This paper forms part of the evidence base for the current NHS thyroid treatment guidelines , it was referenced as evidence to back up their concerns about "low TSH /overtreatment with levo/ risk to bones and heart"

( so they cannot say it is 'not good enough evidence' when you put it under their nose).

However when read carefully ,it actually says that 'low but not supressed' TSH 0.04 - 0.4 on levo had no greater risks than TSH 'in range' does . The risks did increase sharply when TSH was below 0.04 ...

SO .....you can use this paper as a very strong argument that TSH 'itself' is not a increased risk for Fractures / Dysrhythmias (Atrial Fibrilation) / Cardiovascular Disease .... AS LONG AS YOUR TSH is 0.04 or ABOVE .

It was a large, long term study of 17,000 real patients on levo in Scotland.

academic.oup.com/jcem/artic... Serum Thyroid-Stimulating Hormone Concentration and Morbidity from Cardiovascular Disease and Fractures in Patients on Long-Term Thyroxine Therapy

Robert W. Flynn, Sandra R. Bonellie, Roland T. Jung, Thomas M. MacDonald, Andrew D. Morris, Graham P. Leese

The Journal of Clinical Endocrinology & Metabolism, Volume 95, Issue 1, 1 January 2010,

"Abstract

Context: For patients on T4 replacement, the dose is guided by serum TSH concentrations, but some patients request higher doses due to adverse symptoms.

Objective: The aim of the study was to determine the safety of patients having a low but not suppressed serum TSH when receiving long-term T4 replacement.

Design: We conducted an observational cohort study, using data linkage from regional datasets between 1993 and 2001.

Setting: A population-based study of all patients in Tayside, Scotland, was performed.

Patients: All patients taking T4 replacement therapy (n = 17,684) were included.

Main Outcome Measures: Fatal and nonfatal endpoints were considered for cardiovascular disease, dysrhythmias, and fractures. Patients were categorized as having a suppressed TSH (≤0.03 mU/liter), low TSH (0.04–0.4 mU/liter), normal TSH (0.4–4.0 mU/liter), or raised TSH (>4.0 mU/liter).

Results: Cardiovascular disease, dysrhythmias, and fractures were increased in patients with a high TSH: adjusted hazards ratio, 1.95 (1.73–2.21), 1.80 (1.33–2.44), and 1.83 (1.41–2.37), respectively; and patients with a suppressed TSH: 1.37 (1.17–1.60), 1.6 (1.10–2.33), and 2.02 (1.55–2.62), respectively, when compared to patients with a TSH in the laboratory reference range. Patients with a low TSH did not have an increased risk of any of these outcomes [hazards ratio: 1.1 (0.99–1.123), 1.13 (0.88–1.47), and 1.13 (0.92–1.39), respectively].

Conclusions: Patients with a high or suppressed TSH had an increased risk of cardiovascular disease, dysrhythmias, and fractures, but patients with a low but unsuppressed TSH did not. It may be safe for patients treated with T4 to have a low but not suppressed serum TSH concentration.

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

This post deals specifically with the alleged risk to bones.. it links to a recent long term study of patients whose TSH was kept deliberately supressed with levo, long term ( to prevent recurrence of thyroid cancer) ..... it found no significant increase in bone loss with a long term supressed TSH as long as T4 was kept in range.

healthunlocked.com/thyroidu... longterm-subclinical-hyperthyroidism-does-not-affect-bone-density-in-patients-having-had-thyroid-ablation-for-cancer

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

This very recent study (Feb 2023) shows that in euthyroid people over 50yrs old , a higher ratio of T3 to T4 is associated with a reduced osteoporosis / fracture risk. And that higher T4 levels are associated with increased risk ... which if you assume the same applies to those taking thyroid hormone, backs up the idea of giving a bit less Levo and adding a bit of T3 will REDUCE their risk of osteoporosis / fracture. ( i think ?.... it's a bit complicated to understand the results , but diogenes has clarified the findings in a reply to the post )

post discussing: healthunlocked.com/thyroidu...

direct link to paper: pubmed.ncbi.nlm.nih.gov/367...

thankyou            Mollyfan for finding it .

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

For a list of links to other useful discussions on the subject of low TSH/ Risk vs Quality of life ,, please see my reply to this post ( 3rd reply down)

healthunlocked.com/thyroidu... feeling-fine-but-tsh-is-low

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

There are SOME CONCERNS that having high /over rage T4 promotes some kinds of CANCER CELL PROLIFERATION ~ recent research:

healthunlocked.com/thyroidu... levothyroxine-monotherapy-and-cancer

some replies in this post discuss the issue & provide links :

healthunlocked.com/thyroidu... /over-range-t4?

Update : recent video post from    jimh111 healthunlocked.com/thyroidu... thyroid-hormones-and-cancer-video

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

If your GP says , "i have to reduce your dose , because i have to follow the NHS guidelines", then remind them of this bit , it's the first thing said to GP's ,on the first page of the latest NHS (N.I.C.E) guidelines for thyroid disease and management. nice.org.uk/guidance/ng145

" Guideline development process

How we develop NICE guidelines

Your responsibility

The recommendations in this guideline represent the view of NICE, arrived at after careful consideration of the evidence available. When exercising their judgement, professionals and practitioners are expected to take this guideline fully into account, alongside the individual needs, preferences and values of their patients or the people using their service. It is not mandatory to apply the recommendations, and the guideline does not override the responsibility to make decisions appropriate to the circumstances of the individual, in consultation with them and their families and carers or guardian. "

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

UPDATED : this very recent study being is being used (by Prof. Bianco) to show that a low TSH on Levo IS an increased risk factor for death from cardiovascular/ stroke EVEN WHEN fT4 is IN RANGE .

