This new paper (abstract included here to see if relevant to posters) discusses the relationship between TSH/FT4 levels and and heart disease. It's very detailed, but is a comprehensive story about the problem.
Minor perturbations of thyroid homeostasis and major cardiovascular endpoints—Physiological mechanisms and clinical evidence
Frontiers in Cardiovascular Medicine
DOI: 10.3389/fcvm.2022.942971
Abstract
It is well established that thyroid dysfunction is linked to an increased risk of cardiovascular morbidity and mortality. The pleiotropic action of thyroid hormones strongly impacts the cardiovascular system and affects both the generation of the normal heart rhythm and arrhythmia. A meta-analysis of published evidence suggests a positive association of FT4 concentration with major adverse cardiovascular end points (MACE), but this association only partially extends to TSH. The risk for cardiovascular death is increased in both subclinical hypothyroidism and subclinical thyrotoxicosis. Several published studies found associations of TSH and FT4 concentrations, respectively, with major cardiovascular endpoints. Both reduced and elevated TSH concentrations predict the cardiovascular risk, and this association extends to TSH gradients within the reference range. Likewise, increased FT4 concentrations, but high-normal FT4 within its reference range as well, herald a poor outcome. These observations translate to a monotonic and sensitive effect of FT4 and a U-shaped relationship between TSH and cardiovascular risk. Up to now, the pathophysiological mechanism of this complex pattern of association is poorly understood. Integrating the available evidence suggests a dual etiology of elevated FT4 concentration, comprising both ensuing primary hypothyroidism and a raised set point of thyroid function, e. g. in the context of psychiatric disease, chronic stress and type 2 allostatic load. Addressing the association between thyroid homeostasis and cardiovascular diseases from a systems perspective could pave the way to new directions of research and a more personalized approach to the treatment of patients with cardiovascular risk.
Written by
diogenes
Remembering
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Very interesting read & just from the abstract chimes strongly with “Anderson, 2020: Thyroid hormones and atrial fibrillation” so beautifully dissected & analysed here …
Both point to the horrible clinical dilemmas involved with the absence of utilising FT3 & T3 medication where T4-T3 conversion is poor and even NG145 suggests increasing T4 meds into the upper/top of FT4 range where hypothyroid symptoms continue.
The disconnect in the general endocrinological mindset welded to TSH/T4 treatment with heart health is both daunting and dismaying.
Thanks diogenes . I can’t say I understand a great deal of this but I did pick up the PTSD issues ( sort of). Please could you explain this to me in very simple terms? I’ve had chronic PTSD for 22yrs and had sub clinical TSH/FT4/FT3 before starting Levothyroxine. I’m still not feeling well despite TSH now underrange and frees midrange.
This paper finds that patients with high-normal FT4 and lowTSH have a greater chance of earlier death than those with lower-normal FT4 and higher TSH. But remember this is only a statistical trend. It may well be that the higher FT4/lower TSH group are more prone to fatal non-thyroidal disease than the others, rather than it being a direct effect. We don't really know fully how FT3 impinges on all these findings and it could be this that is a bigger culprit.
The studies I've seen suggest T3 is a lesser culprit. T4 has non-genomic actions, it binds to receptors that promote cancer and has direct actions on the heart that I don't understand. It seems that T4 is the active hormone at the cell membrane and T3 active in the nucleus. Too much T3 is harmful but T4 can be harmful even within normal limits.
Sorry 🤦♀️I’ve had PTSD for 22 yrs. Many psychiatrists diagnosed over the years, including a month in a psychiatric unit in 2013. What i meant was are the authors saying PTSD can cause secondary/tertiary hypothyroidism? I’ve not realised the connection.
The main finding is that patients getting PTSD are divisible into combat-related stress with high FT3, and noncombat stress with more normal FT3. It looks as if PTSD is another nonthyroidal illness which because of the stress, keeps FT3 normal I wouldn't think secondary or tertiary disease occurs very often..
I'm amazed at the scope and scale of this work from Johannes and his team, my brain hurts just reading it!
This review points out once again the risks of high normal fT4 and to a lesser extent a low normal TSH. High normal fT4 is associated with cancer and cardiac mortality, along with a shorter life expectancy. TSH has minor beneficial effects on bone formation and cardiac function. Levothyroxine monotherapy usually involves a high normal fT4 with a TSH that is lower than required with combination therapy.
