One of the greatest disappointments, both for the patient and the surgeon, is when transsphenoidal surgery is done to treat Cushing’s Disease and there is failure to cure. Although about 90% of microadenomas and about 55% of macroadenomas are successfully treated by an initial transsphenoidal operation, failure to obtain remission and recurrence can develop in both categories. There are many factors to consider in the rare and infrequently occurring situation when the cortisol response to surgery is unsatisfactory.
Perhaps the first thing to review is the clinical situation. Is the Cushing’s syndrome mild or severe? Are there secondary complications such as hypertension or uncontrolled diabetes? Is it urgent to continue to treat the Cushing’s syndrome in a radical fashion or can less drastic strategies, such as medical therapy or radiosurgery, be considered?
The case must be thoroughly reviewed, making sure the laboratory studies did indeed show Cushing’s Disease, that is elevated cortisol from excess ACTH of pituitary origin. All of the imaging studies need to be reviewed, including MRI scans of the head, chest and abdomen. If inferior petrosal sinus sampling (IPSS) has been done, the results need to be double checked, and if the test has not been done, it should be arranged.
The pathology at the original surgery needs to be reviewed, and is of special concern if an ACTH staining tumor was not removed. One should note if any complications occurred related to the operation. There is considerable evidence that the experience of the surgeon plays a significant role in the success of this kind of surgery, and the avoidance of complications.
The expected response to successful surgery is a rapid fall in the serum cortisol levels, along with some symptoms of adrenal insufficiency such as headache, nausea, and vomiting, similar to flu symptoms. Ordinarily, we see this response within the first 3 days, and it predicts a lasting remission of Cushing’s Disease. If this does not occur, and the patient is quite ill, and all of the data point to a pituitary source for the Cushing’s Disease, then a prompt transsphenoidal pituitary operation should be done within the first 2-3 weeks after the initial operation. This strategy has an ultimate success rate of about 55%. If the patient has mild disease, and if the cortisol decreases, but not to subnormal levels, we would tend to follow the patient for several months to see if a late remission might occur.
We have been asked if repeat surgery is always the first thing recommended. Again, the answer depends on how severe the Cushing’s might be, how convincing the laboratory evidence is, and the ability for the patient to undertake medical therapy, radiosurgery or bilateral adrenalectomy alternatives.
In a patient with previously documented ACTH tumor in the sella, surgery for delayed recurrence can produce a remission in 55-80 % of such individuals, always more likely in microadenomas rather than macroadenomas. It must be emphasized that yet another recurrence may develop, and perhaps is more likely than with a first-time operation. In fact, we have one patient that was operated upon four times, each resulting in a remission, the first three temporary.
As with initial surgery, complications can develop after surgery for recurrence. In general, complications are more likely to occur in repeat operations, mainly related to scarring and distortions of the anatomy.
Medical therapy for Cushing’s Disease continues to develop. Currently there is no medicine that will produce a cure, however, much improved control of persistent Cushing’s Disease can be obtained.
Authors: Dr. Edward R. Laws, MD, FACS and Sherry Iuliano, FNP (Winter, 2013)
Editor’s Note: Dr. Laws is a very experienced neurosurgeon and both authors are part of the Pituitary/Neuroendocrine Center at Brigham & Women’s Hospital, Harvard Medical School, Boston MA.