This provisionally accepted paper discusses the need for individual assessment of patients in TSH measurements - not just taking "within range" as an acceptable diagnosis. It will be accessible when fully published.
Within-person variation in serum thyrotropin concentrations: main sources, potential underlying biological mechanisms, and clinical implications
Evie van der Spoel, Ferdinand Roelfsema and Diana van Heemst
Leiden University Medical Center, Netherlands
Background: Individuals exhibit fluctuations in the concentration of serum thyroid-stimulating hormone (TSH) over time. The scale of these variations ranges from minutes to hours, and from months to years. The main factors contributing to the observed within-person fluctuations in serum TSH comprise pulsatile secretion, circadian rhythm, seasonality, and ageing. In clinical practice and clinical research however, such within-person biological variation in serum TSH concentrations is often not considered. The aim of this review is to present an overview of the main sources of within-person variation in TSH levels, as well as the potential underlying biological mechanisms, and the clinical implications.
Summary: In euthyroid individuals, the circadian rhythm, with a nocturnal surge around 02:00–04:00 h and a nadir during daytime has the greatest impact on variations in serum TSH concentrations. Another source of within-person variation in TSH levels is seasonality, with generally higher levels during the cold winter months. Since TSH is secreted in a pulsatile manner, TSH levels also fluctuate over minutes. Furthermore, elevated TSH levels have been observed with ageing. Other factors that affect TSH levels include thyroid peroxidase (TPO)-antibody positivity, BMI, obesity, smoking, critical illness, and many xenobiotics, including environmental pollutants and drugs. Potential underlying biological mechanisms of within-person variation in TSH levels can be safely concluded from the ability of TSH to respond quickly to changes in cues from the internal or external environment in order to maintain homeostasis. Such cues include the biological clock, environmental temperature, and length of day. The observed increase in TSH level with ageing can be explained at a population level and at an organism level. In clinical practice, the season for thyroid testing can influence a patient’s test result and it occurs frequently that subclinical hypothyroid patients normalize to euthyroid levels over time without intervention.
Conclusions: Serum TSH concentrations vary over time within an individual, which is caused by multiple different internal and external factors. It is important to take the within-person variations in serum TSH concentrations into account when testing a patient in clinical practice, but also in performing clinical research.
Written by
diogenes
Remembering
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And perhaps we could end the practice of refusing to treat older patients with elevated TSH, because "it's a normal part of aging." Oh really? They don't look at elevated blood pressure that way any more. (They found out they could make more money by selling blood pressure medications.)
The problem with treating hypothyroidism is that doing so can obviate the need for all kinds of expensive medications to treat the symptoms, rather than the cause.
Within-person variation in serum thyrotropin concentrations: main sources, potential underlying biological mechanisms, and clinical implications
Note to readers... Thyrotropin is another name for Thyroid Stimulating Hormone (TSH).
Knowing that can be helpful when doing research because some people writing research papers use the name Thyrotropin in preference to using the name TSH.
Half of me is pleased to see it in print , cos it's high time it was... and the other half of me is appalled that such a basic fundamental as 'the normal rhythm of TSH' needs a paper written about it in 2021 when it's been used as 'the only test needed' by so many for so long .
Still... since it's painfully obvious that so many esteemed Endocrinologists and GP's only studied "Ladybird Book 1 ~ TSH is Everything" before being let loose on patients .....i suppose we should be reassured that they will now have chance to read "Ladybird Book 2 ~ Basic Rhythms in TSH"
" In clinical practice, the season for thyroid testing can influence a patient’s test result and it occurs frequently that subclinical hypothyroid patients normalize to euthyroid levels over time without intervention. "
I'm a bit disappointed that the Authors only chose to emphasize this aspect of the problems with diagnosis if TSH rhythms are misunderstood, when they could have equally correctly emphasised the potential for apparently "euthyroid" levels to be concealing hypothyroidism.
But overall, i'll take this paper as a positive development.
This is encouraging, but I'm not sure it will make any clinical difference to a medical profession intent on waiting until TSH is over 10 before treating the patient. Or am I being too negative?
Nonetheless such ideas are being published and will eventually gain traction. Just as an aside I'd like to give some startling information. I and the team have been working over 10 years to understand how the whole complicated 3-gland-body system works and how it can be upset by disease and what are the consequences for choosing treatment or gaining recovery (say after a severe nonthyroidal illness). I hesitate very much to write this, but a very recent idea has been worked on, and the whole beautiful explanation of the system in total has fallen out. Like all beautiful systems its solution is relatively easy if you ask the right questions. Just at this moment I feel like Archimedes and his bath. Lockdown has its upside!
