What are the diagnostic and treatment approaches for congenital adrenal hyperplasia (CAH)?

From the Guidelines

Congenital adrenal hyperplasia (CAH) should be diagnosed and treated promptly, with a focus on glucocorticoid replacement, typically with hydrocortisone at 10-15 mg/m²/day divided into 2-3 doses, and mineralocorticoid replacement with fludrocortisone (0.05-0.2 mg daily) for salt-wasting forms, to prevent adrenal crisis and ensure optimal growth and development 1.

Diagnostic Approaches

• Newborn screening typically measures 17-hydroxyprogesterone levels, with elevated values suggesting CAH
• Confirmatory testing includes comprehensive adrenal hormone panels, ACTH stimulation tests, and genetic testing for mutations in the CYP21A2 gene, which causes the most common form (21-hydroxylase deficiency) 1
• Rapid detailed investigations must be performed in newborns with genital ambiguity to evaluate the chromosomal gonadal sex, hormonal environment, and anatomy of the external and internal genital organs to clarify the type of anomaly 1

Treatment Approaches

• Glucocorticoid replacement with hydrocortisone at 10-15 mg/m²/day divided into 2-3 doses, which suppresses excess ACTH production and reduces androgen levels
• Mineralocorticoid replacement with fludrocortisone (0.05-0.2 mg daily) is necessary for salt-wasting forms of CAH to maintain electrolyte balance
• Infants with salt-wasting CAH also require sodium chloride supplements (1-2 g daily)
• For females with virilized genitalia, surgical reconstruction may be considered, though timing remains controversial with many experts now advocating for delayed surgery to allow patient input 1
• Long-term management requires careful monitoring of growth, bone age, and hormone levels to avoid over or under-treatment
• Stress dosing of glucocorticoids (typically tripling the usual dose) during illness or surgery is essential to prevent adrenal crisis 1

Key Considerations

• Failure to diagnose congenital adrenal hyperplasia can result in serious harm, as a high proportion of patients with this condition are unable to regulate their electrolyte levels and may present with shock, hyponatremia, and hyperkalemia 1
• Regular follow-up with pediatric endocrinologists is crucial for dose adjustments as children grow
• Patients with CAH should be educated on how to manage their condition, including the use of Medic Alert identification jewelry and carrying a steroid/alert card 1

From the FDA Drug Label

Text: wound healing Thin fragile skin Petechiae and ecchymoses Facial erythema Increased sweating May suppress reactions to skin tests Neurological Increased intracranial pressure with papilledema (pseudotumor cerebri) usually after treatment Convulsions Vertigo Headache Endocrine Development of Cushingoid state Suppression of growth in children Secondary adrenocortical and pituitary unresponsiveness, particularly in times of stress, as in trauma, surgery or illness Menstrual irregularities Decreased carbohydrate tolerance Manifestations of latent diabetes mellitus Increased requirements for insulin or oral hypoglycemic agents in diabetics Ophthalmic Posterior subcapsular cataracts Increased intraocular pressure Glaucoma Exophthalmos Metabolic Negative nitrogen balance due to protein catabolism

The FDA drug label does not answer the question.

From the Research

Diagnostic Approaches for Congenital Adrenal Hyperplasia (CAH)

• CAH is a disorder of adrenal steroid synthesis, with 95% of cases caused by 21-hydroxylase deficiency, leading to cortisol deficiency and aldosterone deficiency 2.
• The classic form of CAH is characterized by congenital virilisation in girls, while the non-classic form presents with signs of androgen excess from childhood to adulthood 2.
• Neonatal screening programs have been introduced to detect CAH early, with a prevalence of 1:12,000 in the Netherlands for the classic form 2.
• Diagnosis can also be based on clinical presentation, including genital virilization, and subsequent re-evaluation 3.

Treatment Approaches for Congenital Adrenal Hyperplasia (CAH)

• Treatment of CAH consists of hormonal replacement and surgical correction in case of congenital virilisation in girls 2.
• Life-long glucocorticoid replacement is especially important in classic phenotype CAH 4.
• Surgical procedures, including clitoris reduction and vaginoplasties, may be necessary in patients with female sex assignment 5.
• Early diagnosis is crucial to prevent late sequelae, such as short stature and central precocious puberty 5.

Medication Adherence and Self-Management in CAH

• Medication adherence is crucial in CAH, with self-reported adherence rates varying among patients 4.
• Patients with the more severe form of CAH tend to have higher adherence rates and demonstrate good endocrine knowledge and self-management 4.
• Discordance between physician-assessed and self-reported adherence rates can occur, highlighting the need for careful monitoring and patient education 4.

Challenges and Complications in CAH Management

• Late diagnosis can lead to significant problems, including gender assignment issues, short stature, and central precocious puberty 5.
• Multiple surgical procedures may be necessary, and patients may experience disturbed gender identity 5.
• False negative 17-hydroxyprogesterone screening can occur, emphasizing the importance of careful clinical investigation and consideration of CAH in the differential diagnosis 3.