However it still needs looking at carefully to keep these risks in perspective . It has similar findings to the first study i posted above ...in that the risk was significantly less for low but not supressed TSH (0.1 - 0.5) than it was for supressed TSH (below 0.1)

healthunlocked.com/thyroidu... bianco-video? tattybogles reply.

I think this must be the study Prof Bianco refers to in his answer to the question about evidence of low TSH risk when fT4 is in range ? (fairly recent/ VA data/ half a million ish / TSH and fT4 risks looked at SEPARATELY / looked specifically at cardiovascular / stroke mortality ).

jamanetwork.com/journals/ja... Association of Thyroid Hormone Treatment Intensity With Cardiovascular Mortality Among US Veterans

Josh M. Evron, MD1; Scott L. Hummel, MD, MS2; David Reyes-Gastelum, MS3; Megan R. Haymart, MD3; Mousumi Banerjee, PhD4; Maria Papaleontiou, MD3,5

"The forest plot in the Figure illustrates the association between serum thyrotropin (TSH) and FT4 levels with cardiovascular mortality after adjustment for relevant demographic and cardiovascular risk factors.

Cardiovascular mortality was higher among patients with:

exogenous hyperthyroidism:

thyrotropin levels <0.1 mIU/L: AHR, 1.39 95% CI, 1.32-1.47;

thyrotropin levels of 0.1 to <0.5 mIU/L: AHR, 1.13 95% CI, 1.09-1.17;

FT4 levels >1.9 AHR, 1.29 95% CI, 1.20-1.40)

and those with exogenous hypothyroidism:

thyrotropin levels from >5.5 to <7.5 mlU/L : AHR, 1.42 95% CI, 1.38-1.46;

thyrotropin levels from 7.5 to <10 mIU/L: AHR, 1.76 95% CI, 1.70-1.82;

thyrotropin levels of 10-20 mIU/L: AHR, 2.13 95% CI, 2.05-2.21;

thyrotropin levels >20 mIU/L: AHR, 2.67 95% CI, 2.55-2.80;

FT4 levels <0.7 ng/dL: AHR, 1.56 95% CI, 1.50-1.63),

with risk increasing with higher serum thyrotropin levels compared with individuals with euthyroidism."

So ..... while it does indeed separate the risks for TSH (thyrotropin) and fT4 levels and it does show there IS a higher risk for low TSH ..... it ALSO clearly shows that the risk for TSH between (0.1 -0.5) is significantly LESS than the risks for TSH below 0.1

and LESS than the risk for over range fT4.

and LESS than the risk for slightly over range TSH (5.5 -7.5)

and LESS than the risk for below range fT4.

(AHR ~adjusted hazard ratio where AHR 1 = 'no extra risk' , AHR 0.5= 50% less risk, and AHR 1.5 = 50% increased risk .... so TSH (0.1- 0.5) AHR 1.13 = 13% more risk than TSH in range.

... or at least that is what i think AHR means , i'm not a statistician,, but i know AHR 1.13 is not much more risk than AHR 1 (no risk) ,and it's a lot less risk than AHR 1.56)

so that seems to roughly fit with the first Levo study in this post which found a low but not supressed TSH (0.04 -0.4) had no greater risks than in range TSH did.

I have other concerns/ questions about this study....

1) it doesn't appear to separate people into groups with (low TSH and high fT4) vs (low TSH with fT4 in range) because it looks at TSH and fT4 separately ... so do we know how many with low TSH also had high fT4 ?.. and therefore how do we know it wasn't the high fT4 increasing the risks for many of the subjects with low TSH ?

2) the study group was comprised of 88.7% men ... who are known to have a greater risk for cardiovascular disease than women .. so even though they say they have adjusted for sex etc .... is this really a good enough study to base treatment of women on ??

So personally, it hasn't changed my mind about the risks of running a low but not supressed TSH on levo if i need to ....yes there do seem to be some added risks, but they are significantly smaller than the risks of slightly undertreating hypo and no one seems to give two hoots about that being risky, and they certainly don't bother telling telling us we are risking death from it.

......So until i hear of GP's taking the OTHER risks equally seriously eg. panicking their Levo patients are going to die unless they increase dose when TSH is slightly over range at 5.7 because that risk is greater than having a TSH below 0.1

or insisting fT4 is always checked and sending everyone with a slightly below range fT4 off to the endo pronto because the risks of a below range fT4 are greater than that of TSH below 0.1 ........

......then , i'm not going to take their concerns about low TSH level very seriously either........... If they are flapping like headless chickens about one of the risks while blithely ignoring some others that are greater , they are obviously either biased ... or just to thick to interpret a study carefully for themselves.

The key point to get across to GP's in dose 'discussions' is that whatever the 'risks' associated with low TSH.. they need to be looked at in context of all the other risks that they don't seem half as bothered about ... most importantly in relation to the clear risks of feeling so unwell on a lowered dose that you don't get off the sofa very much .. which is definitely a BIG risk for heart health and bone strength.