What should happen after successful treatment for Cushing’s? As anyone who has had Cushing’s knows, recovery is slow and frustrating. However, patients may not know what to expect regarding post-operative care, particularly about steroid replacement. Surgery for Cushing’s is not like having a gall bladder removed – once the gall bladder is gone, the problem is solved. Not so with Cushing’s – there is more treatment needed (steroid replacement for some period of time), and delay in recovery from the effects of Cushing’s.

Before discussing the specifics of post-operative care and issues of hormone replacement, it is necessary to explain the normal working of the pituitary and adrenal glands as well as what happens to the pituitary gland after surgery for Cushing’s (pituitary or adrenal causes). What is the best possible outcome of surgery? A very low blood cortisol level (less than 1 is ideal) after surgery indicates that the pituitary tumor or adrenal tumor has been removed successfully.

Normally, the pituitary gland secretes ACTH to stimulate the adrenal glands to make cortisol, and the increased cortisol decreases ACTH production so cortisol levels stay in the normal range. With Cushing’s, either a pituitary tumor secretes too much ACTH in spite of elevated cortisol, or an adrenal tumor secretes too much cortisol regardless of the lack of ACTH. The high cortisol levels from the adrenal glands causes suppression of the normal pituitary ACTH producing cells (think of these cells as being “asleep”). When a pituitary tumor is removed (presuming the rest of the gland is left) and when an adrenal tumor is removed, the suppressed (“asleep”) ACTH cells take time to awaken and stimulate the adrenal glands (or remaining adrenal gland after removal of 1 adrenal gland) to produce cortisol. In the case of a single adrenal tumor, the normal adrenal gland often atrophies (goes to “sleep”). It may take weeks to months, or in some cases even longer, for these “sleeping” pituitary and adrenal cells to awaken and function normally.

After successful pituitary or adrenal surgery, cortisol replacement is necessary. This may be hydrocortisone (identical to cortisol) or prednisone (a longer acting steroid that acts like cortisol). In the situation of pituitary Cushing’s, the need for continued cortisol replacement depends on whether or not there is remaining normal pituitary gland. If the entire pituitary gland was removed, the patient will require life-long cortisol replacement. It is not known exactly how much remaining pituitary gland is necessary for recovery, so testing is often needed to see if the normal gland has recovered and if there is adequate ACTH ”reserve” during times of stress. During times of stress (illness; severe emotional stress), the adrenal glands produce more cortisol.

How long does it take for the normal pituitary gland to “wake up” and produce ACTH? How long does a patient have to take hydrocortisone or prednisone after surgery? There is no one answer to this question – every patient is different. It might take several months or longer before the normal pituitary gland recovers.

In our center, all patients are discharged from the hospital on hydrocortisone (if the blood cortisol level is low after surgery) and return 8 weeks after surgery. The hydrocortisone is stopped for 2 days before the visit and the blood ACTH and cortisol levels are measured – if these levels are low, the patient is informed to resume hydrocortisone. This process is repeated about 2 months later (hold the hydrocortisone dose for 2 days and have a blood test for ACTH and cortisol levels). In general, most patients will have return of normal pituitary ACTH function and cortisol production within 6 months after surgery. This is NOT a rule, only an observation of many patients, so some patients may require steroid replacement longer.

Sometimes a stimulation test is performed to determine the need for continued cortisol replacement. The most rigorous test to determine if the pituitary and adrenal glands have “awakened” is giving a small dose of insulin to lower the blood sugar below 40. The body perceives this as stress and should respond by increasing ACTH and cortisol secretion. This is not a comfortable test, the patient usually experiences sweating, hunger, rapid heartbeat and possible confusion. This usually only lasts for 30 minutes or so. Since this test must be supervised by a doctor and have a nurse in the room during the test, it is not offered in many physicians’ offices and may require referral to a University Medical Center that conducts this test. An ACTH stimulation test is also sometimes used. This test involves administration of the pituitary hormone, ACTH, and measuring of the cortisol response. This is a good test but not as rigorous as the insulin hypoglycemia test, since it does not directly measure the body’s ability to respond to stress by elevating the production of ACTH by the pituitary.

In patients who had an adrenal tumor removed, this need for steroid replacement is generally similar, with the exception that the normal pituitary gland was not disturbed, so there is no issue about the amount of pituitary tissue remaining (there was no pituitary surgery, only removal of the adrenal tumor). Again, it may take several months for the normal pituitary gland to “awaken” and stimulate the remaining adrenal gland (the 1 remaining adrenal gland is capable of producing adequate cortisol). Both of the stimulation tests mentioned above also apply to patients who have had a single adrenal gland removed.

