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ATA CONFERENCE BLOG: Considering careers, novel drugs, microcarcinoma and basic science
Endocrine Today caught up with fellows to find out what they are learning at this year’s ATA Annual Meeting in Quebec City.
QUEBEC CITY — In today’s blog post, several fellows summarize and discuss some of Friday’s most exciting sessions, including the Lewis E. Braverman Award Lecture on thyroid hormone analogues; the Early Riser Symposium about management of thyroid microcarcinoma; a Fellows’ Track session focused on finding careers in academia; a Basic Science Symposium about thyroid hormone and the brain; and more.
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During the Lewis E. Braverman Award Lecture, titled “Thyroid Hormone Analogues: Promise and Pitfalls,” on Friday, Paul W. Ladenson, MD, of Johns Hopkins Medicine, spoke about three non-levothyroxine analogues: 3,5-diiodothyropropionic acid (DITPA), tiratricol (Triac) and eprotirome.
Akshay Jain
DITPA was initially developed as a vasodilator for congestive heart failure patients, but researchers found that it was not working well as a heart medication. However, when they re-studied DITPA, they found that it can be used in low doses as treatment for patients with an MCT8 mutation. This mutation, when it occurs, can cause mental retardation because it affects the D1 and D2 receptors in the brain. DITPA, however, does not need those receptors to act on the brain, unlike levothyroine.
Landenson also discussed Triac, which again, acts on different thyrotropin receptors. Generally, there are two types of receptors, the beta and the alpha, and Triac and DITPA might have more beta than alpha action. Triac is especially good for lipid-lowering — much better than levothyroxine. Studies that have been conducted so far also show that Triac causes elevations in nocturnal heart rate compared with levothyroxine.
The final drug, which is the most interesting, is eprotirome. It is supposed to have effects on the liver as well because it has tissue-specific access. According to one study, a 25% to 30% further LDL reduction occurred when eprotirome was used during a period of 4 to 12 weeks. There were no significant changes in HDL or apolipoprotein-B. However, the drug does cause a 35% to 40% reduction in triglycerides, especially in patients who have higher triglyceride levels — greater than 115 mg/dL — and it causes a significant decrease in lipoprotein(a).
There were no untoward skeletal or heart effects, or thyroid-stimulating hormone suppression action observed with eprotirome. One of the issues with DITPA and Triac was their impact on the skeletal system, which causes increased bone turnover and bone loss, just like levothyroxine would. These drugs also have an increased predilection for progressively worsening osteoporosis. This, however, does not occur with eprotirome, at least not in the studies performed to date.
Additionally, combining eprotirome with statins has a synergistic effect in which the lipid-lowering effect of the statin is actually accentuated by using eprotirome. The thyroid-binding globulin reduces with eprotirome. However, although it does not have any skeletal action, the drug does increase juvenile cartilage, thereby promoting growth defects, but no animal studies have been done to corroborate that point.
In the bone chondrocytes, the alpha receptors are almost 10 times more than the beta receptors, which is why these three agents have different actions. Eprotirome has more beta action — selectively only beta action, not alpha action — which is why it does not cause bone loss.
Akshay Jain, MD, is an endocrinology, diabetes and metabolism fellow at the UCLA/City of Hope National Medical Center in Los Angeles. Jain reports no relevant financial disclosures.
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Friday’s Early Riser Symposium discussed thyroid microcarcinoma with Douglas Ross, MD, Marina Nikiforova, MD, and Martha Zieger, MD, FACS, offering perspectives on the scope of the problem, molecular testing aspects and surgical management in the era of molecular testing. I was interested to learn that BRAF testing on a fine needle aspiration (FNA) specimen done correctly in a certified molecular is essentially a clear diagnostic test with a specificity close to 100%. Nikiforova emphasized that ultra-sensitive BRAF assays may inflate the false positive rate and are not helpful.
Devin Steenkamp
The clinical session that followed presented the US population iodine nutrition status from the most recent National Health and Nutrition Examination Survey (NHANES) data, with perspectives from Mark Vanderpump, MB, ChB, MD, FRCP, on the worrisome iodine deficiency noted in teenage girls in the United Kingdom recently. He speculated that decreases in milk intake in the U.K. during childhood may be responsible for the drop in urinary iodine levels reported rather than changes in the dairy industry milking process itself. Lewis Braverman, MD, who is senior faculty at my institution, ended this session with some perspectives on iodine excess disorders stemming from his 52-year career in thyroidology. I always enjoy his lectures and his inclusion of primary groundbreaking data from the 1960s and 1970s is great for young endocrinologists to think through and digest, as we are always so focused on recent data and studies and often forget about the seminal papers in the field from the past that are often still highly relevant.
David S. Cooper, MD, gave a highly entertaining lecture on the cilnical nonentity of Wilson's low temparature syndrome, which concluded a morning session on alternative non-levothyroxine drugs, including neutraceuticals, desiccated thyroid hormone and other complementary therapies, that our patients often view as life-changing while those of us in Western science find it so tough to get our heads around. I was impressed that the ATA would tackle such a tough topic and try to give us some perspective to take home to our patients.
