Thyroid Hormone Therapy for Older Adults with Subclinical Hypothyroidism

I was thinking "There disappears your chance of getting treated if you are over 65." Then I remembered, that would only happen if they read the research… :-)

The conclusion is interesting - it is difficult to accept the last paragraph as a fair statement given all the caveats in the paragraph immediately above it (in the full paper).

N Engl J Med. 2017 Apr 3. doi: 10.1056/NEJMoa1603825. [Epub ahead of print]

Thyroid Hormone Therapy for Older Adults with Subclinical Hypothyroidism.

Stott DJ1, Rodondi N1, Kearney PM1, Ford I1, Westendorp RG1, Mooijaart SP1, Sattar N1, Aubert CE1, Aujesky D1, Bauer DC1, Baumgartner C1, Blum MR1, Browne JP1, Byrne S1, Collet TH1, Dekkers OM1, den Elzen WP1, Du Puy RS1, Ellis G1, Feller M1, Floriani C1, Hendry K1, Hurley C1, Jukema JW1, Kean S1, Kelly M1, Krebs D1, Langhorne P1, McCarthy G1, McCarthy V1, McConnachie A1, McDade M1, Messow M1, O'Flynn A1, O'Riordan D1, Poortvliet RK1, Quinn TJ1, Russell A1, Sinnott C1, Smit JW1, Van Dorland HA1, Walsh KA1, Walsh EK1, Watt T1, Wilson R1, Gussekloo J1; TRUST Study Group.

Author information

1 From the Academic Section of Geriatric Medicine, Institute of Cardiovascular and Medical Sciences (D.J.S., K.H., P.L., M. McDade, T.J.Q.), the Robertson Centre for Biostatistics, Institute of Health and Wellbeing (I.F., S.K., A.M., M. Messow, R.W.), and the Institute of Cardiovascular and Medical Sciences (N.S.), University of Glasgow, Glasgow, and Care of the Elderly-Rehabilitation, Monklands Hospital, NHS Lanarkshire, Airdrie (G.E.) - all in the United Kingdom; the Department of General Internal Medicine, Inselspital, Bern University Hospital (N.R., C.E.A., D.A., C.B., M.R.B., M.F., C.F., D.K., H.A.V.D.), and the Institute of Primary Health Care (N.R., M.F.), University of Bern, Bern, and the Service of Endocrinology, Diabetes, and Metabolism, University Hospital of Lausanne, Lausanne (T.-H.C.) - all in Switzerland; the Department of Epidemiology and Public Health (P.M.K., J.P.B., C.H., G.M., A.O., D.O., C.S., K.A.W., E.K.W.), the Pharmaceutical Care Research Group, School of Pharmacy (S.B., M.K., K.A.W.), the School of Nursing and Midwifery (V.M.), and the Department of General Practice (A.R., E.K.W.), University College Cork, and the Health Research Board Clinical Research Facility, Mercy University Hospital (M.K.) - all in Cork, Ireland; the Department of Public Health and Center for Healthy Aging, University of Copenhagen (R.G.J.W.), and the Department of Medical Endocrinology, Copenhagen University Hospital Rigshospitalet (T.W.), Copenhagen, and the Department of Internal Medicine, Copenhagen University Hospital Herlev, Herlev (T.W.) - all in Denmark; the Departments of Gerontology and Geriatrics (S.P.M.), Internal Medicine (O.M.D.), Clinical Epidemiology (O.M.D.), Clinical Chemistry and Laboratory Medicine (W.P.J.E.), Public Health and Primary Care (R.S.D.P., R.K.E.P., J.G.), and Cardiology (J.W.J.), Leiden University Medical Center, and the Institute for Evidence-based Medicine in Old Age (S.P.M.), Leiden, and Radboud University Medical Center, Nijmegen (J.W.A.S.) - all in the Netherlands; and the Departments of Medicine, Epidemiology, and Biostatistics, University of California, San Francisco, San Francisco (D.C.B.).


Background The use of levothyroxine to treat subclinical hypothyroidism is controversial. We aimed to determine whether levothyroxine provided clinical benefits in older persons with this condition.