So, what does recovery from successful surgery mean for the patient? Some patients feel worse after successful treatment than they did with Cushing’s. The most common symptoms after successful treatment are fatigue, muscle and joint pains. While the emotional disturbances associated with Cushing’s may get better soon after treatment, the physical problems often persist for months. Why? There is no scientific explanation; only the observation that Cushing’s causes loss of muscle and it takes a long time for this to recover. The muscle and joint aches are most likely related to the high cortisol levels before treatment and when replacement steroid is taken, there is a smaller amount of steroid, causing a “relative” steroid withdrawal situation. Sometimes, a higher dose of hydrocortisone or prednisone is given temporarily to relieve the symptoms. There is a downside to taking higher does of steroid for a long time – further delay in recovery from Cushing’s, delay in weight loss and delay in returning to the pre-Cushing’s body. Thus, every patient’s symptoms and situation have to be addressed individually – there is no “cookbook recipe” to manage this problem. What may help with recovery? I recommend a regular light exercise program – walking, swimming to build up muscle strength. Rigorous exercise such as running and weight lifting may cause more pain and fatigue, so it is best to start slowly and gradually increase activity over weeks to months. A physical therapist or personal trainer might be useful in establishing an exercise routine.

What about other hormone replacements? If the patient had pituitary surgery, there is always the possibility of other hormone deficiencies, depending on how much of the pituitary was removed. Other hormone replacements may include thyroid hormone, estrogen and progesterone in pre-menopausal women and growth hormone. In patients with diabetes insipidus, desmopressin (DDAVP) is needed to prevent excessive urination and thirst. Regarding estrogen and progesterone replacement, it is best to wait 3 or 4 months after pituitary surgery to see if menstrual cycles return.

Regarding thyroid hormone replacement, a blood test for thyroid hormone (Free T4, not just a TSH) measured 6 to 8 weeks after surgery is needed to determine if thyroid hormone is required. Thyroid hormone is a hormone necessary for life; it regulates the body’s metabolism. Symptoms of thyroid deficiency include fatigue, weight gain, and difficulty with memory. Diagnosis of thyroid hormone deficiency is straightforward with blood tests to measure free T4 (secreted by the thyroid gland) and TSH (secreted by the pituitary to stimulate the thyroid gland). The free T4 level is the most reliable in a patient who has had pituitary surgery. Thyroid hormone deficiency is not common if the normal pituitary has not been removed.

Growth hormone (GH) deficiency may require a special stimulation test such as an arginine or insulin test (most insurance carriers require documentation of growth hormone deficiency with the results of a stimulation test). Growth hormone, affects body composition (increases muscle mass, decreases fat mass, increases bone mass, it does not cause weight loss). It may also improve blood cholesterol levels and improve energy and exercise ability. GH is not an “anti-aging” hormone. GH deficiency after pituitary surgery depends on the amount of normal pituitary gland removed. If the normal pituitary gland was left intact after the operation, GH deficiency should not be a problem. Again, the diagnosis of GH deficiency usually requires a stimulation test. Patients who have had pituitary surgery that required removal of normal pituitary tissue should be tested for GH deficiency.

The important thing to know is that with appropriate hormone replacement(s), a person can live a normal life. Although “Mother Nature” does it best, current hormone treatments can be almost as good as Mother Nature. This may require adjustment of medications over time. Although very few get “tailor made suits” these days – hormone replacement is like a tailor made suit – it must be adjusted to every patient’s individual needs. It is important for the patient to see her/his Endocrinologist regularly to assess response to treatment and blood tests. In patients who had an adrenal operation, there should be no need for thyroid hormone, estrogen and progesterone or growth hormone replacement – the normal pituitary gland was not disturbed.

In summary, recovery from Cushing’s is slow and frustrating. It is important to recognize this and not have unrealistic expectations. I tell my patients, before surgery, that with successful treatment, she/he may feel worse after the operation and that the recovery will be very slow. This message is rarely remembered by the patient (but is remembered by the family members accompanying the patient) and has to be repeated at the post-operative visit. The key word here is “patience”, on the part of the patient, family members and the physicians caring for the patient. Things do get better – over time, sometimes, a long time. There is a definite light at the end of the tunnel and it is not an oncoming train. The situation does improve.

Author: Dr. Mary Lee Vance MD (Summer, 2009)

Editor’s Note: Dr. Mary Lee Vance, is Professor of Medicine and Neurosurgery at the University of Virginia Health System in Charlottesville, Virginia. Dr. Vance has many years of experience in the diagnosis and treatment of Cushing’s and other endocrine disorders.