Falling Threshold for Treatment of Borderline Elevated Thyrotropin Levels—Balancing Benefits and Risks

Abstract

IMPORTANCE Rates of thyroid hormone prescribing in the United States and the United Kingdom have increased substantially. If some of the increase is due to lowering the thyrotropin threshold for treatment, this may result in less benefit and greater harm. OBJECTIVE To define trends in thyrotropin levels at the initiation of levothyroxine sodium therapy and the risk of developing a suppressed thyrotropin level following treatment. DESIGN, SETTING, PARTICIPANTS, AND EXPOSURE Retrospective cohort study using data from the United Kingdom Clinical Practice Research Datalink. Among 52 298 individuals who received a prescription for levothyroxine between January 1, 2001, and October 30, 2009, we extracted data about the thyrotropin level before levothyroxine therapy initiation, clinical symptoms, and thyrotropin levels up to 5 years after levothyroxine was initiated. We excluded persons who had a history of hyperthyroidism, pituitary disease, or thyroid surgery; those who were taking thyroid-altering medication or if the levothyroxine prescription was related to pregnancy; and those who did not have a thyrotropin level measured within 3 months before the initiation of levothyroxine. MAIN OUTCOMES AND MEASURES The median thyrotropin level at the time of the index levothyroxine prescription, the odds of initiation of levothyroxine therapy at thyrotropin levels of 10.0 mIU/L or less, and the age-stratified odds of developing a low or suppressed thyrotropin level after levothyroxine therapy. RESULTS Between 2001 and 2009, the median thyrotropin level at the initiation of levothyroxine therapy fell from 8.7 to 7.9 mIU/L. The odds ratio for prescribing levothyroxine at thyrotropin levels of 10.0 mIU/L or less in 2009 compared with 2001 (adjusted for changes in population demographics) was 1.30 (95% CI, 1.19-1.42; P < .001). Older individuals and individuals with cardiac risk factors had higher odds of initiation of levothyroxine therapy with a thyrotropin level 10.0 mIU/L or less. At 5 years after levothyroxine initiation, 5.8% of individuals had a thyrotropin level of <0.1 mIU/L. Individuals with depression or tiredness at baseline had increased odds of developing a suppressed thyrotropin level, whereas individuals with cardiac risk factors (eg, atrial fibrillation, diabetes mellitus, hypertension, and raised lipid levels) did not. CONCLUSIONS AND RELEVANCE We observed a trend toward levothyroxine treatment of more marginal degrees of hypothyroidism and a substantial risk of developing a suppressed thyrotropin level following therapy. Large-scale prospective studies are required to assess the risk-benefit ratio of current practice.

Thyroid Hormone Therapy and Risk of Thyrotoxicosis in Community-Resident Older Adults: Findings from the Baltimore Longitudinal Study of Aging

“…This is the first study to estimate rates of thyrotoxicosis in the United States using prospective data. A recent study in the United Kingdom reported a similar cumulative rate of overtreatment-16% over five years (3). There are several interesting differences from the present results, which may be due to differences in patient and physician behavior between the two countries.…”

“…There are several interesting differences from the present results, which may be due to differences in patient and physician behavior between the two countries. For example, Taylor et al (2014) report increased odds for thyrotoxicosis in women to be 1.4-1.5 compared with men, where the present study found that women were five times more likely to develop thyrotoxicosis on treatment compared to men. In the British study, younger patients and those with more severe thyroid disease were at highest risk of overtreatment, while the present study did not find a relationship with age, and among the 17 participants started on therapy for peak observed TSH >7 mIU/L, none became subsequently overtreated.…”

“…More recently in the United Kingdom, 16% of those on thyroid hormone, excluding cancer, were found to have had at least one low TSH by five years of therapy, about a third of these suppressed <0.1 mIU/L (3). Understanding overtreatment is especially relevant to geriatric populations, as representative population data from NHANES demonstrated that subclinical hypothyroidism increases with increasing age (29) and prescribing trends for initiating therapy at lower TSH thresholds have occurred particularly in older persons (3,31).…”

Estimación de la prevalencia de hipotiroidismo según diferentes métodos: dosis diaria definida, dosis diaria prescrita y registro de pacientes en tratamiento

“…Otra dificultad, exclusiva del HT y más difí-cil de cuantificar, sería la provocada por el uso de fármacos en los pacientes con HT subclíni-co 26 . La utilización de LT en los pacientes con niveles adecuados de tiroxina libre pero con niveles de TSH por debajo de 10 mU queda, según las guías de práctica clínica, a criterio del médico prescriptor 16,27 .…”

Current recommendations in the management of hypothyroidism: developed from a statement by the British Thyroid Association Executive

“…The management of such individuals is challenging and sometimes frustrating for patients and clinicians alike. In addition recent community-based surveys have highlighted a series of pressing concerns including the indiscriminate use of thyroid tests, 6 overdiagnosis, and excessive treatment of patients with mild hypothyroidism, 7 and an inconsistent approach to the management of subclinical disease. 8 Accordingly a number of international societies have published best-practice guidelines for the management of hypothyroidism.…”