Methods We conducted a double-blind, randomized, placebo-controlled, parallel-group trial involving 737 adults who were at least 65 years of age and who had persisting subclinical hypothyroidism (thyrotropin level, 4.60 to 19.99 mIU per liter; free thyroxine level within the reference range). A total of 368 patients were assigned to receive levothyroxine (at a starting dose of 50 μg daily, or 25 μg if the body weight was <50 kg or the patient had coronary heart disease), with dose adjustment according to the thyrotropin level; 369 patients were assigned to receive placebo with mock dose adjustment. The two primary outcomes were the change in the Hypothyroid Symptoms score and Tiredness score on a thyroid-related quality-of-life questionnaire at 1 year (range of each scale is 0 to 100, with higher scores indicating more symptoms or tiredness, respectively; minimum clinically important difference, 9 points).

Results The mean age of the patients was 74.4 years, and 396 patients (53.7%) were women. The mean (±SD) thyrotropin level was 6.40±2.01 mIU per liter at baseline; at 1 year, this level had decreased to 5.48 mIU per liter in the placebo group, as compared with 3.63 mIU per liter in the levothyroxine group (P<0.001), at a median dose of 50 μg. We found no differences in the mean change at 1 year in the Hypothyroid Symptoms score (0.2±15.3 in the placebo group and 0.2±14.4 in the levothyroxine group; between-group difference, 0.0; 95% confidence interval [CI], -2.0 to 2.1) or the Tiredness score (3.2±17.7 and 3.8±18.4, respectively; between-group difference, 0.4; 95% CI, -2.1 to 2.9). No beneficial effects of levothyroxine were seen on secondary-outcome measures. There was no significant excess of serious adverse events prespecified as being of special interest.

Conclusions Levothyroxine provided no apparent benefits in older persons with subclinical hypothyroidism. (Funded by European Union FP7 and others; TRUST number, NCT01660126 .).

PMID: 28402245

DOI: 10.1056/NEJMoa1603825

Full paper freely available here:

Suggest you download the PDF.

35 Replies


I have to wonder whether the patients might have felt benefits if the TSH targetted had been 1.0 or lower.

Worryingly, someone's parent had thyroid dose reduced because "TSH is higher in elderly patients".

Quite so. The authors even admit as much!

We cannot exclude the possibility that this more aggressive treatment approach might be beneficial.

i only found out after my mother died that her low thyroid found in hospital should have been treated but was ignored by her GP

I thought that! Would anyone expect a difference between a group of people with mean TSH of 3.63 and another group with a mean of 6.4?

It would be nice to compare them all with a third group whose mean was 1.

Disgusting. It's so sad that so many people have no idea what's going on and are left to wither. And who knows how long these people had such poor thyroid function before they got to an 'average age' of 74. This is the 'doctor knows best' generation.

Yes, and I wonder how many results were false because the patient wanted to 'please' the doctor and not offend him by saying that it wasn't working...

Zephyrbear -very likely the case as that generation still put trust in and look up to Dr's!

I'm that generation....and I bloody don't!!!

liz1952 ha ha ... I'm glad to hear it! But if the 1952 is the give way - you are only just 'borderline' and we all know that doesn't count!

gabkad That is just the word - wither! That is what is ahead for us Hypo's.

And unfortunately helvella, i think, this is precisely the research they will look for, and read and publicise the the final two lines, to justify stopping all thyroid meds at 65...if we get to 65 of course! Whatever chance we have...the people coming up behind us are in for an even worse ride and the dr's become even more narrow minded. And no doubt the next step is to stop companies importing NDT etc from abroad ... already turning shipments back!

I'm not claiming to understand everything they did, in this trial, but that 'caveat' paragraph, did make it sound like they were gearing the 'research' to prove, what they wanted it too? i.e. that over 65's didn't need meds?

And such low and limited doses? And as we know, who really would know what state the thyroids of those people were like, at the time or before the trail, when we know how blinkered a view these 'medics' have anyway? Was that 'symptom' they may have had in the time scale, really a thyroid symptom, or something else - I'd have liked to know what the symptoms were? I did read through and may have missed it. (but as Dr insist all the symptoms we have are not thyroid related? ) Maybe at least some of these people theirs weren't.

