Cushing Syndrome

Cushing Syndrome Lab Tests and health information

Is your cortisol level high?

Our lab tests can accurately measure your hormone levels to see if your body makes excess cortisol and if you have Cushing syndrome.

Cortisol is a hormone that your body produces naturally. However, if your cortisol levels are too high, it can cause serious health problems. High cortisol levels can cause many symptoms, including weight gain, stretch marks, and fatigue. It can also lead to high blood pressure and diabetes, depression, osteoporosis, and infertility due to this condition. If you're experiencing any of these symptoms, it may be time to get tested for Cushing Syndrome.

If you want to learn more about Cushing Syndrome and the lab tests that can help you, click on the title of the article below.

Cushing Syndrome and Lab Testing - What You Need to Know

If you're looking for answers about why your cortisol levels are so high and what to do next, we can help! We offer comprehensive testing services that will give you the information you need to decide your health. The best way to diagnose Cushing's Syndrome is through blood tests that measure your cortisol levels. Our lab testing is quick, easy and accurate, so you know exactly what's going on with your body.

The testing process is simple. Select from the lab tests listed below that are right for you, have your specimen collected at a local testing center, and review your test results typically in 1 to 2 days after your blood is collected. We'll notify you when they're ready, and you'll find everything you need in your private health portal. You can then share these results with your doctor or loved ones. 


Name Matches

Cushing Syndrome Panel

  • ACTH, Plasma
  • Complete Blood Count (CBC) with Differential and Platelets Blood Test
  • Comprehensive Metabolic Panel (CMP)
  • Cortisol, Free, 24-Hour Urine with Creatinine, LC/MS/MS
  • Cortisol, Total
  • Glucose Tolerance Test, 2 Specimens (75g) 

Cushing Syndrome Panel with Dexamethasone

  • ACTH, Plasma
  • Complete Blood Count (CBC) with Differential and Platelets Blood Test
  • Comprehensive Metabolic Panel (CMP)
  • Cortisol, Free, 24-Hour Urine with Creatinine, LC/MS/MS
  • Dexamethasone
  • Glucose Tolerance Test, 2 Specimens (75g) 
  • Cortisol, Total

Most Popular

Cortisol is increased in Cushing's Disease and decreased in Addison's Disease (adrenal insufficiency). Patient needs to have the specimen collected between 7 a.m.-9 a.m.


Most Popular
Cortisol is increased in Cushing's Disease and decreased in Addison's Disease (adrenal insufficiency).

Cortisol, LC/MS/MS, Saliva Collection Kit

  1. Pick up the Cortisol, LC/MS/MS, Saliva Collection Kit from the Patient Service Center that is selected when placing the order.
  2. Collection Instructions

    1. Place contents on a clean and dry surface.
    2. Firmly attach the Collection Tube (E) provided to the base (D) of the Compression tube (C) (Figure 1). In preparation for saliva collection, pool saliva in the mouth. Sample collection may now begin.
    3. Place the tip of the pad of the Collector (A) where saliva has pooled (Figure 2).
    4. The Collector (A) may be removed from the mouth periodically to read the SVAI, but resume collection immediately afterward. Collect until the appearance of the SVAI (B) changes from white to fully red (Figure 3). The collection procedure should last approximately 1-5 minutes.
    6. Place the white absorbent pad end into the Compression Tube (C) holding the Collector (A) in an upright and vertical position and firmly push the plunger downwards to transfer saliva from the absorbent pad into the Collection Tube (E). Push and hold for 30 seconds (Figure 4).
    6. Gently remove the Collection Tube (E) from the end of the Compression Tube (C). It is appropriate to remove the Collection Tube (E) during expression if necessary due to foaming. Close the lid on the tube tightly.
    7. Label the collected sample immediately, include date and time of collection and store at refrigerated temperatures for shipment.
    For Technical Support, call 1-800-642-4657 ext. 2904.

    Transport Temperature

    Room temperature

     


Urinary Free Cortisol is useful in the detection of patients with Cushing's syndrome for whom Free Cortisol concentrations are elevated.

Most Popular

Cortisol is increased in Cushing's Disease and decreased in Addison's Disease (adrenal insufficiency). Patient needs to have the specimen collected between 3 p.m - 5 p.m.


Cortisol is increased in Cushing's disease and decreased in Addison's disease (adrenal insufficiency).

