Other imaging options. MRI is an alternative to CT for patients with contraindications for contrast or radiation exposure. MRI provides less spatial resolution than CT, but chemical shift imaging can measure cytoplasmic lipid content similar to unenhanced CT. A small study found chemical shift MRI more reliable than unenhanced CT, but less reliable than CT with delayed contrast enhancement.25
Positron emission tomography (PET) is useful to noninvasively evaluate biochemical and physiologic processes. PET-CT incorporates unenhanced CT density measurements to improve PET accuracy. In a patient with a history of cancer, PET-CT has a sensitivity of 93% to 100% and a specificity of 95% in differentiating benign from malignant adrenal tumors.26
When to order a biopsy
The need for biopsy has decreased as imaging has improved, but biopsy is required whenever diagnostic imaging fails to differentiatea lesion as benign or malignant. CT guided biopsy provides diagnostic accuracy of 85% to 95%.27 Complications such as pneumothorax, hemorrhage, and bacteremia occur in 3% to 9% of biopsies. Before any adrenal biopsy, measure plasma-free metanephrines to exclude undiagnosed pheochromocytoma, which could precipitate a hypertensive crisis if untreated.22
These 3 laboratory screening tests are critical
Family physicians can perform the initial biochemical evaluation of an adrenal incidentaloma. Guidance is available from the National Institutes of Health (NIH)28 and the American Academy of Clinical Endocrinologists (AACE) (FIGURE 2).29
Regardless of signs or symptoms, perform screening laboratory tests for 3 types of adrenal hyperfunction: hypercortisolism, hyperaldosteronism, and hypersecretion of catecholamines (pheochromocytoma). Screening tests are not recommended for androgen hypersecretion, which is extremely rare and causes recognizable symptoms such as hirsutism (Table 2).29
Hypercortisolism occurs in approximately 5% of adrenal incidentalomas.30 An overnight dexamethasone suppression test (DST) is most reliable for screening, with sensitivity >95% for Cushing syndrome.31 The patient takes a 1-mg dose of oral dexamethasone at 11 pm, and a fasting plasma cortisol sample is drawn the next day at 8 am.
Dexamethasone binds to glucocorticoid receptors in the pituitary gland, suppressing adrenocorticotropic hormone secretion. Cortisol will be depressed the next morning unless the adrenal mass produces cortisol autonomously. Patients with a DST >5 mcg/dL—highly suggestive of Cushing syndrome—require further evaluation, and we suggest referral to an endocrinologist.
Hyperaldosteronism is seen in 1% to 2% of adrenal incidentalomas.32 The aldosterone- to-renin ratio (ARR) is recommended as a screening test for hyperaldosteronism, with an ARR >20 requiring further testing.33 Medications that may affect the ARR include beta-blockers, spironolactone, clonidine, diuretics, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers.29
Refer a patient with evidence of hyperaldosteronism to an endocrinologist and a surgeon with experience in managing these lesions. If the ARR test result suggests an aldosterone excess, a salt-loading test is used to verify failure of aldosterone suppression. Adrenal venous sampling is often performed prior to surgical removal to confirm that an incidentaloma is the source of hyperaldosteronism.
Pheochromocytoma. Approximately 5% of incidental adrenal lesions are pheochromocytomas.30 Many patients with these epinephrine/norepinephrine secreting tumors do not show the classic symptom triad of headache, palpitations, and diaphoresis, and approximately half have normal blood pressure.34
Identifying a pheochromocytoma is important in any patient requiring surgery or biopsy, as surgical manipulation can cause a potentially fatal intraoperative catecholamine surge. Presurgical medical management can mitigate this reaction.
A plasma-free metanephrines test, which has 95% sensitivity, is the most reliable test for pheochromocytoma.35 Medications, including tricyclic antidepressants, decongestants, amphetamines, reserpine, and phenoxybenzamine, can cause falsepositive results.29 Confirm a positive plasma-free metanephrines test with a 24-hour fractionated urine metanephrines test, and refer the patient to an endocrinologist.
Managing adrenal incidentalomas
Refer all patients with adrenal masses >4 cm for surgical evaluation because of the risk of malignancy; all patients who have a history of malignancy and an adrenal mass of any size require a referral to an oncologist. Perform the AACE-recommended 3-element biochemical workup for all masses, with the exception of definitively diagnosed cysts or myelolipomas.
Refer to an endocrinologist all patients with abnormal screening laboratory results, regardless of adrenal mass size, as well as patients with concerning clinical findings. Initiate cardiovascular, diabetes, and bone density evaluation and management for metabolic syndrome.20
Monitoring after a negative workup
Little evidence exists to guide monitoring of small adrenal incidentalomas (<4 cm) with a negative workup. The 2002 NIH report recommended annual radiologic follow-up for 5 years,28 whereas the 2009 AACE guidelines recommend radiographic follow-up at 3 to 6 months, then at one and 2 years.29
Evidence indicates that 14% of lesions will enlarge in 2 years, although the clinical significance of enlargement is unknown. Some authors argue against CT monitoring because the risk of adrenal mass progression is similar to the malignancy risk posed by 3 years of radiation exposure with CT.20