The first part of this series on “dealing with the doctor” discussed the various issues that may lead one to seek medical advice regarding the possibility of Cushing’s Syndrome, and what may be expected from the initial evaluation by the doctor. This article will review what you may expect after you have received treatment.

Care of the patient with Cushing’s Syndrome involves seeing an Endocrinologist, starting with the diagnostic work-up and continuing with follow-up care after treatment has been given. Unlike the situation in which we recommend a pituitary surgeon with extensive experience in Cushing’s surgery, there are many endocrinologists outside major medical centers that should have the expertise to handle the after treatment care for Cushing’s patients. You may want to ask your endocrinologist about his or her experience treating patients with Cushing’s and Addison’s disease. Board certification in Endocrinology and Fellowship in the American College of Endocrinology indicate a level of expertise. Certain other doctors including rheumatologists, pulmonologists, and some general internists also may have experience in the use of steroids within the scope of their practice and may be well versed in tapering patients off of steroids. However, the follow-up care of a Cushing’s patient involves more than the use of steroids or tapering down their dose. The endocrinologist will also assess whether a cure has been achieved, periodically check for recurrence of Cushing’s, assess the function of the pituitary for production of other hormones, and assess for possible complications of Cushing’s.

Not considering steroids given for medical treatment, the most common cause of Cushing’s Syndrome is a tumor in the pituitary gland, a condition called Cushing’s disease. This accounts for over 70% of cases. Other causes are adrenal tumors in up to 20% of cases and tumors outside the pituitary and adrenal glands in about 10% of cases. For adults with Cushing’s disease, the treatment of choice is pituitary surgery. In the hands of an experienced neurosurgeon, the initial cure rate can be 80 to 90% for small tumors, but falls to less than 60% if there is a large tumor or if no discrete tumor can be identified. Adrenal tumors can be benign or malignant and, if possible, should be removed surgically. The cure rate for surgical removal of a benign adrenal adenoma is almost 100%. In contrast, complete surgical removal of malignant adrenal tumor is frequently impossible, and the results are often disappointing.

Following surgery patients will be unable to make adequate amounts of cortisone due to suppression of the remaining pituitary tissue and adrenal gland tissue, secondary to the prior cortisone excess. The patient will be treated with hydrocortisone (or another synthetic steroid such as prednisone or dexamethasone) and the dose will be tapered until a maintenance dose is reached. This steroid taper is complicated, with too rapid a taper causing symptoms of steroid withdrawal (weakness, nausea, muscle aches), and too slow a taper prolonging the recovery of the patient’s own cortisone production.

To assess cure following the initial surgery, a blood test measuring cortisol and ACTH levels is done early in the morning 24 hours after the last dose of maintenance hydrocortisone. This will usually be performed within a week after surgery. Undetectable levels of cortisol and ACTH indicate successful surgery and predict a low likelihood of recurrence. Some centers will place the patient on dexamethasone, instead of hydrocortisone, after surgery, making it possible to do the blood tests the morning following surgery. An undetectable level is preliminary evidence of probable cure. In Cushing’s disease a recurrence rate of about 2% occurs as long as 8 to 10 years after successful surgery. Thus, it is important to periodically reassess for cortisol excess. As a prognostic indicator, the lower the cortisol level after surgery, the less the chances of having a recurrence. Patients are usually reevaluated annually for the first several years after the operation, and less frequently thereafter. Your doctor will check a 24 hour urine cortisol, or perhaps an overnight dexamethasone suppression test, as part of the reevaluation.

In Cushing’s disease, production of other pituitary hormones may be affected by the surgery; thus there is a need to evaluate these other hormones as well. In general, the more extensive the surgery, the greater the likelihood of causing a hormonal deficiency. It is common to see transient diabetes insipidus (DI) within the immediate postoperative period. This is due to a deficiency in ADH, a hormone which plays a significant role in fluid regulation. Patients with DI will have excessive urination, and consequently excessive thirst, and these symptoms should be reported promptly. This may be managed with fluid replacement or the use of a synthetic hormone, dDAVP. Fortunately, permanent ADH deficiency is rare. Thyroid hormone production may also be affected since the pituitary gland is the source of TSH, or thyroid stimulating hormone. Some doctors will start thyroid hormone replacement after surgery and later re-assess if they can take the patient off it.

