Question: What medication is given following successful surgery for Cushing’s syndrome and is there a proper procedure for weaning a patient from replacement medication?

Answer: During and immediately following surgery, the patient is usually placed on high doses of hydrocortisone, 200 to 300 mg/day. Beginning the day after surgery, I normally decrease the dose by half each day, (e.g., 200 mg, 100 mg, 50 mg, then 25 mg). Most patients are taking a replacement dosage within one week of surgery. Exceptions to this are found in cases of surgical complications or infection, in which case the dosage is tapered over a somewhat longer period of time. When the patient leaves the hospital, however, he or she should be taking no more than a replacement dosage of hydrocortisone. Longer-acting glucocorticoids should not be taken if hypothalamic-pituitary- adrenal axis recovery is the anticipated result.

Before release from the hospital, the patient is instructed to wear a Medical Alert bracelet or necklace, is prescribed three or four preloaded 1-mL (4 mg) dexamethasone syringes which should be close by at all times (one on his or her person, one at home, one in the car, one at work, etc.). The patient is instructed when and how to inject the dexamethasone for emergencies, and how to adjust the glucocorticoid dosage for minor illnesses or major stresses.

I advise my patients that they may experience symptoms of glucocorticoid deficiency or dependency. These symptoms are flu-like: malaise, weakness, easy fatigue, mild nausea, muscle and joint aches and pains. Most patients either don’t have these, don’t complain about them, or can tolerate them. In instances where the symptoms are severe, I explain to my patients that, in general, the quicker that they are able to work through this stage, the quicker their overall recovery will be. While I like to reach a true replacement dosage as quickly as possible, I will compromise within limits to make the patient more comfortable. However, too high a replacement dosage for too long a time period can jeopardize the patient’s health. Withdrawal symptoms can be uncomfortable, but they are not dangerous. Patients should be aware of the more serious symptoms of acute adrenal insufficiency, which may include abdominal pain, nausea, vomiting, fever, and low blood pressure, which may cause lightheadedness and fainting when standing up from a lying or sitting position.

The patient is left on the physiological replacement dose only for as long as is necessary to recover from surgery and hospitalization, no longer than six or eight weeks. Recovery of normal hypothalamic-pituitary-adrenal function requires that the patient be weaned from the replacement medication. The steps I take are as follows:

1. If the patient has been taking prednisone or dexamethasone, it should be changed to hydrocortisone.
2. The hydrocortisone should be tapered as quickly as tolerated to 10 mg each morning soon after awaking. Patients who have been taking prednisone or dexamethasone may feel bad in late afternoon. They can take 5 mg of hydrocortisone at 2 or 3 in the afternoon initially, but this should be discontinued as quickly as possible.
3. At some point, usually after a few weeks to a month on the single morning 10 mg hydrocortisone dose, an early morning (i.e., 8 a.m.) plasma cortisol level is obtained. That day’s hydrocortisone tablet is delayed until after the blood is drawn, because the test cannot distinguish between hydrocortisone secreted by the adrenal and that taken by mouth. When the morning plasma cortisol reaches 10 mcg/dL, the daily hydrocortisone medication can be discontinued. However, supplementation for minor illnesses and major stresses is still required.
4. After a few more weeks, a standard Cortrosyn (synthetic corticotropin, or ACTH) stimulation test is performed and is repeated every month or so until it becomes normal (i.e., when the plasma cortisol is equal to or greater than 20 mcg/dL at any time during the test). When the test becomes normal, the function of the hypothalamic-pituitary-adrenal axis is also normal. The bracelet and dexamethasone syringe can be discarded and no further treatment for stress or illness is required.

By Dr. David Orth MD (November, 1996)