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This is a clinician-written, evidence-based summary aligned to the USMLE Step 2 CK Content Outline. It is intended for medical students preparing for USMLE Step 2 CK. Management reflects current ACC/AHA, USPSTF, and APA guidelines. Always cross-reference with UpToDate, institutional protocols, and clinical judgment.
The Bottom Line
- Every adrenal incidentaloma needs assessment for hormone secretion and malignancy risk
- Screen for autonomous cortisol secretion with 1-mg overnight dexamethasone suppression test
- Test for pheochromocytoma with plasma free or urinary fractionated metanephrines unless imaging phenotype clearly excludes it per specialist criteria
- If hypertension or hypokalemia: screen for primary aldosteronism with aldosterone-renin ratio
- Imaging risk: size, unenhanced CT attenuation, heterogeneity, growth, irregular margins, and washout guide surgery vs surveillance
Overview
An adrenal incidentaloma is an adrenal mass discovered incidentally during imaging performed for reasons unrelated to suspected adrenal disease. The key clinical questions are whether the mass secretes hormones and whether it is malignant. Most are benign nonfunctioning adenomas, but clinically important diagnoses include pheochromocytoma, autonomous cortisol secretion, primary aldosteronism, adrenocortical carcinoma, metastasis, myelolipoma, cyst, and hemorrhage.
Epidemiology
Adrenal incidentalomas become more common with age and widespread CT/MRI use. Benign adenomas account for the majority. Malignancy risk rises with larger size, heterogeneous appearance, high unenhanced Hounsfield units, irregular margins, necrosis, local invasion, or known extra-adrenal cancer. Mild autonomous cortisol secretion may worsen hypertension, diabetes, obesity, dyslipidemia, osteoporosis, and cardiovascular risk even without classic Cushingoid features.
Clinical Features
Symptoms
Usually asymptomatic; discovered on CT/MRI for abdominal pain, trauma, kidney stones, or cancer staging
Paroxysmal headache, sweating, palpitations suggesting pheochromocytoma
Resistant hypertension or hypokalemic weakness suggesting primary aldosteronism
Weight gain, bruising, proximal weakness, osteoporosis suggesting cortisol excess
Abdominal/flank pain, weight loss, virilization, or rapid onset symptoms suggesting carcinoma
Signs
Hypertension, diabetes, obesity, osteoporosis, or dyslipidemia may be associated with cortisol secretion
Hypokalemia and metabolic alkalosis if aldosterone-producing lesion
Cushingoid features are often absent in mild autonomous cortisol secretion
Signs of androgen excess or feminization suggest adrenocortical carcinoma
Normal examination does not exclude functioning tumor
Investigations
First-line
Dedicated adrenal imaging reviewAssess size, noncontrast HU, homogeneity, borders, washout, and comparison with prior imaging
1-mg overnight dexamethasone suppression testScreens for autonomous cortisol secretion
Plasma free or urinary fractionated metanephrinesScreens for pheochromocytoma depending on imaging phenotype and guideline context
Aldosterone-renin ratioIf hypertension or hypokalemia is present
Second-line
DHEA-S and androgen profileIf virilization, feminization, or suspected adrenocortical carcinoma
Repeat imagingFor indeterminate masses not undergoing surgery; timing depends on size and imaging phenotype
Cancer staging workupIf imaging suggests adrenocortical carcinoma or metastasis
Specialist
Adrenal protocol CT or MRI chemical shift imagingCharacterizes lipid-rich adenoma vs indeterminate lesion
Multidisciplinary adrenal team reviewLarge, functional, growing, heterogeneous, or suspicious lesions
1
Biochemical evaluation
- Screen for autonomous cortisol secretion with 1-mg dexamethasone suppression
- Screen for pheochromocytoma with metanephrines unless clearly unnecessary by imaging phenotype and local guideline practice
- Screen for primary aldosteronism if hypertension or hypokalemia
- Evaluate sex steroid excess if carcinoma suspected
2
Imaging risk stratification
- Benign lipid-rich adenoma: homogeneous, low unenhanced attenuation, stable size
- Suspicious features: large size, HU >20, heterogeneity, irregular borders, necrosis, invasion, rapid growth
- Known extra-adrenal malignancy changes pretest probability and may require oncologic staging
3
When to operate
- Functional tumors causing clinically significant hormone excess generally need adrenalectomy if surgical candidate
- Pheochromocytoma requires alpha-blockade before surgery
- Suspicious or large masses should be referred for adrenalectomy evaluation by experienced surgeons
4
Surveillance and conservative care
- Nonfunctioning benign-appearing lesions may be monitored or discharged from follow-up depending on imaging certainty and size
- Manage cardiometabolic comorbidities in mild autonomous cortisol secretion and consider surgery case-by-case
Complications
- Missed pheochromocytoma: Can cause hypertensive crisis during biopsy, surgery, or anesthesia
- Adrenocortical carcinoma: Aggressive malignancy; early surgical referral is critical
- Autonomous cortisol secretion: Increases diabetes, hypertension, osteoporosis, infection, and cardiovascular risk
- Primary aldosteronism: Can cause cardiovascular and renal injury beyond BP alone
- Adrenal biopsy harm: Biopsy is contraindicated until pheochromocytoma is excluded and is rarely useful for primary adrenal malignancy diagnosis
USMLE Step 2 CK Exam Tips
- 1Adrenal incidentaloma workup always asks: functional? malignant?
- 2Do not biopsy an adrenal mass until pheochromocytoma has been excluded
- 3Hypertension + adrenal mass + hypokalemia = aldosterone-renin ratio
- 4Spells of headache/sweating/palpitations + adrenal mass = metanephrines
- 5Cortisol autonomy is screened with 1-mg overnight dexamethasone suppression
- 6Large heterogeneous adrenal mass with virilization = adrenocortical carcinoma until proven otherwise
- 7Pheochromocytoma surgery requires alpha-blockade first
- 8Incidentaloma discovered during cancer staging may be metastasis, but biochemical testing still matters before biopsy
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