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Cortisol Stimulation Test – Procedure and Results

The cortisol stimulation test is a diagnostic procedure used to assess adrenal gland function. It evaluates whether the adrenal glands can produce sufficient cortisol in response to a stimulation signal.

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Things worth knowing about "Cortisol Stimulation Test"

The cortisol stimulation test is a diagnostic procedure used to assess adrenal gland function. It evaluates whether the adrenal glands can produce sufficient cortisol in response to a stimulation signal.

What Is the Cortisol Stimulation Test?

The cortisol stimulation test – also known as the ACTH stimulation test, cosyntropin test, or Synacthen test – is an endocrinological diagnostic procedure used to evaluate the function of the adrenal cortex. During the test, a synthetic form of ACTH (adrenocorticotropic hormone), such as tetracosactide (Synacthen) or cosyntropin, is administered to stimulate the adrenal glands to release cortisol. Blood cortisol levels are then measured to determine whether the adrenal glands respond adequately.

When Is the Test Used?

The cortisol stimulation test is primarily indicated in the following situations:

Suspected adrenal insufficiency (primary or secondary)
Evaluation of Addison disease (primary adrenocortical insufficiency)
Suspected pituitary insufficiency (secondary adrenal insufficiency)
Assessment of adrenal function after long-term corticosteroid therapy
Investigation of unexplained chronic fatigue, hypotension, or hyponatremia

How Is the Test Performed?

The cortisol stimulation test follows a standardized protocol:

Baseline measurement: A blood sample is taken to measure the resting cortisol level before stimulation.
Injection: A dose of synthetic ACTH (typically 250 µg of tetracosactide) is administered intravenously or intramuscularly.
Follow-up measurements: Blood samples are collected at 30 and/or 60 minutes after injection to measure the cortisol response.

The test is usually performed in the morning, when baseline cortisol levels are physiologically at their highest.

Interpreting the Results

A healthy adrenal system responds to ACTH stimulation with a significant rise in serum cortisol. Most clinical guidelines define a peak cortisol level of at least 500–550 nmol/L (18–20 µg/dL) as a normal response.

Normal response: Adrenal function is adequate; clinically significant adrenal insufficiency is unlikely.
Insufficient response: Suggests primary or secondary adrenal insufficiency; further diagnostic workup is required.

Primary vs. Secondary Adrenal Insufficiency

In primary adrenal insufficiency (e.g., Addison disease), the adrenal cortex itself is damaged and produces little to no cortisol even with stimulation. In secondary adrenal insufficiency – caused by dysfunction of the pituitary gland or hypothalamus – the response may also be blunted, especially when the adrenal cortex has undergone prolonged atrophy due to lack of ACTH stimulation.

Risks and Side Effects

The cortisol stimulation test is generally very well tolerated. Possible but rare side effects of the ACTH injection include:

Local reactions at the injection site
Mild flushing or sensation of warmth
In rare cases, allergic reactions to the synthetic hormonal preparation

Serious complications are extremely uncommon. The test should always be performed under medical supervision.

Patient Preparation

Patients should be aware of the following before the test:

Corticosteroids (e.g., cortisone, prednisolone) can interfere with results and should be discontinued or adjusted prior to the test if clinically safe.
The test is typically performed fasting or after a light breakfast.
All current medications should be disclosed to the treating physician beforehand.

References

Arlt W. - Assessment of the patient with suspected adrenal insufficiency. - Endocrinology and Metabolism Clinics of North America, 2009.
Bornstein SR et al. - Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline. - Journal of Clinical Endocrinology and Metabolism, 2016.
World Health Organization (WHO) - Endocrine Disorders: Adrenal Insufficiency - Diagnostic Guidelines, 2020.

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