Replacement therapy with L‐thyroxine is not universally successful at reversing all symptoms for people with hypothyroidism.1 For such patients, current guidelines recommend looking for other co‐morbidities including hypoadrenalism, celiac disease, anaemia, hypercalcaemia, sleep apnoea, renal failure and other conditions. If there are ongoing symptoms, recent focus has been on the possible utility of liothyronine. The timely review by Perros et al1 argues about thinking beyond this narrow perspective to look at broadening potential treatments as well as expanding research ideas.
The reviewers (1) explain that somatic symptoms are likely to co‐exist with common conditions such as hypothyroidism. In the same way that people with depression or hypogonadism may benefit from a combination of pharmacological and psychological input, such as cognitive behavioural therapy, it is argued that some people with hypothyroidism may also benefit from such a combined approach. Limited access to clinical psychology in many areas should not limit our aspirations to offer such care and explore which forms of psychological input may help most. Intriguing early data is presented that reducing the “inflammatory” load by thyroidectomy or selenium may help adverse symptoms. Further research is required before these interventions, metformin2 and other approaches to reduce the inflammatory load can be recommended. They also encourage us not to neglect the impact of treating depression, improving physical activity and managing obesity can have on well‐being in people with hypothyroidism. The authors suggest that using liothyronine is ineffective, at least for the vast majority of people with hypothyroidism, as judged by the lack of benefit in meta‐analyses of randomized controlled trials (RCT).
Although liothyronine may not resolve ongoing adverse symptoms in the majority of people with hypothyroidism, it may be premature to dismiss it altogether. Future RCTs may be better focussing on those with persistent adverse symptoms3 rather than anyone with hypothyroidism. Also, the interaction between liothyronine use and genetic polymorphisms is intriguing although not well characterized.4, 5 It is noteworthy that the meta‐analyses do not demonstrate the superiority of L‐thyroxine over combined L‐thyroxine and liothyronine, which throws the focus onto the cost and safety of liothyronine. The excessive cost of liothyronine in the UK is being investigated6 but currently makes it difficult for healthcare providers to recommend liothyronine until there is strong evidence of its benefit. Safety data are as yet limited, but do not identify major concerns on human data.7, 8 The control of tissue liothyronine concentrations involving membrane receptor uptake, de‐iodination, nuclear thyroid receptor binding and other nuclear protein binding is complex.9 Pharmacological tools to manipulate these processes are currently lacking and it is not possible to fine‐tune intracellular liothyronine concentrations, or its downstream intracellular effects.
We have previously reported that only 62% of patients on L‐thyroxine have a serum TSH in the reference range10 and others report similar data,11 suggesting that current treatment goals with L‐thyroxine alone are frequently not achieved. This is however cross‐sectional data. We can report longitudinal data in our local cohort of 11,335 hypothyroid patients treated only with L‐thyroxine. Over a mean of 12‐year follow‐up (range 1–25 years) with an average 1.25 TSH tests per year, only 1360 (12%) never had a serum TSH out with the reference range (unpublished data). If followed up for 15–25 years (mean 19 years), only 4% of 2710 patients always achieved a serum TSH in the reference range. Does this reflect variable drug absorption impacted by foods and other interfering medications, variable drug delivery, variable concordance, variable metabolism and elimination of absorbed thyroxine, or some other issue affecting variable serum TSH concentrations? In reality, it may be all these factors, but it gives plenty of scope to explain and highlights the need to explore, some of the adverse symptoms experienced by patients on L‐thyroxine.
TSH assays are not perfect,12 as there is the potential for assay interference, and unexpected results should be interpreted in the context of previous and repeated tests. Despite this, TSH assays are the best measure adequacy of thyroid replacement that is currently available,13 although there may be potential for better tests in the future.