On a final note, the Fellows’ Track continues to be fantastic in its practicality and relevance. Friday’s sessions included: "How to Set Up a Dedicated Thyroid-Only practice," including onsite nuclear medicine, ultrasound and lab facilities from three expert private thyroidologists who have succesfully run exclusive thyroidectomy practices. The final session for fellows was entitled: "How to Communicate about the Thyroid" from the pathologist, surgeon and endocrinologist perspectives. The sessions were eye-opening for us all, as we rarely think about these things in our day-to-day clinic and research experiences. They are foundational and so practical for all those looking to go into clinical practice.
Devin Steenkamp, MD, is a fellow in endocrinology at Boston Medical Center and has contributed to several of Endocrine Today’s Imaging Analysis columns. Steenkamp reports no relevant financial disclosures.
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The ATA Fellows’ Track luncheon today was geared toward helping young physicians and scientists find their first academic position. David Sharlin, PhD, from Minnesota State University, and Brian Kim, MD, from the University of Miami, presented balanced perspectives and recommendations on successfully entering the competitive academic workforce.
William Duke
They started the discussion by reviewing the types of academic careers and clearly outlining the differences between tenured and non-tenured positions. They also reviewed the pros and cons of both teaching and non-teaching positions and offered advice on securing academic funding and contract negotiation.
The remainder of the discussion focused primarily on the application process and the steps an applicant can take to enhance his or her chance of being offered a position. They started by listing available online resources for job postings, and recommended that applicants establish profiles and set up email alerts so they can be ready to respond quickly to new opportunities.
In addition to having a mentor willing to contact prospective new employers, the speakers also highlighted the benefits of networking at national meetings such as the ATA. They outlined the importance of a letter of recommendation from the applicant’s current mentor, employer or principal investigator. One of their most important pieces of advice is to make sure that the letter specifically mentions which research tools and resources the applicant will be allowed to take with them to their new position, citing many instances where this written documentation helped resolve future disputes about potential thefts of intellectual property.
They then gave useful advice on preparing for the “job talk,” noting that it’s a good sign if you’re asked to give one. They suggested including a brief mention of prior research, but focusing the discussion primarily on a detailed plan for future work. While it is always preferable to have an existing source of funding, in many cases it is beneficial for unfunded applicants to outline the work that they have done to demonstrate that they are close to applying for a grant. This shows the potential employer that the applicant may be able to bring funding into the institution and contribute to their salary relatively soon after the hire date. They also recommended that the talk appeal to a broad audience, as there will likely be many different types of physicians and scientists listening to the talk who sit on the applicant selection committee.
This was a valuable session with many insightful tips to help navigate the difficult and often highly political waters of academic hiring. I think future discussions on this issue would be enhanced by including more information for physicians interested in careers in clinical academic medicine.
William Duke, MD, is a board-certified otolaryngologist and a clinical fellow in head and neck endocrine surgery at Georgia Health Sciences University in Augusta. Duke reports no relevant financial disclosures.
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Got thyroid hormone on the brain? I definitely do. Indeed, attending the Basic Symposia titled “Thyroid Hormone In the Brain,” I was treated to three different lectures on the importance of thyroid hormone in the brain. Juan Bernal, MD, PhD, gave the first talk entitled “Gene Regulation by Thyroid Hormone in the Brain.” Bernal discussed the roles of the thyroid hormone receptors (TRs) in the brain and highlighted the effects of deleting TRalpha1, TRbeta or both in the brains of mice on gene expression.
Kristen Vella
I was struck by the large number of genes that thyroid hormone regulates in the cortex and the striatum, as Bernal profiled thousands of genes. A large percentage of genes, both positive and negative thyroid hormone targets, are affected by deleting both TRalpha1 and TRbeta, such that their expression is similar to that of a hypothyroid mouse. Furthermore, there were a significant percentage of genes that are regulated by thyroid hormone, but TRalpha1 and TRbeta deletion has no effect on their expression. As someone who works primarily on the regulation of genes by thyroid hormone in the hypothalamus, I’m very interested in how Bernal’s work might translate to that area of the brain. How many genes are regulated by thyroid hormone in the hypothalamus and does deletion of both TRalpha1 and TRbeta affect their expression?
On Friday, fellows were invited to attend “Finding your First Academic Position.” The session was chaired by David Sharlin, PhD, assistant professor at Minnesota State University, and Brian Kim, MD, assistant professor at the University of Miami, both who recently started their first academic positions.
Sharlin and Kim led an informal discussion on the ways they went about applying to academic positions, the problems they encountered and gave a lot of tips to the attendees on starting their own process. As someone who will start this process in the near future, I was grateful for this session as one of their main points was to start early and really bring your mentor in to help with the process. Additionally, both Sharlin and Kim had a lot of enthusiasm and shed a lot of light on how positive the process can be.
Kristen Vella, PhD is a postdoctoral fellow in the laboratory of Tony Hollenberg, MD, at BIDMC where she studies the regulation of thyroid hormone levels during states of nutritional stress. She is the co-chair of the Basic Fellows’ Educational Track at the 82nd Annual Meeting of the American Thyroid Association.