From the Guidelines
Congenital Adrenal Hyperplasia (CAH) is primarily caused by genetic mutations that affect enzymes involved in cortisol production, with 21-hydroxylase deficiency accounting for about 95% of cases. The primary cause of CAH is genetic mutations, and the standard treatment consists of lifelong glucocorticoid replacement therapy. The treatment of CAH typically involves glucocorticoid replacement therapy, such as hydrocortisone, to replace deficient hormones and suppress excess androgen production 1.
Key Treatment Components
- Glucocorticoid replacement therapy with hydrocortisone at doses of 10-15 mg/m² per day divided into 2-3 doses
- Mineralocorticoid replacement with fludrocortisone (0.05-0.2 mg daily) for patients with salt-wasting forms of CAH
- Sodium supplementation in infants (1-2 mEq/kg/day)
- Regular monitoring of 17-hydroxyprogesterone, androstenedione, and renin levels to guide therapy adjustments
Important Considerations
- Treatment should begin immediately upon diagnosis, even in newborns, to prevent life-threatening adrenal crises and minimize virilization in females
- Medication doses require careful adjustment based on growth patterns, bone age, and hormone levels, with higher doses sometimes needed during periods of stress or illness
- Long-term management requires a multidisciplinary approach to address potential complications including growth issues, fertility concerns, and psychological support
From the Research
Causes of Congenital Adrenal Hyperplasia (CAH)
- CAH is a group of autosomal recessive disorders that affect adrenal steroidogenesis in the adrenal cortex 2, 3, 4.
- The most common cause of CAH is 21-hydroxylase deficiency, which is responsible for the conversion of 17-hydroxyprogesterone to 11-deoxycortisol and progesterone to deoxycorticosterone 2, 3, 4.
- Other rare types of CAH include 11β-hydroxylase and 3β-hydroxysteroid dehydrogenase deficiency 2, 5.
- The deficiency of 21-hydroxylase enzyme results from pathogenic variants on the CYP21A2 gene, which compromise enzymatic activity and are strongly correlated with the clinical severity of the disease 4.
Treatment of Congenital Adrenal Hyperplasia (CAH)
- The treatment of CAH involves hormone replacement therapy, including glucocorticoids and mineralocorticoids 2, 3, 6.
- Hydrocortisone is commonly used for glucocorticoid replacement, and mineralocorticoid and salt replacement may also be necessary 2.
- The goal of treatment is to control the production of excess hormones, prevent adrenal crises, and promote normal growth and development 2, 3, 6.
- Novel treatment approaches aim to reduce glucocorticoid exposure, improve excess hormone control, and mimic physiological hormone patterns 3, 6.
Clinical Presentations of Congenital Adrenal Hyperplasia (CAH)
- CAH can present at different life stages, depending on the severity of the disease 2, 3.
- Classic CAH is characterized by life-threatening adrenal crises and is the most common cause of atypical genitalia in neonates with 46,XX karyotype 3.
- Non-classic CAH is more common than classic CAH and is often detected in female patients with hirsutism or impaired fertility 3.
- Late-onset symptoms of CAH can include premature adrenarche, growth acceleration, hirsutism, and irregular menses 2.