Adrenal Hyperplasia Diagnosis and Management

Initial Hormonal Evaluation

The American College of Endocrinology recommends measuring serum 17-hydroxyprogesterone as the primary screening test for congenital adrenal hyperplasia, particularly for 21-hydroxylase deficiency, which accounts for 90-95% of CAH cases 1
Obtain DHEA-S, androstenedione, testosterone, and 17-beta-estradiol to assess androgen excess in patients with suspected adrenal hyperplasia 1
Consider 24-hour urine steroid metabolite examination for comprehensive steroid profiling in patients with suspected adrenal hyperplasia 1
Measure basal cortisol and ACTH to evaluate cortisol deficiency in patients with suspected adrenal hyperplasia 1
Check aldosterone/renin ratio and serum potassium if hypertension or hypokalemia are present, as mineralocorticoid deficiency occurs in severe forms of adrenal hyperplasia 1

The American College of Radiology recommends non-contrast CT of the abdomen as the first-line imaging modality to evaluate adrenal gland size and morphology in patients with suspected adrenal hyperplasia 3
Look for bilateral adrenal enlargement, which is the hallmark of adrenal hyperplasia, distinguishing it from unilateral masses 4
MRI serves a complementary role and is preferred in pediatric cases and pregnant women to avoid radiation 1
Obtain chest CT to evaluate for ectopic ACTH-secreting tumors if ACTH-dependent hyperplasia is suspected 1

Focus the history and physical examination on signs of cortisol excess, such as weight gain, central obesity, moon facies, buffalo hump, purple striae, easy bruising, and proximal muscle weakness 2
Evaluate for signs of androgen excess, such as virilization, hirsutism, deepening voice, clitoromegaly, and ambiguous genitalia in females, and precocious puberty in children and infertility in adults in males 2
Assess for signs of mineralocorticoid deficiency, such as hypotension, muscle weakness, and salt-wasting crisis in neonates 1

Do not skip 17-hydroxyprogesterone testing in bilateral adrenal masses, as this is essential for diagnosing CAH 4
Never biopsy suspected adrenal hyperplasia without first excluding pheochromocytoma, as this can precipitate a hypertensive crisis 3
Hold interfering medications before testing when possible, such as beta-blockers, ACE inhibitors, and ARBs, which affect aldosterone/renin ratio, and tricyclic antidepressants, which affect metanephrines 2

Engage endocrinology immediately for all cases of suspected adrenal hyperplasia to guide hormonal workup and interpretation 2
Consider a multidisciplinary team, including endocrinology, radiology, and surgery, if imaging shows nodular hyperplasia or if malignancy cannot be excluded 2, 5