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Adrenal Incidentaloma

An adrenal incidentaloma is an adrenal mass detected during radiological evaluation performed for a reason other than suspected adrenal disease. The prevalence of adrenal incidentalomas by imaging is approximately 3% among patients in their 50s and 7% in patients older than 70 years. Guidelines recommend that all patients with adrenal incidentalomas undergo evaluation for pheochromocytoma and subclinical hypercortisolism. Patients with hypertension should be evaluated for an aldosterone-secreting adenoma.

Most patients with adrenal incidentalomas do not exhibit signs or symptoms of overt hypercortisolism such as purple striae, easy bruising, and proximal muscle weakness. However, they may have subclinical hypercortisolism, which is defined as autonomous cortisol production that is not severe enough to cause overt hypercortisolism. These patients are at increased risk of developing diabetes, hypertension, obesity, hyperlipidemia, and osteoporosis.

Patients with adrenal incidentalomas should undergo hormonal evaluation to rule out pheochromocytoma followed by evaluation for subclinical hypercortisolism and primary hyperaldosteronism, if there is history of hypertension.

The overnight 1-mg dexamethasone suppression test is the best test to evaluate patients with adrenal incidentalomas for subclinical hypercortisolism. The 1-mg overnight dexamethasone suppression test (DST) evaluates the feedback of the hypothalamic-pituitary- adrena (HPA) axis.Patients ingest 1 mg of dexamethasone at 11 PM and have their blood drawn for plasma cortisol measurement at 8 AM the following morning. Normally, dexamethasone suppresses cortisol production. A 1-mg DST plasma cortisol level of greater than 1.8 μg/dL has 99% sensitivity and 80% specificity for the diagnosis of subclinical hypercortisolism. A cortisol value of greater than 5 μg/dL is consistent with autonomous hypercortisolism. Cortisol levels between 1.9 and 5 μg/dL, are consistent with possible autonomous cortisol production.

Adrenocorticotropic hormone (ACTH) levels should not be measured on the morning after a dexamethasone dosing because levels may be falsely suppressed. ACTH level should be measured later in patients with an abnormal DST.

ACTH normally stimulates production of dehydroepiandrosterone sulfate (DHEA-S). Elevated cortisol concentration suppresses ACTH and reduces levels of DHEA-S. Decreased DHEA-S concentration has a sensitivity of 99% and specificity of 92% for subclinical hypercortisolism. The sensitivity of decreased DHEA-S is comparable to the sensitivity of the 1-mg DST.

Measurement of urinary free cortisol in a 24-hour urine collection is not very sensitive for detection of subclinical hypercortisolism and is often within the normal reference range (3.5-45 ug/dL). Cortisol production is not increased enough to exceed the binding capacity of plasma cortisol binding globulin. Measurement of salivary cortisol at 11 PM is also not sensitive enough (77%) to diagnose subclinical hypercortisolism.


Ospina NS et al. Diagnostic Testing for Elevated Cortisol in the Setting of an Adrenal Mass JAMA online, September 21, 2018, pages E1-E2.

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