Levothyroxine may not improve symptom score in subclinical hypothyroidism
Levothyroxine treatment did not significantly improve hypothyroid symptoms score or tiredness score in older adults with subclinical hypothyroidism, according to findings published in The New England Journal of Medicine.
“Our aim is to significantly improve the health and well-being of older people with subclinical hypothyroidism, by resolving uncertainties about how best to manage this condition,” David J. Stott, MBChB, MD, professor of geriatric medicine, University of Glasgow, Institute of Cardiovascular and Medical Sciences, said in a press release. “Treatment with levothyroxine is common in clinical practice, but controversial. Our study concludes this treatment provides no apparent benefits for older adults and should, therefore, no longer be started routinely for this condition. An update of the guidelines is necessary.”
Stott and colleagues evaluated data from clinical laboratory and general practice databases and records on 737 adults (mean age, 74.4 years; 53.7% women) with persisting subclinical hypothyroidism randomly assigned to levothyroxine (n = 368) or placebo (n = 369) to determine whether levothyroxine provides clinical benefits for subclinical hypothyroidism.
Median follow-up was 17.3 months in the placebo group and 18 months in the levothyroxine group. The primary outcomes included change in hypothyroid symptoms score and tiredness score on a thyroid-related quality-of-life questionnaire at 1 year.
Baseline mean thyrotropin levels were 6.4 mIU/L. At 12 months, the mean thyrotropin level was lower in the levothyroxine group (3.63 mIU/L) compared with the placebo group (5.48 mIU/L; P < .001). The levothyroxine group had 2.3 pmol/L higher mean free thyroxine level compared with the placebo group at 6 to 8 weeks and at 12 months (P < .001 for both comparisons).
At 12 months, there were no differences between the two groups for hypothyroid symptoms score or tiredness score.
The two groups had similar incidences of serious adverse events of special interest, including atrial fibrillation, heart failure, fracture or new diagnosis of osteoporosis. However, the number of patients with at least one serious event was higher in the placebo group compared with the levothyroxine group (P = .049).
“In ... older participants with subclinical hypothyroidism, treatment with levothyroxine was associated with a persistently lower serum thyrotropin level than was placebo (between-group difference, approximately 2 mIU/L), with the maximum effects seen at time of first review (6 to 8 weeks),” the researchers wrote. “We found that levothyroxine had no consistent beneficial effect on thyroid-related symptoms. This finding was true in both older men and older women and for different thyrotropin levels at baseline. Our trial had good statistical power to detect a clinically meaningful effect on thyroid-related quality of life, with 95% [CIs] that excluded a beneficial effect greater than 2.1 points (on a scale from 0 to 100) in either of the two primary outcomes. If a symptom benefit was to have occurred, it would have been expected to be seen at 12 months.” – by Amber Cox
Disclosure: Stott reports receiving grant support from European Union FP7 and nonfinancial support from Merck KGaA during the conduct of the study. Please see the full study for a list of all other authors’ relevant financial disclosures.