Others will test thyroid levels three to four weeks following surgery to see if the level remains good. You should discuss the symptoms of hypothyroidism with your doctor, so you will know what to report. Another pituitary hormone that can be affected is growth hormone (GH). In adults, GH deficiency has been linked to obesity, a decrease in muscle and bone mass, and sometimes a general sense of not feeling well. Human GH from recombinant DNA technology has been readily available for children with GH deficiency and within the last several years, GH has been approved for use in GH deficient adults. GH is expensive and requires daily injections, but you may want to ask your endocrinologist about GH deficiency if you have had pituitary surgery. Many major medical centers are currently performing clinical studies of GH and if you are GH deficient, you may wish to discuss entering such a study with your endocrinologist.

Your doctor will also want to assess your gonadal function, which is also regulated by the pituitary. In women, resumption of menstruation would indicate that this function is intact. In men, a testosterone level is checked, especially if there is a complaint of erectile dysfunction or loss of libido.

The chronic high level of steroids in Cushing’s Syndrome will eventually decrease the body’s ability to make its own cortisol. Thus, after treatment, patients need to be on synthetic steroids. Recovery of the pituitary and adrenal gland can take several months and may even take up to a year, hence there may be a need to take replacement steroids for a long time. In some cases, this can be permanent. Those who underwent bilateral adrenalectomy will definitely need to be on lifetime steroid replacement. There are several synthetic steroids available, differing in their potency and duration of action. Those most commonly used are prednisone and hydrocortisone. Prednisone has a longer duration of action and may be better for long-term replacement, as the longer duration of action provides a smoother physiological effect. On the other hand, hydrocortisone, because of its shorter duration of action, gives the pituitary or adrenal gland a faster chance at recovery since the pituitary or adrenal gets more stimulation during those periods where cortisol levels are low. When it is time to taper off of steroid therapy, those patients on prednisone usually should be switched to hydrocortisone to help hasten pituitary recovery. Some patients may exhibit symptoms of steroid withdrawal during the tapering process. Symptoms and signs may be loss of appetite, weight loss, nausea, muscle and joint aches, and lethargy. In these cases, the tapering will need to be done more slowly.

The body normally increases its production of cortisone during periods of stress. However, patients treated for Cushing’s, while waiting for pituitary and adrenal gland recovery, will not be able to increase their cortisol level on their own. As a general rule, for significant illnesses (such as a fever above 102o), the dose of the steroid needs to be increased two to threefold for a few days. If the illness lasts longer than 3 days or gets worse, you should contact your doctor. A discussion of “stress steroid coverage” should be carried out with your physician first following your initial surgery, and should be reviewed at every routine follow-up visit. The use of additional steroid coverage for illness must be continued until testing demonstrates full recovery of both the pituitary and adrenal glands. Those with major illnesses or severe vomiting are best treated with intravenous steroids and fluids in a hospital setting. It is very important that a MedicAlert bracelet or necklace be worn and an emergency medical information card be kept with you at all times to alert medical personnel of your condition. Just in case extreme medical emergencies arise and medical care is not immediately available, you should be prescribed an injectable dexamethasone syringe and be instructed on how to use it. The Medic Alert information and syringe can be discarded when testing has shown that you have normal pituitary-adrenal function.

Signs and symptoms attributed to Cushing’s Syndrome are expected to improve gradually over a period of a few months to a year after treatment. There are a number of complications from Cushing’s that warrant further evaluation during your follow-up visits. Cushing’s syndrome is a major risk factor for development of osteoporosis. A bone density measurement should be performed, and perhaps repeated a year later. There is usually a rapid improvement in the bones within the first 2 years after treatment of Cushing’s, but additional therapy may be advisable if significant osteoporosis is noted. Diabetes, or a mild elevation in blood sugar may be a complication of Cushing’s, but this should also improve with successful therapy. Blood glucose may even return to normal after treatment. Patients may also be at risk for cardiovascular complications, even at a younger age. Your primary care physician may want to assess your cardiac status if you are exhibiting symptoms such as difficulty breathing, easy fatigability, or chest pain.

Cushing’s Syndrome and it’s treatment place a great stress on the body, and have numerous potential complications. However, the majority of patients who receive appropriate treatment are generally able to return to productive live styles with a good quality of life.

Authors: Victor Adalbert deVilla, MD and Robert A. Levine, MD, FACE (Winter, 2001)

Editor’s Note: Robert A. Levine, MD is an endocrinologist in private practice in Nashua, New Hampshire. Victor Adalbert deVilla recently completed a fellowship in Endocrinology and Metabolism at the Lahey Clinic in Burlington, MA and will be joining Dr. Levine in practice. The first article in this series of two appears in the Diagnosis section of Doctor’s Articles on this website.