Acromegaly: Postoperative Evaluation.

From Lewis S Blevins Jr,. MD  –  My approach to the postoperative evaluation of patients with acromegaly is based on over a quarter of a century of experience evaluating and treating patients with the disorder. Various groups have put forth guidelines regarding the evaluation and management of acromegaly. While these are, generally, well constructed and somewhat relevant, in my opinion they address management of a population with disease and do not focus on individual patients, their wants, desires, etc.

I focus on three major things after surgery: 1.) the pituitary tumor; 2.) IGF-I and GH levels; 3.) patient symptoms, co-morbidities, and sense of well-being.

The Pituitary Tumor. Patients should undergo MRI with gadolinium contrast enhancement 6 to 12 weeks after surgery to evaluate the degree of tumor resection. Postoperative images should be compared to preoperative images to ensure that all the tumor has been removed. Anything at all that looks like a remnant of tumor, and especially when it has a similar appearance to the preoperative configuration of the tumor, should be considered possible residual disease until proven otherwise. Sometimes, it can be difficult to distinguish postoperative changes and granulation tissue from normal pituitary and tumor. I will say, however, that comparison to the preoperative scan helps to resolve a lot of the confusion over postoperative images.

IGF-I and GH levels. Our understanding of the biochemistry acromegaly has changed over time. When I was in training, one was thought to have successfully treated acromegaly if the random growth hormone level had been reduced to less than 5 ng/mL. A plethora of papers have been published describing “cure rates” using this cut off. We have recognized, however, that a number of these patients have active progressive clinical symptoms in the setting of residual tumor on MRI. In essence, they weren’t cured of their disease process. Next, it was determined that the IGF-I should be normalized and that the random growth hormone level should be less than 2 ng/mL before a patient could be deemed as having been rendered disease free. Unfortunately, however, some of these patients were not actually free of the active manifestations of acromegaly. Based on outcomes that evaluate survival and life expectancy, the criteria for cure were revised to indicate that IGF-I levels should be normalized and random growth hormone levels reduced to less than 1 ng/mL to reflect control of the disease process. I wrote “control of the disease process” because some believe that acromegaly cannot be cured but instead only controlled. It seems that the term “under control” is best reserved for those patients who have residual disease and have responded appropriately to medical therapy meeting the criteria specified above. I find that I will most often used the term “in remission” for patients who are likely to have recurrence of the biochemical abnormalities of acromegaly and/or their tumor. I use the term “cure” when I am absolutely certain there is no biochemical or radiographic evidence of disease and believe that there will not likely be a recurrence. Some employ the oral glucose tolerance test before and after surgery to evaluate patients with acromegaly. The test was, in fact, first devised as a preoperative diagnostic test. It has, however, been used in the postoperative setting. Some of the best data about the performance of the test, and various growth hormone assays, has been derived from the evaluation of postoperative patients. Previously, it was thought that GH levels less than 2 ng/mL after ingestion of the glucose represented normality. We now know that most normal patients suppress GH levels to less than 0.4 ng/mL after and oral glucose load. However, the most commonly employed cut off for the test is 1 ng/mL. The inference made, when GH levels suppress in response to oral glucose, is that all of the measured GH is coming from normal growth hormone producing pituitary cells. GH from tumor cells is not usually suppressed by oral glucose.

Patient symptoms, etc. As physicians, we want to alleviate suffering. One of the important goals of any treatment is to resolve or improve symptoms and signs of the disease process under consideration. Thus, it is important to compare postoperative symptoms and signs to the preoperative ones described by the affected patients. Things like hypertension, diabetes mellitus, sleep apnea, sweating, soft tissue swelling, and headache improve greatly while arthritis, disfigurement, and headache improve only modestly. It’s important to have a handle on how well the patient is doing after treatment.

There are a number of different postoperativev scenarios that pique my curiosity. I will discuss them next.

