Mooijaart SP, Du Puy RS, Stott DJ, et al. Association Between Levothyroxine Treatment and Thyroid-Related Symptoms Among Adults Aged 80 Years and Older With Subclinical Hypothyroidism. JAMA. 2019 Oct 30:1-11. doi: 10.1001/jama.2019.17274.

Importance: It is unclear whether levothyroxine treatment provides clinically important benefits in adults aged 80 years and older with subclinical hypothyroidism.

Objective: To determine the association of levothyroxine treatment for subclinical hypothyroidism with thyroid-related quality of life in adults aged 80 years and older.

Design, Setting, and Participants: Prospectively 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. The trials were conducted between April 2013 and May 2018. Final follow-up was May 4, 2018.

Exposures: 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).

Main Outcomes and Measures: Co-primary outcomes were Thyroid-Related Quality of Life Patient-Reported Outcome (ThyPRO) questionnaire scores for the domains of hypothyroid symptoms and tiredness at 1 year (range, 0-100; higher scores indicate worse quality of life; minimal clinically important difference, 9).

Results: 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. 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 [95% CI, -2.7 to 5.2]; P = .53). 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 [95% CI, -4.5 to 4.3]; P = .96). 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).

Conclusions and Relevance: 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. These findings do not support routine use of levothyroxine for treatment of subclinical hypothyroidism in adults aged 80 years and older.

Trial Registration: Identifier: NCT01660126; Netherlands Trial Register: NTR3851.

Ratings by Clinicians (at least 3 per Specialty)
Specialty Score
Family Medicine (FM)/General Practice (GP)
General Internal Medicine-Primary Care(US)
Internal Medicine
Comments from MORE raters

General Internal Medicine-Primary Care(US) rater

This type of study reinforces the notion that all labs don`t necessarily need to be "fixed." Although levothyroxine is inexpensive and relatively safe, it is another medication to take and to take properly. So, if not worth it, don`t do it.

Geriatrics rater

Whether or not to treat subclinical hypothyroidism in older patients has been challenging clinicians for decades. This analysis of patients aged 80 and older from two conjoined but similar studies seeks to answer this question using the validated ThyPro hypothyroidism symptom score and the EuroQOL quality-of-life questionnaire. Patient selection, however, limits the usefulness of the study and does not support the conclusion that there is no clinical benefit to treating subclinical hypothyroidism in the very old. The baseline mean and median levels of TSH ( <=6.4 and <= 5.8 mIU/L) were relatively low, suggesting that scores from ThyPro and EuroQOL may have disproportionately derived from prevalent comorbid conditions. These comorbid conditions could have created a statistical noise that obscured the clinical benefit of treatment. It would have been helpful to evaluate a patient sample with higher baseline values of TSH (e.g., upper tertile) to assess whether their response to treatment could be better differentiated from the control group.

Internal Medicine rater

This is an interesting study. The approach toward management of subclinical hypothyroidism is different in the outpatient versus inpatient setting. In the inpatient setting, typically subclinical hypothyroidism is not considered a valid diagnosis due to various factors including but not limited to acute illness, inpatient stay, etc. Inpatients are often recommended to follow-up as an outpatient with repeat thyroid studies in a few weeks. The outpatient setting is approached with a variable response. Some clinicians are more aggressive and others are more conservative with levothyroxine treatment for subclinical hypothyroidism. The nonspecific symptoms like fatigue, tiredness, loss of appetite can often be easily mistaken for hypothyroid symptoms, and clinicians often feel tempted to prescribe levothyroxine. This is an important study that does not support the routine treatment with levothyroxine for subclinical hypothyroidism in an older population.