Nonfunctional Adrenal Masses

Most patients are asymptomatic. With any adrenal mass, adrenal insufficiency is rare unless both glands are involved. Hyperfunction occurs more frequently. This may seem paradoxical for a "nonfunctional mass," but A significant minority of these incidentally found "nonfunctional adrenal masses" do show some autonomous cortisol secretion, which may be manifested as subtle signs of cortisol excess such as weight gain, hypertension, and diabetes.

The major signs of bilateral massive adrenal hemorrhage are:

• Abdominal pain

• Falling hematocrit

• Signs of acute adrenal failure (eg, abdominal pain, loss of consciousness, fatigue, dehydration)

• Suprarenal masses on CT or MRI

Tuberculosis of the adrenals may cause calcification and Addison disease. Nonfunctional adrenal carcinoma usually manifests as invasive or metastatic disease.

• Adrenal hormone measurements

• Fine-needle biopsy

Nonfunctional adrenal masses are usually found incidentally during tests such as CT or MRI conducted for other reasons (1). Nonfunctionality is established clinically and confirmed by adrenal hormonal measurements, but as noted, many may show autonomous cortisol secretion without obvious signs of Cushing syndrome.

Screening adrenal hormonal measurements include dexamethasone suppression testing and serum cortisol (to exclude Cushing syndrome), 24-hour urinary or plasma fractionated metanephrines (to exclude pheochromocytoma) and plasma aldosterone and renin (to exclude primary aldosteronism).

If metastatic or infectious disease is possible, fine-needle biopsy can be diagnostic but is contraindicated if there is suspicion of adrenal carcinoma (to avoid spread of tumor) or pheochromocytoma (to avoid precipitating acute hypertension).

• Sometimes excision, depending on size and/or imaging results

• Periodic monitoring

Although some imaging modalities (eg, in-phase and out-of-phase MRI) may be diagnostic, if the tumor is solid, of adrenal origin, and > 4 cm, it should usually be excised unless the imaging characteristics are clearly benign (1, 2, 3).

Tumors 2 to 4 cm in diameter are a particularly difficult clinical problem. If scanning does not suggest cancer and hormonal function is not altered (eg, normal electrolytes and metanephrines, no evidence of Cushing syndrome), it is reasonable to reevaluate periodically with imaging studies, usually at 6 and 12 months. If no progression occurs by then, further follow-up is unnecessary. If the unenhanced CT Hounsfield units (HU) is < 10 (a measure of tissue x-ray attenuation), then the tumor is benign regardless of size. Many of these tumors secrete cortisol in quantities too small to cause major symptoms, and whether they would eventually cause symptoms and morbidity if untreated is unclear. Most clinicians merely observe patients with these tumors, but clinicians should consider removal of these tumors if there is significant cortisol secretion.

Adrenal adenomas < 2 cm require no special treatment but should be observed regularly over a period of time (eg, at 6 and 12 months) for growth and for development of secretory function (such as by looking for clinical signs and periodically measuring cortisol and ACTH).

Adrenal carcinoma that is non-functioning and has metastasized is not curable by surgery, though mitotane plus glucocorticoids may modify tumor growth. Chemotherapy is also an option, particularly for progressive disease.Adrenal carcinoma that is non-functioning and has metastasized is not curable by surgery, though mitotane plus glucocorticoids may modify tumor growth. Chemotherapy is also an option, particularly for progressive disease.