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Shades of gray
The Endocrine Society Annual Meeting illustrates that the more we learn, the more we have to learn.
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When I told patients the week before leaving for The Endocrine Society Annual Meeting that I would be away at a conference, I was surprised at the responses I received.
Few seemed to mind that there would be a delay in getting their laboratory results. On the contrary, most patients were curious to know what I was going to learn and made a plea for me to bring back new information. With a smile and wink, one man said, “You’re always telling me that we don’t know the answers yet. Are you going to get the answers this weekend?”
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This year’s annual meeting was, true to form, an enriching whirlwind tour of some of the most prevalent, controversial and influential topics in endocrinology today. As always, I came away from the meeting not only having learned a great deal from presenters and colleagues, but also with an ever-expanding new list of previously unappreciated uncertainties and questions.
Questioning the ‘normal’
In the slice of sessions I attended, a commonality seemed to emerge — a sense that every day we learn more, and every day we learn more about how much we do not know. I was struck by the themes common to topics with so little in common.
We were repeatedly encouraged to reconsider conventional treatment goals and to question our definitions of what should be considered “normal.” We were challenged to re-think our treatment targets in diabetes based on the Action to Control Cardiovascular Risk in Diabetes (ACCORD) data, which, in concert with the clinical trials that preceded it, have provided another layer of complexity in formulating evidence-based recommendations for our patients. We were challenged to reconsider our treatment thresholds for subclinical hypothyroidism in people of different ages, as well as our perceptions of what a normal thyroid-stimulating hormone level with increasing age is. What is a normal testosterone level in aging men? Taking one step back, how do we make reliable biochemical assessments of testosterone levels in men, and, equally if not more vexing, we were presented with the numerous inaccuracies inherent in the assessment of testosterone levels in women.
Experts from a wide array of endocrine subspecialties were cautioned in general against reliance upon normal ranges derived from convenience samples. The uncertainties raised were more numerous than the solutions proposed. Over and over, we were reminded that when laboratory results return marked in bold with an “H” or “L,” more often than not, we cannot rely on simplified biochemical assessments of complex clinical syndromes.
Diversity of interpretations
During the meeting I was struck by the remarkable diversity of interpretations that have emerged from review and synthesis of the same data. After an eloquent debate regarding whether long-term treatment with bisphosphonates causes atypical fractures, the audience votes remained nearly split over whether a causal association truly exists. It was clear in discussions regarding osteoporosis management that, in recent years, many clinicians have modified their approaches to bisphosphonate therapy in terms of duration of therapy, strategies for monitoring and thresholds for modification of therapy.
It was striking, however, that an audience presented with a commonly encountered clinical scenario involving a postmenopausal woman on bisphosphonate therapy at moderate fracture risk was split nearly in thirds when asked what to do next — some would continue, some would stop and some would escalate therapy. Everyone seemed to agree that bisphosphonate “drug holidays” are warranted; no one seemed to agree on the details of how to do that, barring the simplest of extremes. The one thing that most could agree on is that we simply need to learn more.
Over and over again, the discussions would end with a plea for additional information to guide us. We are so often charged in clinical practice with the daunting task of distilling sound clinical recommendations out of imperfect information. Yet, many presentations reflected on the difficulties inherent in acquiring the coveted randomized clinical trial data that are so vital to sharpening our approaches to these “gray” areas of clinical endocrinology. Capturing the opportunity to seize upon the sliver in time when equipoise exists, making it possible to practically and ethically justify conduct of the clinical trials that are so needed, is often unattainable.
We often come to meetings seeking more definitive recommendations from the experts. Yet, we often come away with a strangely comforting awareness that the uncertainties we have are universal, even among respected experts and peers. The absence of “answers” is frustrating, but appreciation of existing uncertainties is valuable. It is something that we can share with our peers and bring home to our inquiring patients.
Emily Szmuilowicz, MD, is clinical instructor of medicine at Northwestern University and a member of the Endocrine Today Editorial Board.