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

From the Guidelines

The recommended workup for Congenital Adrenal Hyperplasia (CAH) includes serum 17-hydroxyprogesterone measurement, comprehensive metabolic panel, plasma renin activity, serum electrolytes, and ACTH stimulation testing in borderline cases, with treatment centered on glucocorticoid replacement and mineralocorticoid replacement for salt-wasting forms. When considering the management of CAH, it's crucial to understand the underlying pathophysiology, which involves a deficiency in cortisol and aldosterone production, as noted in patients with primary adrenal insufficiency, such as those with CAH 1. The workup should prioritize identifying the specific form of CAH and assessing the degree of hormonal imbalance. Key components include:

• Serum 17-hydroxyprogesterone measurement as the primary diagnostic marker
• Comprehensive metabolic panel to evaluate electrolyte balance and renal function
• Plasma renin activity to assess aldosterone production
• Serum electrolytes to monitor for signs of adrenal crisis or insufficiency
• ACTH stimulation testing in cases where the diagnosis is unclear or borderline Genetic testing for CYP21A2 mutations can confirm the diagnosis and help in family planning and genetic counseling. Treatment should focus on replacing deficient hormones:
• Glucocorticoid replacement with hydrocortisone, typically at 10-15 mg/m²/day divided into 2-3 doses for adults, with higher doses for children
• Mineralocorticoid replacement with fludrocortisone for salt-wasting forms of CAH, at doses of 0.05-0.2 mg daily Stress dosing, regular monitoring of growth parameters, bone age, serum electrolytes, plasma renin activity, and 17-hydroxyprogesterone levels are essential to ensure adequate treatment and prevent long-term complications, as patients with CAH are at risk of adrenal crisis, similar to those with other forms of adrenal insufficiency 1. Lifelong treatment, medical alert identification, and consideration of surgical correction for females with genital virilization are also critical components of CAH management.

From the FDA Drug Label

DOSAGE & ADMINISTRATION Dosage depends on the severity of the disease and the response of the patient. In the event transient hypertension develops as a consequence of therapy, the dose should be reduced to 0.05 mg daily. Salt-Losing Adrenogenital Syndrome The recommended dosage for treating the salt-losing adrenogenital syndrome is 0.1 mg to 0.2 mg of fludrocortisone acetate tablets daily.

The recommended workup and treatment for Congenital Adrenal Hyperplasia (CAH), specifically the salt-losing adrenogenital syndrome, includes:

• Monitoring for signs that indicate dosage adjustment is necessary
• Fludrocortisone acetate tablets at a dose of 0.1 mg to 0.2 mg daily 2 No information is provided on the workup. Treatment should be individualized and based on the severity of the disease and the response of the patient.

From the Research

Diagnosis of Congenital Adrenal Hyperplasia (CAH)

• 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 3
• The most frequent form of CAH is steroid 21-hydroxylase deficiency, accounting for more than 90% of cases 4, 5
• CAH due to 21-hydroxylase deficiency is diagnosed by confirming elevations of 17-hydroxyprogesterone (OHPG) and androstenedione (ANST) with decreased cortisol 4
• Mass spectrometric methods are considered the gold standard method for the analysis of OHPG in serum or plasma 4

Treatment of Congenital Adrenal Hyperplasia (CAH)

• Classic CAH patients require chronic glucocorticoid treatment at the lowest dose that adequately suppresses adrenal androgens and maintains normal growth and weight gain 5
• Most patients with classic CAH also require mineralocorticoid (fludrocortisone) treatment 5
• The goal of treatment is to suppress adrenal androgen production while replacing deficient hormones 5, 3
• Treatment should be individualized and monitored regularly to avoid over- or under-treatment 5, 6

Monitoring and Follow-up

• Regular measurement of blood pressure should be performed in all patients with CAH to avoid misdiagnosis of 11 beta-hydroxylase deficiency 7
• Serum concentrations of dehydroepiandrosterone sulfate (DHEA-S) and 17-hydroxyprogesterone (17-OHP) can be used to monitor adequacy of control during therapy 6
• DHEA-S concentration can indicate poor control, while a suppressed 17-OHP concentration indicates good control 6
• Transition of care of older patients to adult physicians should be planned in advance as a structured, ongoing process 5