Cortisol is increased in Cushing's disease and decreased in Addison's disease (adrenal insufficiency).

Cortisol is increased in Cushing's disease and decreased in Addison's disease (adrenal insufficiency). This test requires 5 individual serum blood specimens to be drawn; 30 minutes apart. Patient should plan for 3 hours at the patient service center.


Free cortisol is useful in the detection of patients with Cushing's syndrome for whom free cortisol concentrations are elevated.

Reference Range(s)

Adult    
8:00 A.M.-10:00 A.M. 0.07-0.93 µg/dL
4:00 P.M.-6:00 P.M. 0.04-0.45 µg/dL
10:00 P.M.-11:00 P.M. 0.04-0.35 µg/dL

The cortisol response to infusion of synthetic ACTH is useful in diagnosing patients with adrenal insufficiency (Addison's disease).


Determination of ACTH is useful in differentiating between primary and secondary adrenocortical hypo- and hyperfunctional disorders: Addison's disease, Cushing's syndrome, adrenal carcinoma, ectopic ACTH syndrome, and adrenal nodular hyperplasia.

Description: A CBC or Complete Blood Count with Differential and Platelets test is a blood test that measures many important features of your blood’s red and white blood cells and platelets. A Complete Blood Count can be used to evaluate your overall health and detect a wide variety of conditions such as infection, anemia, and leukemia. It also looks at other important aspects of your blood health such as hemoglobin, which carries oxygen. 

Also Known As: CBC test, Complete Blood Count Test, Total Blood Count Test, CBC with Differential and Platelets test, Hemogram test  

Collection Method: Blood Draw 

Specimen Type: Whole Blood 

Test Preparation: No preparation required 

When is this test ordered?  

The complete blood count (CBC) is an extremely common test. When people go to the doctor for a standard checkup or blood work, they often get a CBC. Suppose a person is healthy and their results are within normal ranges. In that case, they may not need another CBC unless their health condition changes, or their healthcare professional believes it is necessary. 

When a person exhibits a variety of signs and symptoms that could be connected to blood cell abnormalities, a CBC may be done. A health practitioner may request a CBC to help diagnose and determine the severity of lethargy or weakness, as well as infection, inflammation, bruises, or bleeding. 

When a person is diagnosed with a disease that affects blood cells, a CBC is frequently done regularly to keep track of their progress. Similarly, if someone is being treated for a blood condition, a CBC may be performed on a regular basis to see if the treatment is working. 

Chemotherapy, for example, can influence the generation of cells in the bone marrow. Some drugs can lower WBC counts in the long run. To monitor various medication regimens, a CBC may be required on a regular basis. 

What is being tested? 

The complete blood count (CBC) is a blood test that determines the number of cells in circulation. White blood cells (WBCs), red blood cells (RBCs), and platelets (PLTs) are three types of cells suspended in a fluid called plasma. They are largely created and matured in the bone marrow and are released into the bloodstream when needed under normal circumstances. 

A CBC is mainly performed with an automated machine that measures a variety of factors, including the number of cells present in a person's blood sample. The findings of a CBC can reveal not only the quantity of different cell types but also the physical properties of some of the cells. 

Significant differences in one or more blood cell populations may suggest the presence of one or more diseases. Other tests are frequently performed to assist in determining the reason for aberrant results. This frequently necessitates visual confirmation via a microscope examination of a blood smear. A skilled laboratory technician can assess the appearance and physical features of blood cells, such as size, shape, and color, and note any anomalies. Any extra information is taken note of and communicated to the healthcare provider. This information provides the health care provider with further information about the cause of abnormal CBC results. 

The CBC focuses on three different types of cells: 

WBCs (White Blood Cells) 

The body uses five different types of WBCs, also known as leukocytes, to keep itself healthy and battle infections and other types of harm. The five different leukocytes are eosinophiles, lymphocytes, neutrophiles, basophils, and monocytes. They are found in relatively steady numbers in the blood. Depending on what is going on in the body, these values may momentarily rise or fall. An infection, for example, can cause the body to manufacture more neutrophils in order to combat bacterial infection. The amount of eosinophils in the body may increase as a result of allergies. A viral infection may cause an increase in lymphocyte production. Abnormal (immature or mature) white cells multiply fast in certain illness situations, such as leukemia, raising the WBC count. 

