What is the initial diagnostic workup and treatment approach for unilateral adrenal issues, such as adenoma or pheochromocytoma?

Diagnostic Workup and Treatment Approach for Unilateral Adrenal Issues

The initial diagnostic workup for unilateral adrenal issues should include both morphologic and functional evaluation with adrenal protocol CT or MRI, followed by comprehensive hormone testing to rule out functional tumors, with treatment determined by tumor functionality and malignancy potential. 1

Initial Diagnostic Workup

Imaging Evaluation

• First-line imaging: Non-contrast CT scan to determine size, heterogeneity, lipid content, and margin characteristics 1

  • Benign lesions typically have <10 Hounsfield Units (HU) on non-contrast CT
  • If >10 HU or indeterminate, proceed with contrast-enhanced CT with washout analysis

    • 60% washout at 15 minutes suggests benign lesion

    • <60% washout suggests possible malignancy 2

• Second-line imaging (if first-line is indeterminate):

  • Washout CT or chemical-shift MRI 1
  • MRI preferred for pregnant women, children, and patients <40 years 1

Functional Evaluation

All patients with unilateral adrenal masses should undergo functional testing:

1. Cortisol secretion (all patients):

   • 1 mg overnight dexamethasone suppression test (preferred) 1
   • Serum ACTH, cortisol, and DHEA-S 1
   • Interpretation:
     • <50 nmol/L (1.8 μg/dL): Normal
     • 51-138 nmol/L (1.9-5.0 μg/dL): Possible autonomous cortisol secretion

     • 138 nmol/L (>5.0 μg/dL): Autonomous cortisol secretion 1

2. Aldosterone secretion (for patients with hypertension and/or hypokalemia):

   • Aldosterone-to-renin ratio 1
   • If elevated, confirm with saline challenge test 1

3. Catecholamine secretion (for masses with >10 HU or signs of adrenergic excess):

   • Plasma free metanephrines or 24-hour urinary metanephrines 1
   • Note: Should be ruled out before any biopsy procedure 1

4. Androgen excess (if suspected adrenocortical carcinoma or virilization):

   • Serum DHEA-S, testosterone 1
   • Additional tests: 17β-estradiol, 17-OH progesterone, androstenedione 1

Treatment Approach

For Functional Tumors

1. Cortisol-secreting adenomas:

   • For overt Cushing's syndrome: Unilateral adrenalectomy (minimally invasive when feasible) 1
   • For mild autonomous cortisol secretion: Consider adrenalectomy in younger patients with progressive metabolic comorbidities; otherwise, annual monitoring 1

2. Aldosterone-secreting adenomas:

   • Confirm unilateral production with adrenal vein sampling before surgery 1
   • Treatment: Laparoscopic adrenalectomy 1
   • If surgery not possible: Medical management with mineralocorticoid receptor antagonists 1

3. Pheochromocytomas:

   • Preoperative preparation: Alpha-blocker therapy for 1-3 weeks (add beta-blockers only after adequate alpha blockade) 1
   • Consider metyrosine to inhibit catecholamine synthesis in selected cases 3
   • Treatment: Minimally invasive adrenalectomy 1

For Non-functional Tumors

1. Benign-appearing adenomas <4 cm:

   • No further follow-up required 1

2. Non-functional adenomas ≥4 cm but radiologically benign (<10 HU):

   • Repeat imaging in 6-12 months 1
   • If growth >5 mm/year: Consider adrenalectomy after repeating functional workup 1
   • If growth <3 mm/year: No further imaging or testing needed 1

3. Indeterminate non-functional lesions:

   • Management options: Repeat imaging in 3-6 months vs. surgical resection 1
   • Decision based on shared decision-making with patient 1

4. Suspected adrenocortical carcinoma:

   • For smaller, contained tumors: Minimally invasive adrenalectomy if safe without capsule rupture 1
   • For larger (>6 cm) or locally advanced tumors: Open adrenalectomy 1
   • Complete imaging of chest, abdomen, and pelvis to evaluate for metastases 1

Special Considerations

• Adrenal biopsy: Generally not recommended for routine workup of adrenal incidentalomas 1

  • Consider only if metastasis is suspected and pheochromocytoma has been ruled out 4

• Multidisciplinary review: Recommended when imaging is not consistent with benign lesion, there is evidence of hormone hypersecretion, significant tumor growth, or when surgery is being considered 1

• Young patients (<40 years): Require urgent assessment due to higher risk of malignancy 1

• Bilateral adrenal masses: Each lesion should be evaluated individually; consider measuring 17-hydroxyprogesterone to rule out congenital adrenal hyperplasia 1

By following this systematic approach to diagnosis and treatment of unilateral adrenal issues, clinicians can optimize patient outcomes while minimizing unnecessary procedures and follow-up.