From the Guidelines
Congenital Adrenal Hyperplasia (CAH) is a group of inherited genetic disorders affecting the adrenal glands, primarily caused by enzyme deficiencies that disrupt cortisol production, and its treatment involves lifelong glucocorticoid replacement and mineralocorticoid replacement in salt-wasting forms, as recommended by recent guidelines 1.
Overview of CAH
CAH is characterized by the inability of the adrenal glands to produce sufficient amounts of cortisol and sometimes aldosterone, while overproducing androgens (male sex hormones). This hormonal imbalance leads to various symptoms depending on the severity, including:
- Ambiguous genitalia in females at birth
- Early puberty
- Rapid growth followed by premature growth plate closure
- Fertility issues
- Salt-wasting crises in severe cases
Diagnosis and Treatment
Diagnosis of CAH is based on clinical indications, physical examination, screening tests, and confirmatory tests, as outlined in recent guidelines 1. Treatment typically involves:
- Lifelong glucocorticoid replacement (such as hydrocortisone 10-15 mg/m²/day divided into 2-3 doses) to suppress excess androgen production and replace missing cortisol
- Mineralocorticoid replacement with fludrocortisone (typically 0.05-0.2 mg daily) for salt-wasting forms
- Regular monitoring of hormone levels, growth, and development, with dose adjustments during illness, surgery, or other stressful situations when additional "stress dosing" is necessary
Importance of Early Diagnosis and Treatment
Early diagnosis and consistent treatment are essential to prevent adrenal crisis and ensure normal growth and development, as highlighted in recent studies 1. Delayed diagnosis and inadequate treatment can lead to significant morbidity and mortality, emphasizing the need for prompt and effective management of CAH.
Key Considerations
Key considerations in the management of CAH include:
- Gender assignment and rearing, particularly in cases of ambiguous genitalia
- Feminizing genitoplasty to ensure consistency with the female sex of rearing
- Regular monitoring and dose adjustments to prevent adrenal crisis and ensure normal growth and development
- Psychological support and counseling to address potential issues related to gender identity and sexual orientation.
From the Research
Definition and Causes of Congenital Adrenal Hyperplasia (CAH)
- Congenital adrenal hyperplasia (CAH) is a family of autosomal recessive disorders caused by mutations that encode for enzymes involved in one of the various steps of adrenal steroid synthesis 2.
- The most common cause of CAH is 21-hydroxylase deficiency, which is caused by mutations in the 21-hydroxylase gene 3, 4, 5.
- CAH can vary from mild to severe depending on the degree of enzymatic defect, with the classical form being the most severe and the non-classical form being milder 4, 2.
Symptoms and Diagnosis of CAH
- Symptoms of CAH can include genital ambiguity, premature development of pubic hair, advanced bone age, accelerated linear growth velocity, and diminished final height in both males and females 4, 2.
- Women with CAH may present with symptoms of androgen excess, including hirsutism, temporal baldness, and infertility, while men may present with early beard growth, acne, and growth spurt 2.
- CAH can be diagnosed by serum elevations of 17-OHP and confirmed with molecular genetic analysis 4, 2.
Treatment of CAH
- Treatment of CAH typically involves glucocorticoid replacement therapy to substitute for the deficient cortisol production and to suppress excess androgen production 3, 6, 5.
- The goal of treatment is to prevent adrenal crises, achieve normal stature, and undergo normal puberty in children, and to prevent adrenal crises, ensure normal fertility, and avoid long-term consequences of glucocorticoid use in adults 5.
- Different glucocorticoid replacement regimens have been compared in clinical trials, but the evidence is limited and no firm conclusions can be drawn about the most effective form of treatment 5.