adrenal incidentaloma

Introduction

Incidentally discovered adrenal mass > 1 cm discovered by CT or MRI.

goals of evaluation

Classification

• determine if functioning (hormone secreting)
  • mild autonomous cortisol secretion is occasionally found with adrenal incidentalomas without clinically obvious Cushing syndrome
    • nonsuppressed serum cortisol > 1.9 ug/dL after overnight low-dose dexamethasone suppression test
    • as likely as patients with Cushing syndrome to have comorbidities:
      • hypertension, diabetes mellitus, dyslipidemia, depression, osteoporosis
    • features of Cushing syndrome no uncommon
      • weight gain (50%), dorsocervical fat pad (24%), facial plethora (23%)
• determine if malignant

Etiology

• adrenal adenoma
  • functional (cortisol, aldosterone, DHEA-secreting)
  • non-functional
  • > 1 cm in size
• primary adrenocortical carcinoma
• metastases
• pheochromocytoma

Epidemiology

• non-functional adrenal adenomas are found in up to 9% of autopsies
• prevalence of adrenal incidentalomas > 10 mm in the general population of adults 18-78 years is 1.4%
  • prevalence in adults >= 65 years is 3.2%
• prevalence of malignant adrenal incidentalomas is < 0.3%
• 20% with autonomous cortisol secretion (usually mild)
• 12% with primary aldosteronism
• prevalence of pheochromocytomas is < 0.3%

Pathology

• functioning adenomas can arise from any of the 3 layers of the adrenal cortex or from the adrenal medulla
  • unlikely to secrete aldosterone
• pheochromocytoma, adrenal carcinoma & metastatic lesions tend to be vascular; adrenal adenomas do not
• adrenocortical carcinomas tend to be large with irregular borders & may show areas of necrosis
• 10-15% of incidentalomas are functional
• up to 15% of incidentalomas are bilateral
  • bilateral adrenal incidentalomas benign in 161 of 161 (all) patients without history of cancer

Laboratory

• overnight dexamethasone suppression test (all patients)
• plasma free metanephrines or
  • 24 hour urine metanephrines (all patients)
• hypertensive patients
  • standing (upright) plasma renin
  • plasma aldosterone/renin ratio
  • serum K+
• 24 hour urinary free cortisol
  • not sufficiently sensitive to assess for cortisol excess in the setting of incidental adrenal nodules
  • not accurate during acute illness
• prior to major surgery
  • overnight dexamethasone suppression test
  • plasma catecholamines
    • plasma epinephrine
    • plasma norepinephrine
  • plasma metanephrines, plasma free metanephrines
• plasma testosterone in women

Radiology

• computed tomography (CT)*
  • low attenuation (< 10 Hounsfield units) suggests benign lesion
    • contrast washout > 50-60% in 10 minutes suggests benign lesion
  • high attenuation (> 20 Hounsfield units) suggests malignancy or pheochromocytoma
    • contrast washout < 50-60% in 10 minutes suggests suspiscious lesion
    • cystic lesion with high attenuation consistent with pheochromocytoma
• CT-guided fine needle aspiration reserved for suspicious lesions
  • will not distinguish benign adrenal mass & adrenocortical carcinoma
  • can be used to distinguish between an adrenal tumor & a metastatic tumor(5_

* also see Management (below)

Complications

• subclinical Cushing's syndrome
  • overt Cushing's syndrome rare
• increased cardiovascular risk (up to 28% over 8 years)
  • mild autonomous cortisol excess increases risk of hypertension & worsening of hypertension, dyslipidemia, &/or diabetes mellitus
  • cardiovascular events occurs more often with mild autonomous cortisol excess than with nonfunctioning adrenal ademonas (16% vs 6%)
    • mortality does not differ
  • cortisol secretion after dexamethasone suppression
    • predicts cardiovascular risk
    • AM serum cortisol 83-137 nmol/L or higher associated with increased mortality (RR: 2.3-3.0)
• non-functioning adrenal incidentalomas are associated with higher risks for cardiovascular & cancer mortality
  • patients with mortality similar to controls after adrenalectomy
• 2.5% increase > 10 mm in size, none become malignant

Management

• non-functional masses < 4 cm in size
  • unlikely to be malignancy, primary or metastatic if CT attenuation < 10 Hounsfield units (< 2%)
  • risk of malignancy increases to 25% if tumor > 6 cm
  • most metastatic malignancies show evidence of disease elsewhere
• surgical excision recommended for:
  • masses > 4 cm
  • enlarging masses; > 1 cm during follow-up period
  • functioning tumors
    • cortisol-producing adenoma
    • pheochromocytoma
      • manipulation of catechoamine-secreting neoplasm without appropriate preoperative management can precipitate a hypertensive crisis
  • resection of non-functioning tumors may reduce mortality
  • radiographic characteristics of malignany
    • high attenuation (> 20 Hounsfield units)
    • irregular shape or borders
• non-functional masses ~4 cm in size with CT attenuation < 10 Hounsfield units may be clinically observed or surgically excised
• repeat CT in 6-12 months for all non-surgical tumors
  • no consensus on repeat testing
  • some experts recommend annual CT for 3-4 years
  • repeat CT after 3-6 months for tumors 2-4 cm in size (GRS11)
    • repeat CT in 6-12 months for tumor < 2 cm

More general terms

• incidentaloma
• adrenal cortical adenoma

Additional terms

• pheochromocytoma; paroxysmal hypertension; adrenal medullary paraganglioma; chromoffinoma