Clinicians are starting L‐thyroxine10 at increasingly lower concentrations of serum TSH.11 Despite guidelines not recommending L‐thyroxine when people have subclinical hypothyroidism with serum TSH between 4 and 10 mU/L and normal free thyroid hormone concentrations, treatment is often started in an attempt to improve symptoms which were unlikely to be due to thyroid dysfunction. This can create unrealistic patient expectation and dissatisfaction when starting on a prolonged course of L‐thyroxine. It is noteworthy that a third of patients previously established on L‐thyroxine remain biochemically euthyroid when L‐thyroxine is stopped.13 This is three times more common if the original diagnosis was subclinical hypothyroidism compared with overt hypothyroidism.14 When patients with troublesome symptoms have biochemistry results returned and the term subclinical disease is used, the question may be raised as to whether this really is “sub” clinical. The temptation can be to start L‐thyroxine to see whether it helps some symptoms even though it has been shown that three or more symptoms of hypothyroidism are required to have any predictive power of distinguishing hypothyroidism from non‐thyroidal illness.15 Perhaps now is the time to abandon the term “subclinical hypothyroidism”. In diabetes the term, “pre‐diabetes” is used to identify patients who are at risk of developing diabetes but who do not have diabetes mellitus. A term such as “pre‐thyroid” or “pre‐hypothyroid” may be preferable. However, the term pre‐hypothyroidism still telescopes the “hypothyroid” propensity of the condition. To avoid this issue, the term pre‐thyroid could be used for what is currently called subclinical hypothyroidism and subclinical hyperthyroidism using a grading scheme similar but subtly different to that previously proposed.16 People with a normal free T4 and free T3 could be categorized as pre‐thyroid disease grade 1 (TSH 4–10 mU/L), grade 2 (TSH > 10mU/L), grade 3 (TSH 0.1–0.4 mU/L), grade 4 (TSH 0.03–0.1 mU/L) and even grade 5 (TSH < 0.03 mU/L). This approach could identify patients with “grade 1 pre‐thyroid disease” who are at risk of thyroid disease but who do not yet have thyroid disease and will not benefit from pharmacological treatment, but who require ongoing monitoring, and thus creating more realistic expectations.
It’s hard to know where to start with this, isn’t it? Maybe each paragraph needs a post and thread of its own...
But I’ll get the ball rolling with this:
The authors suggest that using liothyronine is ineffective, at least for the vast majority of people with hypothyroidism, as judged by the lack of benefit in meta‐analyses of randomized controlled trials (RCT).
I took a look at the underlying article and discovered there was no reference for this statement. I’m sure they did their homework somewhere down the line but it’ll have been homework based on the endocrinology equivalent of Wikipedia, no doubt—research focused on keeping a bunch of poor unfortunate volunteers’ TSHs within the reference range. Which most of us know is tricky to do once someone’s prescribed any amount of liothyronine, let alone a dose which might be effective.
The main problem for many people of using TSH to determine the patient's health is that it does no such thing. It did not matter a damn what the numbers were or the dose I took, I was permanently ill on Levothyroxine alone. I would still be ill and in bed unable to do much at all if I had not given up on doctors and started to take NDT.Unless some serious and relevant effort is undertaken then no official changes will ever take place and hundreds of thousands of patients will continue to suffer until the end of their days.
And the truly criminal thing is that many of them will be told they have mental health issues.
It’s kind of tricky to have good mental health when everything hurts, you can’t think straight and you feel like you’re wading through treacle every day.
It’s kind of tricky to have good mental health when everything hurts, you can’t think straight and you feel like you’re wading through treacle every day.
So well put.... I'm going to 'borrow' this phrase, if I may!
I don't want to do any chest-beating, but I do think the authors have little concept about how poor and uninformative all the trials and meta-analyses on combination treatment actually are - they neither support or deny alternatives. Also the authors are extremely punctilious in ignoring all our work and the conclusions therein, which started long before most of these references. I see somatic -blah-blah-blah again raises its ugly head -cannot the authors recognise the depression and other symptoms are more likely to be directly emanating from hypothyroidism and T3 lack than some kind of failure of personality. This article is a pretty poor, selective chop-logic piece of work. One could go on in many ways, but the wilful refusal to look the problem squarely in the face is almost farcically inadequate. They don't even recognise the difference in TSH ranges in health and disease. At least the Huoang article in an earlier post didn't get itself into the irrational mess these people have done.
I would like to say ditto to all of the above replies - I believe Jim had a document which in essence showed that anyone having had a thyroidectomy needed T3 but unfortunately I have been unable to find it again....
oh . don't worry Mr Leese .. there's no need to go to all that trouble with fiddling around with the terminology .. we've already got 'realistic expectations' ... "Doctor unlikely to listen, unlikely to know how to interpret anything as complicated as looking at TSH /fT4/fT3 together, unlikely to be able to optimise our health using Levo unless we go and figure it out for ourselves... "
Translation of the posted article , ...(with thanks to the 'Just Say What You Mean Society' )
Give it a Title that sounds like a new and positive way forward..... (but isn't)
Mention the possible use of Liothyronnine , so it sounds like you're listening ...(but you're not)
Trot out the old line about 'interesting for further research'..... (but don't get involved in doing any)
Remind everyone that it's probably 'mostly in their head'..... (but then acknowledge there aren't enough mental health services anyway, even if we did desperately need them)
Slip in the horrifying idea that we could reduce the inflammatory load by thyroidectomy in hypothyroidism !......(and move swiftly on, hoping none of us notice what was just suggested)
Remind everyone again that they'd feel much better if they weren't so depressed, fat, and lazy.
