Are guidelines wrong on thyroid hormone therapy for subclinical hypothyroidism?

Debate continues over the value of thyroid hormone therapy in patients with subclinical hypothyroidism, with an Australian endocrinologist disputing the negative findings of a new review.

A systematic review and meta-analysis published in JAMA has found no evidence for routinely treating subclinical hypothyroidism with thyroid hormone therapy.

The review identified 21 studies meeting the inclusion criteria and comprising 2,192 non-pregnant adults with baseline thyrotropin levels of 4.4-12.8 mIU/L.

Participants were randomised to thyroid hormone therapy (thyroxine or levothyroxine), placebo or no therapy for between three and 18 months.

The meta-analysis found treatment resulted in a normalisation of thyrotropin levels however there was no observed impact of treatment compared to placebo or no therapy on quality of life.

Similarly there was no beneficial effect on thyroid-related symptoms, depressive symptoms, fatigue/tiredness, cognitive function, muscle strength, blood pressure or body mass index.

The authors, from several European countries,  said their findings were not consistent with recommendations in the ATA/AACE Clinical Practice Guidelines for Hypothyroidism in Adults.

“Although current guidelines are at first sight cautious with treatment recommendations, more than 90% of persons with subclinical hypothyroidism and a thyrotropin level of less than 10 mIU/L would actually qualify for treatment,” they wrote.

“However, results of this meta-analysis are not consistent with these guideline recommendations. In addition to the absence of an association of thyroid hormone therapy with improved outcomes, thyroid hormone theory is associated with adverse effects when overtreatment occurs,” they said.

Professor John Walsh, from the University of Western Australia and Sir Charles Gairdner Hospital, told the limbic that the findings were very much dominated by a single, large, negative study.

“The key thing to realise is that when they are looking at quality of life and thyroid symptoms, almost all of the analysis is based on a single study which is Stott et al from 2017.”

“So about 75% or 80% of the weight from the meta-analysis actually comes from one study. The thing about the Stott study was although it was very well conducted, it was a study done in older people, over the age of 65, and the thyroid symptoms and quality of life at baseline were not different from the background population.”

“So really what it is saying is that in older people with subclinical hypothyroidism who are asymptomatic, there is no benefit from thyroxine. But it doesn’t really guide a GP or endocrinologist who are seeing younger patients or those presenting with symptoms of tiredness, etcetera.”

He added that subclinical hypothyroidism was very heterogeneous with some people feeling perfectly well while others have symptoms.

“I think what you can say is we should be treating patients, we shouldn’t be treating numbers, and this study provides evidence that treating this particular number in a patient who is well isn’t beneficial.”

“But when you are dealing with a patient who has symptoms that might be arising from hypothyroidism and who has a abnormal blood test, then it is certainly not wrong to treat them and see if they feel better.”

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