L-thyroxine Does Not Help Older Adults With Subclinical Hypothyroidism and Greater Symptom Burden

By Will Boggs MD

May 06, 2020

NEW YORK (Reuters Health) - L-thyroxine treatment does not improve hypothyroid symptoms or tiredness in older adults with subclinical hypothyroidism and a greater symptom burden, according to a secondary analysis of the placebo-controlled TRUST study.

"L-thyroxine is often prescribed for subclinical hypothyroidism (SCH), but there is actually no clear evidence for its clinical benefit to date," Dr. Maria de Montmollin of Bern University Hospital, in Switzerland, told Reuters Health by email.

Since 2014, L-thyroxine has been the most prescribed drug in the United States, with more than 15% of Americans older than 61 years using it. The TRUST study among older adults showed no benefit of L-thyroxine in terms of symptoms or quality of life in patients with SCH.

Dr. de Montmollin and colleagues undertook a secondary analysis of the TRUST data to evaluate whether L-thyroxine improves hypothyroid symptoms and tiredness in older adults with a higher symptom burden at baseline.

Among the 638 participants included in this study, 20.7% had a baseline Hypothyroid Symptoms score greater than 30 and 20.8% had a baseline Tiredness score greater than 40, the team reports in Annals of Internal Medicine.

After one year, the adjusted difference in Hypothyroid Symptoms score between high-symptom burden patients receiving L-thyroxine and those receiving placebo was 2.0, a difference that was neither statistically significant nor clinically important.

Similarly, among patients with a Tiredness score greater than 40, the adjusted between-group difference at one year was 0.0.

There was no evidence that the effect of L-thyroxine treatment differed between those with higher versus lower baseline Hypothyroid Symptoms or Tiredness scores.

Among patients with low health-utility scores at baseline, the score did not change in the L-thyroxine group but improved in the placebo group after one year. Scores did not differ between the groups at follow-up among patients with higher health utility scores at baseline.

Handgrip strength at follow-up did not differ between the L-thyroxine and placebo groups, regardless of baseline strength.

"Interestingly, in our study symptoms improved, but similarly in the L-thyroxine and placebo groups," Dr. de Montmollin said. "This may be due to the natural history of SCH, the placebo effect, or regression to the mean, and may explain why many patients are convinced that L-thyroxine is beneficial."

"Treating physicians should reconsider prescribing/offering this medication to older adults with SCH, even those with consistent symptoms, because there is no clear evidence for its benefit in treating SCH to date and a risk of harm related to overtreatment is still possible," she said. "In addition, it is associated with unnecessary costs for the patient and for the health system."

"However," Dr. de Montmollin cautioned, "our study cannot be generalizable to everybody. It is possible that some patients with very severe symptoms would still benefit from L-thyroxine."

Dr. Christian Nasr, medical director of the Thyroid Center at Cleveland Clinic, in Cleveland, Ohio, who recently reviewed when to treat SCH, told Reuters Health by email, "The results are interesting because they confirm the notion that patients with significant 'hypothyroid' symptoms, when their TSH is a little high and the thyroxine is normal, will not benefit from being prescribed thyroid hormone. This does not mean that an individual patient in this category should not be offered thyroid hormone support, but the expectation should be set before the intervention is undertaken."

"To me, this study reinforces the notion that fatigue and 'hypothyroid symptoms' are not always due to a little bit of hypothyroidism, but I would still continue my practice of discussing with the patient the possible causes of fatigue and that a trial of thyroid hormone in a symptomatic patient may help," he said. "I would also remind us all that the normal range of TSH in the oldest adult might be as high as 7 or 8 and trying to bring the TSH into the 'normal range' might not be a very safe intervention."

SOURCE: https://bit.ly/2z9SC0g Annals of Internal Medicine, online May 5, 2020.