Remind everyone again that all the current research indicates Liothyronnine doesn't work .........(but conveniently don't remind anyone that all the research was done in the wrong way on the wrong people )
This bit is actually GOOD... "Although liothyronine may not resolve ongoing adverse symptoms in the majority of people with hypothyroidism, it may be premature to dismiss it altogether. Future RCTs may be better focussing on those with persistent adverse symptoms rather than anyone with hypothyroidism. ..//..The excessive cost of liothyronine in the UK is being investigated, but currently makes it difficult for healthcare providers to recommend liothyronine until there is strong evidence of its benefit. Safety data are as yet limited, but do not identify major concerns on human data".......... ( then go on to say "but its all too complicated, so we can't be expected to work out how to use it on any of you just now")
Go back to suggesting "TSH not kept in range" is all that is wrong with any of us on treatment with Levo, and remind everyone that a lot of that is our fault for being too disinterested to take it regularly.
Add this bit "..........or some other issue affecting variable serum TSH concentrations? " .....(but conveniently ignore all the research by diogenes et al. that already provides illumination onto what these 'other issues' are, and the light this sheds on interpretation of TSH in relation to fT4 and ft3 levels in treated patients, pointing to 'less reliance on TSH alone' being a reasonable way to get improvement in outcomes )
Admit TSH isn't perfect, but better test might come along later .....(ignore the fact we already have better tests but we don't let Doctors use them... fT4 AND fT3 looked at together with TSH and symptoms)
Suggest yet again that TSH between 4 and 10 is NOT hypothyroidism, and so treatment won't help and we'll be disappointed....( and twist the knife by suggesting most people in that bracket probably never had hypothyroidism in the first place )
Then come up with the Brilliant solution to this problem... (if you don't tell us we've got hypothyroidism in the first place, we wont be disappointed when you don't try and fix it)
So.... just remove the word 'Hypo' from what you call us.....
........... (But it's nowhere near as helpful as your earlier work "Serum Thyroid-Stimulating Hormone Concentration and Morbidity from Cardiovascular Disease and Fractures in Patients on Long Term Thyroxine Therapy"
...in which you conclude,
"compared to patients in the laboratory ref range, patients with a LOW TSH (0.04- 0.4) did NOT have an increased risk of any of these outcomes."
.....which i successfully used to get my Doctor to increase my Levo dose ....even though according to your latest article , i probably shouldn't even be taking it.. since my TSH was only 6.8 and my TT4 was in range at diagnosis.... so according to your brilliant new system, i'd be classed as "grade 1 pre thyroid disease" and be at risk of developing thyroid disease , but do not yet have thyroid disease, and will not benefit from pharmacological treatment.."
.
....If that was true ,i wonder how Mr Leese would account for my TPOab results at the time ?
well, mushroom tea does indeed have that effect on me
Shame he doesn't come up with any suggestions to prevent or slow down our progression from 'pre-thyroid disease' to thyroid disease.
Surely that's the whole point of that category in "pre-diabetes". ...give a chance to prevent/reverse the progression by making changes, and therefore save money and NHS resources later on by not having to treat actual Type 2 diabetes ,and it's consequences ?
But i'm not aware of anything (evidence based) that we can do re. slowing/ reversing 'subclinical' Autoimmune Hypothyroidism other than 'suffer in silence for longer' until TSH crawls over 10.
It already took me 4/5 yrs of not managing to cope very well before anyone thought to test thyroid, and TSH had only got to only 6.8 at that point.
I don't want to think how much longer i'd have had to suffer if they'd made me wait till it was 10.
If it was another 5 years , it would have affected My Kids future as well as mine, whereas with Levo, even though not 100% ,i could manage self employment , take pride i'n my work , set a good example, make them do their homework and cook them proper meals, and let them have friends round ,and generally do enough to allow them to keep on the straight and narrow and do well enough at school and have some sort of interesting holiday .
Without Levo being prescribed when it was, they would probably have been sat in front of the TV eating pizza and not doing much homework.. wonder how many o levels they would have got then, and how much trouble they'd have got in cos they were bored and disillusioned.
They've both got decent jobs now and pay tax, and Levo kept me off benefits... so if Mr Leese thinks he's saving NHS or Government resources by writing stuff promoting "waiting longer before diagnosing , and only treating TSH >10 "
This phrase "explain that somatic symptoms are likely to co‐exist with common conditions such as hypothyroidism".
It just shows how inept some researchers are when dealing with a condition that affects many people, lots of whom remain undiagnosed or untreated or under-treated.
I, for one, can tell the difference between levothyroxine and liothyronine.
The first one made me far more unwell with constant palpitations and visits to the A&E ,especially disturbing sleep during the night.
Cardiologist was puzzled and was considering putting an implant into my heart. This was not required because when T3 was added to T4 symptoms resolved. What a difference a 'dose' makes when it suits the patient rather than the summation of a medical professional.
I shall contact the author and explain why his narrow view of hypothyroid patients; the narrow view of treatment; and the narrow view of TSH stopped me being treated for far too long.
Like ME patients concerns dismissed for so long in the PACE trial that cost taxpayers £2.5m, and is now being condemned as psychobabble; like Mesh, sodium valproate and primodos patients all complaining about the arrogant dismissive attitude of Drs.
All this on top of Davina McCalls (not sure of spelling) Menopause issues, where Drs have to choose to take the menopause medical course, .... that 50% of the population WILL go through..
One is grateful that Dr Leese has exposed the naivety of silo thinking; lack of objectivity.. which is to make the patient well, not keep trying to push round patients into square levothyroxine holes.
There have only been approx 14 studies (reporting results in English) comparing Levo vs Levo/Liothyronine and they are all flawed. Any meta analysis is also going to be flawed.
Id rather discuss those flawed studies than discuss Dr Leese’s flawed article. How did it get through peer review?
An excellent idea - wholly support people making direct contact. After all, what other tools do we have to try to explain to them and change their minds?
It got through peer review because doctor reviewers like them have the same misapprehensions, so that it only seems to consolidate what they too believe is the case. UK doctors and medical researchers are way behind in their understanding. I believe it to come from lack of mathematical/analytical ability.
I believe it to come from lack of mathematical/analytical ability.
.. they must be really bad at maths .. i still need pennyannie's help to do "divide"... but even i can understand papers showing that:
TSH o.oo5 with fT4 20 [12-22] can't possibly mean the same thing as
TSH o.oo5 with fT4 84 [12-22]
and that the results for treated people have a different pattern to untreated, Ft4 is higher , fT3 is lower and TSH is relatively lower (sort of) ....along with all manner of other things that simply don't add up if "TSH tells all"
So it's not just their level of maths ability we should be checking .. i think their reading ability is also very suspect.......
"I believe it to come from lack of mathematical/analytical ability."
Couldn't agree more diogenes .....analytical skills are surely the basis of any diagnosis/conclusion. But, from what I've experienced in relation to matters thyroid, first gathering all the scattered "dots", then joining them together in a logical sequence before drawing a conclusion just doesn't happen.
Graham Leese's initial premise is correct - "Replacement therapy with L‐thyroxine is not universally successful at reversing all symptoms for people with hypothyroidism". Then it falls apart! He is a diabetes consultant!
His conclusion that, "TSH assays are the best measure adequacy of thyroid replacement that is currently available" is enough to make a stone weep.
FT3 Prof Leese, FT3!
I suffered from "doctor knows best" for most of my life until one day , barely able to function, it dawned on me that they did not. In desperation, I attempted to sort out the facts. With the invaluable help of the real experts here I eventually worked out what my problem is (a form of RTH) and how to treat it (a supraphysioligical dose of T3).
Why can't medics work this out....the research is out there! Are medics and scientists so far apart in their thinking?
The one endo (a diabetic specialist) that I saw, only twice, completely dismissed the suggestion of RTH, his explanation had more holes in it than my kitchen colander. I was heading for serious trouble he warned. A damaged heart ( later scan showed a perfectly healthy heart) and crumbling bones (no tests but, having tripped and fallen hard more than once, I'm willing to bet they are up to the job!) were his main threats. By that time I had learned otherwise from my reading. He made no attempt to open his mind and consider that I might just have a point. Ah! But I was an elderly woman, clearly frustrated by my ill health which was most likely "wear and tear" and anxiety. Cart before horse comes to mind! Instead, he advised that I should resume LT4 treatment which had possibly kept me just ticking over, but otherwise increasingly unwell for the previous 20 years. Previous to that nobody had an answer.
Until the defences that are raised by the medical profession are breached and egos that glow bright are extinguished nothing will change, and thyroid patients will continue to suffer what is tantemount to medical neglect. And, until the empty medical jargon tossed around in mid air is accompanied by good old fashioned clinical evaluation we are all doomed. We are human beings in all their varying forms, not machines that have rolled off a production line with accompanying instruction manuals....on-line!
