Clinical Pearls & Morning Reports
Published April 21, 2021
Among adults, the prevalence of adrenal incidentaloma has increased with the growing use of and technological advances in imaging and with the aging of the population. Read the NEJM Clinical Practice here.
Q: What is the etiology of most adrenal incidentalomas?
A: Most adrenal incidentalomas are nonfunctioning benign tumors; 75% are nonfunctioning cortical adenomas. However, there are important clinical consequences in a subset of these masses. For example, approximately 14% of adrenal incidentalomas are functional tumors that secrete excess cortisol, aldosterone, or (rarely) both. Other masses with clinical significance are pheochromocytomas (approximately 7%) and primary adrenal cancers or metastases to the adrenal gland (approximately 4%).
Q: What diagnostic tests should be performed in all patients with an adrenal incidentaloma?
A: An overnight dexamethasone (1 mg) suppression test should be performed in all patients with adrenal incidentaloma. Guidelines recommend that all patients with adrenal incidentaloma undergo biochemical screening for pheochromocytoma because these tumors may be clinically silent. However, some investigators have suggested that biochemical screening for pheochromocytoma is not necessary in a patient who has a lipid-rich tumor with a computed tomography (CT) attenuation of 10 Hounsfield units or less, because these tumors are rarely pheochromocytomas (<0.5% of cases). Any patient with adrenal incidentaloma and hypertension or hypokalemia should be screened for primary hyperaldosteronism with measurement of the mid-morning plasma aldosterone concentration and plasma renin activity.
A: Tumor size and imaging features are key to determining the likelihood of cancer and guiding treatment. Although many studies of the risks of cancer associated with tumor size are limited by small samples, retrospective design, and selection bias, data consistently support associations between tumors that are larger than 4 cm in greatest diameter and an increased risk of cancer among patients with a unilateral adrenal mass. The risk of adrenocortical carcinoma is less than 2% among patients with tumors smaller than 4 cm in diameter, 6% among those with tumors between 4 cm and 6 cm in diameter, and 25% or higher among those with tumors that are at least 6 cm in diameter. However, patient age is an important factor in estimating cancer risk; because benign incidentalomas are uncommon in patients younger than 40 years of age, cancer is a concern even with smaller tumors (<4 cm in diameter) in this age group.
A: On CT imaging, features other than tumor size can help to differentiate benign from malignant adrenal incidentalomas, although the ultimate diagnosis is based on histologic findings or clinical follow-up. Irregular tumor margins, heterogeneity, necrosis, vascularity, and calcification are features that arouse suspicion for cancer. An attenuation of 10 Hounsfield units or less on unenhanced CT is consistent with a benign lesion; in a series of 1161 adrenal tumors with an attenuation of 10 Hounsfield units or less, no malignant tumors were observed. Guidelines differ with respect to follow-up recommendations for nonfunctioning tumors that are smaller than 4 cm in diameter with attenuation of 10 Hounsfield units or less, but the most recent guidelines recommend that no follow-up imaging is needed unless clinical manifestations develop. All other adrenal incidentalomas with indeterminate features on imaging may warrant additional imaging with contrast-enhanced CT, magnetic resonance imaging with chemical-shift analysis, positron-emission tomography–CT with 18F-fluorodeoxyglucose, or all of these tests. The management of these masses should be individualized and should involve a multidisciplinary team consisting of an endocrinologist, an endocrine surgeon, and a radiologist.