What is the appropriate next workup for a patient with a 1.6 cm adrenal adenoma presenting with weight gain and fatigue?

Workup for 1.6 cm Adrenal Adenoma with Weight Gain and Fatigue

All patients with adrenal incidentalomas ≥1 cm require comprehensive biochemical screening for hormone excess regardless of imaging characteristics, and this patient's symptoms of weight gain and fatigue are concerning for autonomous cortisol secretion. 1, 2

Mandatory Initial Hormonal Testing

Perform a 1 mg overnight dexamethasone suppression test immediately - this is the preferred screening test for autonomous cortisol secretion. 1, 3 The patient takes 1 mg dexamethasone at 11 PM, and serum cortisol is measured at 8 AM the next morning. 2, 3

Interpretation of Dexamethasone Suppression Test:

• ≤50 nmol/L (1.8 μg/dL): Excludes autonomous cortisol secretion 2, 3
• 51-138 nmol/L (1.9-5.0 μg/dL): Possible autonomous cortisol secretion 2, 3
• >138 nmol/L (>5.0 μg/dL): Evidence of autonomous cortisol secretion 2, 3

This test is critical because weight gain, central obesity, and fatigue are classic manifestations of cortisol excess, even in subclinical cases. 2 Approximately 5.3% of adrenal incidentalomas are cortisol-secreting adenomas. 3

Additional Required Screening Tests

Pheochromocytoma Screening

Screen for pheochromocytoma ONLY if the mass measures >10 HU on non-contrast CT or if symptoms of catecholamine excess are present (episodic hypertension, headaches, palpitations, diaphoresis, anxiety, tremor, pallor). 1, 2, 3

• If screening is indicated, measure plasma free metanephrines or 24-hour urinary fractionated metanephrines. 1, 2, 3
• Do NOT screen if the mass is confirmed as an adrenocortical adenoma with <10 HU on non-contrast CT and no adrenergic symptoms. 1

Primary Aldosteronism Screening

Measure aldosterone-to-renin ratio if the patient has hypertension or hypokalemia. 1, 2, 3 A ratio >20 ng/dL per ng/mL/hr indicates primary aldosteronism. 2, 3

Androgen Testing

Perform serum androgen testing (DHEAS, testosterone, 17-hydroxyprogesterone, androstenedione) ONLY if there are clinical signs of virilization (hirsutism, deepening voice, clitoromegaly) or if adrenocortical carcinoma is suspected. 1, 2, 3 This is not routinely indicated for a 1.6 cm mass without virilization symptoms. 3

Imaging Confirmation

Obtain non-contrast CT of the adrenals if not already performed - this is the mandatory first-line imaging modality. 2, 3

• ≤10 HU: Confirms benign adenoma with essentially 0% malignancy risk 2
• >10 HU: Requires second-line imaging with washout CT or chemical-shift MRI 1, 2

At 1.6 cm, this mass is well below the 4 cm threshold where size alone raises concern. 1 In patients without known malignancy, lesions <3 cm have a malignancy rate of only 1.5%. 1

Clinical Examination Targets

Focus the physical examination on specific signs of cortisol excess that correlate with the patient's symptoms:

• Central obesity, moon facies, buffalo hump 2
• Purple striae, easy bruising, thin skin 2
• Proximal muscle weakness (ask patient to rise from chair without using arms) 2
• Blood pressure elevation 2
• Signs of glucose intolerance or diabetes 2

Critical Pitfalls to Avoid

Do not skip hormonal screening based on imaging characteristics alone - even radiologically benign-appearing adenomas can be hormonally active. 1, 2 Approximately 12-23% of incidentalomas show subclinical hormone secretion. 1

Hold interfering medications before testing when possible: estrogen and rifampin can affect cortisol testing; beta-blockers, ACE inhibitors, and ARBs can affect aldosterone/renin ratio; tricyclic antidepressants and decongestants can affect metanephrine testing. 2, 3

Do not perform adrenal biopsy - it is rarely indicated and should only be considered if metastatic disease from a known extra-adrenal malignancy would change management, and only after pheochromocytoma has been excluded. 1, 2, 3

Management Based on Results

If Autonomous Cortisol Secretion is Confirmed:

Younger patients with mild autonomous cortisol secretion who have progressive metabolic comorbidities (weight gain, hypertension, diabetes) attributable to cortisol excess should be considered for adrenalectomy after shared decision-making. 1 Minimally invasive surgery should be performed when feasible. 1

If Non-Functional and Benign-Appearing:

No further follow-up imaging or functional testing is required for benign non-functional adenomas <4 cm with ≤10 HU on CT. 1, 3

When to Involve Multidisciplinary Team

Obtain immediate consultation with endocrinology if:

• Evidence of hormone hypersecretion is confirmed 2, 3
• Imaging is not consistent with a benign lesion 2, 3
• Adrenal surgery is being considered 2, 3