Yes, I admit to being a bit lightheaded at the moment. A definitive paradigm for HPT functioning is an enormous step. And to think that it came from a simple question I asked myself, from this forum's posts - namely, why do most patients on T3 only give normal range FT3 yet undetectable TSH? So how does T4 change that? Simple questioning with a beautiful ending.
Your side of thyroid is so very important. And it is wonderful to read of progress.
Now we need a similarly independent and dedicated group to let us know precisely how thyroid hormones act in the body.
When I first started to read about thyroid, I could never find any sensible description of what thyroid hormones actually do. Something like "affect metabolic rate" was about it. There has been progress. But we still don't see the full picture.
Half the time it is discussed as if thyroid hormone is like glucose - some necessary ingredient of metabolic processes. But other times it is discussed as signalling. We see some people seeming to need only a few micrograms of T3, others taking 150 or more micrograms a day of T3.
We see the idea of once-a-week dosing by T4. And others split-dosing their T4.
We now see clinical trials of a slow T3 product announced. Without sufficiently proved theoretical basis. Just (it appears) this is what a healthy thyroid would be doing. Empirical.
So pleased for you that you've had a light bulb moment, they're beautiful aren't they
Now if you could just go on a nice long walk in the hills and come up with an analogy that will enable us muggles to understand it, that would be even better,
Waiting with baited breath to read all you and your colleagues have to say, and thank you all very much for your insights and knowledge. I am over the moon to say that I have found a Doctor (not Endocrinologist) who does not treat by TSH but by FT3 and is happy to prescribe NDT.
Yes I do agree these are important developments which are key in changing perspectives that have become entrenched and unhelpful. A more comprehensive diagnosic methodology looking at the thyroid hormones as well as TSH in concert should surely be an improvement on using TSH alone. I hope it becomes normal practice in the future. Which are the three glands body systems you refer to? Is it the HPT axis? It sounds very interesting.
It is: we seem to have put all three endocrine glands and the body conversion of T4 to T3 into a complete description of what is going on in health and disease.
Thank you Diogenes, as you say it is the beginning of a process and that is encouraging. We can but hope that the medical profession will take hold of the importance of this and related research and act upon it. You and your colleagues' dedication and fortitude in forging new paradigms will pay off, I'm certain. I'm sorry for what probably came across as dismissive. Lockdown has its downsides!
Thank you Diogenes for once again for a very valuable post. I'm very disappointed that there are Dr's that still dose patients withTSH. Patients can never feel well with TSH dosing. It's FT 4 and FT 3 that make patients Optimal. I hope Dr's see this report and reverse their practices of how they treat their patients.
linda96 Helsan MikeM46 I think you'd like to read this whole thread.diogenes This is a really heartening post. So many of us have to battle the TSH argument regularly with our doctors.
Intrigued to see the paper was from the Netherlands. As far as I can tell from conversations with my Dutch cousins the docs there don't accept a need for T3 and seem less educated than some of our GP's. Maybe that's down to where they live, as it is here.I shall look forward very much to reading your latest paper. keep up the good work.
Hi diogenes ,So going back to when I was diagnosed with subclinical 5 years ago tsh fluctuating with highest with a tsh of 9 with positive thyroid antibodies of 368 I might not have needed thyroid meds? As since I have been on this Levo I haven't felt myself now my tsh stays the same supressed at 0 .02 0.04 I'm certainly not hyper as my t4 n t3 are both at the top and within range and I still get your meds need lowering because of Tsh I can honestly say I haven't felt good on these Levo meds
Not knowing your precise details I personally could not say. The matter should be between your doctor and yourself, (and now comes the essential bit). You doctor should have taken BOTH your thyroid fluctuations AND your feelings of health or illness at that time, to make a proper diagnosis. It's no use going by results of tests only: your health at that time would be equally indicative of either waiting or action then.
Under Endo now but haven't heard from him seen him since January 2020 obviously wont atm.. GP not any help really I just try to get as much help n advice on here it's been very helpful!
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Dr. Melnick discusses alarming article from Harvard about the use of the TSH and thyroid treatment!
When using a combo, do the t3/t4 ratios need to be similar to manufactured NDT ratio? 
