Hyperfunctioning Adrenal Cortical Neoplasms

The adrenal cortex is composed of three separate zones: the zona fasciculata, the zona glomerulosa, and the zona reticularis.

The zona fasciculata produces cortisol, the zona glomerulosa produces aldosterone, and the zona reticularis produces androgens. 

All three are produced in response to adrenocorticotropic hormone (ACTH) produced by the pituitary gland; however, only cortisol has negative feedback on ACTH production. 

Hyperfunctioning tumors of the adrenal cortex can produce Cushing syndrome from cortisol overproduction, Conn syndrome from production of aldosterone, or hyperandrogenism from overproduction of androgens. 

Cushing Syndrome.

 Cushing syndrome is defined as increased glucocorticoid levels from any cause and may be divided into ACTH-dependent and ACTH-independent forms.

In Cushing disease, which accounts for approximately 80% of Cushing syndrome cases, a pituitary adenoma secretes excess ACTH, which stimulates the adrenal gland. 

Appropriate work-up of patients with suspected Cushing disease includes measurement of serum ACTH levels, a dexamethasone suppression test, and pituitary MR imaging.

The adrenal glands are often symmetrically enlarged in patients with ACTH-dependent Cushing syndrome; however, up to 30% of patients will have normal-size adrenal glands (Fig).

Adrenal hyperplasia in a woman with Cushing disease. Contrast-enhanced CT scan demonstrates thickening of the limbs of the left adrenal gland but a normal right adrenal gland. The prominent intraabdominal fat and hepatic steatosis seen here are typical findings in this disease.

In 15%–25% of cases of Cushing syndrome, the cause is a primary adrenal neoplasm, usually a benign adenoma. 

Adrenal adenomas causing Cushing syndrome are usually greater than 2.0 cm in diameter and often readily visualized on CT scans.

The role of scintigraphy for the evaluation of patients with Cushing syndrome is limited, particularly with the advances in CT and MR imaging.

Adrenal cortical scintigraphy is sensitive for localization of adrenal remnants in patients who have persistent elevated cortisol levels after adrenalectomy.

Hyperaldosteronism.

 Primary aldosteronism is characterized clinically by hypertension and hypokalemia. 

The cause is an adrenal adenoma in about 80% of patients and adrenal gland hyperplasia in 20%.

Adrenal carcinoma is an extremely rare cause of primary aldosteronism. 

After the diagnosis of hyperaldosteronism has been established through clinical and laboratory tests, a dedicated CT study of the adrenal gland performed with thin (3-mm) collimation is usually the first-line imaging examination (Fig).

Left adrenal aldosteronoma in a 43-year-old woman. Contrast-enhanced helical CT scan shows a 5-mm well-circumscribed left adrenal mass (arrow), which proved at surgery to be an aldosterone-secreting adenoma.

Adrenal adenomas are often small and difficult to detect, since over 20% are less than 1 cm in diameter. 

Adrenal cortical scintigraphy is rarely needed, given the improvements in CT technology, but it can be useful to determine whether the abnormality is unilateral or bilateral. NP-59 is a cholesterol analog that binds to the low-density lipoprotein receptors of the adrenal cortex and is the primary radiopharmaceutical used for adrenal cortical scintigraphy.

It is available only through the University of Michigan (Ann Arbor) radiopharmacy and is still considered investigational by the U.S. Food and Drug Administration despite many years of safe use. 

A normal result of NP-59 imaging is visualization of both adrenal glands on day 5 after the injection or thereafter. Bilateral early adrenal visualization before day 5 suggests adrenal gland hyperplasia. Unilateral early adrenal visualization before day 5 is indicative of an adenoma (Fig).

Functioning right aldosteronoma in a patient with hyperaldosteronism. Posterior image obtained 5 days after intravenous administration of NP-59 shows increased activity in the right adrenal gland (arrow), a finding consistent with a functioning adenoma. Normal activity is seen in the bowel, bladder, and liver.

If these examinations are not diagnostic, adrenal venous sampling should be performed (Fig) to determine whether aldosterone secretion lateralizes to one side (suggestive of an adenoma) or is symmetric (suggestive of bilateral hyperplasia).

Adrenal venous sampling in a 51-year-old man with biochemically proved aldosteronoma. Angiogram shows the catheter, which was placed in the right adrenal vein (arrow) via the inferior vena cava. The adrenal veins were opacified by using gentle hand injection of contrast material, thus confirming correct placement for adrenal venous sampling. Cortrosyn-stimulated aldosterone levels were four times higher on the left than the right. The patient’s symptoms resolved after left adrenalectomy.