Overview

Definition:
-An adrenal incidentaloma is an adrenal mass discovered incidentally during imaging studies performed for unrelated medical conditions
-These masses are typically asymptomatic and are found in 1-10% of the general population, with prevalence increasing with age.
Epidemiology:
-The prevalence of adrenal incidentalomas ranges from 1% to 10% in autopsy series and abdominal imaging studies, with higher rates (up to 30%) in patients undergoing imaging for conditions like obesity or hypertension
-The risk of malignancy is low, estimated at 5-10% of incidentalomas.
Clinical Significance:
-While most adrenal incidentalomas are benign and non-functional, they pose a diagnostic challenge due to the potential for underlying malignancy or hormonal hypersecretion
-Timely and appropriate evaluation is crucial to prevent adverse outcomes from undiagnosed functional tumors or metastatic disease
-Surgical intervention is considered based on specific criteria related to tumor size, imaging characteristics, and hormonal function.

Diagnostic Approach

History Taking:
-Detailed history should focus on symptoms suggestive of hormonal hypersecretion: hypertension, palpitations, sweating (Pheochromocytoma)
-weight gain, moon facies, striae, proximal muscle weakness (Cushing's syndrome)
-hypokalemia, hypertension (Aldosteronoma)
-virilization (adrenal carcinoma)
-Family history of endocrine tumors or adrenal disease is also important.
Physical Examination:
-Focus on signs of hormonal excess: hypertension, tachycardia, pallor (Pheochromocytoma)
-moon facies, buffalo hump, central obesity, skin thinning, striae (Cushing's syndrome)
-hypokalemia, hypertension (Aldosteronoma)
-hirsutism, clitoromegaly, deepening voice (adrenal carcinoma)
-Assess for palpable abdominal masses.
Investigations:
-Initial workup involves biochemical screening for hormone overproduction: 24-hour urinary fractionated metanephrines and normetanephrines or plasma free metanephrines for Pheochromocytoma
-overnight dexamethasone suppression test (DST) for Cushing's syndrome
-plasma aldosterone-to-renin ratio (ARR) for Aldosteronoma
-Imaging includes non-contrast CT to assess size, density (Hounsfield units), and morphology
-contrast-enhanced CT and MRI for better characterization of adrenal lesions
-Iodine-131 metaiodobenzylguanidine (MIBG) scintigraphy or Ga-68 DOTATATE PET-CT may be used for specific indications.
Differential Diagnosis:
-Differential diagnoses include benign adenomas (adenomatous hyperplasia), pheochromocytoma, adrenocortical carcinoma, metastasis from other primary tumors, adrenal cysts, and myelolipomas
-Distinguishing features are size, imaging characteristics (especially lipid content and enhancement patterns), and biochemical profiles
-Solid masses with high Hounsfield units (>20-30 HU on non-contrast CT) or significant contrast enhancement are suspicious for malignancy.

Management

Initial Management:
-For asymptomatic, non-functional incidentalomas, the primary management is observation with serial imaging and biochemical reassessment
-However, prompt workup is initiated for any suspicion of hormonal activity or malignancy.
Medical Management:
-Medical management is primarily aimed at controlling symptoms of hormonal hypersecretion
-For suspected pheochromocytoma, alpha-blockade (e.g., phenoxybenzamine) followed by beta-blockade is initiated pre-operatively
-For Cushing's syndrome, medical therapies like ketoconazole or metyrapone may be used as temporizing measures or in unresectable cases.
Surgical Management:
-Surgical intervention (adrenalectomy) is indicated for incidentalomas meeting specific criteria: 1
-Tumors > 6 cm in diameter
-2
-Tumors with imaging features suggestive of malignancy (e.g., irregular margins, heterogeneous enhancement, rapid growth)
-3
-Functioning tumors (e.g., Pheochromocytoma, Cushing's syndrome, primary hyperaldosteronism)
-4
-Patients with indeterminate lesions on imaging after further characterization, especially if suspicious for adrenocortical carcinoma
-Laparoscopic adrenalectomy is the preferred approach for benign lesions, while open adrenalectomy may be necessary for larger or suspected malignant tumors.
Supportive Care:
-Post-operative care includes monitoring for complications like adrenal insufficiency (requiring steroid replacement), bleeding, and infection
-For hormonally active tumors, careful management of electrolytes and blood pressure is essential in the perioperative period
-Patients with adrenal insufficiency require lifelong glucocorticoid and potentially mineralocorticoid replacement.

