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Cushing's Disease


When the body is exposed to too much of the hormone cortisol, Cushing’s syndrome can develop. Cortisol has an effect on every tissue and organ in the body and these effects combined make up Cushing’s syndrome.

Overusing cortisol medication, such as when treating chronic asthma, rheumatoid arthritis, can cause Cushing’s syndrome (iatrogenic Cushing’s syndrome). A tumor in the adrenal gland or other body parts can cause Cushing’s syndrome (ectopic Cushing’s syndrome). Cushing’s syndrome can be caused by a tumor of the pituitary gland secreting adrenocorticotropic hormone (ACTH) which over produces cortisol.

Cortisol is an important hormone when in check. It is produced in the outer areas of the adrenal glands. It works to help the body respond to stress and change, transports nutrients, responds to inflammation, stimulates the liver to raise blood sugar levels, and controls water levels in the body. The ACTH made in the pituitary gland regulates cortisol production.



  • Around 10-15 million people are affected every year
  • 70% of adult cases are due to Cushing’s disease/pituitary adenomas and 60-70% for children
  • Females are 70% of all cases
  • Ages 20-50 are usually affected



Pituitary Adenomas - Cushing’s Disease

Pituitary adenomas are tumors that are benign in the pituitary gland and secrete extra ACTH leading to excess cortisol production. Most people usually have a single adenoma. Cushing’s disease is the most frequent cause of Cushing’s syndrome; It makes up 60-70% of cases.


Ectopic ACTH syndrome

Some tumors that appear outside of the pituitary gland can make ACTH. This is called ectopic ACTH syndrome. Lung tumors make up around half of these cases. Other tumors that produce ACTH are thymomas, pancreatic islet cell tumors and medullary carcinomas of the thyroid.


Adrenal Tumors

An adrenal tumor or other abnormality with the adrenal glands can lead to Cushing’s syndrome. The majority of these cases deal with benign tumors called adrenal adenomas, which lets out extra cortisol into the blood.

Adrenal cancers are a rare cause of Cushing’s syndrome. Cancer cells secrete extra levels of multiple adrenal cortical hormones such as cortisol or adrenal androgens. Adrenal cancer can lead to extremely high levels of hormones and very fast appearance of symptoms. 


Familial Cushing’s Syndrome

The majority of Cushing syndrome diagnoses are not related to genetics. Some people could develop this syndrome because of a genetic inheritance that makes them develop tumors of the endocrine glands. In primary pigmented micronodular adrenal disease, children or younger adults can get small tumors in the adrenal glands that produce cortisol. In multiple endocrine neoplasia type 1 (MEN I), tumors that secrete hormones of the parathyroid glands, pancreas and pituitary gland can form. Cushing’s syndrome in MEN I could happen because of a pituitary, ectopic, or adrenal tumor. 



  • Gaining weight in the face
  • Gaining weight above the collar bone
  • Gaining weight on the back of the neck
  • Skin changes with easy bruising in the extremities
  • Purplish stretch marks over abdomen or axillary regions
  • Red and round face
  • Weight gain in chest and abdomen
  • Hair growth excessively on face, neck, chest, abdomen, thigh
  • Female balding
  • Weakness or fatigue
  • Blurred vision
  • Vertigo
  • Weakness in the muscles
  • Amenorrhea
  • Decreased sex drive
  • Hypertension
  • Poor wound healing
  • Diabetes mellitus
  • Depression
  • Mood swings



Cushing’s syndrome is diagnosed based on tests, patient history, and examinations, cortisol levels. A patient with Cushing’s syndrome can have an appearance of excess cortisol being made with a 24 hour urinary excretion of cortisol. Also it can be helpful to look at old and recent photos and compare body features.