RBCs (Red Blood Cells) 

The bone marrow produces red blood cells, also known as erythrocytes, which are transferred into the bloodstream after maturing. Hemoglobin, a protein that distributes oxygen throughout the body, is found in these cells. Because RBCs have a 120-day lifespan, the bone marrow must constantly manufacture new RBCs to replace those that have aged and disintegrated or have been lost due to hemorrhage. A variety of diseases, including those that cause severe bleeding, can alter the creation of new RBCs and their longevity. 

The CBC measures the number of RBCs and hemoglobin in the blood, as well as the proportion of RBCs in the blood (hematocrit), and if the RBC population appears to be normal. RBCs are generally homogeneous in size and shape, with only minor differences; however, considerable variances can arise in illnesses including vitamin B12 and folate inadequacy, iron deficiency, and a range of other ailments. Anemia occurs when the concentration of red blood cells and/or the amount of hemoglobin in the blood falls below normal, resulting in symptoms such as weariness and weakness. In a far smaller percentage of cases, there may be an excess of RBCs in the blood (erythrocytosis or polycythemia). This might obstruct the flow of blood through the tiny veins and arteries in extreme circumstances. 

Platelets 

Platelets, also known as thrombocytes, are small cell fragments that aid in the regular clotting of blood. A person with insufficient platelets is more likely to experience excessive bleeding and bruises. Excess platelets can induce excessive clotting or excessive bleeding if the platelets are not operating properly. The platelet count and size are determined by the CBC. 

Related Tests and Panels: 

  • CBC (Blood Count Test) with Smear Review
  • Hemoglobin
  • Hematocrit
  • White Blood Cell Count (WBC Test)
  • Reticulocytes
  • Iron and Total Iron Binding Capacity
  • Basic Metabolic Panel
  • Comprehensive Metabolic Panel
  • Lipid Panel
  • Vitamin B12 and Folate
  • Prothrombin with INR and Partial Thromboplastin Times
  • Sed Rate (ESR)
  • C-Reactive Protein
  • Epstein-Barr Virus
  • Von Willebrand Factor Antigen

Related Conditions: 

  • Anemia
  • Aplastic Anemia
  • Iron Deficiency Anemia
  • Vitamin B12 and Folate Deficiency
  • Sickle Cell Anemia
  • Heart Disease
  • Thalassemia
  • Leukemia
  • Autoimmune Disorders
  • Cancer
  • Bleeding Disorders
  • Inflammation
  • Epstein-Barr Virus
  • Mononucleosis

Commonly Asked Questions: 

How is this type of test used by my health care provider? 

The complete blood count (CBC) is a common, comprehensive screening test used to measure a person's overall health status.  

What do my Complete Blood Count results mean? 

A low Red Blood Cell Count, also known as anemia, could be due many different causes such as chronic bleeding, a bone marrow disorder, and nutritional deficiency just to name a few. A high Red Blood Cell Count, also known as polycythemia, could be due to several conditions including lung disease, dehydration, and smoking. Both Hemoglobin and Hematocrit tend to reflect Red Blood Cell Count results, so if your Red Blood Cell Count is low, your Hematocrit and Hemoglobin will likely also be low. Results should be discussed with your health care provider who can provide interpretation of your results and determine the appropriate next steps or lab tests to further investigate your health. 

What do my Differential results mean? 

A low White Blood Cell count or low WBC count, also known as leukopenia, could be due to a number of different disorders including autoimmune issues, severe infection, and lymphoma. A high White Blood Cell count, or high WBC count, also known as leukocytosis, can also be due to many different disorders including infection, leukemia, and inflammation. Abnormal levels in your White Blood Cell Count will be reflected in one or more of your different white blood cells. Knowing which white blood cell types are affected will help your healthcare provider narrow down the issue. Results should be discussed with your health care provider who can provide interpretation of your results and determine the appropriate next steps or lab tests to further investigate your health. 

What do my Platelet results mean? 

A low Platelet Count, also known as thrombocytopenia, could be due to a number of different disorders including autoimmune issues, viral infection, and leukemia. A high Platelet Count, also known as Thrombocytosis, can also be due to many different disorders including cancer, iron deficiency, and rheumatoid arthritis. Results should be discussed with your health care provider who can provide interpretation of your results and determine the appropriate next steps or lab tests to further investigate your health. 

NOTE: Only measurable biomarkers will be reported. Certain biomarkers do not appear in healthy individuals.

We advise having your results reviewed by a licensed medical physician for proper interpretation of your results.


