Overview
Definition
A group of autosomal recessive disorders characterized by enzyme deficiencies in the cortisol synthesis pathway, most commonly 21-hydroxylase deficiency, leading to excess androgen production.
Epidemiology
Classic form occurs in ~1 in 15,000 live births. Screened at birth in many countries.
Etiology & Risk Factors
- Autosomal recessive genetic mutation in the CYP21A2 gene (21-hydroxylase deficiency in >90% of cases)
Clinical Symptoms
- Classic Salt-Wasting (neonatal crisis: vomiting, dehydration, hyponatremia, hyperkalemia, shock)
- Ambiguous genitalia in newborn females
- Precocious puberty, rapid growth, and short stature in childhood
Clinical Approach
Diagnosis
- Elevated serum 17-hydroxyprogesterone (17-OHP)
- Hyponatremia, hyperkalemia, and elevated renin in salt-wasting form
Management
- Glucocorticoid replacement (Hydrocortisone/Fludrocortisone to replace cortisol/aldosterone and suppress ACTH)
- Stress dosing during illness
Complications
- Life-threatening Adrenal Crisis
- Infertility
- Virilization in females