Adrenocortical carcinoma risk factors

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Ahmad Al Maradni, M.D. [2]

Overview

The most potent risk factors in the development of adrenocortical cancer are TP53 mutation, Beckwith-Wiedemann syndrome and Carney complex.

Risk Factors

Risk factor associated with adrenocortical carcinoma are:

• Li-Fraumeni syndrome
• Beckwith-Wiedemann syndrome
• Carney complex
• Adrenal incidentaloma must be differentiated from other diseases that cause adrenal masses such as adrenal adenoma, adrenocortical carcinoma, Cushing's syndrome, pheochromocytoma, and metastasis.

Differential Diagnosis	Clinical picture	Imagings	Laboratory tests
Adrenal adenoma		Round and homogeneous density, smooth contour and sharp margination [15] Diameter less than 4 cm, unilateral location Low unenhanced CT attenuation values (<10 HU) (image 1) Rapid contrast medium washout (10 minutes after administration of contrast, an absolute contrast medium washout of more than 50 percent) Isointensity with liver on both T1 and T2 weighted MRI sequences Chemical shift evidence of lipid on MRI
Adrenocortical carcinoma	Mass effect symptoms; symptoms related to excess glucocorticoid, mineralocorticoid, androgen, or estrogen secretion	Irregular shape Inhomogeneous density because of central areas of low attenuation due to tumor necrosis (image 4) Tumor calcification Diameter usually >4 cm Unilateral location High unenhanced CT attenuation values (>20 HU) Inhomogeneous enhancement on CT with intravenous contrast Delay in contrast medium washout (10 minutes after administration of contrast, an absolute contrast medium washout of less than 50 percent) Hypointensity compared with liver on T1 weighted MRI and high to intermediate signal intensity on T2 weighted MRI High standardized uptake value (SUV) on FDG-PET-CT study Evidence of local invasion or metastases	Serum DHEAS Measures of clinicallyindicated steroid
Cushing's syndrome	Rapid weight gain, particularly of the trunk and face with limbs sparing (central obesity) Proximal muscle weakness A round face often referred to as a "moon face" Excess sweating Headache	Imaging may show adenoma if presents	24-hour urine cortisol Midnight salivary cortisol Low dose dexamethasone suppression test; high cortisol level after the dexamethasone test is suggestive of hypercortisolism.
Pheochromocytoma	Palpitations especially in epinephrine producing tumors.[3] Anxiety often resembling that of a panic attack Sweating Headaches occurs in 90 % of patients. Paroxysmal attacks of hypertension but some patients have normal blood pressure. It may be asymptomatic and discovered incidentally after screening for MEN patients.	Increased attenuation on nonenhanced CT (>20 HU) Increased mass vascularity (image 2) Delay in contrast medium washout (10 minutes after administration of contrast, an absolute contrast medium washout of less than 50 percent) High signal intensity on T2 weighted MRI (image 3) Cystic and hemorrhagic changes Variable size and may be bilateral	Plasma fractionated metanephrines  24-hour urinary fractionated metanephrines
Adrenal metastasis	Symptoms and signs of primary malignancy especially lung cancer. General constitutional symptoms: Fever Fatigue Weight loss	Irregular shape and inhomogeneous nature Tendency to be bilateral High unenhanced CT attenuation values (>20 HU) and enhancement with intravenous contrast on CT Delay in contrast medium washout (10 minutes after administration of contrast, an absolute contrast medium washout of less than 50 percent) Isointensity or slightly less intense than the liver on T1 weighted MRI and high to intermediate signal intensity on T2 weighted MRI (representing an increased water content) Elevated standardized uptake value on FDG-PET scan