Description: A Comprehensive Metabolic Panel or CMP is a blood test that is a combination of a Basic Metabolic Panel, a Liver Panel, and electrolyte panel, and is used to screen for, diagnose, and monitor a variety of conditions and diseases such as liver disease, diabetes, and kidney disease. 

Also Known As: CMP, Chem, Chem-14, Chem-12, Chem-21, Chemistry Panel, Chem Panel, Chem Screen, Chemistry Screen, SMA 12, SMA 20, SMA 21, SMAC, Chem test

Collection Method: 

Blood Draw 

Specimen Type: 

Serum 

Test Preparation: 

9-12 hours fasting is preferred. 

When is this test ordered:  

A CMP is frequently requested as part of a lab test for a medical evaluation or yearly physical. A CMP test consists of many different tests that give healthcare providers a range of information about your health, including liver and kidney function, electrolyte balance, and blood sugar levels. To confirm or rule out a suspected diagnosis, abnormal test results are frequently followed up with other tests that provide a more in depth or targeted analysis of key areas that need investigating. 

What is being tested? 

The complete metabolic panel (CMP) is a set of 20 tests that provides critical information to a healthcare professional about a person's current metabolic status, check for liver or kidney disease, electrolyte and acid/base balance, and blood glucose and blood protein levels. Abnormal results, particularly when they are combined, can suggest a problem that needs to be addressed. 

The following tests are included in the CMP: 

  • Albumin: this is a measure of Albumin levels in your blood. Albumin is a protein made by the liver that is responsible for many vital roles including transporting nutrients throughout the body and preventing fluid from leaking out of blood vessels. 

  • Albumin/Globulin Ratio: this is a ratio between your total Albumin and Globulin  

  • Alkaline Phosphatase: this is a measure of Alkaline phosphatase or ALP in your blood. Alkaline phosphatase is a protein found in all body tissues, however the ALP found in blood comes from the liver and bones. Elevated levels are often associated with liver damage, gallbladder disease, or bone disorder. 

  • Alt: this is a measure of Alanine transaminase or ALT in your blood. Alanine Aminotransferase is an enzyme found in the highest amounts in the liver with small amounts in the heart and muscles. Elevated levels are often associated with liver damage. 

  • AST: this is a measure of Aspartate Aminotransferase or AST. Aspartate Aminotransferase is an enzyme found mostly in the heart and liver, with smaller amounts in the kidney and muscles. Elevated levels are often associated with liver damage. 

  • Bilirubin, Total: this is a measure of bilirubin in your blood. Bilirubin is an orange-yellowish waste product produced from the breakdown of heme which is a component of hemoglobin found in red blood cells. The liver is responsible for removal of bilirubin from the body. 

  • Bun/Creatinine Ratio: this is a ratio between your Urea Nitrogen (BUN) result and Creatinine result.  

  • Calcium: this is a measurement of calcium in your blood. Calcium is the most abundant and one of the most important minerals in the body as it essential for proper nerve, muscle, and heart function. 

  • Calcium: is used for blood clot formation and the formation and maintenance of bones and teeth. 

  • Carbon Dioxide: this is a measure of carbon dioxide in your blood. Carbon dioxide is a negatively charged electrolyte that works with other electrolytes such as chloride, potassium, and sodium to regulate the body’s acid-base balance and fluid levels.  

  • Chloride: this is a measure of Chloride in your blood. Chloride is a negatively charged electrolyte that works with other electrolytes such as potassium and sodium to regulate the body’s acid-base balance and fluid levels. 

  • Creatinine: this is a measure of Creatinine levels in your blood. Creatinine is created from the breakdown of creatine in your muscles and is removed from your body by the kidneys. Elevated creatinine levels are often associated with kidney damage. 

  • Egfr African American: this is a measure of how well your kidneys are functioning. Glomeruli are tiny filters in your kidneys that filter out waste products from your blood for removal while retaining important substances such as nutrients and blood cells. 

  • Egfr Non-Afr. American: this is a measure of how well your kidneys are functioning. Glomeruli are tiny filters in your kidneys that filter out waste products from your blood for removal while retaining important substances such as nutrients and blood cells. 

  • Globulin: this is a measure of all blood proteins in your blood that are not albumin. 

  • Glucose: this is a measure of glucose in your blood. Glucose is created from the breakdown of carbohydrates during digestion and is the body’s primary source of energy. 

