Call to use T4 instead of TSH levels for thyroid tests

In what would require a paradigm shift, clinicians have been urged to look at thyroid hormone levels (T4) and not just TSH levels when assessing the thyroid status of patients.

A systematic review and meta-analysis of the evidence, published by Australian clinicians in Thyroid, found 58 studies which addressed associations between clinical conditions known to be associated with thyroid dysfunction and thyroid hormone and TSH levels. 

Conditions included atrial fibrillation, cardiac conditions, cognitive decline, frailty, osteoporosis, obesity and premature deliveries. 

The study found free T4 levels (FT4) had a significant and superior association with a clinical parameter in 50% of the analyses and TT3/FT3 levels in 53% compared to TSH in only 23%.

“The results indicate that, contrary to the current paradigm, that thyroid hormone levels associate more strongly with clinical parameters than TSH levels,” the study authors said.

“In our sample we found no indication of, or reference to any work, that suggested that TSH levels consistently indicate thyroid status of any organ or tissue more strongly than thyroid hormone levels.”

Lead investigator Dr Stephen Fitzgerald, a physician at the Royal Adelaide Hospital, told the limbic it was apparent we were doing things back to front – that no other organ was judged by levels of a controlling hormone.

“We look at no other medical parameter like thyroid. Thyroid is quite atypical. We don’t usually judge other parameters like this so it makes no sense.

“I think there have been a few mistakes made in understanding thyroid physiology and physiology in general over the years, and they have been passed on. It could have also been because the original test might not have been so good for thyroid function.” 

“But I think it’s been a mistake for 100 years and overlooked.” 

He said one of the problems was that people who have a normal T4 but an abnormal TSH were told they had an abnormality. 

“So they are told they’ve got subclinical thyroid disease and get treated for it. Whereas other people who have got thyroid hormones that are a little bit abnormal but a normal TSH are told they are normal so it’s around the wrong way.”

“There are millions of people who have been put on treatment or told they have a disorder who don’t really.”

Dr Fitzgerald said he was open to an expected “vigorous discussion”.  

“I think this is going to come as a shock to a lot of people. To get it through the editorial process was long and difficult because obviously they were very suspicious of something so radical. I don’t think the current status can continue though.”

“Having said that there is always the possibility that I am wrong and we have made some error somewhere. We have to wait and see if anyone can spot a flaw in our paper but failing that, this could be a major shake-up in the way we think about thyroid function.” 

Commenting on the study, Professor John Walsh, Consultant Endocrinologist at Sir Charles Gairdner Hospital in Perth, said it was interesting but unlikely to have an impact on the diagnosis and management of thyroid disease.

“The relationship between TSH and free T4 is such that small differences in free T4 result in large changes in TSH,” he told the limbic.

“Numerous studies have shown that TSH is superior to free T4 as the initial test for diagnosing thyroid disease. When TSH is in range, free T4 is almost always in range as well, whereas quite commonly TSH is out of range when free T4 is in range.”

He said the American Thyroid Association, National Academy of Clinical Biochemistry and the Endocrine Society of Australia all endorse TSH as the most useful test in diagnosing thyroid dysfunction.

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