Falling Threshold for Treatment of Borderline Elevated Thyrotropin Levels—Balancing Benefits and Risks: Evidence From a Large Community-Based Study

Study Questions:

In a large population-based United Kingdom database, what are trends in thyrotropin levels before and after initiation of therapy with levothyroxine?

Methods:

This was a retrospective analysis of the Clinical Practice Research Datalink. The authors extracted the following data about persons who had initiated levothyroxine treatment between January 1, 2001, and October 30, 2009: thyrotropin level before levothyroxine therapy initiation, clinical symptoms, and thyrotropin levels up to 5 years after levothyroxine was initiated. The following were the main outcomes: median thyrotropin level at the time of the index levothyroxine prescription, the odds of initiation of levothyroxine therapy at thyrotropin therapy at ≤10.0 mIU/L, and the age-stratified odds of developing a low or suppressed thyrotropin level after levothyroxine therapy.

Results:

In analyses adjusted for age, gender, key clinical characteristics before levothyroxine therapy, and co-morbidities, the odds ratio for having an index levothyroxine prescription with a thyrotropin level of ≤10.0 mIU/L in 2009 compared with 2001 was 1.30 (95% confidence interval, 1.19-1.42; p < 0.001). This has been accompanied by a decline in the median thyrotropin threshold at the time of the index levothyroxine prescription from 8.7 to 7.9 mIU/L; 34.6% of individuals who were prescribed levothyroxine for a borderline thyrotropin level of 4.0-10.0 mIU/L had only one abnormal thyrotropin reading before initiation of therapy. At 5 years after therapy with levothyroxine, the percentage of those with a thyrotropin level <0.1 mIU/L increased from 2.7% to 5.8%.

Conclusions:

There has been a trend toward greater treatment of marginal degrees of hypothyroidism (with thyrotropin <10 mIU/L) from 2001 to 2009, with a substantial risk of developing suppressed thyrotropin levels following therapy.

Perspective:

This retrospective analysis draws attention to the potential overprescription of levothyroxine for borderline thyrotropin levels. This practice may be associated with marginal benefit, and may lead to harm with the development of suppressed thyrotropin levels. Confirmatory testing of single borderline thyrotropin levels may reduce unnecessary prescriptions of levothyroxine. Future studies are necessary to better define the risks and benefits of thyroid replacement therapy for marginal degrees of hypothyroidism.

Keywords: Odds Ratio, Great Britain, Triiodothyronine, Thyroxine, Comorbidity, Homeodomain Proteins, Risk Factors, Hypothyroidism, Thyrotropin, Biological Markers, Troponin I, Cardiology, Confidence Intervals, Risk Assessment


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