I suspect my mother had an overactive thyroid all her life - was never picked up - even though had goitres 14 years ago - was supposedly checked then. She survived to the grand age of 90. But it was TC that killed her. She always had mad salt intake - would pile the salt on....

I have no idea how they think a dose of 25mcg or 50mcg alone would be beneficial.

A degree of sarcasm overcame me:

Well, their TSH levels dropped (a little)! So of course it worked.


shaws 75 mcg is not much better either. Extra T3 helps.

They were doing a review of people who had sub-clinical hypo who aren't usually prescribed until finally diagnosed as hypo - and I assume they don't normally prescribe.

They state:-

"The use of levothyroxine to treat subclinical hypothyroidism is controversial. We aimed to determine whether levothyroxine provided clinical benefits in older persons with this condition. "

These people I think would have had symptoms, but TSH didn't rise enough so they should have had a decent dose of levothyroxine to see if it did relieve symptoms i.e. up to 100 or 150. If still not relieved, then a trial of T4/T3 could have helped. The low trial dose might have even made subjects worse.

They only did a miserable trial probably only looking at the blood results and obviously with such a low dose they couldn't possibly improve the sub-clinical symptoms.

Why did they waste their time?

Both my GP and endo thought 50mcg was a fine dose for me with no heart issues and way above 50kg. A yet there were all those symptoms ....

Before the blood test we took NDT and between 200 and 400mcg whatever made us well. One doctor said we are now on too low a dose nowadays to keep us 'in range'. They adjust our dose according to the TSH and don't take any notice of symptoms being relieved or not.

Hence starting dissicated Thyroid and as if a miracle my body has lapped it up and is giving me my life back. Doctors on here, yes we know that you are here, well done but please take note of our experiences as well as labs. And read research with some consideration to the people and the lives they are trying to live.

Yep shaws is all about a bit of paper! I think it is called covering their a****! 'Tick box' treatment - they could probably train monkeys to do what most GP do theses days.

Most of them do not even look at us never mind 'clinical' assessment.

Before blood tests for thyroid were introduced, when you went to the doctor they held your hand (was it cold, clammy. Pulse was it slow/fast). looked at our tongue - swollen? and any other outward signs the patient had. The patient also told them their symptoms.

Yep shaws - the 'old fashioned' clinical observations - apparently they could tell a lot by our hands, eyes tongues etc...basically by 'looking at us and listening to 'US' when was last time any of us experienced that at our GP's???

Not just reading a blood test - that most don't seem to understand anyway!

One wonders:

Was it truly sub-clinical - no symptoms?

Were the patients just under medicated on levo and so didn't improve?

What were their FT3 levels?

Just seems to suggest that (probabaly) undermedicating people on levo doesn't do a lot for them.

I suspect the big scandal will be that Levo probably causes more harm than good - as by time most people, who are 'lucky' enough to actually get a diagnosis, and get any t4, they are so far down the line, thyroids are damaged beyond repair and so struggle to convert. So get us all off t3 etc, just give t4 and no one will be any wiser....

There has often been crises I believe with levo and there has been evidence which the Endocrine Associations ignore, as well as their patients so doctors follow suit. They turn a blind eye and deaf ears:-

Dr. Lowe: First let me say that what you experienced is fairly common. Many patients react to low-dose T4-replacement as you did— badly —regardless of the brand of T4.

There are two potential sources I know of for people feeling awful when they are on T4-replacement. One source is the extremely low dosage that doctors typically prescribe nowadays. A low dose of T4 can effectively reduce TSH secretion. The lower TSH can in turn lower the thyroid gland’s output of thyroid hormone. At the same time, low-dose T4 may not compensate for the thyroid gland’s reduced output of thyroid hormone. The patient then has too little thyroid hormone to properly regulate the metabolism of most of her body’s tissues. She then ends up with abnormally low metabolism and troubling hypothyroid symptoms. I’ve written about this before on

