What is the management of a patient with bilateral adrenal tumors secreting cortisol?

Management of Bilateral Adrenal Tumors Secreting Cortisol

Bilateral adrenal tumors secreting cortisol should be managed with individualized surgical intervention based on the degree of cortisol excess and presence of severe complications, with bilateral adrenalectomy reserved for life-threatening hypercortisolism and unilateral adrenalectomy considered for selected cases to avoid lifelong adrenal insufficiency. 1, 2

Initial Diagnostic Workup

Confirm Autonomous Cortisol Secretion

• Perform 1 mg overnight dexamethasone suppression test as the initial screening test 1, 3
• Serum cortisol >138 nmol/L (>5.0 mg/dL) post-dexamethasone indicates autonomous cortisol secretion 1
• Measure ACTH levels to confirm ACTH-independent hypercortisolism (ACTH should be low or undetectable) 2, 4, 5
• Consider 24-hour urinary free cortisol and midnight cortisol to establish the degree of cortisol excess 4

Rule Out Congenital Adrenal Hyperplasia

• Measure 17-hydroxyprogesterone levels in all patients with bilateral adrenal masses to exclude congenital adrenal hyperplasia 1

Evaluate Each Mass Individually

• Perform imaging characterization separately for each lesion using unenhanced CT to assess for benign features (low Hounsfield units <10) 1
• Screen for pheochromocytoma with plasma free metanephrines or 24-hour urinary fractionated metanephrines 6
• Screen for primary aldosteronism if hypertension and hypokalemia are present 1

Consider Adrenal Venous Sampling

• Adrenal venous sampling (AVS) is essential when bilateral functional adenomas are suspected to lateralize hormone production 5, 7
• AVS can distinguish whether cortisol is being secreted predominantly from one side or bilaterally 5, 7

Screen for Cortisol-Related Comorbidities

All patients with autonomous cortisol secretion require screening for:

• Hypertension 1, 3
• Type 2 diabetes mellitus 1, 3
• Asymptomatic vertebral fractures/osteoporosis 1
• Left ventricular hypertrophy (echocardiogram if severe hypercortisolism suspected) 2

Surgical Decision Algorithm

Indications for Bilateral Adrenalectomy

Bilateral adrenalectomy should be performed when:

• Severe, refractory Cushing's syndrome with life-threatening complications (e.g., left ventricular hypertrophy, cirrhosis, severe metabolic derangements) requiring rapid cortisol normalization 2
• Overt and severe hypercortisolism that cannot be controlled medically 4

Critical caveat: ESE guidelines specifically recommend against bilateral adrenalectomy for asymptomatic cortisol-secreting adenomas due to the burden of lifelong steroid dependency 1

Indications for Unilateral Adrenalectomy

Unilateral adrenalectomy should be considered when:

• AVS demonstrates lateralization of cortisol production to one adrenal gland 4, 5
• Autonomous cortisol secretion is present with cortisol-related comorbidities (hypertension, diabetes, osteoporosis) that are potentially reversible with surgery 1, 3
• The patient has moderate hypercortisolism without life-threatening complications 4

Surgical approach: Laparoscopic adrenalectomy is the preferred modality for contained masses 1

Medical Management

Medical therapy with steroidogenesis inhibitors may be considered when:

• Surgery is not an option due to patient comorbidities or refusal 4
• Control of hypercortisolism is desired but bilateral adrenalectomy would result in unacceptable morbidity 4

Note: Medical therapy is not yet an established standard approach and long-term clinical benefits remain to be demonstrated 4

Post-Operative Management

After Bilateral Adrenalectomy

• Lifelong glucocorticoid and mineralocorticoid replacement therapy is mandatory 2
• Regular MRI monitoring of the pituitary is required to screen for Nelson syndrome (risk appears higher in younger patients) 2
• Close monitoring for adrenal insufficiency is essential 2

After Unilateral Adrenalectomy

• Monitor for recovery of the hypothalamic-pituitary-adrenal axis 2
• Temporary corticosteroid supplementation is typically required 2
• Reassess cortisol levels to ensure normalization 5
• Monitor for improvement in hypertension (improves in ~67% of cases) and diabetes mellitus (improves in ~60% of cases) 8

Special Considerations and Pitfalls

Screen for Extra-Adrenal Malignancy

• Patients with bilateral adrenal tumors and autonomous cortisol secretion have a high prevalence (73%) of extra-adrenal malignancies 8
• Consider screening for malignancy in various tissues, particularly if bilateral adrenal uptake is seen on functional imaging 8

Avoid Bilateral Adrenalectomy Unless Absolutely Necessary

• The burden of lifelong adrenal insufficiency, risk of adrenal crisis, and Nelson syndrome make bilateral adrenalectomy a last resort 1, 2
• Unilateral adrenalectomy may provide adequate control in selected patients with lateralized production 4, 5

Consider Partial Adrenalectomy in Rare Cases

• Partial adrenalectomy may be considered in rare genetic syndromes (e.g., bilateral pheochromocytomas) to preserve some adrenal function 1