What is the diagnostic and treatment approach for a patient presenting with symptoms suggestive of an adrenal mass?

Diagnostic and Treatment Approach for Adrenal Mass Symptoms

The diagnostic approach for patients with suspected adrenal masses requires comprehensive hormonal evaluation and dedicated adrenal imaging, followed by appropriate management based on functional status and malignancy risk. 1, 2

Clinical Presentation and Initial Evaluation

Key Symptoms by Adrenal Mass Type

• Hypercortisolism (Cushing's syndrome)

  • History: Weight gain, central obesity, easy bruising, severe hypertension, diabetes, proximal muscle weakness, fatigue, depression, sleep disturbances, menstrual irregularities, virilization, fragility fractures
  • Physical exam: Hypertension, central obesity, supraclavicular fat accumulation, dorsocervical fat pad, facial plethora, thinned skin, wide purple striae, acne, ecchymoses, hirsutism, proximal muscle weakness 1

• Primary Aldosteronism

  • History: Hypertension, hypokalemia, muscle cramping/weakness, headaches, intermittent paralysis
  • Physical exam: Hypertension, fluid retention 1

• Pheochromocytoma

  • History: Headaches, anxiety attacks, sweating, palpitations, family history of genetic syndromes (von Hippel-Lindau, MEN2, familial paraganglioma, neurofibromatosis)
  • Physical exam: Severe hypertension, tachycardia, arrhythmias, heart failure, excessive sweating, anxiety, pallor 1

• Adrenocortical Carcinoma

  • History: Flank pain, abdominal discomfort, hypercortisolism, virilization, feminization, aldosteronism
  • Physical exam: Weight loss, hirsutism, gynecomastia, signs of hypercortisolism 1

• Metastasis

  • History: Personal/family history of malignancy, weight loss, unexplained fevers, smoking history
  • Physical exam: Lymphadenopathy, lung/breast/renal masses, suspicious skin lesions 1

Diagnostic Algorithm

1. Hormonal Evaluation (Required for All Adrenal Masses)

• Cortisol Screening (All patients)

  • 1-mg overnight dexamethasone suppression test (DST) - preferred first-line test
    • ≤50 nmol/L (≤1.8 μg/dL): Excludes cortisol hypersecretion
    • 51-138 nmol/L: Possible autonomous cortisol secretion

    • 138 nmol/L: Evidence of cortisol hypersecretion 1, 2, 3

  • Additional testing if needed: Plasma ACTH, 24-hour urinary free cortisol, midnight salivary cortisol

• Catecholamine Screening (All patients)

  • Plasma free metanephrines or 24-hour urinary fractionated metanephrines
  • Values >2× upper limit of normal strongly suggest pheochromocytoma 1, 2, 4
  • Critical to exclude pheochromocytoma before any invasive procedure 2

• Aldosterone Screening (For patients with hypertension and/or hypokalemia)

  • Aldosterone-to-renin ratio (ARR)
  • ARR >20 ng/dL per ng/mL/hr has >90% sensitivity/specificity for hyperaldosteronism
  • Best performed in morning after patient has been up for 2 hours and seated 5-15 minutes
  • Patient should be potassium-replete with interfering medications substituted 1

• Androgen Evaluation (For suspected adrenocortical carcinoma or virilization)

  • DHEAS, testosterone
  • Higher levels suggest greater disease burden 1

2. Imaging Studies

• Non-contrast CT (First-line imaging)

  • Hounsfield Units (HU) assessment:
    • HU ≤10: Benign adenoma (0% risk of adrenocortical carcinoma)
    • HU >20: Increased suspicion for malignancy 1, 2

• Contrast-enhanced CT washout study (For indeterminate lesions)

  • 60% washout at 15 minutes suggests benign lesion

  • Sensitivity >95%, specificity >97% for adenoma detection 2

• Chemical shift MRI (Alternative for indeterminate masses)

  • Particularly useful when:
    • Patient has contraindication to CT contrast
    • Suspected pheochromocytoma
    • Homogeneous signal intensity drop indicates lipid-rich adenoma 1, 2

• FDG-PET (For radiologically indeterminate cases)

  • Useful for distinguishing potentially malignant from benign tumors
  • Shows high tracer uptake in malignant neoplasms 2

Management Algorithm

Surgical Indications

Surgery is recommended for:

1. Size-based criteria:

   • Masses >4 cm with inhomogeneous appearance or HU >20 1, 2, 3
   • All masses >6 cm regardless of appearance 5, 6

2. Functional status:

   • All biochemically confirmed pheochromocytomas 1, 2, 4
   • Aldosterone-secreting adenomas causing primary hyperaldosteronism 1, 2
   • Cortisol-secreting adenomas causing overt Cushing's syndrome 1, 2
   • Consider surgery for mild autonomous cortisol secretion (MACS) with related comorbidities 3

3. Imaging characteristics:

   • Irregular margins
   • Heterogeneous appearance
   • Poor contrast washout (<60% at 15 minutes)
   • Growth >5 mm/year on follow-up imaging 2

Surgical Approach

• Minimally invasive surgery (MIS): Preferred for benign adenomas when feasible
• Open adrenalectomy: Consider for larger tumors or those with features concerning for malignancy 2
• Perioperative management: Mandatory steroid coverage for cortisol-producing adenomas to prevent adrenal crisis 2
• Special consideration for pheochromocytoma: Preoperative alpha-blockade and metyrosine may be used to reduce catecholamine synthesis (35-80% reduction) and associated symptoms 4

Follow-up for Non-operated Patients

• Benign-appearing adenomas <4 cm:

  • No further follow-up imaging or functional testing if clearly benign (HU ≤10) 2, 7
  • For more indeterminate lesions: Repeat imaging in 3-12 months 7

• Benign-appearing adenomas ≥4 cm:

  • Repeat imaging in 6-12 months 2
  • Consider surgery if growth >5 mm/year after repeating functional workup 2
  • No further imaging or testing needed if growth <3 mm/year 2

• Functional testing follow-up:

  • For non-operated patients with non-functioning masses: Consider repeat screening for pheochromocytoma and hypercortisolism at 1-2 years 7
  • For stable masses without hormonal hypersecretion over 4 years, further follow-up may not be warranted 5

Key Pitfalls to Avoid

1. Failing to screen for pheochromocytoma before any invasive procedure or biopsy, which could trigger life-threatening hypertensive crisis

2. Relying solely on imaging without hormonal evaluation, as even radiologically benign-appearing masses can be hormonally active

3. Missing mild autonomous cortisol secretion (MACS), which increases morbidity and mortality despite absence of overt Cushing's syndrome

4. Overlooking the need for perioperative steroid coverage in patients with cortisol-producing adenomas

5. Inadequate follow-up of indeterminate adrenal masses that don't meet immediate surgical criteria