BACKGROUND
Hypothyroidism is a common disorder associated with high levels of TSH and low levels of thyroid hormone. Hypothyroidism is usually treated with levothyroxine in a dose to normalize TSH levels. However, we know that many people on levothyroxine do not always have normal TSH, with frequent high (undertreatment) and low (overtreatment) TSH levels commonly seen. These results usually lead to a change in the levothyroxine dose.

Thyroid hormone has a direct effect on the heart. High levels of thyroid hormone, as seen in hyperthyroidism, leads to increase heart rate, palpitations and irregular hear rhythms. Low levels of thyroid hormone can lead to a low heart rate. Both conditions can cause heart problems. Studies have shown that both under and over treatment with levothyroxine are also associated with increased heart problems and can lead to an increased risk of death. In most of these studies, thyroid function was evaluated over a short period of time.

This study sought to assess changes in thyroid function (called the TSH trajectory) over a longer time frame and evaluate how that correlated with heart health markers.

THE FULL ARTICLE TITLE
Ettleson MD, et al. TSH trajectories during levothyroxine treatment in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) cohort. J Clin Endocrinol Metab. Epub 2024 May 23:dgae294; doi: 10.1210/clinem/ dgae294. PMID: 38780968.

SUMMARY OF THE STUDY
The authors used data from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), a group of over 15,000 Brazilian civil servants ages 35 to 74 years from six Brazilian cities. Only participants with a reported history of hypothyroidism and continuous levothyroxine treatment were included. They excluded patients with a history of thyroid cancer and recent /current pregnancy and identified 621 participants with data over 3 time periods called waves (wave 1 at baseline in 2008–2010, wave 2 in 2012–2014, and wave 3 in 2017–2019).

Data collected included health questionnaires, clinical measurements and blood samples. It was also noted whether participants were taking medication for high blood pressure, elevated cholesterol and/or diabetes. An advanced statistical method was used to identify groups with similar changes in TSH levels (TSH trajectories) and then changes in cardiovascular health markers and related medications were compared between the three study waves.

Of the 621 participants with an average age of 54.2, 85.7% were female, 63.6% were White, and 63.4% had completed college. Four TSH trajectories were identified. (1) high–high normal TSH (HHN) (55.9%); (2) normal TSH (N) (30.3%); (3) normal to low TSH (NL) (6.8%); and (4) low to normal TSH (LN) (7.1%). Changes in cardiovascular health markers and cardiovascular medication over time were compared within each trajectory. At baseline (wave 1) there were no significant differences in cardiovascular health makers between the four groups. However, current smokers were more common in the LN group, while males were more common in the HHN group and the average baseline levothyroxine dose was lowest in the HHN group.

One or more cardiovascular health marker increased over time in all the groups, as well as usage of cardiovascular related medication. The biggest changes appeared in the HHN and LN classes.

WHAT ARE THE IMPLICATIONS OF THIS STUDY?
This study expands upon previous reports showing the association of poor thyroid hormone control and worsening CV health. Its strength is the longer duration of time that subjects were monitored. However, the sample size was too small to compare results between the 4 groups. Thus, it is difficult to separate the effect of thyroid hormone control versus aging over the ten years of observation. More studies are needed to fully evaluate the risks of over- or under-treatment of hypothyroidism and heart problems.

—Marjorie Safran, MD

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