The following tests can be helpful to see if excess cortisol is being made:

  • 24 hours urinary cortisol test: measures cortisol amount produced in urine over 24 hours. Levels that are higher than 50-100 micrograms a day in adults shows a possibility of Cushing's syndrome. Mild cases of Cushing’s syndrome may not have a change in cortisol levels so many 24 hour urine tests should be taken.
  • Low-dose dexamethasone suppression test: Measures adrenal gland’s response to ACTH. Taking a small dosage of a drug similar to cortisol, dexamethasone (1mg), at 11 p.m., then having blood drawn the next morning to screen for cortisol. If a patient does not have Cushing’s syndrome, the cortisol level will be low which means that ACTH secretion was suppressed by the dexamethasone dose. If a patient has Cushing’s syndrome, the cortisol level in the morning will be high. This shows that they do not suppress cortisol to a low level (2.8 mg/dl). This test is around 95-97% accurate. Mild cases of Cushing’s syndrome can sometimes suppress their cortisol levels to low levels which makes it very difficult to diagnose.
  • Late night salivary cortisol test: This is a newer test checking for cortisol level around 11 p.m. to midnight. It is done at this time since cortisol secretion is quite low during this time of night. But, patients with Cushing’s syndrome will not have low cortisol secretion at this time. This test can be done multiple times and is easy to perform. This test is 93-100% accurate to come to a diagnosis.

After a diagnosis is made, the source of the syndrome must be found. This is done first by looking at the measurement of ACTH. If the patient has an ACTH-secreting tumor, they will have normal to high levels of ACTH. Patients with an excess of adrenal cortisol will have below normal levels of ACTH. A high-dose dexamethasone suppression test is also useful. Patients with pituitary tumors may suppress their serum cortisol level but those with adrenal tumors can maintain a higher level of cortisol. If the levels of cortisol are high, this leads the doctor in the direction of a non-pituitary source. Figuring out a pituitary from a non-pituitary ACTH-secreting tumor is difficult. MOst patients with ACTH-secreting tumors have a pituitary lesion that is small. 

Here are some other recommended tests:

  • Magnetic Resonance Imaging (MRI) of the pituitary gland with gadolinium enhancement. An obvious pituitary tumor can be seen with an MRI. 50% of patients will have a normal MRI of the pituitary while 10% will have incidental tumors that are not related to ACTH production.
  • Petrosal sinus sampling can be done to see the source of ACTH secretion. This test should be done after Cushing’s syndrome is confirmed. ACTH and other pituitary hormones produced in the pituitary gland will enter the bloodstream by drainage through the inferior petrosal sinuses. A catheter is placed in the inferior petrosal sinuses at the same time and blood is checked for ACTH before and after the administration of the corticotropin-releasing hormone (CRH) and at two, five, and ten minute intervals. This test is a 95-98% diagnostic accuracy when done correctly.



The amount of excess cortisol will determine the treatment for Cushing’s syndrome. This could include surgery, radiation, chemotherapy, cortisol inhibiting drugs. If the cause is iatrogenic, the dose of external steroid will be reduced to the lowest possible dose to control that disorder.  The dose can then be altered or taken on different days once a control is established.



The ideal treatment for ACTH-secreting pituitary adenoma is a microsurgical resection. This has around an 80-90% cure rate. This surgery does not leave an apparent scare because it is done through a transnasal transsphenoidal approach. This surgery can be done minimally invasively with either a microscope or endoscope. If the adenomas is not clearly identifiable partial removal of the pituitary gland could be done.


In patients to whom a remission is not received after surgery, these medications can block the production of cortisol:

  • Ketoconazole
  • Mitotane
  • Metyrapone
  • Mifepristone

This treatment is less effective than surgery and should be considered as a second path. If a patient does not respond to any treatments, adrenal gland removal bilaterally could be a possibility.

After a surgery where the tumor was successfully removed, the ACTH production will drop lower than normal. This is normal and will not last long. Patients will be given a synthetic form of cortisol like hydrocortisone or prednisone. The replacement therapy can be stopped within 6-12 months but sometimes people end up taking these steroids for years or life. Adrenal surgery patients may also need steroid replacements.

Radiation therapy is another option of treatment who cannot go through the other treatment paths. Radiation therapy is done over a six week time frame to the pituitary gland. This has helped around 40-50 percent of adults and 85 percent of children. 

Stereotactic radiosurgery has also been shown as a possible treatment option. Endocrine remission in 54% of patients and tumor growth control in 96% of patients have been shown with stereotactic radiosurgery. The tumor growth must continually be observed as well as disease recurrence, developing new deficiencies in other hormones, and damage to the brain. 


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