  • Potassium: this is a measure of Potassium in your blood. Potassium is an electrolyte that plays a vital role in cell metabolism, nerve and muscle function, and transport of nutrients into cells and removal of wastes products out of cells. 

  • Protein, Total: this is a measure of total protein levels in your blood. 
    Sodium: this is a measure of Sodium in your blood. Sodium is an electrolyte that plays a vital role in nerve and muscle function. 

  • Urea Nitrogen (Bun): this is a measure of Urea Nitrogen in your blood, also known as Blood UreaNitrogen (BUN). Urea is a waste product created in the liver when proteins are broken down into amino acids. Elevated levels are often associated with kidney damage. 

Related Tests and Panels: 

  • Complete Blood Count with Differential and Platelets
  • Iron and Total Iron Binding Capacity
  • Basic Metabolic Panel
  • Lipid Panel
  • Vitamin B12 and Folate
  • Prothrombin with INR and Partial Thromboplastin Times
  • Sed Rate (ESR)
  • C-Reactive Protein

Related Conditions: 

  • Diabetes
  • Kidney Disease
  • Liver Disease
  • Hypertension

Commonly Asked Questions: 

How is this test used by my health care provider? 

The comprehensive metabolic panel (CMP) is a broad screening tool for assessing organ function and detecting diseases like diabetes, liver disease, and kidney disease. The CMP test may also be requested to monitor known disorders such as hypertension and to check for any renal or liver-related side effects in persons taking specific drugs. If a health practitioner wants to follow two or more separate CMP components, the full CMP might be ordered because it contains more information. 

What do my Comprehensive Metabolic Panel test results mean? 

The results of the tests included in the CMP are usually analyzed together to look for patterns. A single abnormal test result may indicate something different than a series of abnormal test findings. A high result on one of the liver enzyme tests, for example, is not the same as a high result on several liver enzyme tests. 

Several sets of CMPs, frequently performed on various days, may be examined to gain insights into the underlying disease and response to treatment, especially in hospitalized patients. 

Out-of-range findings for any of the CMP tests can be caused by a variety of illnesses, including kidney failure, breathing issues, and diabetes-related complications, to name a few. If any of the results are abnormal, one or more follow-up tests are usually ordered to help determine the reason and/or establish a diagnosis. 

Is there anything else I should know? 

A wide range of prescription and over-the-counter medications can have an impact on the results of the CMP's components. Any medications you're taking should be disclosed to your healthcare professional. Similarly, it is critical to provide a thorough history because many other circumstances can influence how your results are interpreted. 

What's the difference between the CMP and the BMP tests, and why would my doctor choose one over the other? 

The CMP consists of 14 tests, while the basic metabolic panel (BMP) is a subset of those with eight tests. The liver (ALP, ALT, AST, and bilirubin) and protein (albumin and total protein) tests are not included. If a healthcare provider wants a more thorough picture of a person's organ function or to check for specific illnesses like diabetes or liver or kidney disease, he or she may prescribe a CMP rather than a BMP. 

We advise having your results reviewed by a licensed medical physician for proper interpretation of your results.

Please note the following regarding BUN/Creatinine ratio: 

The lab does not report the calculation for the BUN/Creatinine Ratio unless one or both biomarkers’ results fall out of the published range. 

If you still wish to see the value, it's easy to calculate. Simply take your Urea Nitrogen (BUN) result and divide it by your Creatinine result.  

As an example, if your Urea Nitrogen result is 11 and your Creatinine result is 0.86, then you would divide 11 by 0.86 and get a BUN/Creatinine Ratio result of 12.79. 


Dexamethasone

 

Clinical Significance

Test used in the differential diagnosis of Cushing's syndrome.


This test is used for the routine diagnosis of diabetes in children and the non-pregnant adult. For pregnant females see test "Glucose Tolerance Test, Gestational, 4 Specimens (100 g)". For appropriate interpretation of this test, the patient must fast overnight and ingest a 75 g load of glucose, immediately after, a fasting specimen is obtained. For children, the glucose load is 1.75 g/Kg of ideal body weight, up to 75 g glucose. The diagnosis of diabetes is made if the fasting glucose is ?126 mg/dL or if the 2-hour specimen is ?200 mg/dL.


The signs and symptoms of Cushing Syndrome are the results of cortisol levels that are abnormally high, which is referred to as hypercortisolism. Cortisol is a steroidal hormone that is produced by the cortex, which is the outer layer of the adrenal gland.

