Cushing syndrome

Diagnosis

Diagnosing Cushing syndrome typically requires a thorough and comprehensive evaluation to eliminate other possible causes. This process can be intricate and time–consuming. It often involves in–depth discussions regarding symptoms, careful examination of medications being taken, and a comprehensive physical examination.

During the physical examination, healthcare providers will assess for specific symptoms associated with Cushing syndrome, including a rounded face, a hump on the back of the neck, and thin, easily bruised skin with stretch marks. 

If there is suspicion that glucocorticoid medications may be responsible for inducing the syndrome, healthcare providers will carefully examine the various forms of medication, such as pills, injections, creams, and inhalers, to determine if any of them could potentially trigger the condition.

In cases where healthcare providers have confirmed that glucocorticoid medications are the cause of Cushing syndrome, further testing may not be required. However, if the cause is not evident or additional confirmation is needed, laboratory tests are typically conducted to confirm the presence of hypercortisolism. These tests may include: 

• Blood and urine tests: A blood test will determine the level of ACTH in the blood. If the levels are low, an adrenal tumor may be present. If the levels are normal or high, a pituitary or ectopic tumor may exist. 

The 24–hour urinary cortisol test measures the level of cortisol in the urine in micrograms (mcg). This requires collecting the urine during a 24–hour period for the urine test. Generally, these tests assess hormone levels and determine whether the body produces too much cortisol.

• Saliva test: This test measures cortisol levels between 11 pm and midnight. Normally, cortisol levels are very low late at night, but with Cushing syndrome, cortisol levels will be unusually high throughout that hour. 
• Imaging tests: A CT scan or an MRI may be performed to look for a tumor in the pituitary and adrenal glands.
• Inferior petrosal sinus sampling: During the procedure, drugs to keep the patient calm and comfortable is given intravenously. ACTH levels will be compared between the two sample locations. The first sample will be obtained through a tiny tube inserted into the groin or neck area and threaded to the petrosal sinuses. A second blood sample is drawn from the forearm. Medication to induce the tumor to produce more ACTH is given. After which, blood samples from the same regions are obtained again. 

Generally, this test identifies the site of ACTH secretion. The pituitary gland secretes ACTH and other pituitary hormones into the bloodstream. If the ACTH level in the sinus sample is higher, the problem is pituitary. If the ACTH levels in the sinuses and forearm are comparable, the problem is not with the pituitary gland. This test has an accuracy rating of 95% to 98%. 

Treatment

The treatment approach for Cushing syndrome depends on the underlying cause of the elevated cortisol levels. The primary goal is to reduce cortisol levels in the body. If the use of glucocorticoids is responsible, the healthcare provider may recommend reducing the dosage or finding alternative medications. Additional treatment options include medication therapy, surgical intervention, or radiation therapy, depending on the specific circumstances and individual needs of the patient. 

• Reducing glucocorticoid use: Symptoms of Cushing syndrome may be managed by lowering the dosage of glucocorticoid medicine. This is done gradually while still controlling the disease that requires this medication. Decreasing the medication gradually permits the body to produce a healthy quantity of cortisol. Stopping these medications too early can result in low cortisol levels in the body.
• Surgery: Surgical removal of pituitary, adrenal, and ectopic tumors is effective, but the patient must adapt to new, lower cortisol levels. Cortisol drugs or cortisol replacement medicine in the form of hydrocortisone pills is necessary after Cushing syndrome surgery. Most of the time, usually after six to 18 months, the doctor can gradually reduce the replacement medication. 

Pituitary tumors are frequently removed through the nose. ACTH–producing tumors in other regions of the body can be removed through traditional surgery or through less invasive procedures with smaller incisions. Adrenal gland tumors can be removed through a midsection or back incision using a minimally invasive procedure. 

If an ACTH–producing tumor is not detected, or if it cannot be completely removed, and Cushing syndrome persists, bilateral adrenalectomy may be recommended. This method immediately prevents the body from producing excessive cortisol. After both adrenal glands are removed, lifetime medication to replace cortisol and another adrenal hormone called aldosterone is necessary. 

• Radiation therapy: A six–week period of radiation, or a single large dose may be recommended for those who are unable to undergo surgery, or if the tumor was not completely removed after the surgery. The treatment may be designed to minimize radiation exposure to other tissues. Discuss with the doctor all possible side effects. 
• Medications: While treatment options for Cushing syndrome, such as medication, surgery, or radiation therapy, are not universally effective in completely eliminating all symptoms associated with excess cortisol, their primary aim is to control and manage cortisol levels in the body. The goal is to bring cortisol levels within a normal range, thereby alleviating symptoms and minimizing the adverse effects of cortisol excess. These medications are prescribed prior to surgery in individuals with severe Cushing syndrome, or if other treatments are not possible or failed to work.

Certain medications used to treat hypercortisolism can have significant side effects on the brain and nervous system, as well as the potential for liver damage. In addition, common side effects of these medications include fatigue, gastrointestinal disturbances (such as upset stomach and vomiting), headaches, muscle aches, elevated blood pressure, low potassium levels, and edema. It is important for healthcare providers to closely monitor and manage these potential side effects during the course of treatment.

Typical medications prescribed for Cushing syndrome include:

• • Mifepristone. This does not reduce the quantity of cortisol produced by the body, but it does prevent the effect of cortisol on tissues. This medication is approved for Cushing syndrome patients who have type 2 diabetes or high blood sugar levels. 
  • Pasireotide. Cortisol levels are reduced by decreasing the amount of ACTH produced by the tumor. This medication is administered as an injection twice a day.
  • Other drugs. Ketoconazole, osilodrostat, mitotane, levoketoconazole, and metyrapone are medications used to regulate cortisol production in the adrenal gland.