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What are Cushing’s Syndrome and Cushing’s Disease?


Cushing’s syndrome is a rare condition that is the result of too much of the hormone cortisol in the body. Cortisol is a hormone normally made by the adrenal glands and it is necessary for life. It allows people to respond to stressful situations such as illness, and has effects on almost all body tissues.

It is produced in bursts, most in the early morning, with very few at night.

When too much cortisol is made by the body itself, it is called Cushing’s syndrome, regardless of the cause. Some patients have Cushing’s syndrome because the adrenal glands have a tumor(s) making too much cortisol. Other patients have Cushing’s syndrome because they make too much of the hormone ACTH, which causes the adrenal glands to make cortisol. When the ACTH comes from the pituitary gland it is called Cushing’s disease.

Cushing’s syndrome is fairly rare. It is more often found in women than in men and often occurs between the ages of 20 and 40.


Image from Mayo Clinic

What Causes Cushing’s Syndrome and Cushing’s Disease?


Cushing’s syndrome can be caused by medication or by a tumor. Sometimes, there is a tumor of the adrenal gland that makes too much cortisol. It may also be caused by a tumor in the pituitary gland (a small gland under the brain that produces hormones that in turn regulate the body’s other hormone glands).

Some pituitary tumors produce a hormone called adrenocorticotropic hormone (ACTH), which stimulates the adrenal glands and causes them to make too much cortisol. This is termed Cushing’s disease. ACTH-producing tumors can also originate elsewhere in the body and these are referred to as ectopic tumors.

See below for an illustration of the differences between these three situations. It is important to note that pituitary tumors are almost never cancerous.

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In Cushing’s disease a pituitary tumor makes ACTH, which stimulates adrenal gland production of cortisol. High cortisol levels inhibit CRH secretion and ACTH secretion from normal pituitary cells.

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In ectopic ACTH secretion, a non-pituitary tumor makes ACTH, which stimulates adrenal gland production of cortisol. High cortisol levels inhibit CRH secretion and ACTH secretion from normal pituitary cells.

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In primary adrenal disease, the adrenal glands independently make too much cortisol. High cortisol levels inhibit CRH secretion and ACTH secretion from normal pituitary cells.

Patient on Scale

What are the Symptoms of Cushing’s Syndrome?


The main signs and symptoms are shown in Table 1. Not all people with the condition have all these signs and symptoms. Some people have few or “mild” symptoms - perhaps just weight gain and irregular menstrual periods. Other people with a more “severe” form of the disease may have nearly all the symptoms.

The most common symptoms in adults are weight gain (especially in the trunk, and often not accompanied by weight gain in the arms and legs), high blood pressure (hypertension), and changes in memory, mood and concentration. Additional problems such as muscle weakness arise because of loss of protein in body tissues.



Weight Gain


Poor Short-term Memory


Excess Hair Growth (Women)

Red, Ruddy Face

Extra Fat Around Neck

Round Face


Poor Concentration

Menstrual Irregularity



Recurrent Infection

Thin Skin and Stretch Marks

Easy Bruising


Weak Bones


Balding (Women)

Hip and Shoulder Weakness

Swelling of Feet/Legs


Checking Blood Pressure



Because not all people with Cushing’s syndrome have all signs and symptoms, and because many of the features of Cushing’s syndrome, such as weight gain and high blood pressure, are common in the general population, it can be difficult to make the diagnosis of Cushing’s syndrome based on the symptoms alone.

As a result, doctors use laboratory tests to help diagnose Cushing’s syndrome and, if that diagnosis is made, go on to determine whether it is caused by Cushing’s disease or not. These tests determine if too much cortisol is made spontaneously, or if the normal control of hormones isn’t working properly.


Cortisol Measurements
The most commonly used tests measure the amount of cortisol in the saliva or urine. It is also possible to check whether there is too much production of cortisol by giving a small tablet called dexamethasone that mimics cortisol. This is called a dexamethasone suppression test. If the body is regulating cortisol correctly, the cortisol levels will decrease, but this will not happen in someone with Cushing’s syndrome.

