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A Review of the Clinical Consequences of Variation in Thyroid Function Within the Reference Range

Next time your doctor suggests that simply having TSH within reference range is adequate, show her/him the paper below. Even just the conclusion.

Many here have searched for and read some of the papers which went into this Review. Many here have said as much. Many here should be very pleased to see people within the profession apparently taking on board this information.

Let us hope that, rather than a simple "trickle down", this Review causes an inundation of awareness in the rest of the profession - consultants and GPs.

Of course, many here will argue that TSH doesn't work. My view is that in some people it works to an acceptable level but that it must always be considered that it might not be working in a way that allows for diagnosis and monitoring of treatment. Even in people in whom it has previously appeared to work.


|2013 Archive

|September 2013

|Taylor et al. 98 (9): 3562

Special Features

A Review of the Clinical Consequences of Variation in Thyroid Function Within the Reference Range

Peter N. Taylor,

Salman Razvi,

Simon H. Pearce and

Colin M. Dayan

- Author Affiliations

Thyroid Research Group (P.N.T., C.M.D.), Institute of Molecular Medicine, Cardiff University School of Medicine, Cardiff CF14 4XN, United Kingdom; Institute of Genetic Medicine (S.R.), Newcastle University and Department of Endocrinology, Gateshead Health NHS Foundation Trust, Gateshead NE9 6SX, United Kingdom; and Institute of Genetic Medicine (S.H.P.), Newcastle University and Endocrine Unit, Royal Victoria Infirmary, Newcastle upon Tyne NE1 4LP, United Kingdom


Context: Overt thyroid disease is associated with profound adverse health outcomes; however, data are conflicting for studies of borderline/subclinical thyroid dysfunction. Many studies of subclinical thyroid disease have had low power and were prone to selection bias. In contrast, large datasets are available from community studies in healthy individuals. Studies of the effects of variation of thyroid function across the reference range on health outcomes in these populations may provide useful information regarding thresholds for treatment of abnormal thyroid function.

Evidence Acquisition: MEDLINE and the Cochrane Database of Systematic Reviews and Controlled Trials Register were searched for articles studying the effect of variation in thyroid hormone parameters within the reference range on cardiovascular, bone, metabolic, pregnancy, neurological, and psychological outcomes.

Evidence Synthesis: Higher TSH/lower thyroid hormone levels are associated with more cardiovascular risk factors and cardiovascular events and worse metabolic parameters and pregnancy outcomes, whereas lower TSH/higher thyroid hormone levels are associated with reduced bone mineral density and increased fracture risk. The evidence base was good for cardiovascular, metabolic, bone, and pregnancy outcomes; however, high-quality data remained lacking for neurological and psychological outcomes.

Conclusions: Common variation in persons with thyroid function in the normal range are associated with adverse health outcomes. These data suggest, by extrapolation, that carefully monitored treatment of even modest elevations of TSH may have substantial health benefits. Appropriately powered large-scale clinical trials analyzing the risks vs benefits of treating subclinical thyroid disease are required to determine whether these benefits can be achieved with levothyroxine therapy.


The full paper is available here:



10 Replies

"Treatments for subclinical thyroid disease are effective, cheap, and easy to monitor; it is the uncertainty regarding the magnitude of the clinical benefit of treatment that has led to divergent opinions regarding screening and management!"


In my own case, that is probably true - at least so far!

I am simply on 100 micrograms of levothyroxine, usually one TSH test a year, and feeling considerable benefit. Long may that continue. :-)

It seems to me more likely that this will apply in someone who might never have become overtly hypothyroid, and is negative for TPO antibodies.

Perhaps that last sentence "...whether these benefits can be achieved with levothyroxine therapy." actually implies some scepticism as to whether that is possible? And that some form of T4/T3 therapy might be needed - in some cases.

The recognition that even an in-range TSH might be worth treating surely knocks on the head the idea that anywhere in range is acceptable?


Another one for the Scottish Parliament round table discussion! :-)


Oh my. Have scanned the full report and it's full of little gems. A very very important paper worth it's weight in gold for those needing evidence to educate their doctors. Couple of small parts not so helpful like reference to the US standards but you can't have it all. Thank you for posting this helvella.

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Rod - thanks again for posting this. I follow some endos and GPs on Twitter and have posted it on there. Hope the one that heads up our local hospital endo team see's it. He needs educating especially as all he ever posts about is diabetes. Even the endo department is called Diabetes Clinic.

Can you tell me how to italicise and embolden text in posts please? Thanks.

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Thanks for this Rod, let's hope the medical profession get to read this and further study is undertaken!

I had a quick scan of this and one section on bone stood out for me:

"The relationship between fT3 and fracture may be more complex than previously believed because fT3 was strongly positively associated with handgrip and balance (47), key protective factors in determining an individual's risk of falls."

I am still confused about the risk of osteoporosis with thyroid treatment. What is over-replacement and how can we tell? My GP won't do a bone density scan which doesn't help. But I'm now on T3 alone and I noticed that my grip had improved at the petrol pump! I think this and balance may be down to increased muscle tone?

Your insight is as always welcome!


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The conclusion doesn'tshow a lot of faith in Levo, does it?

Maybe as they're half thinking about Wilsons' Syndrone which is similar to UAT but can be treated with short cycles of split dose T3 and has the effect of resetting the metabloism. There was a good link on this site to it, not far back.

The cause of the sydrome is long term sustained stress, which locks up the adrenals and all that hangs with them in matters metabolic-.ACTH,Cortisol, Thyroxin etc...

I hope the info in report hits home - at least it's UK research!

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Pleased I stumbled across this... could be useful: long term sustained stress brought mine on (albeit is was sitting there waiting to happen) - I have explained/described this too. Just the ticket for me to tackle someone on that list of authors + his department. Thank you :-)

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Very pleased that you found it! Really hope it helps.

Do let us know - could be useful for others.

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Thanks so much Rod - 'fraid it's now time to 'go for it'... many of us continue to suffer in an area with a large teaching hospital... highlighting itself internationally while some of us are on our knees... ignored and worse.

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