Bano (ref. below) showed that people with an fT4 in the lowest tertile lived an average of 3.5 years longer than those with fT4 in the middle or highest tertile. This study looked at people around 65 years old, the age at which hypothyroidism is common.
We can do some sums. I will round up numbers to make the arithmetic easy. If average life expectancy is 70 years then those who live 3.5 years longer will live 5% (1 in 20) longer. It seems daft to put hypothyroid patients on levothyroxine monotherapy with a high normal fT4 and lower TSH. One third of hypothyroid patients, who would have been in the lucky group, will be shunted into the shorter lifespan group. An extra 5% mortality. If there are say 1,800,000 patients on levothyroxine this results in 1,800,000 x 1/3 x 1/20 = 20,000 excess deaths each year.
If we decided to optimise thyroid therapy and put all patients on combination therapy, keeping fT4 in the lower part of its reference interval we could potentially save 3 x 20,000 = 60,000 deaths each year. These numbers are not reliable, there will be confounding factors but they give an idea of the scale of the problem.
Levothyroxine monotherapy results in thousands of unncessary deaths each year and so levothyroxine monotherapy should not be routinely used.
Bano A, Chaker L, Mattace-Raso FUS, Terzikhan N, Kavousi M, Ikram MA, Peeters RP, Franco OH. Thyroid function and life expectancy with and without noncommunicable diseases: A population-based study. PLoS Med. 2019 Oct 25;16(10):e1002957. doi.org/10.1371/journal.pme... .
I hate that I have an unusual hypothyroid presentation. On diagnosis I had a TSH of 2.9 with a below range T4 (10 in the range 12-22). I am now confident that this was Central hypothyroidism. My T4 got quite high, to the top of the range over 7 years, not good for my heart it seems! Still no resolution of symptoms.
But I also have poor conversion as I found out by DIO2 test, also I have faulty DIO1 genetics.
So my TSH is always low because it isn't reliable and doesn't rise to low T3 or T4 and because now that I'm on combination therapy, my TSH isn't triggered anyway as getting T3 directly.
You can imagine how difficult it is to get my Endo to understand all this 😢
Not sure if my current status is bad for my heart, i.e. suppressed TSH and high T3 with low T4.
This also shows that a higher FT3/FT4 ratio, with FT4 not too high, reduces CVD risk. Thus, it appears that conversion ability which does not allow FT4 to get too high for a given FT3 is a key player in the risk levels. So, with athyreotic patients on T4 only, a need to get a useful FT3 at the expense of high FT4 is contraindicated. Poor converters are therefore at risk if combo therapy is not given.
This is great but what about people like me who ,because of accute Graves in the past have gone into Hashimoto phase but have a a downregulated TSH so we "look " euthyroidal or subclinical from bloods until T3 considered (which NHS deliberately avoids for budget reasons)
MikeM46 Thanks for the link to the study. I have a very bad cold so not up to reading it at the moment. In general I don't like fT3 / fT4 ratios because they are dynamic, the deiodinases act to preserve serum fT3 so TSH and fT4 tend to change. Also, the ratio can get a bit dodgy if you are taking thyroid hormone - a ratio can be the same if fT3 and fT4 are both high or low.
Nontheless, this study again shows that losely speaking fT3 is 'good' and fT4 'bad' in that it is better to be euthyroid with a low normal fT4 than an average or above average (normal) fT4. Levothyroxine monotherapy should not be routinely used.
We shouldn't read too much into it but it's interesting to note that in Table 2 the Model 3 HR values for fT4 (and fT3/fT4) were similar for All Cause and Cardiovascular mortality. Now not everyone dies of cardiovascular disease. So, this data tends to tell us that higher fT4 levels are just as hazardous for other fatal illnessses as they are for cardiovascular disease. I suspect a large part of this is due to the link between fT4 and cancer.
This study did not look at atrial fibrillation, this is also associated with fT4, see ahajournals.org/doi/10.1161... . (I can't remember if this is the best study on the topic, I've justed grabbed the first one I have).
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suppressed TSH and high FT4
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The relationship between Tsh and T4 
