Another paper (USA) showing TSH alone is not a ... - Thyroid UK

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Another paper (USA) showing TSH alone is not a good indicator of therapy.

diogenes profile image

Annals of Thyroid Research


Thyroid Stimulating Hormone (TSH) alone is often used as

a primary marker to screen for thyroid function. Significant intra-individual

variation of TSH concentrations occur in healthy individuals. Intra-individual sex

and time-based variations pose the question of whether TSH can reliably screen

for thyroid disorders.

Objective: To quantify the degree of diurnal fluctuations in TSH

concentrations of healthy individuals and assess its diagnostic reliability. To

propose preliminary sex and time dependent TSH reference intervals.

Design and Methods: Healthy volunteers (n=102) were recruited from

4 participating sites. Couplet (AM and PM) serum samples were drawn and

analyzed for TSH concentration using immunoassay.

Results: Significant AM to PM increases in TSH levels for both men (P <

0.0001) and women (P = 0.0003) were noted.

Conclusion: TSH should not be used as a single marker for the assessment

of thyroid function. We recommend that TSH be used in conjunction with Free

Thyroxine (FT4), Free Triiodothyronine (FT3), and Total T3 measured by LCMS/


Keywords: Thyroid stimulating hormone; Congenital hypothyroidism;

Immunoassays; Thyroid function

Highlights: Significant differences exist in:

1. Intra-individual TSH concentrations

2. Diurnal and sex-based TSH concentrations

1 and 2 together with the many drugs and steroids that lower TSH

concentrations, suggest we should question the reliability of TSH as a

single marker of thyroid function.

TSH Should not be used as a Single Marker of Thyroid


Sheikh S, Parikh TP, Kushchayeva Y, Stolze

B, Masika LS, Ozarda Y, Jonklaas J, Nigussie

G, Remaley AT, Sampson

27 Replies

I didn't add the full reference: Annals Thyroid Res. 2018; 4(2): 151-154. Open Access.

helvella profile image
helvellaAdministrator in reply to diogenes

Link to PDF of paper:

I don’t recognise any of the names except J Jonklaas, who was the lead author of the American Thyroid Association’s 2014 Hypothyroid Guidelines. These guidelines focused very much on measuring TSH, so this change of direction to include ft4 and ft3 is very welcome.

I wonder why they are keen on including a total t3? I think that's no longer tested here in Aus = just free T3. (Or maybe that's just the lab my doctor likes?)

diogenes profile image
diogenes in reply to

Its because the US has never taken in the idea of FT3 at all. Reasons? NIH - not invented here.

in reply to diogenes

Ahh. They did include free T3 as well. I think it's been more than a decade since my doctor explained that he wasn't interested in total, just free, and why.

in reply to diogenes

I did think it was interesting that they referred to TSH for *screening* for thyroid problems.

MaisieGray profile image
MaisieGray in reply to

I think it's being used to mean simply "test for", nothing particularly ominous. Which reminds me of that wonderful sketch by Michael McIntyre about how Americans use English.

in reply to MaisieGray

Oh no, I saw it in a positive way! Like - this is just a screening test, it has limitations, you'll need proper testing if it flags a problem. Maybe I misread it!

"Results: Significant AM to PM increases in TSH levels for both men (P <

0.0001) and women (P = 0.0003) were noted."

Haven't they got that the wrong way around? I thought TSH is highest in the morning.

helvella profile image
helvellaAdministrator in reply to

Might not be quite so clear because they refer to windows of 06:00 to 09:00 and 18:00 to 21:00.

In the real world, we pretty much have to have our blood drawn in "office" hours so our shorthand description of TSH getting lower through the day works. But it does start to rise again in the late afternoon and by 21:00 certainly does show on a graph as a higher number. It would be necessary to check carefully exactly what they are saying. But just comparing those two time windows could miss the middle-afternoon trough.

in reply to helvella

Yes, makes sense

in reply to

I think it is lowest at about 3am, which for most of us isn't very useful. I can be waiting at the pathology place for when they open, but opening is usually 8am!

humanbean profile image
humanbean in reply to helvella

Hidden I noticed "AM to PM increases" as well, and was going to comment, but you beat me to it.

I wonder if I can make a prediction...

Patients "in the know" are now doing what they can to get thyroid function testing done as early in the day as possible.

If any endos ever read this paper they will start telling patients they must get their blood tests done in the afternoon because TSH is highest during the PM. They will not take into account the specifics of what AM and PM refer to in this case, and will refuse to believe that they could possibly be wrong.

in reply to humanbean

lol, most likely!

in reply to

An endo told me blood test first thing in the morning, levo straight afterward.

in reply to

Wow, they've wised up!!!

in reply to

That was many years ago! But I'm in Australia, where our care seems to be different. It was also in the context of a clinical trial, so possibly they just wanted everyone to be consistent.

