Cushing's Syndrome & Disease - FAQs

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Frequently Asked Questions (FAQ)

I have been told I might have Cushing’s syndrome and have been referred to an endocrinologist. Why is this?
An endocrinologist is a physician who specializes in hormone disorders. Cushing’s syndrome and disease are fairly rare and often quite complex and the best results can be expected when these are treated by a specialist endocrinologist, often together with a neurosurgeon.
I have been told I need pituitary surgery. What does this involve?
The most common way to remove pituitary tumors is through the transsphenoidal approach. This involves entering the pituitary gland by making an incision in the back of the nose, and approaching the pituitary gland through the sphenoid sinus. Using a microscope or endoscope, the surgeon will explore the pituitary gland, hopefully find the tumor, and remove it.
What are the risks of this surgery?
Since these tumors are very small, it can be difficult to find them, and the gland can be damaged during the procedure. If this happens other hormone function can be lost. Since the pituitary gland controls the production of thyroid hormone, estrogen in women and testosterone in men, and growth hormone – in addition to ACTH – replacement therapy for these other hormones might be required. Also, if the posterior part of the pituitary is damaged, anti-diuretic hormone can be lost. This hormone is responsible for water reabsorption by the kidneys, and without it patients urinate frequently and in large amounts (“diabetes insipidus”), leading to dehydration. This hormone can be replaced with a daily dose of a nasal spray or pill.
Are there other risks associated with this surgery?
Since the pituitary gland is bordered by the optic nerves and carotid arteries, there is a very small risk that these structures could be damaged (less than 1%). However, if this were to happen, the patient could suffer visual loss or a stroke. The pituitary is separated from the spinal fluid by a thin membrane. If this membrane is damaged during the surgery, a spinal fluid leak can result. If spinal fluid leakage occurs and is undetected, a serious infection, meningitis, can result. Most surgeons take a small piece of fat from the abdominal wall to use as a plug to prevent this leakage from occurring. The risk of this happening is about 1%. Since the pituitary gland is involved in water and sodium balance, this can be affected transiently by the surgery as well, and your endocrinologist will monitor your sodium levels after the surgery. All of these risks are minimized in the hands of an experienced surgeon.
How will I feel after the surgery?
Direct effects of the surgery include nasal congestion and possibly headache. These symptoms will resolve after 1–2 weeks. If the operation is successful, however, the cortisol levels will drop dramatically. Patients can experience symptoms of cortisol withdrawal, which can include profound fatigue, and this can sometimes last for weeks or months after the surgery. If the operation is successful, the patient will have to take cortisol replacement until the remaining normal pituitary gland recovers (see below, n8).
How will I know if my treatment has been successful?
Your endocrinologist will test your urine and/or blood and/or saliva cortisol levels a few days after the surgery. Usually success can be determined within a few days of the operation.
Will I feel better?
Almost all of the symptoms of Cushing’s disease are reversible. When the cortisol levels drop, the obesity improves and appetite normalizes. Muscles and bones become stronger. Diabetes and hypertension improve. These effects may require many months
I had surgery for Cushing's, why do I have to take steroid replacement?
A patient cured of Cushing’s disease should have very little if any measurable cortisol. Once the tumor has been removed completely , the rest of the pituitary gland is still suppressed (relatively "asleep"). It may take several months for the normal ACTH producing cells to start functioning again. In the mean time, steroid replacement is necessary to protect against too little cortisol (adrenal insufficiency). In patients cured of Cushing’s disease, taking cortisol replacement is essential for life. At a later date, the need for continued steroid replacement is determined by blood tests. Most, but not all patients who are cured of Cushing’s disease will not need steroids after a year is over and sometimes sooner. If a person has to take steroid replacement he/she should wear a medical alert bracelet or necklace, which identifies the need for steroid treatment and extra dosing during acute sickness
I have been cured of my Cushing's - why don't I feel normal, many months after my surgery?