Surgical Thresholds

Size Criteria:
-Lesions greater than 4 cm are generally considered for surgical evaluation, with a strong recommendation for surgery if the size exceeds 6 cm
-Smaller lesions are managed based on other criteria.
Imaging Features: Suspicious imaging features warranting further evaluation and potential surgery include heterogeneous attenuation on CT (>20 HU on non-contrast), significant contrast enhancement (>15-20 HU at 10 min post-contrast), irregular margins, central necrosis, and rapid growth on serial imaging.
Hormonal Function:
-Any incidentaloma demonstrating hormonal hypersecretion (Pheochromocytoma, Cushing's syndrome, or aldosterone-producing adenoma) requires surgical consideration, often irrespective of size, due to associated morbidities
-Indeterminate findings on imaging also necessitate further workup and potential surgical resection.
Adrenocortical Carcinoma Suspicion: Lesions with high Hounsfield units (>30 HU) on non-contrast CT, significant growth over time, or specific imaging patterns suggestive of invasion or metastasis are highly suspicious for adrenocortical carcinoma and generally require surgical resection.

Complications

Early Complications:
-Risks associated with adrenalectomy include bleeding, infection, injury to adjacent organs (e.g., spleen, pancreas, kidney), and adrenal insufficiency
-Hypertensive crisis can occur perioperatively in patients with undiagnosed pheochromocytoma.
Late Complications:
-Long-term complications primarily relate to adrenal insufficiency if steroid replacement is inadequate or if bilateral adrenalectomy is performed
-Recurrence of disease (benign or malignant) can occur, necessitating surveillance.
Prevention Strategies:
-Thorough preoperative biochemical and imaging assessment is crucial to identify functional tumors or suspicious lesions
-Meticulous surgical technique, including careful dissection and hemostasis, minimizes operative risks
-Appropriate perioperative medical management, particularly alpha and beta blockade for pheochromocytoma, is vital.

Prognosis

Factors Affecting Prognosis:
-Prognosis is generally favorable for benign adenomas and functional tumors successfully treated with adrenalectomy
-For adrenocortical carcinoma, prognosis depends on stage, grade, resectability, and response to adjuvant therapy
-Size, presence of metastasis, and hormonal activity are key prognostic indicators.
Outcomes:
-Benign incidentalomas, if asymptomatic and non-functional, have excellent prognosis with observation
-Surgically treated functional tumors usually resolve their hormonal excess
-Adrenocortical carcinoma prognosis is more guarded, with a 5-year survival rate typically below 50%, heavily influenced by stage at diagnosis.
Follow Up:
-Patients with non-operative management require regular clinical assessment, biochemical screening for hormonal function, and serial imaging (e.g., CT scan annually for the first 1-2 years) to monitor for growth or new functional activity
-Post-adrenalectomy follow-up depends on the pathology, with surveillance protocols tailored to the risk of recurrence or metastasis, especially for adrenocortical carcinoma.

Key Points

Exam Focus:
-Understand the size and imaging criteria for surgical intervention of adrenal incidentalomas
-Differentiate between benign and malignant features on CT
-Recognize the hormonal syndromes associated with functional incidentalomas and their preoperative management
-Know the indications for adrenalectomy.
Clinical Pearls:
-Always consider hormonal evaluation for adrenal masses, even if asymptomatic
-A 10-Hounsfield Unit threshold on non-contrast CT can help differentiate lipid-poor adenomas from other lesions
-Preoperative blockade for suspected pheochromocytoma is life-saving
-Laparoscopic adrenalectomy is preferred for most benign lesions.
Common Mistakes:
-Underestimating the risk of malignancy in larger or radiologically suspicious lesions
-Failing to perform adequate biochemical screening for hormonal hypersecretion
-Delaying surgical referral for lesions meeting size or imaging criteria
-Inadequate preoperative management of functional tumors, particularly pheochromocytoma.