What is the treatment for bilateral adrenal hyperplasia?

Treatment of Bilateral Adrenal Hyperplasia

The treatment of bilateral adrenal hyperplasia depends critically on the underlying etiology: for primary aldosteronism (idiopathic hyperaldosteronism), medical management with mineralocorticoid receptor antagonists is first-line therapy; for congenital adrenal hyperplasia, glucocorticoid and mineralocorticoid replacement is standard; and for Cushing's disease causing bilateral hyperplasia, treating the pituitary source is primary, with bilateral adrenalectomy reserved for severe, refractory cases. 1, 2, 3

Initial Diagnostic Workup

Before initiating treatment, you must determine the specific cause of bilateral adrenal hyperplasia:

• Screen for congenital adrenal hyperplasia by measuring 17-hydroxyprogesterone levels in all patients presenting with bilateral adrenal masses 4
• Assess for primary aldosteronism with plasma aldosterone concentration, plasma renin activity, and aldosterone-to-renin ratio (typically >30 in Conn syndrome) 5
• Evaluate for Cushing's disease by measuring ACTH levels—elevated ACTH indicates pituitary or ectopic sources driving adrenal hyperplasia rather than primary adrenal pathology 1
• Rule out metastatic disease if the patient has a known malignancy elsewhere, as this would fundamentally change management 4

Treatment Algorithm by Etiology

Primary Aldosteronism (Bilateral Adrenal Hyperplasia/Idiopathic Hyperaldosteronism)

Medical management is the definitive treatment for bilateral disease:

• Start spironolactone at 12.5-25 mg daily and titrate up to 100 mg daily as first-line therapy, monitoring serum potassium and creatinine closely during initiation 2, 3
• Alternative: eplerenone 50-100 mg daily if spironolactone side effects (gynecomastia, sexual dysfunction) are problematic 3
• Add potassium-sparing diuretics (amiloride or triamterene) or calcium channel antagonists if blood pressure remains uncontrolled despite maximum mineralocorticoid receptor antagonist dosing 3
• Long-term maintenance therapy with mineralocorticoid receptor antagonists is indicated for patients with bilateral micro- or macronodular adrenal hyperplasia 2

Important caveat: Rarely, a focal hyperplastic nodule can become autonomous over time and behave like an adenoma—monitor patients for recurrence of symptoms despite adequate medical therapy, as selective adrenal venous sampling may reveal lateralization requiring unilateral adrenalectomy 6

Bilateral Adrenalectomy for Refractory Cases

Bilateral adrenalectomy should be considered only when:

• Medical therapy fails despite maximum doses of spironolactone (100 mg daily) and additional antihypertensives, with persistent severe hypertension and hypokalemia 7
• Severe complications are present requiring rapid cortisol normalization (in Cushing's disease context with end-organ damage like left ventricular hypertrophy or cirrhosis) 1

Post-adrenalectomy requirements:

• Lifelong glucocorticoid and mineralocorticoid replacement is mandatory following bilateral adrenalectomy 1, 8
• Monitor for Nelson syndrome with regular pituitary MRI imaging, particularly in younger patients who face higher risk 1
• Close monitoring for adrenal insufficiency is essential in the immediate postoperative period 1

Congenital Adrenal Hyperplasia (21-Hydroxylase Deficiency)

Standard medical therapy:

• Glucocorticoid replacement to suppress excessive ACTH and adrenal androgen production is the cornerstone of treatment 8
• Mineralocorticoid replacement for salt-wasting forms 8

Bilateral laparoscopic adrenalectomy may be considered in highly selected cases:

• Adult females with classic, salt-wasting CAH and poor hormonal control despite optimal medical management 8
• Persistent hyperandrogenism causing hirsutism, acne, amenorrhea, or infertility despite maximum medical therapy 8
• Post-adrenalectomy: Glucocorticoid and mineralocorticoid replacement doses are typically lower than preoperative medical therapy, though adrenal rest tissue may eventually require dose increases 8

Cushing's Disease with Bilateral Adrenal Hyperplasia

The primary treatment targets the pituitary source:

• Transsphenoidal resection of the pituitary adenoma is the definitive treatment, which addresses the root cause of adrenal hyperplasia 1
• Medical management with adrenostatic agents if the pituitary tumor is unresectable 1
• Bilateral adrenalectomy is reserved for severe, refractory Cushing's disease or life-threatening emergencies requiring immediate cortisol control 1
• Following successful pituitary treatment, monitor for recovery of the hypothalamic-pituitary-adrenal axis, as temporary corticosteroid supplementation is typically required 1

Common Pitfalls to Avoid

• Do not perform bilateral adrenalectomy for primary aldosteronism without first attempting adequate medical therapy—two-thirds of primary aldosteronism cases are bilateral hyperplasia requiring medical rather than surgical management 3, 9
• Do not assume all bilateral adrenal hyperplasia is the same etiology—failure to screen for congenital adrenal hyperplasia with 17-hydroxyprogesterone can lead to inappropriate treatment 4
• Do not overlook the possibility of unilateral autonomous function developing within bilateral hyperplasia—if symptoms recur despite adequate medical therapy, repeat adrenal venous sampling may reveal lateralization amenable to unilateral adrenalectomy 6
• Do not forget lifelong hormone replacement counseling before bilateral adrenalectomy—patients must understand the permanent need for glucocorticoid and mineralocorticoid replacement and the risk of adrenal crisis 1, 8