This is a common question and a very common problem. Cushing's affects every system of the body; it causes problems gradually, particularly its effect on muscles and body fat. With Cushing's, muscles become thin and weak. It takes a long time for the body to "repair" itself, usually 9 to 12 months. It is quite common for patients to still feel weak and have achy muscles several months after successful surgery or successful radiation treatment. More positively, the problems with depression, concentration and memory may improve fairly soon successful pituitary surgery. Most patients have improvement in mood and depression 6 months after successful treatment. However, they are still frustrated that they are not “back to normal”. Unfortunately, the excess weight does not "magically" disappear - it takes time and a weight reduction diet to return to normal body weight. The important word here is: patience. Occasionally some patients may experience an increase in depression and anxiety after cure of Cushing’s as the body re-adjusts to large changes in cortisol going from very high to low levels.
What if the treatment is not successful?
There are a number of options if the initial transsphenoidal operation is unsuccessful. Sometimes, a second operation is recommended if no tumor was found during the initial operation. Alternatively, radiation therapy of the pituitary gland can be considered. Medical control of cortisol levels is required while awaiting the beneficial effects of radiation. Finally, the adrenal glands themselves can be removed. This stops the body from making any cortisol, and so the symptoms of Cushing’s disease resolve, although the pituitary tumor itself remains untreated. Choosing between these options requires a careful discussion between the patient, endocrinologist, and surgeon.
Are there any medical treatments for Cushing’s?
There are presently no approved medical treatments in the US for the pituitary tumors that cause Cushing’s. A new medication (Pasireotide, SOM230) has been just approved in Europe as bi-daily injection for treatment of Cushing’s disease. This medication is not yet available in the US. However, there are medications that can reduce cortisol production by the adrenal glands, but do not have any effect on the pituitary overproduction of the hormone ACTH (the pituitary hormone that stimulates the adrenal glands to make too much cortisol). By blocking the production of cortisol by the adrenal glands these medications can reduce many of the problems such as hypertension, weight gain, diabetes, tendency to infections, and depression. Ketoconazole (Nizoral) is a medication that reduces adrenal gland cortisol production. This medication is most often used in patients who are not cured of Cushing's after surgery, are too ill to be operated on and need to have cortisol levels quickly lowered before surgery and while waiting for therapy to become effective in patients treated with radiotherapy. If a drug to lower cortisol is prescribed, careful monitoring is necessary to determine if the dose is effective (measure 24 hour urine cortisol level), to make sure it does not reduce cortisol to below normal (measure morning blood cortisol level) and to make sure there is no ill effect on the liver. This drug is usually given twice a day. Sometimes, when giving the exact amount of ketoconazole is difficult, a very small amount of a steroid, for example dexamethasone, is used together with ketoconazole to keep the adrenal glands blocked down but to prevent the patients from having too little cortisol.

Another drug that may be used in patients who cannot tolerate ketoconazole is metyrapone. This medication blocks the production pathway of cortisol by the adrenal glands. It may stimulate ACTH from the tumor and therefore is not usually the first drug used unless ketoconazole cannot be given. This is difficult to obtain in the USA.

Another drug is called mitotane, but this is rarely used due to severe side effects
What are the side effects of ketoconazole (Nizoral) and metyrapone?
Ketoconazole (Nizoral): the most common side effect is nausea and abnormalities in liver function. Before this medication is taken, a blood test should be measured to make sure there are no significant liver abnormalities. If the patient develops fatigue or jaundice, liver tests should be measured again and the medication stopped immediately. If liver tests become abnormal, they usually return to normal after the ketoconazole is stopped. Other side effects include vomiting, abdominal pain and itching. If a patient is on a stomach medication to reduce acid secretion, absorption of ketoconazole may be reduced. This problem may be solved by taking the medication with an acid beverage, such as Coca Cola.
Metyrapone: the most common side effects are nausea and sometimes vomiting.