These tests are not always able to definitively diagnose Cushing’s syndrome because other illnesses or problems can cause excess cortisol or abnormal control of cortisol production. These conditions that mimic Cushing’s syndrome are called ‘pseudo-Cushing’s states’ and include the conditions shown in Table 2. Because of the similarity in symptoms and laboratory test results between Cushing’s syndrome and pseudo-Cushing’s states, doctors may have to do a number of tests and may have to treat conditions that might cause pseudo-Cushing’s states – such as depression – to see if the high cortisol levels become normal during treatment. If they do not, and especially if the physical features get worse, it is more likely that the person has true Cushing’s syndrome.



Strenuous Exercise

Sleep Apnea

Depression and Other Psychiatric Disorders




Uncontrolled Diabetes


Extreme Obesity

Doctor and Patient

What Tests are Needed Specifically to Diagnose Cushing’s Disease?


Patients with adrenal causes of Cushing’s syndrome have low blood ACTH levels and patients with the other causes of Cushing’s syndrome have normal or high levels. A doctor can diagnose too much ACTH by measuring its level in the blood.

Inferior Petrosal Sinus Sampling (IPSS)
The best test to distinguish an ACTH-producing tumor on the pituitary from one in another part of the body is a procedure called inferior petrosal sinus sampling or IPSS. This involves inserting small plastic tubes into both the right- and left-sided veins in the groin (or neck) and threading them up to the veins near the pituitary gland. Blood is then taken from these locations and also from a vein not connected to the pituitary gland.

During the procedure, a medication that increases ACTH levels from the pituitary is injected. By comparing the levels of ACTH produced close to the pituitary gland in response to the medication with those produced by other parts of the body, a diagnosis can be made.

Further Tests
There are other tests used for the diagnosis of Cushing’s disease such as the dexamethasone suppression and corticotropin-releasing hormone (CRH) stimulation tests. However, these are not as reliable in distinguishing between the causes as IPSS. A doctor may want to do multiple tests to confirm the results. It is also possible to visualize the pituitary gland using a process called magnetic resonance imaging (>MRI). This involves an injection of an agent that will help the tumor to show up on the MRI scan. If this test shows a definite tumor above a certain size and the CRH and dexamethasone test results are compatible with Cushing’s disease, IPSS may not be needed. However, up to 10% of healthy people have an abnormal area on their pituitary consistent with a tumor. Therefore, the presence of an abnormality alone is not diagnostic of Cushing’s disease. Also, in about 50% of patients with Cushing’s disease, the tumor is too small to be seen. Thus the absence of a tumor on a MRI scan does not necessarily exclude Cushing’s disease.

On a Walk



  • Look after your general health, eat well, and take regular exercise. However, because bones may weaken, avoid high impact exercise or sports that involve falls, to reduce the chance of a bone break.

  • Ask your doctor if you are getting enough calcium and vitamin D in your diet. These may help strengthen the bones.

  • Give up smoking. This decreases the chance of having problems with surgery.

  • Don’t drink too much alcohol.

  • Make sure you take the full course of any medicines that your doctor may give you.

  • Do go back and see your doctor if any of your symptoms worsen.

  • After pituitary surgery, if you feel sick or suffer flu-like symptoms, do contact your doctor.




The only effective treatments for Cushing’s disease are to remove the tumor, to reduce its ability to make ACTH, or to remove the adrenal glands. There are other complementary approaches that may be used to treat some of the symptoms.

For example, diabetes, depression and high blood pressure will be treated with the usual medicines used for these conditions. Also, doctors may prescribe additional calcium or vitamin D, or other medicine to prevent thinning of the bone.

Pituitary Tumor Removal by Surgery
Removal of the pituitary tumor by surgery is the best way to treat Cushing’s disease. This is recommended for those who have a tumor that is not extending into areas outside of the pituitary gland, and who are well enough to have anesthesia. This is usually carried out by going via the nose or upper lip and through the sphenoid sinus to reach the tumor. This is known as transsphenoidal surgery and avoids having to get to the pituitary via the upper skull. This route is less traumatic for the patient and allows quicker recovery.

