New paper on TSH and FT4 reference ranges

[HypoHim]

Thought some people might be interested in this new paper on PubMed:

ncbi.nlm.nih.gov/pubmed/260...

This large study showed the variation in the reference ranges with age, sex, ethnicity, time of day and month of year.

Some excerpts I found interesting from within the article:

1. "To avoid incorrectly identifying TSH values as abnormal, the TSH reference range needs to take into account the subject’s age and the time of day when the blood sample was drawn. For example, a TSH value of 7.5mIU/L would generally be considered elevated and indicative of subclinical hypothyroidism. However, if the sample was drawn from an 80 year old woman at midnight, a TSH of 7.5 mIU/L is within the 95% reference range and is in fact normal."

2. "TSH suppression is standard treatment of thyroid cancer (57,58), and documenting TSH suppression is based upon a single TSH measurement. The measurement is usually obtained between the hours of 0700 and 2000, when TSH is normally lowest. TSH suppression during the day does not invariably mean that TSH is suppressed at night. Studies to determine the relationship between daytime TSH suppression and nighttime TSH sup- pression and the relationship between partial and complete 24 hour TSH suppression on thyroid cancer need to be performed. Determining TSH suppression in patients with thyroid cancer from a single daytime TSH value is similar to determining glycemic control in an individual with diabetes based upon a single blood glucose measurement. Selection bias makes the interpretation of the results and their clinical relevance questionable."

3. "The study assumes that immunoactivity corresponds with bioactivity. This is not necessarily the case. Thyrotroph cells secrete a variety of isoforms of TSH and immunoreactivity of the isoforms does not parallel bioactivity. Additionally, isoform variation can affect immunoassay results (61). The nocturnal TSH surge may reflect a variation in TSH isoform secretion from the pituitary (58) and not necessarily a change the concentration of bioactive TSH (61–63). The nocturnal rise in T3, however, suggests that the nocturnal TSH rise does in fact have target tissue effects (22)."

More about TSH isoforms here:

ncbi.nlm.nih.gov/pubmed/240...

Turns out the standard TSH immunoassay tests determine a total concentration of 'TSH' made up of various 'isoforms' or chemical and structural variants of TSH which all have the same immunoreactivity. But the different isoforms can have different biological activity in the sense that they have different effects on thyroid tissue, hormone production etc. So the measured 'TSH' may not correspond to the effective TSH activity in the body.

The human body gets more complicated with every article I read...

[Clutter]

Hypohim, It's tragic that the more that's discovered about the complexity of metabolic reaction, the more thyroid testing is dumbed down to TSH testing only in a lot of cases.

Very interesting point about daytime and 24 hour TSH suppression in thyCa patients. I like the analogy to glycaemic control. I'll mention that to my endo next time I'm told my 'daytime' TSH can be less suppressed.

[HypoHim in reply to Clutter]

There was actually another point made by the authors I found interesting - although there is a daily variation in TSH levels, it will not be quite the same for certain groups of people who have different biological clocks. They suggested for example that shift workers, or people who like to stay up late at night, have quite different daily variation and this should also be taken into account when interpreting one-off TSH values.

I think the story the science is telling, but which some doctors don't want to hear, is that it's very hard to interpret the meaning of thyroid hormone test results. In an ideal world, they would test your TSH, T4 and T3 at multiple times throughout a day (the way some heart/blood pressure patients wear a 24 hour monitor for testing or the way diabetics check their glucose regularly throughout the day) to see what's really going on. But we're not there yet with simple hormone tests that could be done that frequently, cheaply.

[HypoHim]

The point of this article was to determine the variation of the boundaries of the 95% normal range for TSH and FT4. It was more a basic science article in that sense, rather than giving specific clinical advice, and so assumed the standard 95% reference range width. I think the interpretation of the study results and how they would apply to clinical practice were based on looking at what current guidelines say.

However, I agree that the bodies which make the guidelines should look at these more recent studies and hopefully change their recommendations for the clinical definitions of normal... Or at least the guidelines for what situations should permit a treatment trial.

[HypoHim]

Agree, TSH alone seems more and more like a bad idea... Hopefully as testing becomes cheaper and more automated too, doctors and labs will be more likely to do all the tests rather than TSH.

Although at least from my experience of the NHS labs in Edinburgh, I always get TSH, FT4 and TT3 tested when my doctor requests them without a problem. The fact I get TT3 and not FT3, however, is based on my endocrinologist's opinion of the accuracy of the FT3 test...

[Marz in reply to HypoHim]

The man who was involved in creating the latest FT3 and TSH testing said - the FT3 results are only as good as the person interpreting them - when asked by a conference member what his thoughts were

He is a member of this forum. I believe he also said - if my memory serves me well - that there could be inaccuracies in the FT3 test either way - both up and down by quite a percentage - if only I could remember what it was ! So your Endocrinologist could be right.

[HypoHim in reply to Marz]

Yes, I think the problem with FT3 is they are trying to measure a very very small quantity of something, and there are simply inherent inaccuracies in how it's done. My endo seems to have found in his experience clinical symptoms tend to mirror TT3 level well, so he just uses that along with FT4 and TSH.

[HypoHim]

I think it is bit unfair and unrealistic to write off all doctors and researchers based on personal experience of a few clinicians. My endocrinologist for example is a member of those organisations, in fact he was president of two of them, and he certainly does not rely on TSH only. And my GPs across three different practices have always tested at least both TSH and FT4.

[sue_b in reply to HypoHim]

Hello Hypohim, I agree, it is a bit unfair to paint them all with the same brush but perhaps you are one of the very few lucky ones because there is clearly no uniformity. In 9 years of being on the Hypo radar I have had my T4 tested once, by an endocrinologist and my TSH tested about 6 times in total. My Aunt has had thyroid problems for much longer than me and has only ever had TSH tests done and even then, results of those have been ignored, requiring a Locum to notice what the usual doctor had been ignoring or failed to see. Of course we women are more inclined to be emotional about our suffering and therefore more likely to be misdiagnosed even when we are existing thyroid patients. This is partly due to the fact that since approx 1975 Medical Schools have stopped teaching doctors how to clinically diagnose thyroid problems. Check out the CT3M Handbook Appendix C and the reasons we are in this predicament will be made all too clear.

[HypoHim in reply to sue_b]

I know from on here a lot of people have real trouble getting the proper testing done! It's quite shocking.

But I think people should also keep things in perspective, in that actually the majority of thyroid patients seem to be happy with their diagnosis and treatment. Those of us posting on here are the self selecting group who have had problems with treatment. Only this week I discovered two people I know have hypothyroidism who had it diagnosed by doctors and treated without them ever complaining of any symptoms. From their perspective their treatment has been excellent.

Those of us who have had issues are in the minority.

[HypoHim]

Even he has his flaws 😁

[HypoHim]

Having read Dr Peatfield's book I am not convinced he was a 'good doctor'. The others I don't know much about.

My personal experience as a thyroid patient who was almost in a coma because of profound hypothyroidism is that most of my doctors were actually good. The first who did not recognise my initial symptoms was bad. But since then I have seen different GPs and endocrinologists who as far as I can see have been trying their best. The GPs could not help much as they had no experience of dealing with such severe thyroid dysfunction, but they were happy to run all necessary tests and refer me to specialists. They have actually been very supportive.

I just think making blanket statements about an entire profession is dangerous.