Clinical Significance of TSH Circadian Variability in Patients with Hypothyroidism

Clinical Significance of TSH Circadian Variability in Patients with Hypothyroidism

In October 2011, I wrote a blog:

This identifies the way in which TSH, FT4 and FT3 vary through 24 hours.

Have now noticed a paper published August 2012 which expresses very clearly the importance of time of day in TSH testing.

(Also good to see a Russian paper appearing. They must have an immense amount of research which has hardly been known about in the English-speaking world. Hope much more becomes available.)

Endocr Res. 2013;38(1):24-31. doi: 10.3109/07435800.2012.710696. Epub 2012 Aug 2.


Clinical Significance of TSH Circadian Variability in Patients with Hypothyroidism.

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


Federal Endocrinological Research Centre , Moscow , Russia.


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




24 Replies

Rod, this looks so interesting - bit of a slight problem accessing it as I have Dyscalculia...could you please put it in a form for number-thickos like myself? Would be so grateful, whenever you have the time :)

Thanks for this Rod as I was going to have my next blood test at around 4 oclock in the afternoon but with an already really low TSH and a GP trying to reduce meds I now know to keep my blood test appts in the mornings.

Moggie x

I suppose you can't get your blood drawn just after midnight, can you? :-)

That they ignore the circadian side totally is yet another demonstration of the absurdity of relying on TSH only.

And I'd like to see day-length also included in theories of TSH and thyroid testing.

Thats a great site - I have been reading all the other articles in the related conditions box at the side of your article. Found the one where bloods were taken every hour for 24hrs really interesting.

Wouldn't want my bloods drawn just after midnight Rod as I take my T3, all in one go, at about 11 oclock - can you imagine my doc reading those

Thanks again for sharing this article and site with us, its fasinating.

Moggie x

I posted a brief guide to PubMed some time ago:

Thanks Rod

Moggie x

Hi Moggie

Can I enquire how your one dose at night is going please?



Very well thank you, although if you look at my recent blog regarding heart palps and sweeteners I have been having a few problems - more to do with my stupidity with the sweeteners than the timings of my dosages.

I used to split my 20mcg's T3 into 3 doses but, as I am a firm believer of taking T3 well away from food and drink, I found it very difficult so took advice from a very knowledgable lady on here and now take it with my T4 just before I turn off my light. No more messing about with cutting little tablets into even smaller pieces and no more watching the timings of food, all I do is make sure I dont eat after about 8'ish of an evening.

Dr.Lowe also used to take his T3 all in one go at night and in my blog shaws has posted links to Dr.Lowe's question and answer section where this is discussed. Have linked my blog for you to look at, scroll down to near the bottom for shaws links.

Hope this answers your question.

Moggie x

Thanks Moggie,

I split my dose at the moment but sometimes get palps when first lying down in bed, so am a bit nervous about taking any more at night. So out of interest when were you getting the heart palps - all the time or at certain times?


Hi Mary,

Mainly after eating, which would indicate insulin problems, but I was getting them all day every day. Since stopping the sweeteners things have got a little better but for the fist time in ages last night I went to bed again with palps.

I'll do you a private message on this as I dont want to highjack Rod's blog so look out for it. Talking to someone in the same situation can help so a private message might be best.

Moggie x

Im off to have my blood test at 11-30 this morning, wish Id thought about not taking my thyroxine.

That was most interesting and have printed out a few for my files.

I didn't know much about the circadian side of it and found this easy to understand:

This fact was very interesting:

"How do circadian rhythms affect body function and health?

Circadian rhythms can influence sleep-wake cycles, hormone release, body temperature and other important bodily functions. They have been linked to various sleep disorders, such as insomnia. Abnormal circadian rhythms have also been associated with obesity, diabetes, depression, bipolar disorder and seasonal affective disorder."

I think they can add thyroid disorders to that don't you?

You could always contact them to suggest they update it to explicitly include mention of thyroid. :-)


I have many times had things changed by pointing simple things out in a, hopefully, pleasant manner.

I'll have a go!

Help! bit out of my depth. Out of all this lot which one would "circadian rhythms" come under??? I can't find anything on the page that would give me a clue.

I think I might use this link and explain in the text:

Done! Perhaps you would do the same? Coming from you would sound better than my feeble effort!

Leave it a few weeks (2? 3?) - you should expect some sort of acknowledgement - and keep an eye on the page.Let me by PM if it doesn't get updated and I shall then send my comments. But I think you will have done fine.

Hi Rod

Really interesting and, of course, to be expected. I have long wondered whether the menstrual cycle affects the thyroid levels. Do you know anything about this too (I know you're a bloke, but you do seem to know quite a lot about the literature!).


Considering how oestrogen affects thyroid binding globulin, it would be amazing if there were not some effect.

Hopefully someone else will be able to come in here - with experience.

Thanks Rod. One for the files. I wonder when the highest level would be. Some time in the early morning?

Actually you answered my question in your October blog that you mention at the top. This stuff you find is really useful. Thanks a lot. I was just trying to make sense of my very high cortisol levels at around 8am and I think this helps.

Some of the things being published are of very great significance. Clearly, at least researchers appreciate that there is as much to be found out as is already known.

So true.

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