What is the appropriate management for a patient with a lipid laden adrenal adenoma, potentially causing hormonal imbalances?

Management of Lipid-Laden Adrenal Adenoma

Initial Assessment

All patients with a lipid-laden adrenal adenoma require comprehensive hormonal evaluation regardless of symptoms, as hormonal activity occurs in up to 17% of adrenal incidentalomas and can significantly impact morbidity and mortality. 1

Mandatory Hormonal Screening

Every patient must undergo the following tests to exclude hormone excess 1:

• 1-mg overnight dexamethasone suppression test (DST) with a cutoff of serum cortisol ≤50 nmol/L (≤1.8 µg/dL) to exclude mild autonomous cortisol secretion (MACS) or overt Cushing syndrome 1
• Plasma or urinary fractionated metanephrines to exclude pheochromocytoma, as failure to identify catecholamine-secreting tumors can result in life-threatening intraoperative complications 2, 1
• Plasma aldosterone and renin activity if hypertension or hypokalemia is present, with a ratio >30 suggesting primary aldosteronism 3
• Serum DHEAS and testosterone if clinical signs of hyperandrogenism are present (hirsutism, virilization, menstrual irregularities) 4, 5

Imaging Characterization

Lipid-laden adenomas with homogeneous appearance and ≤10 Hounsfield units (HU) on unenhanced CT are definitively benign and require no additional imaging independent of size. 1

• Lesions with these characteristics have essentially zero malignancy risk and can be managed conservatively 1
• If the lesion has HU >10 or inhomogeneous features, further characterization with contrast-enhanced CT washout or MRI chemical shift imaging is warranted 1

Management Based on Hormonal Status

Non-Functioning Adenomas (<10 HU, No Hormone Excess)

For asymptomatic, hormonally inactive lipid-rich adenomas, surgery is not indicated regardless of size. 1

Follow-up protocol:

• Repeat unenhanced CT at 12 months to assess stability 6
• Annual hormonal screening (DST and metanephrines) for 4 years, as new-onset hormone secretion occurs in 17% at 1 year, 29% at 2 years, and 47% at 5 years 6
• If growth >1 cm occurs during follow-up, surgical resection should be recommended 7
• After demonstrating stability at 1 year with no hormonal changes over 4 years, further surveillance can be discontinued 6

Mild Autonomous Cortisol Secretion (MACS)

Patients with post-DST cortisol >50 nmol/L (>1.8 µg/dL) without overt Cushing syndrome features have MACS and harbor increased risk of cardiovascular morbidity and mortality. 1

Management approach:

• Screen for and aggressively treat cortisol-related comorbidities including hypertension, type 2 diabetes, dyslipidemia, and osteoporosis 1
• Consider adrenalectomy in patients with MACS who have relevant comorbidities that are potentially attributable to cortisol excess, particularly if comorbidities are difficult to control medically 1
• Laparoscopic adrenalectomy is the preferred surgical approach for lesions <6 cm without features of malignancy 6

Overt Hormone Excess

Any adenoma causing overt Cushing syndrome, pheochromocytoma, primary aldosteronism, or virilization requires surgical resection. 6, 1

Preoperative management:

• For pheochromocytoma: 10-14 days of alpha-blockade (or calcium channel blockers) to prevent intraoperative hypertensive crisis 6
• For Cushing syndrome: optimize blood pressure, glucose control, and consider prophylactic antibiotics given immunosuppression 6
• For primary aldosteronism: adrenal vein sampling is mandatory before surgery to confirm lateralization and prevent inappropriate adrenalectomy 8, 3

Surgical approach:

• Laparoscopic adrenalectomy is standard for benign-appearing lesions <6 cm 6, 1
• Open adrenalectomy is recommended for lesions >6 cm or those with imaging features concerning for malignancy 6

Size-Based Considerations

While lipid-rich adenomas are benign regardless of size, lesions >4 cm warrant multidisciplinary discussion, and those >6 cm have substantially higher malignancy risk (37.7%) if they lack typical benign features. 4

• For lipid-laden adenomas with classic benign imaging (≤10 HU), size alone does not mandate surgery 1
• However, if imaging is atypical or the lesion is inhomogeneous despite lipid content, size >4 cm increases concern for malignancy 1

Critical Pitfalls to Avoid

• Never proceed to surgery without excluding pheochromocytoma, as undiagnosed catecholamine excess can cause fatal intraoperative complications 2, 1
• Do not assume hormonal inactivity based on lack of symptoms—subclinical hypercortisolemia is the most common hormonal abnormality and carries significant morbidity 9, 4
• Avoid biopsy of potentially resectable adrenal masses, as it is rarely informative and risks tumor dissemination 6
• Do not discontinue follow-up prematurely—malignant transformation is rare but possible, and new hormone secretion develops in nearly half of patients by 5 years 6, 7