Who should be screened for hypercortisolism?

It can be difficult to assess which patients should be screened for hypercortisolism due to the constellation of possible signs and symptoms.1,2
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Screening recommendations and considerations

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Clinical spectrum of hypercortisolism

Patients in the above photos were diagnosed with hypercortisolism/Cushing syndrome. Photos used with permission.

Because Cushing syndrome tends to progress over time, accumulation of new features increases the probability that hypercortisolism is present.1


  • Patients with multiple signs and symptoms consistent with classically described overt Cushing syndrome
  • All patients with adrenal adenomas
  • Patients with pituitary adenomas in the presence of other features suggesting hypercortisolism


  • Patients with diabetes <50 years of age (poorly controlled)
  • Patients with hypertension <50 years of age (poorly controlled)
  • Patients with low bone mineral density (BMD) vs matched controls, BMD that rapidly declines, or fragility fractures
  • Patients with suspected polycystic ovary syndrome

Evaluate adrenal adenomas

It is important to evaluate adrenal adenomas for secretory function. Of adults who underwent magnetic resonance imaging (MRI), 4% to 7% were found to have an incidental adrenal adenoma. It was estimated that 5% to 30% of the adrenal adenomas found were of the autonomous cortisol-secreting type.4,5

“We recommend that every patient with an adrenal incidentaloma should undergo careful assessment, including clinical examination for symptoms and signs of adrenal hormone excess.”
European Society of Endocrinology Clinical Practice Guideline 20166

up to 30% of screened adrenal adenomas are found to be cortisol secreting

Diagnosing hypercortisolism

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Consider the index of suspicion1,7

Exclude exogenous hypercortisolism
Due to long-term use of high-dose glucocorticoid medications such as steroids

Check for endogenous hypercortisolism
Due to pituitary, adrenal, or other adenomas causing overproduction of cortisol

Once endogenous hypercortisolism has been identified...

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Identify hypercortisolism

Three Recommended Tests8

  • 1-mg overnight dexamethasone suppression test (DST)
  • Late-night salivary cortisol (LNSC)
  • 24-hour urinary-free cortisol (UFC)

Learn more about these tests

If 2 tests from the list are positive and physiological causes of hypercortisolism have been excluded...

step three arrow

Determine the cause

Determine ACTH-dependent vs ACTH-independent cause7,9
Early-morning ACTH levels

A low ACTH level indicates an ACTH-independent source

Normal or high levels indicate an ACTH-dependent source

The final step in the diagnosis of hypercortisolism is determining the cause of excess cortisol. Initial test results may be equivocal, and additional tests, such as the CRH stimulation test, high-dose DST, or DHEA-S level may be helpful to identify the cause of excess cortisol.10

how the results of cortisol tests determine cushing disease
CRH=corticotropin-releasing hormone; DST=dexamethasone suppression test; DHEA-S=dehydroepiandrosterone sulfate; ACTH=adrenocorticotropic hormone; CT=computed tomography; MRI=magnetic resonance imaging
*Adrenal computed tomography (CT) is then performed, and a more detailed analysis is needed to differentiate among the subtypes of adrenal Cushing syndrome.

Keep up-to-date with the latest information

General approach to adrenal adenoma10,11

What to rule out

  • Malignancy
  • Aldosteronoma (if hypertension)
  • Pheochromocytoma

Testing for autonomous cortisol secretion

  • The 1-mg overnight DST: >1.8 µg/dL (50 nmol/L)*
  • LNSC: May be elevated
  • 2-day DST: Use with certain populations (psychiatric, morbid obesity, alcoholism diabetes, kidney failure)
  • UFC: Low sensitivity

Additional testing for a well-rounded clinical picture

  • Adrenocorticotropic hormone: May be subnormal
  • Dehydroepiandrosterone sulfate: May be subnormal
  • Concurrent metabolic and cardiorenal derangements: Raises level of suspicion
*>1.8 µg/dL (50 nmol/L) is considered abnormal. Adrenal computed tomography is performed, and a more detailed analysis is needed to differentiate among the subtypes of adrenal Cushing syndrome.
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