ACTH test how it is performed what are the risks and potential outcomes

If you are experiencing persistent fatigue or noticing unexplained changes in your health, an ACTH test may help uncover what is happening inside your body. The Adrenocorticotropic Hormone (ACTH) stimulation test is an important diagnostic tool used to evaluate adrenal gland disorders, such as adrenal insufficiency (Addison’s disease) and excess adrenal activity (Cushing’s syndrome).Through this test, doctors assess the adrenal glands’ ability to produce cortisol, a vital hormone that plays a key role in regulating stress response, metabolism, blood pressure, and immune function.But what exactly is this test? How is it performed? And what risks might it involve? In this Dalili Medical article, we will walk you through everything you need to know about the ACTH test, including:

Reasons for performing the test
How to prepare for it
How results are interpreted
Possible risks and side effects

Whether you are experiencing hormone-related symptoms or simply want a better understanding of your health, the ACTH test is an essential step toward an accurate diagnosis and effective treatment plan.

his test helps diagnose adrenal gland disorders and determines whether the adrenal glands are producing adequate cortisol.

How Is the ACTH Test Performed?

Preparation:
A blood sample is taken to measure baseline (pre-stimulation) cortisol levels.
Injection:
A synthetic ACTH hormone (such as cosyntropin) is injected intravenously to stimulate cortisol production.
Waiting Period:
After the injection, blood samples are taken again after 30–60 minutes to measure cortisol levels post-stimulation.
Interpretation:
Cortisol levels before and after stimulation are compared to evaluate adrenal gland function.

Indications for the ACTH Stimulation Test

The test is commonly used to diagnose hormonal conditions such as:

Adrenal insufficiency (Addison’s disease) – inadequate cortisol production
Cushing’s syndrome – excessive cortisol production
Pituitary gland disorders affecting ACTH secretion
Monitoring patients on long-term steroid therapy

Symptoms of Adrenal Insufficiency (Addison’s Disease)

Severe fatigue or generalized weakness
Unexplained weight loss
Low blood pressure, especially upon standing
Persistent nausea and vomiting
Skin hyperpigmentation (especially palms and mouth)

Symptoms of Cushing’s Syndrome

Weight gain, especially in the abdomen and face
Purple or red stretch marks on the skin
High blood pressure
Muscle weakness or osteoporosis
Mood changes such as depression or anxiety

Difference Between the ACTH Test and a Cortisol Test

Cortisol test: Measures cortisol levels at a specific time.
ACTH stimulation test: Measures cortisol levels before and after ACTH stimulation to assess adrenal responsiveness and function.

What Conditions Can Be Diagnosed with the ACTH Test?

The ACTH test is mainly used to diagnose adrenal insufficiency and to determine whether the problem originates in the adrenal glands, pituitary gland, or hypothalamus. The results guide physicians in choosing the most appropriate treatment.

Do I Need to Fast Before the ACTH Test?

In many cases, fasting for 6–8 hours is recommended to ensure accurate results. Requirements may vary depending on your medical condition, so always follow your healthcare provider’s instructions.

Is the ACTH Test Painful?

The test involves blood draws and an injection, which may cause mild discomfort. Most patients tolerate it well. If you have needle anxiety, inform your healthcare provider for additional support.

What If the ACTH Test Results Are Abnormal?

Abnormal results may indicate adrenal dysfunction. Your doctor may recommend further blood tests, imaging studies, or hormone replacement therapy to identify the underlying cause and plan appropriate treatment.

Can Medications Affect ACTH Test Results?

Yes. Medications such as corticosteroids (e.g., prednisone), oral contraceptives, and certain anti-inflammatory drugs can influence cortisol levels. Always inform your healthcare provider about all medications you are taking.

How Long Does the ACTH Test Take?

The test usually takes about one hour, including blood sampling and monitoring after ACTH administration. It is generally a quick outpatient procedure.

Are There Side Effects of the ACTH Test?

Side effects are rare but may include:

Mild redness at the injection site
Temporary nausea
Short-term increase in heart rate

These effects usually resolve quickly. Report any unusual symptoms to your healthcare provider.

Can Stress Affect ACTH Test Results?

Yes. Stress can raise cortisol levels and potentially affect test accuracy. Try to remain calm and relaxed before and during the test. If stress influences results, the test may be repeated later.

Normal Cortisol Levels in the ACTH Stimulation Test

Baseline cortisol: 6–20 µg/dL
Post-ACTH cortisol: At least 18–20 µg/dL is considered a normal response

Reference ranges may vary by laboratory, so interpretation should always be done by a physician.

How Often Is the ACTH Test Needed?

Patients with adrenal insufficiency may need periodic testing to monitor treatment response.
For initial diagnosis, the test may be performed once unless follow-up is required.

Clinical Uses of the ACTH Stimulation Test

Diagnosing primary adrenal insufficiency (Addison’s disease)
Evaluating secondary or tertiary adrenal insufficiency
Monitoring adrenal function after surgery
Detecting congenital adrenal hyperplasia

How Does the ACTH Stimulation Test Work?

The test evaluates how well the adrenal glands respond to synthetic ACTH stimulation:

Timing: Usually performed in the early morning when cortisol levels are highest.
Medication adjustment: Certain medications may need to be stopped beforehand to ensure accurate results.

