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

From the Guidelines

The treatment for congenital adrenal hyperplasia (CAH) primarily involves glucocorticoid replacement therapy to suppress excess adrenal androgen production and replace deficient hormones, with oral hydrocortisone being the preferred glucocorticoid, typically dosed at 10-15 mg/m² body surface area daily, divided into 2-3 doses, as recommended by the most recent and highest quality study 1. The goal of therapy is to provide adequate hormone replacement while minimizing side effects of glucocorticoid excess such as growth suppression, weight gain, and osteoporosis.

• Key considerations in the treatment of CAH include:
  • Glucocorticoid replacement therapy to suppress excess adrenal androgen production and replace deficient hormones
  • Mineralocorticoid replacement with fludrocortisone for patients with the salt-wasting form of CAH
  • Regular monitoring of hormone levels, growth parameters, and bone age
  • Increased glucocorticoid doses during times of illness, surgery, or significant stress to prevent adrenal crisis
  • Additional treatments for hirsutism or menstrual irregularities in adolescent and adult females
• According to the study by 1, the diagnosis and treatment of primary adrenal insufficiency, which is related to CAH, should be based on the measurement of serum cortisol and plasma ACTH levels, and treatment should be individualized based on the patient's clinical status and laboratory results.
• The study by 1 provides insight into the effects of androgen exposure on the developing brain and behavior in individuals with CAH, highlighting the importance of early hormone environment in shaping human sexual behavior and gender identity.
• However, the most recent and highest quality study 1 provides the most relevant guidance for the treatment of CAH, and its recommendations should be prioritized in clinical practice.

From the FDA Drug Label

INDICATIONS AND USAGE ... Congenital adrenal hyperplasia. ... Primary or secondary adrenocortical insufficiency (hydrocortisone or cortisone is the drug of choice; synthetic analogs may be used in conjunction with mineralocorticoids where applicable; in infancy, mineralocorticoid supplementation is of particular importance) ... 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;

Treatment for Congenital Adrenal Hyperplasia may include:

• Dexamethasone (2)
• Prednisolone (3) Key points:
• Hydrocortisone or cortisone is the drug of choice
• Synthetic analogs may be used in conjunction with mineralocorticoids
• Mineralocorticoid supplementation is of particular importance in infancy

From the Research

Treatment Options for Congenital Adrenal Hyperplasia

• The primary treatment for congenital adrenal hyperplasia (CAH) involves replacing glucocorticoids with oral glucocorticoids, such as prednisolone and hydrocortisone, to suppress adrenocorticotrophic hormones and replace mineralocorticoids to prevent salt wasting 4.
• The goal of treatment in children is to prevent adrenal crises, achieve normal stature, optimal adult height, and undergo normal puberty, while in adults, the aim is to prevent adrenal crises, ensure normal fertility, and avoid the long-term consequences of glucocorticoid use 4.
• Current glucocorticoid treatment regimens often fail to optimally replicate the normal physiological cortisol level, leading to over-treatment or under-treatment 4.

Alternative Treatment Approaches

• Modified-release hydrocortisone (MR-HC) has been investigated as a potential treatment option, which mimics physiologic cortisol secretion and may improve disease control 5.
• MR-HC has been shown to improve biochemical disease control in adults with CAH, with a reduction in steroid dose over time and patient-reported benefits, including the restoration of menses and pregnancies 5.
• Other alternative treatment approaches are being developed, including treatments designed to replace cortisol in a physiological manner and adjunct agents intended to control excess androgens and enable reductions in glucocorticoid doses 6.

Challenges in CAH Management

• Management of CAH is complicated by a combination of comorbidities that arise from disease-related hormonal derangements and treatment-related adverse effects 6.
• Standard-of-care glucocorticoid formulations fall short of replicating the circadian rhythm of cortisol and controlling efficient adrenocorticotrophic hormone-driven adrenal androgen production 6.
• Adrenal-derived 11-oxygenated androgens have emerged as potential new biomarkers for CAH, which may help address the challenges in management 6.

Future Directions

• Future trials should include both children and adults with CAH and have a longer duration of follow-up to monitor biochemical and clinical outcomes 4.
• The development of new treatment options, such as MR-HC and other alternative approaches, may help improve patient outcomes and address the challenges in CAH management 5, 6.