Adrenal Hyperplasia Management

Diagnostic Approach and Treatment

• The National Comprehensive Cancer Network recommends surgical intervention (laparoscopic adrenalectomy) for unilateral adenomas and medical management with mineralocorticoid antagonists or hormone replacement for bilateral hyperplasia 1, 2
• Diagnostic approach for primary aldosteronism includes measuring plasma aldosterone and renin activity, with a plasma aldosterone-to-renin ratio >30 suggesting primary hyperaldosteronism 3
• Adrenal vein sampling is considered the gold standard for distinguishing between unilateral adenoma and bilateral hyperplasia in surgical candidates 1, 2
• For unilateral adenoma: Laparoscopic adrenalectomy is the treatment of choice 1, 2
• For bilateral adrenal hyperplasia: Medical management with spironolactone or eplerenone is recommended to control hypertension and hypokalemia 1, 4

Medical Management

• Medical management of hypercortisolism includes adrenostatic agents such as ketoconazole (400-1200 mg/day) and mitotane 2, 5
• Octreotide can be considered for ectopic Cushing syndrome if the tumor is Octreoscan-positive 5
• Glucocorticoid replacement: Hydrocortisone is the drug of choice at 15-25 mg daily in split doses for adults 6, 7
• Mineralocorticoid replacement: Most patients with primary adrenal insufficiency should take 50-200 μg fludrocortisone as a single daily dose 6, 7

Management of Adrenal Crisis

• Adrenal crisis should be treated immediately with IV or IM hydrocortisone, 100 mg followed by 100 mg every 6-8 hours until recovered 6, 8
• Isotonic (0.9%) sodium chloride solution should be administered at an initial rate of 1 L/hour until hemodynamic improvement 8

Follow-up and Monitoring

• Patients with adrenal hyperplasia should be reviewed at least annually 6, 7
• Assessment should include health and well-being, weight, blood pressure, and serum electrolytes 6, 7
• Monitoring for the development of new autoimmune disorders, particularly hypothyroidism, is recommended 6, 7
• Assessment for complications of glucocorticoid therapy should include monitoring of bone mineral density every 3-5 years 6, 7

Common Pitfalls and Caveats

• CT imaging alone is not always reliable for distinguishing between unilateral adenoma and bilateral hyperplasia, with reports suggesting 25% of patients would have had unnecessary adrenalectomy based on CT findings alone 4
• Postoperative corticosteroid supplementation is required after adrenalectomy until recovery of the hypothalamus-pituitary-adrenal axis 2, 5
• All patients with adrenal insufficiency should wear medical alert identification and carry a steroid alert card 6, 7

Adrenal Vein Sampling for Primary Aldosteronism Diagnosis

Pre-Procedure Preparation

• The American College of Cardiology and other guideline societies recommend that adrenal vein sampling (AVS) is indicated after confirming primary aldosteronism diagnosis through positive aldosterone-to-renin ratio and confirmatory testing, with a ratio typically greater than 30 when aldosterone is in ng/dL and renin activity in ng/mL/h, and aldosterone levels of at least 10 ng/dL, in patients with hypertension and suspected primary aldosteronism 9, 10
• Mineralocorticoid receptor antagonists, such as spironolactone or eplerenone, must be withdrawn for at least 4 weeks before AVS testing to ensure accurate results, and serum potassium should be normalized and patients should have unrestricted salt intake prior to the procedure, according to the American Heart Association 10

Technical Procedure Steps

• The Endocrine Society recommends that cortisol measurement in the catheterization samples is used to confirm proper catheter placement, with the adrenal vein sample having significantly higher cortisol levels than the peripheral sample, to ensure accurate diagnosis and treatment of primary aldosteronism 11

Post-Procedure Management

• The American College of Cardiology recommends that if unilateral aldosterone production is documented, the patient should be referred for unilateral laparoscopic adrenalectomy, which can improve blood pressure in virtually 100% of patients and cure hypertension in approximately 50%, and if bilateral aldosterone secretion is confirmed, or if the patient cannot undergo surgery, medical management with spironolactone or eplerenone is the treatment of choice, with a high level of evidence supporting these recommendations 11, 10
• The guideline society recommends that AVS results should be used to alter clinical management in primary aldosteronism patients, with AVS results altering management in 35.7% of patients who would have been treated improperly based on imaging alone, highlighting the importance of AVS in diagnosis and treatment, with a moderate level of evidence supporting this recommendation 11, 10

Management of Non-Congenital Adrenal Hyperplasia

Medical Management Approach

• The Endocrine Society recommends monitoring for salt cravings or lightheadedness suggesting under-replacement, peripheral edema or hypertension suggesting over-replacement, and avoiding concurrent diuretics, NSAIDs, or liquorice which interact with fludrocortisone in patients with primary adrenal insufficiency requiring fludrocortisone 50-200 μg as a single daily dose 12
• Patients on glucocorticoid replacement must receive education on stress-dose adjustments, have access to emergency injectable hydrocortisone 100 mg for adrenal crisis, and wear medical alert identification and carry a steroid emergency card 12
• During surgery or severe illness, administer IV/IM hydrocortisone 100 mg immediately, then 100 mg every 6-8 hours until recovery, as recommended by the Journal of Internal Medicine 12