The hormone has multiple functions, including: 

  • The break-down of fat. 
  • Encourages glucose production in the liver. 
  • Assists in the reaction to emotional and physical stress. 
  • Regulates blood pressure. 
  • Controls inflammation. 
  • Affects the function of the cardiovascular system. 

The adrenal glands, located at the apex of each kidney, form part of the endocrine system, which is a network of glands in the body that are responsible for the production of hormones. The adrenal cortex is specifically tasked with the production of cortisol, aldosterone as well as adrenal androgens (mainly dehydroepiandrosterone or DHEA). 

A feedback system revolving around the pituitary gland, the adrenal glands and the hypothalamus (a gland located in the lower brain) is responsible for regulating cortisol production. When the hypothalamus detects low levels of cortisol, it produces corticotropin-releasing hormones or CRH. This hormone stimulates the production of adrenocorticotropic hormones or ACTH in the pituitary gland. This hormone, also referred to as corticotropin, in turn, stimulates the production and release of cortisol in the adrenal glands. High levels of cortisol reduce the production of CRH and ACTH to suppress cortisol production. 

Common Causes of Cushing Syndrome 

  • Extended glucocorticoid treatment resulting in iatrogenic Cushing Syndrome. Glucocorticoids are synthetic steroids that mimic cortisol on a chemical basis like Prednisone, which is used to treat health conditions such as asthma, rheumatoid arthritis, lupus, and other diseases that are inflammatory in nature. These hormones may also be prescribed after organ transplants to prevent organ rejection by lowering the immune system. 
  • Cushing’s Disease, which is a type of Cushing Syndrome, results from the overproduction of ACTH by the pituitary gland, which continuously signals the adrenal glands to produce excess endogenous cortisol. Most commonly, Cushing’s Disease, which makes up 40% of cases, is the result of a tumor called an adenoma on the pituitary gland that secretes ACTH. 
  • A tumor on the adrenal gland called adrenal hyperplasia, which causes excess production of cortisol.  
  • Tumors in other parts of the body, such as the thyroid, pancreas, or lungs that produce ACTH. This is referred to as the ectopic production of ACTH as it is produced in parts of the body other than the pituitary gland. 
  • Gene mutations that are inherited like Multiple Endocrine Neoplasia Type 1 (MEN-1) increases the risk of tumor development in the endocrine system, including the adrenal and pituitary glands. These genetic conditions are, however, rare in causing Cushing Syndrome. 
  • Obesity and the development of Type II Diabetes or those who have poorly regulated blood glucose levels are at a greater risk of developing Cushing Syndrome. 

Cushing Syndrome may develop in any person. However, it is more frequently seen in adults between 20 and 50 years of age, and women are three times more likely to develop the condition than men. An estimated two new cases per million people are diagnosed every year.  

Signs and Symptoms of Cushing Syndrome 

The multiple signs and symptoms of Cushing Syndrome may vary but commonly include: 

  • Central obesity or obesity in the torso with thinner arms and legs. 
  • “Moon face” or the appearance of a large, rounded face. 
  • “Buffalo hump,” which refers to excessive fat in the neck and shoulder area. 
  • Excessive urination and thirst. 
  • Vision conditions, such as glaucoma and cataracts. 
  • Greater susceptibility to infection. 
  • Thin, fragile skin that heals slowly and is prone to bruising. 
  • Pink streaks, like stretch marks in the abdomen, buttocks, and thighs. 
  • Weakness of the muscles. 
  • Reduced endurance. 
  • Decreased bone density or osteoporosis. 
  • Mental health conditions, such as confusion and psychosis. 
  • Children who have Cushing Syndrome develop slower than normal, are shorter in height, and are commonly obese. 
  • Women may grow excess hair on the face and chest and have irregular menstruation. 
  • Men may be impotent or lack sex drive. 

Laboratory Testing for Cushing Syndrome 

A single laboratory test is insufficient to diagnose Cushing Syndrome, and more than one test is the standard. Cortisol levels vary throughout the day, meaning that a singular blood sample for cortisol is not accurate. Testing is, therefore, conducted in two stages. Initial testing is to determine whether increased levels of cortisol are present. The second phase of testing is to identify the cause of the increase in cortisol levels, whether this is due to adrenal, pituitary, or other causes.

