How much do TSH, FT3, and FT4 values change in healthy subjects?

[diogenes]

This paper (behind a paywall) shows the ongoing biological variation in thyroid hormone parameters in healthy subjects. It shows that such variations are much less for FT3 and FT4 as compared with TSH variation. This study gives the lie to any GP's or endocrinologists that, for example, FT3 levels vary so much in patients (except of course when direct T3 dosing is done). It implies that T4-only treatment will not be accompanied by large swings in FT3.

European Biological Variation Study (EuBIVAS): within- and between-subject biological variation estimates for serum thyroid biomarkers based on weekly samplings from 91 healthy participants

February 2021Clinical Chemistry and Laboratory Medicine

DOI: 10.1515/cclm-2020-1885

Project: Biological Variation : new estimates from EuBIVAS , a project drawn by EFLM WG on BV

Michela Bottani, Aasne K Aarsand, Giuseppe Banfi, Anna Carobene

Abstract

Objectives: Thyroid biomarkers are fundamental for the diagnosis of thyroid disorders and for the monitoring and treatment of patients with these diseases. The knowledge of biological variation (BV) is important to define analytical performance specifications (APS) and reference change values (RCV). The aim of this study was to deliver BV estimates for thyroid stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), thyroglobulin (TG), and calcitonin (CT).

Methods: Analyses were performed on serum samples obtained from the European Biological Variation Study population (91 healthy individuals from six European laboratories; 21-69 years) on the Roche Cobas e801 at the San Raffaele Hospital (Milan, Italy). All samples from each individual were evaluated in duplicate within a single run. The BV estimates with 95% CIs were obtained by CV-ANOVA, after analysis of variance homogeneity and outliers.

Results: The within-subject (CV I ) BV estimates were for TSH 17.7%, FT3 5.0%, FT4 4.8%, TG 10.3, and CT 13.0%, all significantly lower than those reported in the literature. No significant differences were observed for BV estimates between men and women. Conclusions: The availability of updated, in the case of CT not previously published, BV estimates for thyroid markers based on the large scale EuBIVAS study allows for refined APS and associated RCV applicable in the diagnosis and management of thyroid and related diseases.

[dolphin5]

That’s extremely helpful! Thank you 🙏.

[humanbean]

Thank you, diogenes.

I've found a link with the entire paper :

degruyter.com/document/doi/...

[tattybogle in reply to humanbean]

just read it .. thankyou for link.

Is it me ? ... ?? they've seriously gone to the trouble of designing a study looking at this and they've not recorded or even discussed the 'time of day test was taken' ... not even in passing in the 'study limitatons' .. ??

if you're wondering what that banging noise is .. it me banging my head on the wall.

[diogenes Remembering in reply to tattybogle]

I don't think you should be too worried about timing. It's very unlikely that, for example, a subject's blood taken regularly would artificially show level results if the actual ones were unstable but the instabilities missed by accident. For TSH of course, this is more problematic because it changes so much over 24 hours. I think the study is good enough to get a reasonable stab at finding true change in the parameters.

[tattybogle in reply to diogenes]

I agree it's good enough to see the range of expected normal variation versus a 'true change' in level , And it's useful to have evidence of the sort of variations found 'in real life' since GP's do test at all sorts of times of the day without taking it into account.

I'm just having a little difficulty wondering how anybody gets away with designing a study looking at TSH variability and not even mentioning the possibility of diurnal TSH variation...... which could be as much as ? 40% in some people ... and as little as 'not much at all' in others.

If i was designing this study , i think the first variable i'd want to get nailed down would be 'time of day' .

[Timetraveler67]

My endo got quite angry with me this week during a telephone consultation I asked her about my low t3 she quickly spoke me down by saying she doesn’t really care about t3 as it can fluctuate throughout the day and can’t be relied upon, she only goes by tsh only then added she thought I may need help with my anxiety I told her I was only anxious because I feel ill all the time that’s all. Today I got a text from my gp saying my endo has requested I be seen by a therapist for my anxiety and depression. I’m so angry I’m not being here’d. Thank you for sharing your information which led me me to share what happened this week with me.

[Catseyes235 in reply to Timetraveler67]

That is awful. I truly feel your frustration. I remember saying to my doctor in the seventies that if there was nothing wrong with me then I must be mad. He was happy to refer me to psych. I never went but in a way wish I had as shrinks were often taught to look out for thyroid conditions. Now I battle with the holy grail of TSH mine being really really low although I felt fine. Maybe take them up on offer of a therapist and explain to them what is going on ...at least they are trained to listen! ,

[lynmynott Partner Thyroid UK in reply to Timetraveler67]

That is dreadful treatment by a professional. I am frustrated for you. Hopefully, new research around T3 will make your endo sit up and listen.

[tattybogle in reply to Timetraveler67]

Can you ask your GP to send a txt to your endocrinologist saying " your patient has suggested you be seen by a research scientist to help with your poor understanding of natural fT3 levels "

What a bloody cheek .... don't let them into your head.

The only reason most of us ever need to talk to a therapist, is to deal with how encounters like this undermine our belief in ourselves .

And if we did happen to want t talk to someone about anxiety/depression we'd go and find one ....... not wait for months to see an Endocrinologist who doesn't know her fT3 from her elbow.

[Timetraveler67 in reply to tattybogle]

Bless you tattybogle for saying that, it has got to me because that Isn’t the first time that endo has twisted my words and that’s not fair is it s he isn’t happy I went over her head and got my gp to up my dose to 100mg - she told me 75mg was fine for me and that I was in range with a tsh of 6.7 - I’m really feeling upset over it all, so appreciate your reply

[Charlie-Farley in reply to tattybogle]

So Eloquently said!😊👍