From the Guidelines
The workup for an infant with suspected Congenital Adrenal Hyperplasia (CAH) should begin with immediate serum electrolytes, glucose, and 17-hydroxyprogesterone (17-OHP) measurements, as well as karyotyping for those with ambiguous genitalia, to rapidly diagnose and manage this life-threatening condition. The diagnosis of CAH is critical to prevent morbidity and mortality associated with adrenal crisis and to manage long-term health outcomes.
Initial Evaluation
The initial evaluation should include:
- Serum electrolytes, glucose, and 17-OHP measurements to assess for signs of adrenal insufficiency or excess
- Plasma renin activity, serum aldosterone, androstenedione, testosterone, and ACTH levels to evaluate the hormonal environment
- A comprehensive newborn screen that includes 17-OHP should be verified to confirm the diagnosis
- Karyotyping for infants with ambiguous genitalia to determine chromosomal sex
Treatment
If the infant shows signs of salt-wasting crisis (hyponatremia, hyperkalemia, hypoglycemia), immediate treatment with hydrocortisone (12-15 mg/m²/day divided every 8 hours) and fludrocortisone (0.1-0.2 mg daily) should be initiated, along with sodium chloride supplements (1-2 mEq/kg/day) 1. Fluid resuscitation with normal saline may be necessary for dehydration.
Specialist Consultation
Prompt endocrinology consultation is crucial to manage CAH, as it results from enzymatic defects in cortisol production, most commonly 21-hydroxylase deficiency, leading to cortisol deficiency and androgen excess 1. Early diagnosis and treatment are critical to prevent life-threatening adrenal crisis and manage long-term health outcomes.
Additional Testing
An ACTH stimulation test may be performed to confirm the diagnosis if initial results are inconclusive. Collecting 17-hydroxyprogesterone levels can also help rule out congenital adrenal hyperplasia in certain cases 1.
Gender Assignment
For newborns with ambiguous genitalia secondary to congenital adrenal hyperplasia, female gender assignment is warranted, as these individuals have the potential for normal sexual function and fertility, and almost always identify as female if gender assignment is made early in life 1. Feminizing genitoplasty may be performed within the first 2 months of life to ensure the appearance of the external genitalia is consistent with the female sex of rearing.
From the Research
Diagnosis of Congenital Adrenal Hyperplasia (CAH)
The diagnosis of CAH is typically made during infancy, with elevated 17-hydroxyprogesterone levels on the newborn screen in the United States 2. The following steps are involved in the workup for an infant with suspected CAH:
- Newborn screening using dissociation-enhanced lanthanide fluorescence immunoassay to detect elevated levels of 17-hydroxyprogesterone 3
- Confirmation of diagnosis through follow-up serum 17-hydroxyprogesterone and/or the adrenocorticotropin stimulation test 4
- Measurement of levels of steroid precursors after stimulation with cosyntropin for a definitive diagnosis 3
- Molecular testing to identify patients who may benefit from reassessment of their salt-retaining ability 4
Clinical Evaluation
The clinical evaluation of an infant with suspected CAH includes:
- Physical examination to identify signs of androgen excess, such as virilization and ambiguous genitalia in girls 5, 6
- Laboratory tests to evaluate electrolyte imbalance and adrenal function 6, 3
- Assessment of growth and development to monitor for potential complications, such as premature adrenarche and growth acceleration 2, 5
Treatment and Management
The treatment and management of CAH in infants involves: