What is subclinical hypothyroidism?

[diogenes]

We have had a letter to the European journal of Endocrinology journal

It questions how SCH should be considered:

Treatment options for subclinical hypothyroidism

Rudolf Hoermann John E M Midgley , Rolf Larisch and Johannes W Dietrich

1 Department for Nuclear Medicine, Klinikum Lüdenscheid, Paulmannshöherstr, Lüdenscheid, Germany,2 North Lakes Clinical, Consulting Division, Ilkley, UK,3 Medical Department I, Endocrinology and Diabetology, Bergmannsheil University Hospitals, Ruhr University of Bochum, Buerkle-de-la-Camp-Platz 1, Bochum, Germany, and4 Ruhr Center for Rare Diseases (CeSER), Ruhr University of Bochum and Witten/Herdecke University, Alexandrinenstr, Bochum, Germany

We read with great interest the current debate on the controversial issues that have long surrounded the treatment of subclinical hypothyroidism (1). The fact that the two discussants disagreed so strongly in their approach to a prevalent problem, routinely faced by clinicians around the globe, may indicate severe shortcomings in the current approach. Although this controversy had started many years ago, it remains unresolved. Unlike in many other diseases, thyroid diagnosis has evolved through definition by exclusive reliance on a single biochemical measure, as opposed to symptomatic presentation of the disease.

In our opinion, the problem begins with the term and very definition of ‘subclinical hypothyroidism’. What is subclinical hypothyroidism? Is it a true disease or a mere laboratory constellation? According to current guidelines, the diagnosis of subclinical hypothyroidism is made when a confirmed TSH measurement has been obtained that exceeds the upper reference range of the pituitary hormone while the concentrations of thyroid hormones still remain within their reference range (2). Adding to the confusion, therapeutic targets have been separated from diagnostic criteria of the disease by recent guidelines (2). LT4 substitution has been recommended to be withheld in patients with diagnosed subclinical hypothyroidism unless their TSH concentration exceeds a much higher threshold (of 10 mIU/L or even up to 20 mIU/L) than the diagnostic threshold (of approximately 4 mIU/L) (2, 3). This disease understanding has left clinicians with a conundrum to explain to many patients why they suffer from a disease, yet would not require any therapeutic intervention. This may be particularly difficult to accept for patients presenting with symptoms which are in their opinion suggestive of a thyroid condition.

Perhaps, it is time to consider a different approach, potentially more satisfying to clinicians. As implied in the original term ‘subclinical’, the new strategy should re-focus on the clinical manifestation rather than the biochemistry. In recent years, the over-reliance on a TSHcentred diagnostic strategy has been strongly challenged (4, 5). The apparent deficiencies of this approach and its lack of diagnostic specificity and reliability have been reviewed elsewhere (6). The problem is deeply rooted in the guiding principles of hypothalamus–pituitary–thyroid (HPT) regulation (7).

In patients with subclinical hypothyroidism due to autoimmune thyroiditis and sufficient intact thyroid tissue, thyroid regulation importantly includes, in addition to the classical feedback of circulating thyroid hormones onto pituitary TSH secretion, the feedforward control of TSH over preferential thyroidal triiodothyronine (T3) secretion (8). The system is designed to take pro-active action in anticipation rather than reactive to the event of a shortage of thyroid hormone supply to the body. The manifestation of a clinical disease is determined either by the success or failure of the central attempt at compensation. Measurement of a slightly elevated TSH in subclinical hypothyroidism, cannot reliably discriminate between the two outcomes. It must therefore be regarded as an ambiguous signal, unless all thyroid hormones and clinical endpoints are taken into account.

Subclinical hypothyroidism, as a laboratory constellation, has been implicated to increase the risk of cardiovascular mortality (9). This conclusion may also be premature, because slightly elevated TSH levels together with ‘normal’ thyroid hormone concentrations may not necessarily indicate early thyroid failure (10). Alternatively, this may reflect an increase in the homeostatic set point of the HPT axis (10). Set point adjustments frequently occur in association with chronic psychosocial stress or allostatic load type 2 (10). The latter, in turn, is a wellrecognized cardiovascular risk factor. The high individual variability in the expression of the HPT set point is further augmented by genetic traits.

Given the inherent ambiguity arising from TSH being a controlling parameter, its non-ergodic behaviour and complex relationship with both thyroid hormones and clinical endpoint results obtained in clinical studies require careful consideration of their design, statistical analysis (risk of collider stratification bias) and interpretation (risk of confounding between set point elevation and thyroid failure). Consequently, we suggest that a disease defining role should be assigned to thyroid hormones, derived structural thyroid parameters (estimated functional thyroid capacity, set point reconstruction) and markers of tissue response to develop a clinically useful algorithm to be verified in clinical trials.

Recent advances in our understanding of system regulation may help put the role of TSH into a better clinical perspective. The debate should encourage further efforts to address unresolved issues and find a more clinically inclusive definition for subclinical thyroid disease, more deserving of this name.

European Journal

of Endocrinology

eje.bioscientifica.com doi.org/10.1530/EJE-20-1405

© 2021 European Society of Endocrinology Printed in Great Britain

R Hoermann and others

Subclinical hypothyroidism

[helvella Administrator Thyroid UK]

Do you think it likely you will get any direct responses to that?

[diogenes Remembering in reply to helvella]

We did from the original authors who rather missed the points we were making and ideas for alternative approaches

[helvella Administrator Thyroid UK in reply to diogenes]

It is pitiful that those involved struggle to understand what you wrote.

Clearly, a considerable number here appreciate and understand (up to a certain level) better than some authors.

[tattybogle in reply to helvella]

yeah... it think it say's " its a bloody complicated system so you should try and think about how it works a bit more than you have been doing .... and for the record , calling people with life altering symptoms 'sub-clinical' - is likely to piss them off a bit, so you should perhaps think about that too"

[TSH110]

A very good read! What is so hard for the “experts” to understand. The flat earth syndrome as outlined by Dr Tania Smith? I believe your work will become mainstream and revolutionise life for those with thyroid disorders…it is just a question of time now.

[diogenes Remembering in reply to TSH110]

I know I bang on about this, but I firmly believe that the problem comes from treating the individual by reference to a statistical range covering everyone (except 2.5% bottom and top of range). The individual is not a range - its a person who might vary say 20% in an FT3 number from occasion to occasion but certainly will not cover the whole range. You can say that one can divide the patient range into three groups - the bottom third, middle third and top third. This helps but does not solve the dilemma between statistical diagnosis and personal diagnosis. Medicine still remains an art rather than a science.

[Tythrop in reply to diogenes]

The "one size fits all" myth

[TSH110 in reply to Tythrop]

Imagine if we were forced to wear any old shoe between 4 and 10 and the shoe shop claimed any of them would fit. It shows the absurdity of the one size or any where within the available size range fits all. It’s clearly stupid reasoning.

[TSH110 in reply to diogenes]

But I was treated as an individual where the ranges were concerned my problem my was only being given T4 when I needed T3 as well as T4 to feel well again . T3 was never mentioned (bar being told my thyroid hormones were not properly balanced and I would have to get just get used to feeling unwell for the rest of my life 😳) let alone it being offered to me - at a time when that was possible unlike these days - on the NHS. I feel the T4 monotherapy obsession was the biggest barrier to my being able to feel well again, bar being left for decades undiagnosed.

[tattybogle in reply to TSH110]

Me 2

[jgelliss in reply to diogenes]

You are so *Spot On* . Diogenes personally I learned with my thyroid journey over the years after my TT What feels right might not look good on lab results and the same in reverse. What looks good on lab results don't feel well for me. I agree with you 1000% it's more *Art Than Science*.

Thank you for for validating something that many of us have felt all along.

[Tythrop in reply to jgelliss]

Yes validation just what we need. Its a good word

[UrsaP]

Well done again diogenes to you and the team. It has driven me mad about SCH. NICE guidance stated don't treat SCH as 50% might right itself within 6 months. But putting it simply, and imo clearly, that 'might' also means it 'might not'. And presumably it means the other 50% won't. So potentially 100% of SCH is likely to actually be untreated hypothyroid. Overt, if not then and there, at some point in the future, it is likely the start of a thyroid problem. Negligence. If, as often quoted, c90% of Hypo is due to Auto immune, that is 6 months wasted whilst the patient suffers potential irreparable thyroid damage. Potential Harm. It always smacked at nothing more than an excuse to a) not diagnose so no treatment = save money b) patient not entitled to be included in the Free prescription cohort = saving money. How many of us suffered with symptoms that were ignored or dismissed for a decade or more. It should not be taking so many years for people to get diagnosed. It is a massive failing of the medical world. Other conditions also take an average of 7. - 10 years for diagnosis, Lupus, Sjogrens etc, largely because medics do not listen/believe their patients. Time this stopped.

[TSH110 in reply to UrsaP]

Largely because of sexism and ageism in my opinion

[Tythrop in reply to TSH110]

Yep, but I bet the consultants would treat their spouses/daughters/sons /mums/dads if they kept showing clinical symptoms. I would like to know if there are any people in these categories signed-up to TUK because untrested.

[UrsaP in reply to TSH110]

I was talking to someone about this too, as many of these conditions tend to affect women more than men. That said I do think that with hypoT men might be subject to ‘delayed’ diagnosis as HypoT is not seen as a ‘male’ condition. That said it would be interesting to know if, once diagnosed do men suffer the same disrespectful stereotypical attitude we females are subjected to? Somehow I suspect not, though .

[clubby29 in reply to UrsaP]

Hi sadly yes we do. Or at least I do

[TSH110 in reply to UrsaP]

This article someone posted on TUK in a thread might explain some of it:

m.huffpost.com/us/entry/us_...

A bit shocking what?

[knitwitty]

What is subclinical hypothyroidism?

An excuse to not treat people who are obviously hypothyroid !!

[diogenes Remembering in reply to knitwitty]

I'm afraid it is more than that. Medicine has become defensive owing to the threat of litigation. I find this very unsatisfactory because the patient has a powerful mechanism that puts any honest mistake by a doctor in a real danger as regards suing him/her. Doctors aren't angels with infallible decisions as to treatment, and we shouldn't so treat them. But in this field the situation arises owing to ignorance and poor teaching. Medicine has wherever possible tried to become a science. That is impossible given the variation in the human condition. This is what I mean by treatment of the individual as an individual and not as a statistic.

[knitwitty in reply to diogenes]

I agree with every word you say, my comment was somewhat 'tongue in cheek' but based on the experiences of so many on this forum.There does seem to be a great deal of ignorance in the medical profession and what is even worse a reluctance to even acknowledge that they may have to look further into a patient's condition than the holy grail of the TSH blood test.

Thanks for the original post.

[Tythrop in reply to knitwitty]

Yes yes yes to the point about medics needing to question themselves and think outside the box. Im guessing they are just knackered.

[tattybogle in reply to diogenes]

I agree , i hate what the culture of litigation/suing people has done to every aspect of life . i've been watching it remove autonomy and personal decision's from things for 40 yrs and i'm sick of it , but it looks like we're stuck with it ..

And the only winners are the lawyers.

[TSH110 in reply to tattybogle]

But sometime litigation is needed, where there’s gross incompetence like that awful breast surgeon doing terrible things to women. They are insured too.

[TSH110 in reply to diogenes]

But why would anyone sue a doctor for treating their SCH? Has anyone ever sued a doctor over their treatment for thyroid disorders?

Well more than I thought over 14 years (2002- 2016):

Out of 189 cases reviewed, an outcome was decided in 134 cases; of which, 67.9% were successful for the claimant, resulting in compensation being paid. The most common reasons for successful claims were treatment complications (47 cases) and delay or failure of diagnosis (22 cases). Nerve and/or vocal cord damage and hypoparathyroidism were cited in 12 and 3 cases, respectively. Common specialties involved in successful claims were general surgery, ENT and endocrinology. The median (range) costs paid for compensation were £50,701.35 (£189.00 to £4.5 million). The median (interquartile range) time from incident to settlement was 1254 (992–1756) days. The number of claims (overall and successful) has reduced over the 14-year period, but there has been no change in the total cost per successful claim from 2002 to 2014 (p = 0.151)

tandfonline.com/doi/full/10...

so less than 10 year were successful in fact by my calculation around 6.4 a year. It doesn’t sound like a huge threat to practitioners to me

[TSH110 in reply to knitwitty]

Exactly