Bilateral Adrenal Hyperplasia: Diagnosis and Treatment
Initial Diagnostic Workup
The cornerstone of diagnosis is measuring plasma ACTH levels to distinguish ACTH-dependent from ACTH-independent causes, followed by targeted hormonal assessment based on clinical presentation. 1
Hormonal Assessment
Perform a 1 mg dexamethasone suppression test with morning serum cortisol measurement: values >50 nmol/L (>1.8 μg/dL) indicate autonomous cortisol secretion and warrant further evaluation for Cushing syndrome 1, 2
Measure plasma aldosterone-to-renin ratio in all patients presenting with hypertension or hypokalemia: a ratio >30 suggests primary aldosteronism and requires confirmatory testing 1, 2
Check 17-hydroxyprogesterone levels to exclude congenital adrenal hyperplasia, particularly 21-hydroxylase deficiency, which is the most common enzymatic defect 1, 2
Test for 21-hydroxylase autoantibodies (21OH-Ab) as first-line screening for autoimmune causes, which account for approximately 85% of primary adrenal insufficiency cases in Western populations 1
Critical Safety Step
- Exclude pheochromocytoma with plasma or 24-hour urinary metanephrines before any invasive procedures or surgical intervention to prevent hypertensive crisis 1, 3
Imaging Evaluation
CT is the primary imaging modality for adult adrenal evaluation due to superior spatial resolution and reproducibility, while MRI serves a complementary role 4
Ultrasound and MRI are preferred in pediatric cases to minimize radiation exposure when evaluating congenital adrenal hyperplasia 4
Adrenal vein sampling should be obtained in surgical candidates with confirmed primary aldosteronism to distinguish bilateral hyperplasia from unilateral adenoma, as this fundamentally changes management 2
Treatment Approach by Etiology
Primary Aldosteronism from Bilateral Hyperplasia
Medical management with mineralocorticoid receptor antagonists is the definitive treatment, as bilateral adrenalectomy would cause permanent adrenal insufficiency. 1
Initiate spironolactone 50-200 mg daily as first-line therapy to control hypertension and hypokalemia, or use eplerenone as an alternative if gynecomastia or sexual side effects occur 1
Monitor blood pressure, serum potassium, and renal function regularly during titration 1
ACTH-Independent Hypercortisolism
Ketoconazole 400-1200 mg/day is the first-line adrenostatic agent for medical management of hypercortisolism from bilateral adrenal hyperplasia 1, 3
Bilateral adrenalectomy may be considered in cases of bilateral cortisol hypersecretion refractory to medical therapy, though this commits patients to lifelong hormone replacement 3, 5
The surgical approach depends on adrenal gland size: posterior approach for small glands (typical in primary pigmented micronodular disease), anterior approach for massively enlarged glands (>30 grams, seen in macronodular disease) 5
Congenital Adrenal Hyperplasia
Standard medical management with glucocorticoid replacement remains first-line therapy 6
Bilateral adrenalectomy is reserved for severe cases with uncontrolled hyperandrogenism despite optimal medical therapy, particularly when high glucocorticoid doses cause iatrogenic Cushing syndrome or when persistent androgen excess leads to virilization, premature growth plate closure, or infertility 6
Post-Treatment Management
Hormone Replacement (for patients post-bilateral adrenalectomy)
All patients require lifelong glucocorticoid and mineralocorticoid replacement with stress-dose protocols. 1
Hydrocortisone 15-25 mg daily in 2-3 divided doses for glucocorticoid replacement (typically 10 mg morning, 5 mg afternoon, 5 mg evening) 1
Fludrocortisone 50-200 μg daily for mineralocorticoid replacement 1
Immediate IV hydrocortisone 100 mg for any acute illness, injury, or surgical stress to prevent adrenal crisis 1
Long-Term Monitoring
Annual minimum assessment including weight, blood pressure, serum electrolytes, and overall health status 1
Screen for autoimmune disorders annually, particularly hypothyroidism with TSH and TPO antibodies, as autoimmune adrenal disease clusters with other autoimmune conditions 1
Monitor bone mineral density every 3-5 years to detect glucocorticoid-induced osteoporosis early 1
Critical Pitfalls to Avoid
Never proceed with adrenal vein sampling or surgery without excluding pheochromocytoma, as catecholamine release during manipulation can be fatal 1, 3
Do not perform bilateral adrenalectomy for primary aldosteronism from bilateral hyperplasia, as medical management is equally effective without causing permanent adrenal insufficiency 1
Ensure proper patient education on stress-dose steroids post-adrenalectomy, as failure to increase glucocorticoid dosing during illness is a common cause of preventable adrenal crisis 1
Distinguish between micronodular and macronodular disease on imaging, as this affects surgical approach and genetic counseling 5, 7