What is the initial workup for a patient suspected of having adrenal hyperplasia?

Adrenal Hyperplasia Workup

All patients with suspected adrenal hyperplasia require comprehensive hormonal screening with 17-hydroxyprogesterone as the key diagnostic test, combined with non-contrast CT imaging to assess adrenal gland morphology. 1, 2

Initial Hormonal Evaluation

The workup differs fundamentally based on whether you suspect congenital adrenal hyperplasia (CAH) versus acquired adrenal hyperplasia:

For Suspected Congenital Adrenal Hyperplasia

• Measure serum 17-hydroxyprogesterone as the primary screening test, particularly for 21-hydroxylase deficiency which accounts for 90-95% of CAH cases 3, 4
• Obtain DHEA-S, androstenedione, testosterone, and 17-beta-estradiol (in men and postmenopausal women) to assess androgen excess 1
• Consider 24-hour urine steroid metabolite examination for comprehensive steroid profiling 1
• Measure basal cortisol and ACTH to evaluate cortisol deficiency 1
• Check aldosterone/renin ratio and serum potassium if hypertension or hypokalemia present, as mineralocorticoid deficiency occurs in severe forms 1

For Suspected Acquired Adrenal Hyperplasia (ACTH-Dependent)

• Perform 1 mg overnight dexamethasone suppression test to screen for autonomous cortisol secretion 1, 2
• Measure basal ACTH to distinguish ACTH-dependent from ACTH-independent causes 1
• Obtain 24-hour urinary free cortisol and basal serum cortisol (minimum 3 of 4 tests for glucocorticoid excess) 1
• Screen for pheochromocytoma with plasma metanephrines or 24-hour urinary metanephrines if the patient has symptoms of catecholamine excess or if imaging shows masses >10 HU 1

Imaging Protocol

• Non-contrast CT of the abdomen is the first-line imaging modality to evaluate adrenal gland size and morphology 1, 2
• Look for bilateral adrenal enlargement which is the hallmark of adrenal hyperplasia, distinguishing it from unilateral masses 1, 5
• MRI serves a complementary role and is preferred in pediatric cases and pregnant women to avoid radiation 1, 6
• Obtain chest CT to evaluate for ectopic ACTH-secreting tumors if ACTH-dependent hyperplasia is suspected 1

Clinical Assessment Targets

Focus your history and physical examination on these specific findings:

Signs of Cortisol Excess (Cushing's Syndrome)

• Weight gain, central obesity, moon facies, buffalo hump, purple striae >1 cm, easy bruising, proximal muscle weakness 2
• Hypertension, diabetes mellitus, osteoporosis 2

Signs of Androgen Excess (Particularly in CAH)

• In females: Virilization, hirsutism, deepening voice, clitoromegaly, ambiguous genitalia in neonates 2, 3
• In males: Precocious puberty in children, infertility in adults 3

Signs of Mineralocorticoid Deficiency (Classic CAH)

• Salt-wasting crisis in neonates (hyponatremia, hyperkalemia, dehydration, shock) 3, 4
• Hypotension, muscle weakness 1

Signs of Aldosterone Excess (11β-Hydroxylase Deficiency)

• Resistant hypertension with hypokalemia 4

Critical Pitfalls to Avoid

• Do not skip 17-hydroxyprogesterone testing in bilateral adrenal masses, as this is essential for diagnosing CAH 1, 2
• Never biopsy suspected adrenal hyperplasia without first excluding pheochromocytoma, as this can precipitate a hypertensive crisis 1
• Hold interfering medications before testing when possible: beta-blockers, ACE inhibitors, and ARBs affect aldosterone/renin ratio; tricyclic antidepressants affect metanephrines; estrogen and rifampin affect cortisol 2
• Recognize that non-classic CAH presents later in life and mimics polycystic ovary syndrome—actively screen for it in women with hyperandrogenism 3

When to Involve Specialists

• Engage endocrinology immediately for all cases of suspected adrenal hyperplasia to guide hormonal workup and interpretation 2
• Involve pediatric endocrinology for neonates and children with suspected CAH, as this requires specialized management 3
• Consult genetics for confirmed CAH cases for family counseling and mutation analysis 3
• Consider multidisciplinary team (endocrinology, radiology, surgery) if imaging shows nodular hyperplasia or if malignancy cannot be excluded 2, 7

Interpretation Algorithm

If 17-hydroxyprogesterone is elevated (>200 ng/dL): Suspect 21-hydroxylase deficiency CAH and proceed with genetic testing and ACTH stimulation test 3, 4

If ACTH is elevated with bilateral hyperplasia: Consider ACTH-dependent Cushing's syndrome (pituitary adenoma or ectopic ACTH) and proceed with pituitary MRI and inferior petrosal sinus sampling 1

If ACTH is suppressed with bilateral hyperplasia: Consider primary pigmented nodular adrenocortical disease or bilateral macronodular hyperplasia 5