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Expert Perspectives on Factors Impacting TSH Values and the role of TSH Variability in Clinical Outcomes in Patients with Primary Hypothyroidism - Episode 4

Key Data on Off Target TSH Levels in Patients with Hypothyroidism

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James Hennessey, MD, FACP, provides an overview of clinical trial data for patients with hypothyroidism, highlighting the negative effect and poor health-related consequences of off target TSH levels.

James Hennessey, MD, FACP: Can I mention a few of those studies to you?

Antonio Bianco, MD, PhD: Yes. Sure. Please.

James Hennessey, MD, FACP: As far back as 2010, this is where it started to become known to me, Flynn was looking at patients in Scotland, and they were on levothyroxine that they were able to categorize as either having normal TSH [thyroid-stimulating hormone] on average, high TSHs on average, or suppressed TSHs either undetectable or just low. When they looked at cardiovascular admissions or death due to cardiovascular disease, they found that when the TSHs were suppressed, there was a 37% increase in those on levothyroxine versus people who had normal TSH. Subsequently, even those with elevated TSHs, for example persistent hypothyroidism, had and elevated risk of about 80%. The same type of pattern was seen for dysrhythmias as well as fracture related admissions, with both suppressed as well as elevated TSHs leading to increased risk. More recently, in 2019, a very large study was reported by Thea Karen in the British Medical Journal, where they looked at over 160,000 people who were treated for incident hypothyroidism with levothyroxine. They did a similar categorization of TSHs by doing weighted TSHs, and they weren’t just looking at individual levels but for trends. They were able to measure outcomes when it came to multiple morbidities, which is very important. They concluded that if the TSH was in the normal range, between 2 to 5 is what they used as their absolute reference, but as long as the TSH was within the stated normal range in the laboratory, the outcomes for things like ischemic heart disease were the same. But if the TSHs were elevated, the ischemic heart disease outcomes were elevated. When it came to things like fractures like the Flynn study, the same thing was noticed in a normal TSH versus an elevated TSH, the elevated TSH was a risk factor. More recently, there’s a brand-new study out of the VA system with over 700,000 adults on levothyroxine, and they looked at cardiovascular death, which is a chilling, but hard end point.

Antonio Bianco, MD, PhD: That’s the VA study.

James Hennessey, MD, FACP: That’s right. After a median follow up of about 4 years, they were able to demonstrate that if the TSH was between 0.5 and 5.5, which they designated as a normal hazard ratio of 1, then anything that was below the normal range, like the thyrotoxic patients, had elevated risk of cardiovascular; it was similar for those with hypothyroidism. I’ve concluded that getting it into that normal range and keeping it there is very important.

Antonio Bianco, MD, PhD: Yes, that for me is surprising. Especially Matt Adelson, who was a fellow here at The University of Chicago, and he did a study which he looked at serum TSH levels and of individuals that were admitted for all types of admission in the hospital. Then he looked at readmission rates and mortality rates, and he saw that patients that had TSH greater than 10 had a significantly greater rate of readmission and increased mortality. I think that’s super important for those who run pre-op clinics. For example, if you’re doing an elective procedure, sometimes the TSH will come back to you, and the surgery is already scheduled. No one wants to stop that surgery and say, let’s move forward with this, we had no data to show whether it will be a liability or it would be a negative factor for the admission, but now we know it’s probably not a good idea and it’s better to postpone the procedure if it’s elective; normalize that serum TSH because the outcome is going to be a better thing. This is a combination of many recent studies showing that keeping a TSH on target is an important thing, not only for our satisfaction that we are normalizing everything with the doses of levothyroxine, but because the clinical outcomes are important and really affected.

Transcript edited for clarity

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