Elevated free thyroxine and non-suppressed thyrotropin (TSH)

Elevated free thyroxine and non-suppressed thyrotropin (TSH)

We are all different. Most of us would be extremely ill with an FT4 of 36.9 (without needing to check the precise reference range!). At the same time, we would probably have a suppressed TSH - not one in the range 6.78 to 22.1. But this case seems to prove that for one individual these results really do make sense.

BMJ Case Rep. 2013 Oct 28;2013. pii: bcr2013201527. doi: 10.1136/bcr-2013-201527.

Elevated free thyroxine and non-suppressed thyrotropin.

Mok SF, Loh TP, Venkatesh B, Deepak DS.


Department of Medicine, National University Hospital, Singapore, Singapore.


A young man was diagnosed with hyperthyroidism 10 years prior to current presentation after a random health screening revealed an elevated free thyroxine (fT4) of 36.9 pmol/L. During that time, he saw multiple physicians and was treated with carbimazole intermittently. His repeat thyroid function tests showed persistently elevated fT4 ranging 25-35.7 pmol/L and non-suppressed thyroid-stimulating hormone (TSH) concentrations of 6.78-22.1 mIU/L. He had a smooth, firm and non-tender goitre. At our institution, laboratory interference was first excluded by serial dilution study (TSH) and retesting of TSH and fT4 on alternate assay, which gave reproducible results. His normal α-subunit and sex hormone binding globulin, partially suppressed TSH by high dose triiodothyronine (T3), and positive TSH response to thyrotropin-releasing hormone stimulation were consistent with resistance to thyroid hormone syndrome. The diagnosis was confirmed by direct sequencing of thyroid hormone receptor-β gene, revealing a heterozygous R320 L mutation that causes reduced T3 affinity and reduced corepressor dissociation.

PMID: 24165508 [PubMed - in process]



Last edited by

8 Replies

  • Thanks Rod xx

  • Interesting Rod.

    At diagnosis I had high T4 and high TSH both in twenties or thirties. Diagnosis was hypothyroid because of the high TSH. I suppose I could have been diagnosed hyperthyroid if they had ignored the TSH and gone with the T4!

    Nearly 10 years down the line both are low and I don't feel much better than when they were so high!

    Wish I'd known more then and insisted on seeing an Endo at that stage.

  • I wish that GPs would understand when they do not understand instead of fumbling through in ignorance. At least it is reasonable to expect an endo to know something of these issues. (Though whether an individual does or does not is, obviously, another matter.)

    It is not too late to ask for a referral and gene testing is much more readily available (even if you have to pay for your own).


  • Thanks Rod.

    I have since seen two Endos but they don't look back at the original problem and only look at the blood tests since starting the meds seemingly uninterested in the original cause - told me it didn't matter why I had the problem!

    As soon as started meds both TSH and T4 dropped dramatically and TSH has never risen again even if I reduce meds as was asked to do once as my TSH is suppressed.

    I've always thought that the answer lies in the cause - I have no antibodies so it isn't Hashis.

    Is there any way of getting the full article to see what happened to this guy? Preferably in a form I could follow - was getting lost in the medical terms towards the end of the abstract.

    If I was to get gene tested are Endos likely to just dismiss it - after all my bloods are ok now to them!

  • No, but...

    Go to this link:


    You can read around the page and see that people with access to Athens via their institutions (primarily universities) could gain access. So I'd expect a hospital doctor or many people with university credentials to be able to get hold of it.

    It is not impossible that your local library could help - indeed, that is quite likely, though there may be a charge of some sort.

    Things are often easier when they are printed out! I don't claim to fully understand but if I can help, I will.

    I think the last sentence is saying that he had two different versions of a gene that affects the thyroid hormone receptor. (That is, heterozygous, one from mother and a different one from father.) So the receptor didn't grab hold of any passing T3 nearly as well as it does in most of us.

    If you do have a form of resistance to thyroid hormone then blood levels can need to be significantly higher than in the rest of us.

    I am obviously intent on pushing hard-to-read documents at you :-) , so here is another one (free to access and print!):



  • Thanks Rod. We should all get honorary degrees at the end of this! :)

  • Can the converse also be true - i.e. that some people have extra-efficient, rather than impaired, cell receptors and therefore have 'normal' bloods but are symptomatic?

  • Certainly we see people all the time who have what appear OK TSH and FT4 levels - even FT3 if they have been tested - but are symptomatic of hypothyroidism.

    These people often have a deficiency in one or other vitamin/mineral. Vitamin B12, Iron/ferritin, folate, vitamin D - these are the top of the pile. Other possibilities might include zinc, copper, selenium, etc. Correction of any identified issues frequently helps.

    Or, perhaps, something is interfering with their lab results - for example antibodies to TSH itself can show a falsely raised TSH test result.

    But there always seem to be a few in whom the numbers never make sense. I'd not like to jump to any conclusions - but it would not be surprising if something different about them is causing things not to conform to everyone else's "normal".


You may also like...