adrenal Hyperplasia (CAH) may involve the use of prednisone. 2

From the Research

Treatment Strategies for Congenital Adrenal Hyperplasia (CAH)

• The standard treatment for CAH is hydrocortisone, with improved strategies for timing and dosage having a positive impact on patient outcomes 3.
• Neonatal screening enables earlier diagnosis and treatment, preventing adrenal crises and improving growth and development in children with CAH 3.
• Novel modified release glucocorticoid therapies are being developed to decrease adrenal androgen production, but their long-term effects are unknown 3, 4.

Glucocorticoid Replacement Regimens

• Current glucocorticoid treatment regimens cannot optimally replicate normal physiological cortisol levels, leading to over-treatment or under-treatment 5.
• Different glucocorticoid replacement regimens, such as hydrocortisone and prednisolone, have been compared in clinical trials, but the evidence is limited and of low quality 5, 6.
• Modified-release hydrocortisone (MR-HC) has shown promise in improving biochemical disease control and reducing steroid dose over time, with patient-reported benefits including restoration of menses and pregnancies 7.

Management Challenges and Therapeutic Advances

• Management of CAH is complicated by comorbidities arising from disease-related hormonal derangements and treatment-related adverse effects 4.
• Adrenal-derived 11-oxygenated androgens have emerged as potential new biomarkers for CAH, which could improve management and treatment outcomes 4.
• Multiple alternative treatment approaches are being developed, including treatments designed to replace cortisol in a physiological manner and adjunct agents intended to control excess androgens 4.