BACKGROUND
Hypothyroidism (underactive thyroid) is common and an increased TSH level and, usually, a low FT4 level make the diagnosis. Hypothyroidism is treated with thyroid hormone replacement, usually in the form of levothyroxine. The goal of treating hypothyroidism is achieving a TSH in the normal range, which is usually sufficient in relieved the symptoms of hypothyroidism. However, it is important to not over or undertreat the condition. If a TSH remains high on levothyroxine (undertreatment), the patient is likely to have continued symptoms. If the TSH is too low (overtreatment), the patient may have symptoms of hyperthyroidism.

Not keeping the levels in the normal range can increase risk for heart issues and increase the risk of death from heart disease (cardiovascular mortality). A persistently increased TSH can lead to increased levels of cholesterol, which can cause heart disease. Similarly, a persistently low TSH can lead to an increased risk for atrial fibrillation, which causes the heart to beat irregularly, and increase risk of stroke. This study looks into the association of overtreatment and undertreatment of hypothyroidism and the risk of death due to heart disease.

THE FULL ARTICLE TITLE
Evron JM et al 2022 Association of thyroid hormone treatment intensity with cardiovascular mortality among US veterans. JAMA Netw Open 5(5):e2211863. PMID: 35552725.

SUMMARY OF THE STUDY
The authors looked into data from charts from the U.S. Veterans Health Administration Corporate Data Warehouse in order to identify those receiving thyroid hormone treatments from January 1, 2004, and December 31, 2017. They also used the National Death Index to assess death rates and cause of death.

They used the reference ranges for TSH and free thyroxine (FT4) levels at the Ann Arbor Veterans Administration laboratory for analysis. Patients with a history of thyroid cancer and those who used amiodarone or lithium were not part of the study. Overtreatment of thyroid hormone was defined as TSH levels lower than 0.5 mIU/L or FT4 levels higher than 1.9 ng/dl. Normal use of thyroid hormone treatment was defined as TSH levels from 0.5 to 5.5 mIU/L and FT4 levels from 0.7 to 1.9 ng/dl. Undertrreatment of thyroid hormone was defined as TSH levels higher than 5.5 mIU/L or FT4 levels lower than 0.7 ng/dl. Of the 705,307 patients in the study, 625,444 (88.7%) were men, and the average age was 67 years. Overall, 75,963 patients (10.8%) died of cardiovascular causes during an average follow-up of 4 years.

Risk of death was correlated with both a decreased and an increased TSH levels. Risk of death was increased by 39% if the TSH was suppressed and 13% if the TSH was low but detectable. Risk of death increased steadily as the TSH increased above the normal range, from 42% for a slightly increased TSH to 267% if the TSH was >20. The risk was even higher in older patients (>85) when compared with younger patients, ranging age to 18 to 49 years.

WHAT ARE THE IMPLICATIONS OF THIS STUDY?
Both overtreatment and undertreatment of hypothyroidism with of thyroid hormone was linked to an increased risk of death due to heart disease. These data clearly show that it is important to keep the TSH levels in the normal range while on thyroid hormone in order to decrease the cardiac risk and death in those patients with hypothyroidism.

— Joanna Miragaya, MD

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