Incidentaloma diagnostic criteria

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mohammed Abdelwahed M.D[2]

Overview

There are no definitive diagnostic criteria for adrenal incidentaloma management but there are guidelines to diagnose and treat the mass according to Endocrine Society. Radiological evaluation including noncontrast CT attenuation value expressed in Hounsfield unit (HU) is the best tool to differentiate between benign and malignant adrenal masses. All patients should undergo hormonal evaluation for subclinical Cushing's syndrome and pheochromocytoma, and those with hypertension should also be evaluated for primary hyperaldosteronism.

Diagnostic Criteria

• There are no definitive diagnostic criteria for adrenal incidentaloma management but there are guidelines to diagnose and treat the mass according to Endocrine Society.

• The guidelines recommend urgent assessment of adrenal mass in children, adolescents, pregnant females, and adults younger than 40 years of age because of a higher likelihood of malignancy.

• The diagnostic approach in patients with adrenal incidentalomas depends on two important questions:
  • Whether the lesion is malignant, or
  • Whether it is hormonally active.
• Radiological evaluation including noncontrast CT attenuation value expressed in Hounsfield unit (HU) is the best tool to differentiate between benign and malignant adrenal masses.
• All adrenal tumors with suspicious radiological features, most functional tumors, and all tumors more than 4 cm in size with malignant radiological features should be removed surgically.
• All patients have to perform hormonal evaluation for subclinical Cushing's syndrome and pheochromocytoma, and those with hypertension should also be evaluated for primary hyperaldosteronism.
• Annual biochemical follow-up of most patients with an adrenal incidentaloma (particularly if the tumor is more than 3 cm in size) for up to 5 years is sufficient.
• Patients with adrenal masses less than 4 cm in size and a non-contrast attenuation value greater than 10 HU should have a repeat CT study in 3–6 months and then yearly for 2 years.
• Adrenal tumors with indeterminate radiological features that grow at least 0.8 cm over 3–12 months should be considered for surgical resection once other imaging and clinical characteristics have been taken into consideration.

Adrenal mass

CT attenuation value< 10HU*

CT attenuation value> 10HU

Nonfunctional

Functional

< 4cm

> 4cm

Yearly hormonal evlauation for up to 5 years

Surgical removal

Functional

Nonfunctional

Surgical removal

surgical removal

Calculate enhancement washout within 15 minutes

<60%

>60%

Surgical removal

No change in size in 12 months

> 0.8cm increase in size in 12 months

Follow up CT image for two years

HU;Hounsfield unit.

• Comprehensive history taking and physical examination is important to assess for features of hormonal hypersecretion followed by imaging and hormonal evaluation.
• There are two possibilities that can be found on imaging (tumor size and attenuation on unenhanced CT Additional imaging like enhanced CT, MRI, 18F-FDG PET-CT); benign features (tumor <4 cm in diameter, less than10 Hounsfield units on CT, CT contrast washout more than 40–60%, signal loss on MRI chemical-shift analysis, on 18F-FDG PET-CT, SUVmax <5 or adrenal-to-spleen or adrenal-to liver signal-intensity ratio <1), or suspicious features (Tumor more than 3 cm in diameter, >10 Hounsfield units on CT, CT contrast washout <40–60%, on MRI, hyperintense on T2 imaging or no signal loss on chemical-shift analysis, on 18F-FDG PET-CT, SUVmax more than 4 or adrenal-to-spleen or adrenal-to liver signal-intensity ratio equal or more than 1).
• In case of benign features, no further follow-up imaging needed unless symptoms or signs indicating hormone excess develop. On the other hand, in case of suspicious features, consider adrenalectomy, and consider biopsy if metastasis is suspected and confirmation would change treatment plan. If adrenalectomy not performed, consider follow-up imaging in 6 months to 1 year.
• Hormonal evaluation using overnight 1-mg dexamethasone suppression test, measurement of plasma-free metanephrine level or fractionated metanephrine level in 24-hr urinary specimen. If hypertension or hypokalemia present, measurement of plasma aldosterone concentration and plasma renin activity.
• If the hormonal evaluation turned out to be negative, no further follow-up after hormonal evaluation unless symptoms or signs indicating hormonal excess develop. However, if it is positive, confirmatory testing for mild autonomous cortisol excess and primary hyperaldosteronism. Positive results indicate the need for adrenalectomy for pheochromocytoma after alpha-blockade (and after beta-blockade, if necessary) and consider adrenalectomy for autonomous cortisol hypersecretion and primary hyperaldosteronism.
• Nonfunctioning adrenal incidentalomas with features that are suggestive of an adenoma on imaging (attenuation ≤10 HU on CT) and their size is less than 4 cm in diameter are often benign and do not require additional follow-up imaging.

