High Normal TSH in Type 2 Diabetes May Mean Lower Risk of Stroke

with Tamar de Vries, MD, PhD candidate, and Alexandra L. Czap, MD

As you may well know, having type 2 diabetes puts you at increased risk of heart disease; so too does having an abnormally functioning thyroid. Even when you have good blood glucose control, there is still a residual risk for cardiac issues.1,2

However, there is some potentially good news for anyone with thyroid hormones in the normal high range. Dutch researchers report that in adults with blood levels of thyroid-stimulating hormone (TSH) on the high end of the desirable range have a lower risk of stroke.1

Heart disease is a problem for anyone with type 2 diabetes, but thyroid levels might help lessen heart disease-related risk.Anyone with type 2 diabetes and a high normal thyroid-stimulating hormone (TSH) level may have a lower risk of stroke.. Photo: istock

In this study, we looked at 1,265 men and women with type 2 diabetes and a TSH within the normal range, and didn’t find any link (eg, no reduced risk, no higher risk) related to heart disease events such as heart attack, says study coauthor Tamar de Vries, MD, PhD candidate in internal medicine in the department of vascular medicine at the University Medical Center of Utrecht in the Netherlands. But we did find that for every 1 mIU/L increase in blood levels of TSH, there is a 46% reduction in risk of having a stroke.1

While this may be very comforting to anyone with a TSH level consistently falling on the higher end of the desired range, an independent expert urges caution in interpreting the study since the numbers were relatively small to state the findings with any certainty.

Evaluating Risk of Heart Disease in Individuals with Diabetes and a Healthy Thyroid

The Dutch investigators followed both men and women, all with type 2 diabetes and a high risk of heart disease but who had no signs of thyroid disease (TSH in the normal range, 0.35 to 5 mIU/L) at the start of the study. The data was collected beginning in 2003 and continued through 2017.1

Over the course of 17 years, the researchers tracked which individuals had any of the heart-related complications identified before the study start, including heart attack, stroke, vascular death (such as after stroke), death from any cause. They check the TSH blood levels of all participants and compared levels to heart disease outcomes to determine if there were any noted patterns relative to the risk for the four vascular outcomes.1

The only observed cardiovascular measure that matched up with TSH levels was the risk of stroke, Dr. DeVrie tells EndocrineWeb, suggesting a possible protective effect when this thyroid measure was at the high end of the designated range.

How to explain this possible link and what it means for anyone who falls into this thyroid category (ie, high normal TSH)? "There are two main mechanisms that may be implicated in the reduced stroke risk associated with higher TSH levels," she says. However, it's important first to realize that TSH has an inverse with thyroid hormone (T3 and T4) levels.

TSH Levels Over Time May Predict Stroke Risk Better than Single Measures

With that in mind, doctors know that elevated thyroid hormone levels are associated with an increased risk of incident atrial fibrillation (AFib, or an irregular heartbeat), which is a leading cause of ischemic stroke. Ischemic stroke occurs when the blood supply to the brain is blocked by a clot or plaque.

This inverse relationship between TSH and circulating thyroid hormone levels potentially leads to the observation that a TSH level at the upper range of normal may be associated with a lower risk of stroke, Dr. de Vries says: "As we did not measure thyroid hormone levels themselves and only TSH, we do not have more evidence to support this."

As for why no link was found between high-normal TSH and other cardiac problems. "It is possible that diabetes itself is so strongly associated with both classical risk factors for cardiovascular disease and cardiovascular disease itself, that the potential additive effect of thyroid function on these risk factors is negligible,” Dr. De Vries says; “furthermore, studies into the association between TSH and risk factors (such as blood pressure and lipid levels) are typically cross-sectional [meaning it gives us a snapshot over time], so causality [a cause and effect] cannot be confirmed.''

And the researchers point out that it has been know that both overt and subclinical thyroid issues—both overactive and underactive thyroid—are considered risk factors for increasing a person’s risk for heart disease issues.3-5

Comanaging the Common Challenges of Thyroid Function, Diabetes, and Heart Disease

Alexandra L. Czap, MD, a vascular neurology fellow at McGovern Medical School at UT Health in Houston, reviewed the study findings for EndocrineWeb. While the report is very interesting, she is quick to point out that there was a relatively small number of strokes occurring in a large group of patients.

Because of this, Dr. Czap believes that the link found between TSH levels and stroke risk is likely related to the patient's TSH levels at the study start, rather than reflecting a trend over time. "Therefore, caution must be used in interpreting the results," she tells EndocrineWeb.

What is need next, she says, is for other researchers to study the question to see if they can arrive at similar findings. And, researchers need to look at multiple timepoints during the course of the study to see if and how the TSH levels vary and what effect these measures may have on risk.

Monitoring individuals for possible thyroid problems is, of course, important, just it certainly holds that those with type 2 diabetes should be monitored regularly for blood glucose control, as well as risks associated with heart disease, the Dutch researchers say. 

"Thyroid disorders can have a major impact on glucose control, and patients with subclinical hypothyroidism may be at greater risk of having microvascular complications," says Dr. de Vries. "Therefore, management of thyroid problems may be beneficial if you have diabetes. However, thyroid replacement therapy is also associated with some well-known adverse effects, so any potential benefit of treating thyroid problems should be weighed carefully for every individual."

Change in Thyroid Reference Range May Be Warranted if CVD Link Holds Up

Given our findings, Dr. de Vries and the research team suggest that it might be time to re-evaluate the reference ranges for TSH. The question of what levels should be considered normal for TSH is causing some debate among researchers, she adds.

"TSH levels within the normal range have been associated with many different clinical outcomes, including atrial fibrillation, heart failure, bone fractures, dementia, and chronic kidney disease, as reported in several prospective studies. This might suggest that the current standards are not correct,'' she says.

On the other hand, says Dr. de Vries: "many people with TSH levels at the outer limits of the current range are perfectly healthy. In fact, some individuals with a normally functioning thyroid gland would be classified as ‘abnormal’ if the reference standards were to change. And, currently, there is no evidence that treatment for subclinical thyroid abnormalities has a beneficial effect on clinical outcomes associated with heart disease, which begs the question—what are there clinical consequences of changing the reference standard?”

“For now, I believe the data are too preliminary to warrant any change to the current reference standard," she says.

What Does this Study Mean for Anyone with Type 2 Diabetes and a Healthy Thyroid?

The best advice for those with concerns about thyroid levels and T2D? "I would advise my patients to continue seeing their primary care of endocrinology doctor for management of your blood glucose, checking for any thyroid dysfunction, and addressing any vascular risk factors that may arise separately," Dr. Czap says.

She agrees with the researchers that it may be premature to revise the reference ranges, citing a few reasons, including the relatively few number of actual strokes—just 54—during a median follow-up of 6.4 years,1 which seems too low to draw any conclusions about changing current standards of care.

That said, Dr. Czap hopes to learn more about the relationship between TSH upper normal levels and heart disease risk from additional studies, addressing the same questions examined by the Dutch researchers. This is the best way to help keep anyone with type 2 diabetes and thyroid problems avoid the added concerns that come with cardiovascular disease.

Neither Dr. de Vries nor Dr. Czap have reported any financial conflicts related to this study. 

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