Removing only the tumor leaves the rest of the pituitary gland intact so that it will eventually function normally. This is successful for 70–90% of people when performed by the best pituitary surgeons. The success rates reflect the experience of the surgeon performing the operation. However, the tumor can return in up to 15% of patients, probably because of incomplete tumor removal at the earlier surgery.

Other options for treatment include radiation therapy to the entire pituitary gland or targeted radiation therapy (called radiosurgery), when the tumor is seen on MRI. This may be used as the only treatment or it may be given if pituitary surgery is not completely successful. These approaches can take up to 10 years to have full effect. In the meantime patients take medicine to reduce adrenal gland production of cortisol. One important side effect of radiation therapy is that it can affect other pituitary cells that make other hormones. As a result, up to 50% of patients need to take other hormone replacement within 10 years of the treatment.

Adrenal Gland Removal by Surgery
Removal of both adrenal glands also removes the ability of the body to produce cortisol. Since adrenal hormones are necessary for life, patients must then take a cortisol-like hormone and the hormone florinef, which controls salt and water balance, every day for the rest of their life. An experienced pituitary- or neuro-endocrinologist can help to decide the best course of treatment.

Drug Treatments
While some promising drugs are being tested in clinical studies, currently available medications to reduce cortisol levels, when given alone, do not work well as a long-term treatment. These medicines are most often used in conjunction with radiation therapy.

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After Treatment


Most people will start to feel gradually better after surgery and the hospital stay may be quite short if there are no complications. It can take some time to feel completely back to normal, to lose weight, to regain strength, and to recover from depression or loss of memory.

It is important to remember that the high cortisol levels physically change the body and brain, and that these changes may reverse quite slowly. This is a normal feature of the recovery period and patience is definitely a virtue here.

Following Pituitary Surgery
After successful pituitary surgery, cortisol levels are very low. This can continue for 3–18 months after surgery. These low levels of cortisol can cause nausea, vomiting, diarrhea, aches and pains, and a flu-like feeling. These feelings are common in the first days and weeks after surgery as the body adjusts to the lower cortisol levels. Doctors give people a cortisol-like medicine until recovery of the pituitary and adrenal glands is either well under way or complete.

Hydrocortisone or prednisone is usually used for this purpose. Doctors monitor the recovery of the pituitary and adrenal glands by measuring morning cortisol values, or by testing the ability of the adrenal glands to secrete cortisol in response to an injected medication similar to ACTH.

Until the pituitary and adrenal glands recover, the body does not respond normally to stress – such as illness – by increasing cortisol production. As a result people who suffer with ‘flu’, fever or nausea may have to double the oral dose of the glucocorticoid when they are sick. However, this increased dosage should only be used for 1–3 days. On occasion, people can suffer vomiting or severe diarrhea that prevents them from absorbing the glucocorticoids taken by mouth.

In this situation, it may be necessary to receive injections of dexamethasone or another glucocorticoid, and seek emergency medical care. Patients should wear a MedicAlert bracelet until glucocorticoid replacement is stopped.

If it is necessary to have a prolonged increase in hydrocortisone, a doctor should evaluate this need, and a ‘tapering’ regimen may be needed to reduce the dose back to the daily requirement.

Following Adrenal Gland Surgery
People who have had their adrenal glands removed will have to take a glucocorticoid (like cortisone) and mineralocorticoid fludrocortisone (brand-name Florinef) for the rest of their life. There may be a concern that the pituitary tumor will enlarge, so MRI imaging of the pituitary gland may be done after this surgery. People whose adrenal glands have been removed may have initial symptoms that are similar to those after pituitary surgery, and they should take extra glucocorticoid during illness as described above, and wear a MedicAlert bracelet.

It is important to note that, if you are taking replacement cortisol, there may be a number of occasions when you need additional replacement. This can include stressful situations, such as surgical procedures – whether or not related to Cushing’s syndrome – dental procedures, and so on. You should discuss your specific condition with your endocrinologist and ensure you know what situations to look out for and what action to take.

What are Cushing's Syndrome an Disease
Manage Symptom
Treatment Options
After Treatment

Frequently Asked Questions

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