Three tests are commonly used to diagnose Cushing Syndrome: 

  • Measurement of midnight plasma cortisol and late-night salivary cortisol. Commonly, cortisol production is reduced at midnight. With Cushing Syndrome, this does not happen, and an increased cortisol level in the blood or plasma at this time may indicate the condition. The blood test usually requires admission to the hospital for at least one night. The alternative is to collect a saliva sample at home, late at night, to be submitted for later testing. The recommendation is for saliva samples to be collected over three consecutive nights. In the case where a single saliva sample was tested, and the results are outside the established range of reference, the test should be repeated in order to eliminate a false-positive. 
  • 24-Hour urine cortisol test (or the urine free cortisol test or UFC) is generally performed to measure overall cortisol production. When one out of four samples tested within a 24-hour period is normal, or the overall results are abnormal, further testing may be required, such as the midnight plasma cortisol test in order to prevent a false-positive. 
  • Dexamethasone suppression screening test (DSS test) which introduces synthetic cortisol to evaluate the production of CRH and ACTH production. The normal response to the introduction of dexamethasone would be a suppression of the hormones CRH, ACTH, and cortisol. The test can be administered in different dosage at various times of the day.  

A low dose of 1mg can be administered at night in order to reduce the increase of ACTH and cortisol that are normally produced during sleep. A blood sample drawn the morning after will then be measured to detect cortisol levels. Cushing syndrome will prevent the suppression of this production, whereas healthy individuals will show a marked suppression in the production of ACTH and cortisol. 

Alternatively, 0.5mg can be administered every six hours over a period of 48 hours and a 24-hour urine sample collected on the second day for urine free cortisol testing. The urine free cortisol test should show suppression to extremely low levels in healthy individuals and high levels in persons with Cushing Syndrome. 

If any of the above tests show increased levels of cortisol, then it is a clear indication that cortisol levels are not being regulated normally. The second phase of testing to determine the cause of the increased levels of cortisol will then be ordered. 

Testing to Establish the Cause of Cushing Syndrome:

  • Corticotrophin releasing hormone (CRH) stimulation test is used to distinguish between individuals who have a pituitary gland condition and those with tumors existing outside of the pituitary gland and are responsible for producing ectopic ACTH. Baseline ACTH levels are measured before CRH is injected. Cortisol and ACTH levels are then measured at either 30 minutes or 1-hour timed intervals. Normal responses to this test should first show an increase in ACTH levels and then a peak in cortisol levels. Cushing Syndrome caused by adrenal tumors or tumors producing ACTH will show no response to the injected CRH. 
  • High-dose dexamethasone suppression test (HDDST) is like the lower dose version used to detect irregular cortisol levels in the initial phase of testing. The test is administered to distinguish between pituitary tumors producing ACTH and the other causes of Cushing Syndrome. The high dose of dexamethasone should suppress cortisol levels in those with pituitary tumors but not in persons where the cause is a tumor producing ectopic ACTH. 
  • Dexamethasone-corticotropin-releasing hormone test is to differentiate between Cushing Syndrome and pseudo-Cushing syndrome. Pseudo-Cushing Syndrome is where cortisone levels are elevated, but the long-term, progressive symptoms and signs are not in evidence. Excessive alcohol consumption, severe obesity, unmanaged diabetes as well as depression and anxiety can all result in higher cortisol levels, but symptoms such as muscle weakness, osteoporosis, or fragile skin may not be present. The test is a combination of the dexamethasone test and the CRH test mentioned above. Elevated levels of cortisol suggest Cushing Syndrome, whereas levels that do not increase suggest pseudo-Cushing Syndrome. 
  • Petrosal sinus sampling is commonly used in conjunction with the CRH stimulation test. Blood samples are obtained from the petrosal sinuses, which are veins that carry blood from the pituitary gland. The samples are collected from a catheter placed in the neck and used to measure ACTH levels. Cortisol levels are then compared with those of blood that is taken from the forearm. ACTH levels that are higher in the blood obtained from petrosal sinuses are indicative of a pituitary tumor. If the levels are similar in both samples, it indicates that the increased levels of cortisol are caused by a tumor other than on the pituitary gland. 

Additional Lab Tests for Cushing Syndrome 

CBC differential to measure high levels of WBC and a greater number of neutrophils. 

A glucose tolerance test to measure impairment. 

Testing for hypokalemia which is a decreased level of potassium