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Discussion
Dr Richard Hodin (Boston, MA): I’m curious how you defined “nonfunctional” and how carefully those patients were actually tested for some subtle functionality of the tumor.
Dr Alaa Sada: That’s a good question. We defined functionality based on full biochemical evaluation. We started with around 300 patients, and we excluded those for whom a complete biochemical workup was not obtained.
Having said that, not all of these testings were performed at the Mayo Clinic. We included patients if they had functional testing performed outside Mayo if the results were scanned and docu- mented in our electronic medical records.
Dr Richard Hodin (Boston, MA): Specifically, when looking for Cushing’s Syndrome, for example, was it with blood testing, 24- hour urinary levels, ACTH, etc .? How carefully could you tease that out?
Dr Alaa Sada: That’s an excellent question. Basically, all these patients had serum cortisol, 24-hour urine cortisol, ACTH, and 1 milligram dexamethasone suppression testing for Cushing’s Syndrome.
Dr Matthew Nehs (Boston, MA): Your results are consistent with what we see at Brigham & Women’s Hospital in Boston. But it seems to be the opposite of what one might expect, because a nonfunctional tumor lies indolent in someone’s retroperitoneum presumably for years and years, whereas a functional tumor creates an endocrinopathy that’s detectable.
What do you surmise is the reason for this? Is it the functionality of the tumor such as cortisol driving Cushing’s Syndrome or
hyperglycemia that could account for this difference? Or are these tumors more aggressive independent of their hormonal function?
Dr Alaa Sada: That’s a good point. I agree with you. The litera- ture shows that functional tumors tend to have worse prognosis. The difference in prognosis might be related to tumor stage as we have seen that in functional lesions, the rate of stage 4 disease is two times higher compared to nonfunctional tumors or it may be related to the hormones themselves, like cortisol and its effect on physiology.
Another explanation for the difference in prognosis is that functional and non-functional ACC may have different molecular and biological profiles that can affect their recurrence and clinical behavior.
Dr Marybeth Hughes (Norfolk, VA): What’s fascinating and most surprising about your results is that you didn’t find a differ- ence in complications with the functional tumors. So the literature is pretty clear that hypercortisolism puts these patients at a lot higher risk of postoperative complications. How do you explain that you didn’t find that difference?
Dr Alaa Sada: Thank you for the interesting question. You are correct. It is well known that hypercortisolism increases post-sur- gical complications. I think as surgeons and health care providers typically expect higher complication rates for functional tumors, they tend to monitor these patients more closely. In addition, these patients tend to require multidisciplinary teams care specifically from endocrinology stand point so I think close monitoring from multiple levels may have helped improved these patients outcomes.