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

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

This is, potentially, a VERY important review paper. Even if you ignore the rest, read the conclusions.

J Clin Endocrinol Metab. 2013 Jul 3. [Epub ahead of print]

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

Taylor PN, Razvi S, Pearce SH, Dayan C.


Thyroid Research Group (P.N.T., C.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.



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.


Common variations 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 journal's own site is still on the June edition - maybe this will be listed in July?



13 Replies

  • Excellent find Rod. I hope you don't mind me sharing that to our Thyroid Petition facebook page?

  • So long as I don't have to - while I appreciate the usefulness of FB, for myself, no thanks!

    Help yourself.


  • Great news and a paper that I'm sure many people will find very useful. Thanks Rod :)

  • It is certainly some positive news for those with borderline levels. I do wonder if the outcomes for those who were treated sooner are better than for those who were not treated until TSH was above 10. This would be an interesting area of study. Maybe it's already been done. Hopefully someone will find this very useful when trying to persuade their doctor for a trial of thyroid treatment:)

    Thanks for posting it

    C xxx

  • :-)

    The current treatment of so many defies belief. It's like leaving a granny to suffer hypothermia because you can't be sure that warmth is the issue until core blood temperature drops below 34.0 (or what ever value is used). Crazy. There is no need. If the issue has been identified, letting it get worse before treatment is far more likely to leave unresolved issues - surely?

    Also noticed this rather pertinent quote in another new paper:

    When considering a diagnosis of anxiety and depression, medical causes of the symptoms must be excluded. Common conditions, such as thyroid disorders, stimulant abuse, asthma, cardiac arrhythmias, alcohol withdrawal and rarely pheochromocytoma, causing a similar spectrum of symptoms should be excluded by history and clinical examination.



  • Yet the almighty TSH test always seems to get in the way of such common sense :(

  • It's a start, but it only mentions levothyroxine therapy and not any alternatives. I wonder who is funding the study?

  • If you're suggesting it's being funded by a pharma company that makes levothyroxine, I think you're barking up the wrong tree. In the UK, the profit to be made from levothyroxine is simply not worth it!

  • I hope you're right :)

  • As I read it, the conclusions very much questioned whether levothyroxine alone could reap all the hoped for benefits.


  • Ok - I picked up on the last sentence, which could I suppose be read more than one way.

  • I have been diagnosed with subclinicial Hypothyroidism. I have many symptoms that are similar to overt Hypothyroidism but my GI doctor who I am under for motility problems said I am making enough Thyroxine for my needs even if it is in the higher end and there is nothing wrong with my Thyroid. I am on BP drugs, had an early menopause aged 40. This is worrying that our hearts could be affected or bones, I already have a squint back I was told. I am going to ask my own doctor if I should have a recheck.

  • What has really ticked me off, now, is that my endo - actually a lovely man who is bending over....who is leaning backwards a little to help me on the NHS, has put the frighteners on me by telling me that, because my TSH is not even measurable it is so suppressed, I am in danger of both osteoporosis (totally normal bone density scan) AND all the heart attack/stoke risks! Can't have it both ways!

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