Discordant IGF-I and GH results after surgery. Sometimes, the IGF-I level is elevated and the growth hormone level is normal. Whenever I encounter this pattern of laboratory abnormalities at the six-week follow-up visit, or at any point during follow up after presumed remission, I will repeat the IGF-I levels six weeks later. If the levels repeat abnormal then I presume patients have residual disease. Next, I carefully review the MRI to determine if there is a need for either medication, additional surgery or gamma knife radiosurgery and medication. Occasionally, I see patients who have normalized there IGF-I levels but have elevated GH levels. If these patients have symptoms of persistent disease, and especially if there is anything at all on MRI suggestive of residual tumor, I presume active disease and proceed with treatment. The principal hypothesis guiding this decision regarding treatment is that, though normal, the IGF-I level must be higher than the patients set point if they have active symptoms of acromegaly. In the absence of symptoms of active disease and MRI evidence of residual tumor the only scenario where I would treat a patient with a history of acromegaly and a normal IGF-I and an elevated GH is in the setting of some other active malignancy. For example, I had a patient who had marked elevations in GH in the setting of a normal, albeit high normal, IGF-1 level and no evidence for residual tumor. She had metastatic breast carcinoma and was undergoing chemotherapy after surgery and radiation. I felt it prudent to trade with medications to achieve the Target GH in order to give her the best chance to survive breast cancer.

Discordant biochemical and radiographic studies after surgery. We only very occasionally encounter patients who have no evidence for residual tumor on the MRI but do indeed have abnormal biochemistry indicative of residual disease. The working hypothesis is that these patients have microscopic residual tumor that is producing sufficient amounts of growth hormone to lead to elevations in IGF-I. They deserve treatment. Some patients have normal biochemistry but evidence for residual tumor, or something suspicious for residual tumor, on their postoperative MRI studies. Patients who present with this scenario who also have symptoms of active acromegaly probably deserve treatment. Otherwise, these patients can be followed until either the suspicious area increases in size suggesting that it was indeed tumor, or the biochemistry becomes abnormal thereby illustrating concordance of laboratory and radiographic measures of disease activity.

We’ve all heard the old adage “don’t jump to conclusions.” Well, the same applies to acromegaly and the adage can be modified to state “don’t jump to treatment” when it comes to adjuvant therapy after failed surgery or else in the setting of a recurrence. There must be indications for treatment. The indications usually fall in the three main categories I reviewed at the beginning of this brief essay. In brief, we are most likely to recommend treatment for patients with active disease based on symptoms, signs, and biochemical evidence for disease and/ or, the presence of viable tumor as demonstrated by radiographic studies.

© 2014, Pituitary World News. All rights reserved.

1 COMMENT

  1. Science works with patterns, references and ranges. If each hormone had its own melody the hormones cycles would have some “recognizable” (I don´t know if this word exhists in English…) symphony. For me, I feel that the numbers in the paper are not enough to catch the ever changing dynamics of hormones after something (like surgery) has happened to the pituitary. That´s why my guess is that my lethargy is due to hormonal imbalance (some biochemestry messed up) even though it doesn´t show in the reference chart. Yesterday I wrote down the values, and they fit the normality, but who knows if my body is missing the extra that I had… Just wondering, no need to reply…
    Surgery in the begining of February 2013.
    Values:
    IGF1
    31/10/2012 8:19 a.m. 441 ng/mL
    04/12/2012 7:30 a.m. 491 ng/mL
    01/02/2013 07:50 a.m. 580 ng/mL
    04/03/2013 7:30 AM 237 ng/mL
    22/05/2013 7:24 AM 187,70 ng/mL
    04/09/2013 7:04 AM 187,80 ng/mL
    28/06/2014 7:30 a.m 215 ng/mL
    22/10/2014 8:30 a.m. 176 ng/mL

    GH

    13/09/2012 8:00 2.73 ng/mL
    31/10/2012 8:19 a.m. 5,30 ng/mL
    01/02/2013 07:50 a.m. 3,10 ng/mL
    04/03/2013 7:30 AM 0,18 ng/mL

    22/05/2013 7:24 AM 0,10 ng/mL
    28/06/2014 7:30 a.m 1,36ng/mL
    22/10/2014 8:30 a.m. 0,26 ng/mL

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