What is the first line of treatment for a patient with bilateral adrenal tumors secreting cortisol?

First-Line Treatment for Bilateral Adrenal Tumors Secreting Cortisol

The first-line approach depends on disease severity: bilateral adrenalectomy is reserved exclusively for severe, refractory Cushing's syndrome with life-threatening complications requiring rapid cortisol normalization, while unilateral adrenalectomy (of the dominant side) is preferred for most other cases of autonomous cortisol secretion with bilateral masses. 1

Initial Diagnostic Workup Required

Before determining surgical approach, you must establish:

• Confirm autonomous cortisol secretion using 1 mg overnight dexamethasone suppression test (cortisol >138 nmol/L or >5.0 mg/dL indicates autonomy) 1
• Measure ACTH levels to confirm ACTH-independent hypercortisolism (ACTH should be low or undetectable) 1
• Exclude congenital adrenal hyperplasia by measuring 17-hydroxyprogesterone levels in all patients with bilateral adrenal masses 1
• Screen for pheochromocytoma with plasma free metanephrines or 24-hour urinary fractionated metanephrines 1
• Perform adrenal venous sampling (AVS) to determine lateralization of cortisol secretion, as imaging findings do not reliably predict functional laterality 2, 3

Critical Decision Point: Assess Disease Severity

Indications for Bilateral Adrenalectomy (Rare)

Bilateral adrenalectomy should only be performed when severe, refractory Cushing's syndrome with life-threatening complications is present. 1 Specific indications include:

• Presence of severe end-organ damage such as left ventricular hypertrophy AND cirrhosis 4
• Life-threatening emergencies requiring immediate and definitive control of hypercortisolism 4
• Severe complications requiring rapid cortisol normalization 5

The European Society of Endocrinology explicitly recommends against bilateral adrenalectomy for asymptomatic cortisol-secreting adenomas due to the burden of lifelong steroid dependency. 1

Preferred First-Line Approach: Unilateral Adrenalectomy

For most patients with bilateral adrenal masses and autonomous cortisol secretion, unilateral adrenalectomy of the dominant side is the preferred first-line surgical approach. 1, 6

When to Pursue Unilateral Adrenalectomy

Unilateral adrenalectomy should be considered when autonomous cortisol secretion is present with cortisol-related comorbidities (hypertension, diabetes, osteoporosis) that are potentially reversible with surgery. 1

Using AVS to Guide Unilateral Surgery

AVS demonstrates high specificity for determining laterality 2, 3:

• Unilateral disease criteria: AV/IVC cortisol ratio >9 for one side, <2.0 for the opposite side, and cortisol lateralization ratio (CLR) >2.3 (specificity 95-100%) 2
• Bilateral disease criteria: AV/IVC cortisol ratio >5.1 bilaterally and CLR <1.1 (specificity 80-90%) 2
• AVS success rate is approximately 85% 3

Among patients with bilateral adrenal masses on imaging, 55% (11/20) actually had unilateral cortisol overproduction on AVS, making this test essential for surgical planning. 3

Benefits of Unilateral Over Bilateral Approach

• Avoids lifelong steroid dependency that is mandatory after bilateral adrenalectomy 1
• Improves hypertension in 66.3% of patients 7
• Reduces BMI in 47.4% of patients 7
• Improves hyperlipidemia in 63.2% of patients 7
• Reduces cardiovascular risk more effectively than medical therapy 7

Surgical Technique

Laparoscopic adrenalectomy is the preferred modality for contained masses. 1

Post-Operative Management Differs by Approach

After Unilateral Adrenalectomy

• Temporary corticosteroid supplementation is typically required as the contralateral gland recovers 1
• Monitor for recovery of the hypothalamic-pituitary-adrenal axis 4

After Bilateral Adrenalectomy (If Performed)

• Lifelong glucocorticoid and mineralocorticoid replacement therapy is mandatory 1
• Regular MRI monitoring of the pituitary is required to screen for Nelson syndrome (risk appears higher in younger patients) 1
• Close monitoring for adrenal insufficiency is essential 1

Medical Therapy: Not First-Line

Medical therapy with steroidogenesis inhibitors is not an established first-line approach but may be considered when control of hypercortisolism is desired but surgery is not an option 6. If the pituitary tumor is unresectable in Cushing's disease, medical management with adrenostatic agents may be necessary 4.

Critical Pitfall to Avoid

Do not assume bilateral imaging findings indicate bilateral cortisol secretion—AVS frequently reveals unilateral hypersecretion despite bilateral masses, fundamentally changing surgical management. 3 Additionally, patients with bilateral adrenal tumors and autonomous cortisol secretion have a 73% prevalence of extra-adrenal malignancies, warranting cancer screening 8.