Furface profile image
Furface in reply to humanbean

The last Endo I saw said it only varies .2 throughout the day and no medication affects it, it is the gold standard test. No surprises there really, eh, not from an Endo who will not tolerate (his words) suppressed TSH regardless of what the FT3 is (even when its bottom of the range).

humanbean profile image
humanbean in reply to Furface

I would give that endo a miss in future, or give him a copy of this paper :

He's totally wrong about how much TSH varies throughout a 24-hour day. See the graphs on page 2 and 3 to see what I mean.

Furface profile image
Furface in reply to humanbean

That's a very detailed paper and only backs up what I already thought, thank you. The tricky bit is convincing this Endo who said he would prescribe combo T4 and T3 BUT he will NOT TOLERATE a suppressed TSH. I know from the time I have been on NDT that I only feel well when it is suppressed. When it is not, I have breathing problems, balance problems and my heart races plus lots more unpleasant symptoms. My problem is, this is my fourth Endo and GP wont keep referring, he said this is the last time. (None of the Endos have known what they are talking about. All of them denied I needed help and the 3rd one tried to finish me off by saying my blood tests showed I had no endocrine issues (despite having Vitaligo) - I was on NDT at the time so the bloods reflected this. This is truly a terrible system of thyroid care with clueless people in charge of whether we thrive or barely survive. The stress of this is overwhelming.

diogenes profile image
diogenes in reply to Furface

Also try this direct paper:

Endocr Res. 2013;38(1):24-31. doi: 10.3109/07435800.2012.710696.

Clinical significance of TSH circadian variability in patients with hypothyroidism.

Sviridonova MA1, Fadeyev VV, Sych YP, Melnichenko GA.



To investigate the clinical significance of thyroid-stimulating hormone (TSH) circadian variability in patients with hypothyroidism.


A total of 20 women with subclinical hypothyroidism and 22 patients taking L-thyroxine replacement therapy for hypothyroidism were enrolled in the study. Measurements of serum TSH levels were done twice a day from 08.00 to 09.00 a.m. and from 2.00 to 4.00 p.m.


The morning median TSH value in the patients with subclinical hypothyroidism was 5.83 mU/L; in the afternoon, it was 3.79 mU/L. The range of TSH circadian variability reached the level of 73%. According to the current TSH reference interval, hypothyroidism was not diagnosed in about 50% of the cases in the afternoon. The morning median TSH value in the patients taking l-thyroxine was 3.27 mU/L; it decreased to the value of 2.18 mU/L in the afternoon. The range of TSH circadian variability reached the level of 64.7%. Further analysis demonstrated inadequate compensation of hypothyroidism, which was defined in 45.5% of the morning samples and in 9% of the afternoon samples (p < 0.05).


The time of blood sampling has an important role in the interpretation of TSH levels. Moreover, the high TSH circadian variability should be considered in discussions about the narrowing of its reference range.

Furface profile image
Furface in reply to diogenes

Well according to this, there is a little more variation than the .2 that this Endo was vehement about. It causes a lot of problems when patients are not given blood test appointments until late in the day, I have experienced this yet when you question it, we are told it makes no difference. However it makes a massive difference to the patient as they often get their medication cut. This is what that Endo said he would do if I had a suppressed TSH. Lots of threats and I don't even have the T3 yet, he told me he would know how much T3 to give me once he knew how much T3 and T4 was in my NDT. He could have googled it but no, told me to go home and email him (now I think he never intended to give it to me all along. Why are these Endos allowed to get away with treating people in this cruel way). He made me feel as though I was asking for cocaine rather than a hormone that will help me be normal . . . . i know its just about price and so they set the patient up to fail.

Soldin is a very odd bod with firm ideas. He has championed a particular way of measuring thyroid parameters which I for one think dodgy. That is not to say his message with Jonkclaas isn't true overall. I wonder sometimes at his methodology though. And that is putting it mildly.

in reply to diogenes

Suppose the main point is that TSH does vary, and is therefore not a reliable marker of thyroid function

Thanks for this. Hey - if they’d had asked us we could have told them and saved all that money on research and bloodletting! But still good to see some studies concluding what to us is bloody obvious.

No thats not true. FT4 in health does not change through 24 hours, and FT3 only has a small (10%) rise, about 90 min after the TSH peak in the night, whereafter it returns to a stable normal level. We cannot relate healthy situations to treatment, where again FT4 and Ft3 will remain constant (on T4 therapy but not on combined or T3 only) and the TSH cycle is lost.

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