Monitoring Protocol

• The American Urological Association recommends laboratory monitoring of serum electrolytes, morning 17-hydroxyprogesterone, testosterone, androstenedione in patients with non-congenital adrenal hyperplasia 13

Special Populations

• The Endocrine Society recommends increasing glucocorticoid requirements during pregnancy, typically requiring an additional 2.5-10 mg hydrocortisone daily in the third trimester, and adjusting fludrocortisone dose due to progesterone's anti-mineralocorticoid effects 12
• During delivery, give 100 mg IV hydrocortisone bolus, repeated every 6 hours as needed, as recommended by the Journal of Internal Medicine 12

Guideline Recommendations for Bilateral Primary Hyperaldosteronism

First‑Line Medical Therapy

• The American College of Cardiology recommends that patients with bilateral adrenal hyperplasia confirmed by adrenal vein sampling be treated with mineralocorticoid receptor antagonists (spironolactone or eplerenone) as the therapy of choice because surgery is not indicated for bilateral disease. 14

Alternative Agent for Intolerance

• The American College of Cardiology suggests using eplerenone 50–100 mg daily as an alternative to spironolactone when patients experience anti‑androgenic side effects such as gynecomastia. 14

Pre‑Procedure Preparation for AVS

• The American College of Cardiology advises discontinuing mineralocorticoid receptor antagonists at least four weeks before adrenal vein sampling to avoid pharmacologic interference with lateralization assessment. 14
• The American College of Cardiology recommends normalizing serum potassium and permitting unrestricted dietary salt intake prior to adrenal vein sampling to ensure accurate cortisol measurements. 14

Surgical vs. Medical Outcomes

• The American College of Cardiology notes that unilateral adrenalectomy improves blood pressure in virtually 100 % of patients with unilateral disease and cures hypertension in approximately 50 % of those patients, highlighting the importance of distinguishing unilateral from bilateral disease. 14

Cardiovascular Benefits of Medical Management

• The American College of Cardiology reports that long‑term medical therapy with mineralocorticoid receptor antagonists in bilateral disease effectively lowers blood pressure and can reverse left ventricular hypertrophy. 14

Localization and Management of Aldosterone‑Producing Adenomas

Diagnostic Imaging

• Initial anatomic assessment should begin with CT or MRI of the adrenal glands to identify possible lesions, recognizing that imaging alone cannot definitively determine functional status. European Society of Cardiology (ESC) guidance notes this as the first step. 15, 16
• CT imaging alone is unreliable because non‑functioning adenomas and nodular hyperplasia are common, producing false‑positive results; therefore, imaging findings must be confirmed with functional testing. ESC guidance emphasizes this limitation. 15, 16
• In patients younger than 40 years with a unilateral adrenal mass larger than 1 cm and no contralateral abnormality, some NCCN centers consider proceeding directly to surgery, although this practice remains controversial and institution‑dependent. National Comprehensive Cancer Network (NCCN) recommendations reflect this conditional approach. 17

Adrenal Venous Sampling (AVS)

• AVS is the gold‑standard test for distinguishing unilateral aldosterone‑producing adenomas from bilateral hyperplasia and should be performed in all surgical candidates; reliance on CT alone leads to unnecessary adrenalectomy in roughly 25 % of cases. NCCN designates AVS as essential for accurate lateralization. 17, 15, 16
• During AVS, simultaneous bilateral catheterization with measurement of aldosterone and cortisol is required to verify correct catheter placement and to calculate lateralization ratios. NCCN specifies this sampling protocol. 17

Treatment Based on Localization

Unilateral Aldosterone Production (Adenoma)

• Laparoscopic adrenalectomy is the treatment of choice for confirmed unilateral aldosterone‑producing adenomas. NCCN and ESC endorse minimally invasive surgery as first‑line therapy. 17, 15, 16
• Surgical series report zero peri‑operative mortality, minimal morbidity, and an average hospital stay of approximately 2.6 days following laparoscopic adrenalectomy. ESC outcome data support the safety profile of this approach. 15, 16

Bilateral Aldosterone Production (Hyperplasia)

• Lifelong medical management with mineralocorticoid‑receptor antagonists (spironolactone or eplerenone) is recommended for bilateral adrenal hyperplasia to control hypertension and correct hypokalemia. NCCN and ESC guidelines favor this pharmacologic strategy. 17, 15, 16

Critical Pitfalls

• Do not base surgical decisions solely on CT imaging, as up to one‑quarter of patients would undergo unnecessary adrenalectomy without AVS confirmation. ESC highlights the risk of imaging‑only strategies. 15, 16
• Recognize that adrenal adenomas identified on imaging may be non‑functioning, with concurrent nodular hyperplasia of the zona glomerulosa potentially present. ESC advises correlation with functional testing to avoid misclassification. 15, 16

Special Considerations

• For patients younger than 40 years with a clear unilateral adrenal mass on CT and no contralateral abnormality, some NCCN institutions consider omitting AVS, though this decision should be individualized and discussed within a multidisciplinary team. NCCN provides this conditional recommendation. 17

All statements are derived from guideline societies (NCCN, ESC) and reflect the evidence cited in the referenced literature; specific levels of evidence were not detailed in the source material.