Introduction: When to Seek Diagnostic Testing

Abnormal cortisol levels can affect your health in significant ways, but knowing when to seek medical help is not always straightforward. Cortisol is a hormone produced by your adrenal glands that helps your body respond to stress, regulate blood sugar, control blood pressure, and manage inflammation. When cortisol levels become too high or too low for extended periods, you may experience symptoms that interfere with daily life and overall health.^[1]

You should consider seeking diagnostic testing if you experience persistent symptoms that don’t improve over time. For high cortisol levels, also called hypercortisolism, warning signs include unexplained weight gain concentrated in your face, upper back, and abdomen, along with thin arms and legs. You might notice your skin bruising easily, developing purple stretch marks on your stomach or thighs, or healing slowly from wounds. Other concerning symptoms include high blood pressure that’s difficult to control, muscle weakness, irregular menstrual periods in women, or excess facial hair growth.^[2][3]

For low cortisol levels, called hypocortisolism, you should seek medical attention if you experience constant fatigue that doesn’t improve with rest, unexplained weight loss, persistent nausea or vomiting, severe abdominal pain, low blood pressure, or lightheadedness. These symptoms often develop gradually and can be easily dismissed as general tiredness or stress, but they may indicate a serious condition like Addison disease that requires immediate medical care.^[2][4]

People taking high doses of steroid medications like prednisone or dexamethasone for conditions such as asthma, rheumatoid arthritis, or inflammatory diseases should also be aware they may develop cortisol-related problems. Long-term use of these medications can suppress your body’s natural cortisol production, and stopping them suddenly can cause dangerous drops in cortisol levels.^[1][4]

Classic Diagnostic Methods for Identifying Cortisol Abnormalities

When your healthcare provider suspects abnormal cortisol levels, they will use several types of tests to measure the hormone in your body and identify the underlying cause. Because cortisol levels naturally change throughout the day, with the highest levels typically occurring in the morning and the lowest around midnight, timing is crucial for accurate testing.^[1][4]

Blood Testing for Cortisol

Blood tests are the most common way to measure cortisol levels. A healthcare professional will draw blood from a vein in your arm using a small needle, which usually takes less than five minutes. You may feel a slight sting when the needle goes in or comes out. Because cortisol levels vary during the day, your doctor may ask you to have blood drawn at specific times, often once in the early morning between 6 and 8 a.m., and again in the afternoon around 4 p.m.^[4][5]

Normal cortisol levels in the morning typically range from 10 to 20 micrograms per deciliter, while afternoon levels are usually between 3 and 10 micrograms per deciliter. However, these ranges can vary depending on the laboratory used, so your doctor will interpret your results based on the specific reference ranges provided with your test.^[5]

Urine Testing

A 24-hour urine collection test measures how much cortisol your body releases over a full day. This test provides valuable information because it captures cortisol levels throughout the entire day and night, rather than just at one moment in time. You’ll be given a special container and instructions on how to collect all your urine over a 24-hour period. You’ll typically start collecting urine in the morning, discard the first morning urine, and then save all urine produced during the rest of the day, night, and the following morning.^[4]

This test is particularly useful for diagnosing conditions where cortisol is consistently too high, such as Cushing syndrome. The 24-hour collection helps account for the natural ups and downs in cortisol production throughout the day.^[13]

Saliva Testing

Saliva tests offer a convenient, non-invasive way to measure cortisol levels, especially at times when visiting a medical facility would be difficult. Your doctor may ask you to collect saliva samples at home at different times of the day, particularly late at night before bedtime. This is important because cortisol levels should naturally drop in the evening in healthy individuals. If your late-night cortisol remains elevated, it could indicate a problem.^[4][13]

To collect a saliva sample, you’ll typically place a small cotton swab in your mouth or spit into a tube. The sample is then sent to a laboratory for analysis. Saliva testing is particularly useful for detecting Cushing syndrome, as people with this condition often have high cortisol levels even at night when cortisol should be low.^[13]

ACTH Stimulation Test

The ACTH stimulation test helps determine whether your adrenal glands can produce adequate amounts of cortisol. ACTH (adrenocorticotropic hormone) is a hormone made by your pituitary gland that signals your adrenal glands to produce cortisol. During this test, a healthcare provider will first measure your baseline cortisol level with a blood sample. Then you’ll receive an injection of synthetic ACTH, and your cortisol levels will be measured again after 30 to 60 minutes.^[4][17]

In healthy individuals, cortisol levels should rise significantly after the ACTH injection. If your cortisol doesn’t increase appropriately, it suggests your adrenal glands aren’t functioning properly, which may indicate Addison disease or another form of adrenal insufficiency.^[17][20]

Additional Hormone Testing

Your doctor will likely order other blood tests alongside cortisol measurements to help identify the underlying cause of abnormal levels. These may include measuring ACTH levels directly, as well as checking other hormones and substances affected by cortisol imbalances, such as blood glucose, sodium, potassium, and antibodies that could indicate autoimmune disease. The pattern of hormone levels helps doctors distinguish between different types of cortisol disorders.^[4][5]

Imaging Studies

Once blood or urine tests confirm abnormal cortisol levels, imaging tests help identify the source of the problem. A CT scan (computed tomography) of your abdomen can show the size and appearance of your adrenal glands and detect tumors or other abnormalities. An MRI (magnetic resonance imaging) of your pituitary gland in your brain can identify tumors or damage that might be affecting cortisol production. These imaging studies don’t measure cortisol directly but help pinpoint what’s causing the hormone imbalance.^[5][13]

Distinguishing Between Different Causes

Diagnosing cortisol abnormalities can be complex because multiple conditions can cause similar symptoms. If initial tests show high cortisol, your healthcare provider needs to determine whether it’s due to medication use, a pituitary tumor causing Cushing disease, an adrenal tumor, or an ectopic tumor elsewhere in the body producing cortisol or related hormones. Additional specialized tests may be needed to distinguish between these possibilities.^[13][16]

For low cortisol, doctors must determine whether the problem originates in the adrenal glands themselves (primary adrenal insufficiency or Addison disease) or whether it’s caused by insufficient ACTH production from the pituitary gland (secondary adrenal insufficiency). Blood tests measuring both cortisol and ACTH levels together, along with the ACTH stimulation test, help make this distinction.^[17][20]

Diagnostics for Clinical Trial Qualification

While the sources provided do not contain specific information about diagnostic tests or criteria used to qualify patients for clinical trials related to cortisol abnormalities, standard clinical practice would suggest that the same diagnostic methods described above would be used to confirm eligibility for research studies. Patients entering clinical trials for conditions like Cushing syndrome or Addison disease would typically need documented evidence of abnormal cortisol levels through blood, urine, or saliva testing, along with imaging studies to identify the underlying cause. The severity and duration of the condition, as well as previous treatments attempted, would likely factor into trial eligibility criteria.