Levothyroxine offers no benefit in subclinical hypothyroidism in elderly, finds JAMA Study

Delhi: Treatment with levothyroxine compared with placebo did not significantly improve hypothyroid symptoms or fatigue in adults aged 80 years and older with subclinical hypothyroidism, reveals prospectively planned analysis of data from 2 clinical trials. Thereby, the findings, published in the journal JAMA do not support the routine use of levothyroxine for treatment of subclinical hypothyroidism in such individuals.

According to Mayo Clinic, levothyroxine is used to treat hypothyroidism, a condition where the thyroid gland does not produce enough thyroid hormone. Levothyroxine is a manufactured form of the thyroid hormone thyroxine. But whether levothyroxine treatment provides clinically important benefits in adults aged 80 years and older with subclinical hypothyroidism is still unclear.

Simon P. Mooijaart, Leiden University Medical Center, Leiden, the Netherlands, and colleagues determined the association of levothyroxine treatment for subclinical hypothyroidism with thyroid-related quality of life in adults aged 80 years and older.

The study involved a prospective planned combined analysis of data involving community-dwelling adults aged 80 years and older with subclinical hypothyroidism. Data from a randomized clinical trial were combined with a subgroup of participants aged 80 years and older from a second clinical trial. Participants were randomly assigned to receive levothyroxine (n = 112; 52 participants from the first trial and 60 from the second trial) or placebo (n = 139; 53 participants from the first trial and 86 from the second trial). The trials were conducted between April 2013 and May 2018. Final follow-up was May 4, 2018.

Of 251 participants (mean age, 85 years; 118 [47%] women), 105 were included from the first clinical trial and 146 were included from the second clinical trial. A total of 212 participants (84%) completed the study.

Key findings of the study include:

• The hypothyroid symptoms score decreased from 21.7 at baseline to 19.3 at 12 months in the levothyroxine group vs from 19.8 at baseline to 17.4 at 12 months in the placebo group (adjusted between-group difference, 1.3).


• The tiredness score increased from 25.5 at baseline to 28.2 at 12 months in the levothyroxine group vs from 25.1 at baseline to 28.7 at 12 months in the placebo group (adjusted between-group difference, −0.1).


• At least 1 adverse event occurred in 33 participants (29.5%) in the levothyroxine group (the most common adverse event was cerebrovascular accident, which occurred in 3 participants [2.2%]) and 40 participants (28.8%) in the placebo group (the most common adverse event was pneumonia, which occurred in 4 [3.6%] participants).

"In this prospectively planned analysis of data from 2 clinical trials involving adults aged 80 years and older with subclinical hypothyroidism, treatment with levothyroxine, compared with placebo, was not significantly associated with improvement in hypothyroid symptoms or fatigue," wrote the authors.

Based on the study findings, Anne R. Cappola, Department of Medicine, University of Pennsylvania, Philadelphia, calls for a change in the thyrotropin reference range in older patients, in an accompanying editorial.

"The reference range provided with the laboratory test result should align with the threshold for additional clinical action. When the reference range denoting a normal result is not aligned with the reference range needed for optimal health, confusion arises," she wrote. "Patients interpret the reference range as a normal range and question why abnormal test results are being ignored. Clinicians looking for an explanation for a patient’s symptoms may incorrectly focus on a result outside of the reference range. Accurate laboratory reference ranges are essential for good clinical care."

More Information: "Association Between Levothyroxine Treatment and Thyroid-Related Symptoms Among Adults Aged 80 Years and Older With Subclinical Hypothyroidism" published in the JAMA journal.

DOI: 10.1001/jama.2019.17274

Journal Information: JAMA