I'm only a 75 year old patient who has had to work out for myself why my body was slowly shutting down, I haven't had the benefit of a long medical training....but I got there in the end. Why was I (and TUK) my last hope!!
I'm in awe of the work most medics carry out ( I've seen it within my own family) but I despair at the treatment meted out to thyroid patients and, if we have to depend on flawed understanding like this then we are indeed all doomed to years of misery
Sorry, long rant. My soap box refuses to staying the cupboard!
PS..
Professor Graham Leese is an NHS consultant in Endocrinology and Diabetes. He has diverse research interest, but they are especially focussed on the diabetic foot, diabetic eye disease and Endocrine epidemiology.
At the end of the argument, what matters is appropriate therapy henceforward for optimal living by the patient, however and whatever is needed to bring this about. Healthy people age thyroidally imperceptibly - that is, like everything else in the body, age-related automatic changes occur over time. With patients with no or little thyroid, there is no such automatic adjustment - they have to realise that even if contented now, a sharp eye has to be kept on perceived health, and adjustments made accordingly to regain the best option. That there may be a small statistical possibility of adverse effects is really bye the bye. Virtually everyone with thyroid disease would prefer a best perceived outcome for the rest of their lives, even at the expense of a small hypothetical danger, which might well never occur. The trouble with medicine nowadays is the fear of litigation by the patient if an unexpected problem arises related to the medicine. This is I'm afraid to be laid partly at the door of patients, who cannot be adequately cured, but think that the doctor is omnipotent, and if the treatment doesn't work it's the GP/Endo's fault. We do have to cut doctors some slack, but I don't think this applies to treating the thyroidal condition. The evidence of inferior treatment is there for anyone to see.
For such patients, current guidelines recommend looking for other co‐morbidities including hypoadrenalism, celiac disease, anaemia, hypercalcaemia, sleep apnoea, renal failure and other conditions.
He is also right to say that questioningly.
But it appears he fails to appreciate that many apparent co-morbidities are nothing of the sort. They can be and possibly actually are less obvious, less common, additional symptoms and issues due to thyroid problems.
Doctors love the saying about horses and zebras - which do you expect when you hear hooves stampeding towards you? The standard, trite, answer is obviously horses. But that does depend on the assumption you are not on the plains of Africa at the time.
Having already accepted the horse (hypothyroidism), why positively cast your eyes away and look for zebras, tapirs and other odd-toed ungulates? Sure, don't ignore the possibility there are other such animals but check all the horses.
For such patients, current guidelines recommend looking for other co‐morbidities including hypoadrenalism, celiac disease, anaemia, hypercalcaemia, sleep apnoea, renal failure and other conditions.
.. well it wouldn't be so bad if they actually did that , but i don't see much evidence of it on here... unless patients themselves push for these checks they seem to only get investigated for 'being depressed'
But that does depend on the assumption you are not on the plains of Africa at the time. ....Thanks for this morning's laugh
but check all the horses.
.. not for the first time, i seriously wonder if we wouldn't all have done better if we'd gone to the Vet.....The other day i was behind a nice smart looking van and it said " Equine endocrine and musculoskeletal specialist and physiotherapy "... seriously ,i nearly followed it .
Whilst I endorse your point about actually checking, we have had a few patients who appear to have had reserved seats at the phlebotomy clinic, and multiple bookings at the various imaging and other diagnostic procedure clinics.
Which is a massive waste if the issue does end up being inadequate or poor thyroid treatment. (Though exclusion can be and is a valid and important part of medicine.)
I was scoped, scanned and otherwise examined for various ailments over about 50 years with no firm diagnosis of anything, apart from FM and CFS which never convinced me. Nobody thought to do a thyroid test until I asked for one. Result, hypothyroidism and " this little white pill which you must take for life will make you well again".It didn't but nobody believed it was either the hypo or the levo.
I told one doctor that there must be a reason and that I was going to search for it. Condescending response followed, " oh, don't upset yourself by doing that, just do as we tell you". She forgot that there may also be zebras out there.
As you may know it turned out to be a form of RTH....and at last I have a reasonable quality of life on a self medicated supraphysiolgical dose of T3.
My GP knows this and still panics about suppressed TSH.
Failure to "join up the dots" persists!
I would probably have been deemed one of the Witches of Scotland between the 16th and 18th centuries ...and executed. No-one convicted or executed in Scotland has received an apology or pardon. They were not understood !!
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Is It Better To Take Thyroid In The Morning Or Evening?
