How should an incidentally discovered enlarged adrenal gland be evaluated and managed?

Evaluation of an Incidentally Discovered Enlarged Adrenal Gland

All patients with an incidentally discovered enlarged adrenal gland require both hormonal evaluation (regardless of size or imaging characteristics) and imaging characterization to exclude malignancy, with the 1 mg dexamethasone suppression test (DST) being mandatory for everyone. 1

Algorithmic Approach to Evaluation

Step 1: Obtain Proper Imaging Characterization

Imaging priority:

• Non-contrast CT is the gold standard for initial characterization 2
• Measure Hounsfield Units (HU) on non-contrast CT:
  • <10 HU = benign adenoma (0% malignancy risk) 3
  • 10-20 HU = indeterminate (0.5% malignancy risk) 3
  • >20 HU = suspicious (6.3% malignancy risk) 3
• If HU ≥10 or non-contrast CT unavailable, obtain contrast-enhanced CT with washout protocol or MRI 2

Size matters for malignancy risk:

• <4 cm: 7% malignancy risk
• 4-6 cm: 6% malignancy risk
• >6 cm: >25% malignancy risk 2

Step 2: Mandatory Hormonal Screening (ALL Patients)

Universal screening (everyone gets this):

1. 1 mg DST for autonomous cortisol secretion 1
   • Give 1 mg dexamethasone at 11 PM
   • Measure serum cortisol at 8 AM
   • <50 nmol/L = excludes hypersecretion
   • 51-138 nmol/L = possible autonomous cortisol secretion (MACS)
   • >138 nmol/L = evidence of cortisol hypersecretion
   • If abnormal, confirm ACTH independency with plasma ACTH

Conditional screening based on clinical features:

1. Aldosterone/renin ratio (ARR) if hypertension and/or hypokalemia present 1

   • Test in morning after 2 hours upright, seated 5-15 minutes
   • Ensure potassium-replete
   • ARR >20 ng/dL per ng/mL/hr = >90% sensitivity/specificity for hyperaldosteronism 1

2. Plasma free metanephrines if HU ≥10 OR signs/symptoms of catecholamine excess 1

   • Look for: headaches, anxiety attacks, sweating, palpitations, severe hypertension, tachycardia
   • >2X upper limit of normal = positive 1

3. DHEAS and testosterone if suspected adrenocortical carcinoma (ACC) or virilization 1

   • Consider if: flank pain, weight loss, hirsutism, virilization, feminization

Step 3: Targeted History and Physical Examination

Look specifically for these clinical syndromes:

Hypercortisolism: Weight gain, central obesity, easy bruising, severe hypertension, diabetes, proximal muscle weakness, purple striae >1 cm wide, facial plethora, dorsocervical fat pad 1

Primary aldosteronism: Hypertension with hypokalemia, muscle cramping/weakness, headaches 1

Pheochromocytoma: Episodic headaches, sweating, palpitations, severe/paroxysmal hypertension, family history of von Hippel-Lindau, MEN2, paraganglioma syndrome, neurofibromatosis type 1 1

ACC: Flank pain, rapid virilization, weight loss, hirsutism, gynecomastia 1

Metastasis: Personal/family history of malignancy, weight loss, unexplained fevers, smoking history, lymphadenopathy 1

Step 4: Determine Management Based on Results

Immediate surgical referral if:

• Functional tumor (any hormone excess)
• Size >4 cm with indeterminate imaging features 2
• Any concerning features for ACC
• Growth ≥5 mm with >20% increase in maximum diameter 2
• Growth rate >0.8 cm/year 3

Follow-up imaging at 6-12 months if:

• Indeterminate lesion (HU 10-20 or indeterminate on contrast washout)
• Size <4 cm with benign imaging but patient <40 years old 2
• Non-functional lesion with benign features but size approaching 4 cm

No further imaging if:

• HU <10 on non-contrast CT
• Non-functional
• Stable for 12 months 2

Critical Pitfalls to Avoid

Never skip pheochromocytoma screening before surgery if HU ≥10 or imaging unavailable—operating on undiagnosed pheochromocytoma can cause hypertensive crisis and death 1

Don't assume non-functional based on lack of symptoms—up to 30-50% have mild autonomous cortisol secretion (MACS) without overt Cushing's features, which increases cardiovascular morbidity, diabetes, hypertension, and fracture risk 3, 4

Young patients (<40 years) and pregnant patients require urgent MRI and more aggressive evaluation due to higher malignancy risk—consider surgery for anything not characteristically benign 2

Growth assessment requires proper comparison—benign adenomas can grow <3 mm/year, but growth ≥8 mm in 12 months warrants investigation 2

All patients require multidisciplinary discussion if they have hormone excess, indeterminate lesions, interval growth, or are being considered for surgery 2