Assessment for Cancer

• An adrenal incidentaloma can be a primary malignant tumor that arises from the adrenal cortex (adrenocortical carcinoma) or medulla (pheochromocytoma), or can be metastatic tumor in rare occasions from lung cancer, renal cell carcinoma, gastrointestinal cancer, or melanoma. Imaging features and tumor size are essential for determining the probability of malignancy and also guiding treatment.
• Presence of irregular tumor margins, hemorrhage and necrosis, heterogeneity, increased vascularity, and calcification on imaging suggest cancer.

Imaging Features of Adrenal Incidentaloma

Adrenocortical Adenoma

• Small size, less than 4 cm in diameter
• Smooth margin
• Homogenous consistency
• Usually unilateral but can be bilateral in 15% of cases
• Unenhanced CT attenuation: less than 10 HU
• Contrast-enhanced CT features: low attenuation, low vascularity, and fast washout
• MRI features: isointense in relation to liver on T2-weighted image and signal drop on chemical-shift imaging
• 18F-FDG PET-CT features: not avid, SUVmax less than 5, adrenal to spleen or adrenal to liver signal intensity ratio less than 1, and absent hemorrhage, necrosis and calcification

Pheochromocytoma

• Large size
• Smooth margin
• Heterogenous consistency
• Usually unilateral but can be bilateral
• Unenhanced CT attenuation: more than 10 HU
• Contrast-enhanced CT features: high attenuation, high vascularity, and slow washout
• MRI features: hyperintense in relation to liver on T2-weighted image and no signal drop on chemical-shift imaging
• 18F-FDG PET-CT features: avid, SUVmax more than 5, adrenal to spleen or adrenal to liver signal intensity ratio is equal or more than than 1-1.5, and hemorrhage, necrosis and calcification

Adrenocortical Carcinoma

• Large size, more than 6 cm
• Irregular margin
• Heterogenous consistency
• Usually unilateral
• Unenhanced CT attenuation: more than 10 HU
• Contrast-enhanced CT features: high attenuation, high vascularity, and slow washout
• MRI features: markedly hyperintense in relation to liver on T2-weighted image and no signal drop on chemical-shift imaging
• 18F-FDG PET-CT features: avid, SUVmax more than 5, adrenal to spleen or adrenal to liver signal intensity ratio is equal or more than than 1-1.5, and hemorrhage, necrosis and calcification

Metastasis

• Variable size
• Irregular margin
• Heterogenous consistency
• Usually unilateral but can be bilateral
• Unenhanced CT attenuation: more than 10 HU
• Contrast-enhanced CT features: high attenuation, high vascularity, and slow washout
• MRI features: hyperintense in relation to liver on T2-weighted image and no signal drop on chemical-shift imaging
• 18F-FDG PET-CT features: avid, SUVmax more than 5, adrenal to spleen or adrenal to liver signal intensity ratio is equal or more than than 1-1.5, and hemorrhage, necrosis and calcification in large tumors

Assessment of Bilateral Adrenal Masses

• The differential diagnosis of bilateral adrenal masses include bilateral macronodular adrenal hyperplasia or adenomas, congenital adrenal hyperplasia, bilateral pheochromocytoma, bilateral adrenal hyperplasia, metastases, partial glucocorticoid resistance, myelolipomas, hemorrhage, and infection.
• Hormonal assessments as mentioned in solitary adrenal incidentaloma.
• Measurement of the serum 17-hydroxyprogesterone level to exclude congenital adrenal hyperplasia.
• If the imaging of bilateral adrenal masses shows hemorrhagic or infiltrative features, testing for adrenal insufficiency should be performed.