Mishaps in Diagnosing and Treating Hypothyroidism

Doctors have become increasingly aggressive at initiating treatment for borderline hypothyroidism, potentially raising the risk for thyroid suppression as an unintended consequence….

According to the authors, doctors have become increasingly aggressive at initiating treatment for borderline hypothyroidism, possibly raising the risk for thyroid suppression as an unintended consequence. The American Thyroid Association recommends considering levothyroxine therapy at thyroid-stimulating hormone (TSH; thyrotropin) levels of 10 mIU/L or lower if symptoms of hypothyroidism, positive thyroid autoantibodies, or evidence of atherosclerotic cardiovascular disease or heart failure are present. But starting levothyroxine at or below 10 mIU/L in those without symptoms may do more harm than good, it cautions.

This retrospective cohort study included 52,298 individuals who received a prescription for levothyroxine between January 1, 2001, and October 30, 2009. The authors extracted data about the thyrotropin level before levothyroxine therapy initiation, clinical symptoms, and thyrotropin levels up to 5 years after levothyroxine was initiated. The main outcomes were 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. In the results of the study, 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 (P < .001). Thus, the number of individuals who received levothyroxine for a thyrotropin level of less than 10 mIU/L increased by 30% over the course of the study. The number of new levothyroxine prescriptions increased by 74% over the study period. 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. Free thyroxine values were available in 68.3% of individuals prescribed levothyroxine with a thyrotropin level between 4.0 and 10.0 mIU/L, and 82.7% of this group had FT₄ values within the reference range, consistent with a diagnosis of subclinical hypothyroidism.

Contrary to American Thyroid Association guidelines, another concern is that 34.6% of individuals prescribed levothyroxine with a thyrotropin level between 4.0 and 10.0 mIU/L had only one abnormal thyrotropin reading before initiation of therapy. Greater use of confirmatory testing might reduce unnecessary prescriptions given that 46% of individuals with a thyrotropin level between 4.5 and 7.0 mIU/L reverted to normal levels within 2 years without treatment.

In summary, the authors conclude that there is widespread prescribing of levothyroxine for borderline thyrotropin levels among individuals with limited evidence of benefit. This practice may be harmful given the high risk of developing a suppressed thyrotropin level after treatment. While thyroidologists are still debating whether subclinical hypothyroidism should be more widely treated, it is increasingly apparent that this is already happening in primary care.

Practice Pearls:

• Doctors have become increasingly aggressive at initiating treatment for borderline hypothyroidism.
• The number of new levothyroxine prescriptions increased by 74% over the study period.
• The number of individuals who received levothyroxine for a thyrotropin level of less than 10 mIU/L increased by 30% over the course of the study.

JAMA Internal Medicine, October 2013