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What tests can be used to diagnose hypercortisolism?

After ruling out hypercortisolism due to exogenous cortisol exposure, there are 3 biochemical tests that can be used to screen patients for endogenous hypercortisolism.1-3

overnight, salivary, and urinary test icons

Screening considerations

Hypercortisolism is a challenging disease to screen for. Few features are unique, and more often patients have a number of signs and symptoms that are caused by excess cortisol but that are common in the general population.3,4

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Understanding the different cortisol tests3,5

Below are the most common screening tests.

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1-mg overnight dexamethasone suppression test (DST)

Assesses responsiveness of the hypothalamic–pituitary–adrenal axis to glucocorticoids3,6

Detects autonomous cortisol secretion

Abnormal range: >1.8 μg/dL

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Late-night salivary cortisol
(LNSC)

Measures free cortisol in the saliva when cortisol should be at its lowest level3,5,7

Detects the loss of diurnal rhythm

Abnormal range: Exceeds the upper limit of normal for the assay†

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Urinary-free cortisol
(UFC)

Measures excretion of circulating unbound cortisol in the urine over a 24-hour period3,5,7

Detects the gross overproduction of cortisol over a period of time

Abnormal range: Exceeds the upper limit of normal for the assay

†Abnormal range: >0.145 μg/dL (based on enzyme-linked immunosorbent assay and liquid chromatography with tandem mass spectrometry assay validation).

The Endocrine Society Practice Guidelines suggest using the 1-mg DST or the LNSC in patients suspected of having less severe hypercortisolism.3

The American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) Disease State Clinical Review suggests that the LNSC test seems to be the best choice as an early predictor of Cushing disease recurrence.8

The American Association of Endocrine Surgeons (AACE/AAES) Medical Guidelines suggest that UFC is not an ideal marker for making a diagnosis of less severe hypercortisolism.6

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