From the Guidelines
Congenital adrenal hyperplasia (CAH) is a group of inherited genetic disorders affecting the adrenal glands, primarily caused by enzyme deficiencies in cortisol production, resulting in overproduction of adrenal steroids, including androgens, and leading to virilization in females and other complications 1.
Definition and Causes
CAH is characterized by an enzymatic defect that leads to the overproduction of adrenal steroids, including androgens, causing virilization in females and other complications. The most common form of CAH results from 21-hydroxylase deficiency, accounting for about 95% of cases 1.
Clinical Presentation and Diagnosis
Females with CAH are exposed to androgens during gestation and are typically born with some degree of genital virilization. Postnatal exposure to androgens would also occur until adrenal hormone replacement therapy is begun 1. The diagnosis of CAH is based on clinical presentation, laboratory tests, and genetic analysis.
Treatment and Management
Treatment focuses on hormone replacement therapy with glucocorticoids like hydrocortisone (typically 10-15 mg/m² daily divided into 2-3 doses), and in salt-wasting forms, mineralocorticoid replacement with fludrocortisone (0.05-0.2 mg daily) 1. Lifelong treatment is necessary to prevent adrenal crisis, which requires immediate administration of hydrocortisone (100 mg IV) and fluid resuscitation. Patients should carry emergency identification and medication. In females, CAH may cause virilization requiring surgical correction. Regular monitoring of growth, bone age, and hormone levels is essential to adjust medication and prevent complications.
Key Considerations
- CAH results from mutations in genes coding for steroidogenic enzymes, leading to cortisol deficiency and accumulation of precursors that are shunted into androgen pathways, causing the characteristic symptoms of virilization and, in severe cases, salt wasting due to aldosterone deficiency 1.
- The condition can have significant effects on gender identity and behavioral development, with females with CAH being more likely to have bisexual or homosexual interests than women without the condition 1.
- Early diagnosis and treatment are crucial to prevent long-term complications and improve quality of life for individuals with CAH 1.
From the Research
Definition and Causes of Congenital Adrenal Hyperplasia (CAH)
- Congenital adrenal hyperplasia (CAH) is an autosomal recessive condition that leads to glucocorticoid deficiency and is the most common cause of adrenal insufficiency in children 2.
- CAH is caused by the deficiency of one of the enzymes involved in cortisol synthesis, with more than 95% of cases occurring as a result of defects in the gene encoding 21-hydroxylase (CYP21A2) 3.
- 21-hydroxylase deficiency is characterized by cortisol and in some cases aldosterone deficiency associated with androgen excess 4.
Forms and Presentations of CAH
- CAH can be divided into classical and non-classical forms, with the classical form further divided into salt-wasting and non-salt-wasting forms 5.
- Classical CAH presents with virilized external genitalia in females and potentially lethal adrenal insufficiency, while non-classical CAH may present with precocious pubarche in children or polycystic ovarian syndrome in young women 5.
- CAH can present at different life stages, depending on disease severity, and may be diagnosed during infancy, childhood, or adolescence 6.
Diagnosis and Treatment of CAH
- Diagnosis of CAH is typically made through newborn screening or clinical presentation, and confirmed by hormonal and molecular studies 5, 6.
- Treatment of CAH involves replacing deficient hormones with glucocorticoids and mineralocorticoids, and controlling androgen excess 2, 3, 4.
- The goals of treatment are to prevent adrenal crises, achieve normal stature and puberty, and prevent long-term complications such as cardiometabolic risk factors and impaired cognitive function 2, 6.