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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

Recommended1,3

  • 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

Suggested1,3

  • 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

Patient Story

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“I tried taking blood pressure medication. I tried going off birth control. I even tried taking phentermine to counteract the weight gain. Nothing helped ...”

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.3-5

“Patients with an adrenal incidentaloma should undergo evaluation clinically, biochemically, and radiographically for signs and symptoms of hypercortisolism.”

—AACE/AAES Guidelines6
A portion of screened adrenal adenomas are found to be cortisol secretingAn estimated 5%-30% of screened adrenal adenomas were found to be cortisol-secreting

Diagnosing hypercortisolism

Step 1

Consider the index of suspicion6,7

  • Rule out exogenous hypercortisolism
  • Adrenal adenomas: Rule out malignancy, aldosteronoma (if hypertensive), and pheochromocytoma

Step 2

Identify hypercortisolism8

Perform one of the
following tests

  • 1-mg DST
  • LNSC (≥2 tests)
  • UFC (≥2 tests)

Look for a cause if

  • 2 tests from the list are positive
  • Physiologic causes of hypercortisolism have been excluded

Learn more about cortisol testing

Step 3

Determine the
cause7,9-11

Determine ACTH-dependent vs ACTH-independent cause

  • A low ACTH level suggests ACTH-independent source
  • Inappropriately normal or high levels suggest an ACTH-dependent source

The following additional tests may further support the diagnosis of hypercortisolism and/or help in identifying the source of excess cortisol:

Suspected ACTH-independent source

  • DHEA-S
  • Adrenal CT

Suspected ACTH-dependent source

  • IPSS
  • CRH stimulation test
  • Pituitary MRI
ACTH=adrenocorticotropic hormone; CRH=corticotropin-releasing hormone; CT=computed tomography; DHEA-S=dehydroepiandrosterone sulfate; DST=overnight dexamethasone suppression test; IPSS=inferior petrosal sinus sampling; LNSC=late night salivary cortisol; MRI=magnetic resonance imaging; UFC=urinary free cortisol.

General approach to adrenal adenoma6,10

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What to rule out

  • Malignancy
  • Aldosteronoma (if hypertensive)
  • Pheochromocytoma
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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
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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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