This test plays a crucial role in diagnosing adrenal and hormonal disorders and guiding effective treatment decisions.

2. Test Procedure

Baseline blood sample:
An initial blood sample is drawn to measure the baseline cortisol level before any stimulation.

Injection of synthetic ACTH:
A synthetic form of ACTH (such as cosyntropin) is injected intravenously. ACTH stimulates the adrenal glands to release cortisol more rapidly and effectively.

Waiting period (30–60 minutes):
After the injection, a short waiting period allows the adrenal glands to secrete cortisol in response to stimulation.

Second blood sample:
After the specified time, a second blood sample is taken to measure cortisol levels following adrenal stimulation.

3. Interpretation of Results

Normal results:
If the adrenal glands are functioning normally, cortisol levels will rise significantly after stimulation. Normal post-stimulation levels typically range from 18–22 µg/dL.

Abnormal results:
If cortisol levels do not rise adequately after stimulation, this may indicate adrenal insufficiency (such as Addison’s disease) or adrenal hyperfunction (such as Cushing’s syndrome). In some cases, an abnormal response may be due to pituitary gland problems or other hormonal disorders.

4. Additional Tests

In some cases, the doctor may request further investigations to determine the cause of abnormal results, such as:

Urinary free cortisol test
Tests to measure other hormone levels, such as prolactin or thyroid-stimulating hormone (TSH)

Requirements for the ACTH Stimulation Test

The ACTH stimulation test is a sensitive examination that requires careful preparation to ensure accurate results.

1. Appropriate timing

The test is usually performed early in the morning (between 7:00 and 9:00 AM), when cortisol levels are naturally highest. Testing later in the day may reduce accuracy due to the normal decline of cortisol in the evening.

2. Discontinuation of certain medications

Corticosteroids: Medications such as prednisone or dexamethasone should be stopped before the test, as they can suppress adrenal function and lead to inaccurate results.
Other medications: Antifungals, antidepressants, or blood pressure medications may also affect results.
Medical consultation: Always inform your doctor about all medications you take; dosage adjustments or temporary discontinuation may be required.

3. Rest and stress avoidance

Avoid physical and emotional stress: Stress can temporarily raise cortisol levels.
Avoid strenuous exercise before the test.

4. Fasting

In some cases, fasting for 6–8 hours before the test may be required to minimize dietary effects on hormone levels.

5. Medical history disclosure

Inform your doctor if you have conditions such as thyroid disease, liver or kidney disease, acute infections, or pituitary disorders, as these may affect test results.

6. Pregnancy

During pregnancy, physiological changes can alter cortisol levels. Inform your doctor if you are pregnant before the test.

7. Dietary supplements

Some supplements or herbal products (e.g., vitamin D or antioxidants) may affect adrenal function. Discuss any supplements you take with your doctor.

Factors That May Affect ACTH Test Results

1. Medications

Corticosteroids can suppress cortisol production.
Other hormone-affecting medications (antifungals, antidepressants) may alter results.

2. Timing of the test

Performing the test outside the recommended morning hours may lead to falsely low cortisol levels.

3. Stress and anxiety

Emotional stress, anxiety, or intense physical exercise can temporarily elevate cortisol levels.

4. Other medical conditions

Acute infections or inflammation
Pituitary disorders affecting ACTH secretion
Liver or kidney disease affecting cortisol metabolism

5. Pregnancy

Physiological hormonal changes during pregnancy may alter cortisol measurements.

6. Other hormonal disorders

Thyroid disorders
Hormone-secreting tumors (pituitary or adrenal tumors)

7. Nutrition and diet

Malnutrition or vitamin deficiencies
Heavy meals or prolonged fasting

8. Physical stress

Recent injuries or surgery can temporarily raise cortisol levels.

9. Environmental changes or travel

Time zone changes or environmental stress may disrupt hormonal balance.

Risks of the ACTH Stimulation Test

The ACTH test is generally safe, but mild side effects may occur:

1. Pain or bruising at the injection site

Mild pain, swelling, or bruising may occur and usually resolves quickly.

2. Dizziness or fainting

Some individuals may feel lightheaded, especially if anxious or sensitive to needles.

3. Temporary rise in cortisol

This may cause short-term sweating or anxiety.

4. Rare allergic reactions

Symptoms may include rash, itching, or swelling of the face or throat. Immediate medical attention is required if this occurs.

5. Temporary increase in blood pressure or anxiety

Usually short-lived and resolves within hours.

6. Gastrointestinal discomfort

Mild nausea or stomach cramps may occur temporarily.

Stages of Interpreting ACTH Test Results

1. Normal results

Baseline cortisol:
Usually 5–25 µg/dL in the early morning.

Post-stimulation cortisol:
Should rise to 18–22 µg/dL, indicating normal adrenal function.

2. Abnormal results

Adrenal insufficiency (Addison’s disease)

Finding: Inadequate rise in cortisol after stimulation
Interpretation: The adrenal glands cannot respond properly to ACTH
Symptoms: Fatigue, weight loss, low blood pressure, nausea, skin pigmentation, dizziness

Cushing’s syndrome (adrenal hyperfunction)

Finding: Persistently high cortisol levels (>22 µg/dL)
Interpretation: Excessive cortisol production
Symptoms: Central weight gain, purple stretch marks, osteoporosis, hypertension, high blood sugar