The second possible reason for your bad reaction to Synthroid is that T4-replacement simply won’t work for you. It doesn’t work for many hypothyroid patients. In a recent study in the United Kingdom, for example, T4-replacement left 50% of patient suffering from hypothyroid symptoms (Saravanan, P., Chau, W.F., Roberts, N., et al.: Psychological well-being in patients on ‘adequate doses of L-thyroxine: results of a large, controlled community-based questionnaire study. Clin. Endocrinol. (Oxf.), 57(5):577-585, 2002.) Unfortunately, through faulty reasoning, these researchers concluded that a much smaller percentage of patients suffered from symptoms despite being on T4-replacement. They are mistaken about the percentage. The evidence is overwhelming that T4-replacement is the lousiest approach to thyroid hormone therapy. I’ve documented the widespread failures of the approach in two critiques:

Another excerpt from same page:

"I did some research on the Internet and came across the FDA site where you can look up a drug to see if it's approved or pending approval. I was stunned when I read that Synthroid was awaiting approval or rather re-approval after so many complaints about its ineffectiveness. I copied some ten pages, took them to my internist, and asked for a different thyroid medicine. He looked me in the eye and told me that the drug was approved— when it was not. He told me he would never prescribe a medication that was not approved. He also told me there was nothing wrong with the drug, although the FDA site contradicts this. In so many words, he called me a liar.

I sat there speechless, with all of my downloaded pages, my proof, in my hands.

Panda321 Joyia j_bee

Hi shaws This is why I get so cross at the 'party line' of 'the vast majority of patients, with HypoT, do well on t4' ....I doubt they do. I know from experience that dr's continue to ignore the fact that t4 does not solve hypo symptoms, only increases them and makes them worse, whilst further damaged is done to the thyroid. Vicious circle.

How many of us will be still here to claim any pensions....?? Oh right...that is what all this is about!

I think they may treat us robots, that if one thing goes wrong the exact same identical thing will fix it automatically.

And since when did that ever happen in medicine! Mad isn't it!

An absolutely pointless experiment. It proves nothing.

Why oh why can't somebody, somewhere do a trial that proves the bleedin' obvious, which is that for 10%, or probably more, of those with Primary Hypothyroidism, levothyroxine may very well give PERFECT results according to the stupid ways they judge it, but is entirely the WRONG MEDICINE as it fails to minimise the rotten feelings we continue to get?

This is especially so for every one of us (maybe a few exceptions?) who no longer has any thyroid gland at all.

As there exists the possibility that I may be put onto a placebo, perhaps even levothyroxine, if I were to volunteer, there's no way I could ever be persuaded to take part. I could not bear going through that hell on earth again.

But, as said elsewhere, NDT should not need any trials to prove its benefits. It was the only "drug" available for many decades and I have failed to find any bad reports from that period, except where doctors have accidentally overdosed their patients.


Panda321 maybe because now doctors do not know how to interpret results and drug companies would not make any money!

Adding to this post another abstract about subclinical hypothyroidism.

I note this sentence in particular: The risk increases with increasing levels of thyroid stimulating hormone, and is particularly high in patients with TSH levels ≥10.0 mu/L.

Doesn't that suggest that leaving treatment until TSH reaches 10 exposes patients to a particularly high risk of coronary heart disease, heart failure and cerebrovascular disease? So why not treat before it reaches that level of risk? And if (as appears to be suggested) only coronary heart disease risk is reduced by levothyroxine, is there another thyroid hormone that could be tried? Just to see if it helps with the heart failure and cerebrovascular disease? Maybe something with one of the iodine atoms removed?

Post Reprod Health. 2017 Jan 1:2053369117705058. doi: 10.1177/2053369117705058. [Epub ahead of print]

Subclinical hypothyroidism: Should we treat?

Redford C1, Vaidya B1,2.

Author information

1 Department of Endocrinology, Royal Devon & Exeter Hospital Foundation Trust, Exeter, UK.

2 Department of Endocrinology, University of Exeter Medical School, Exeter, UK.


Subclinical hypothyroidism (also known as compensated hypothyroidism or mild hypothyroidism) is a condition associated with a raised serum concentration of thyroid stimulating hormone (TSH) but a normal serum free thyroxine (FT4). It is common, affecting about 10% of women above the age of 55 years. Autoimmunity is the commonest cause of subclinical hypothyroidism. About 2.5% of patients with subclinical hypothyroidism progress to clinically overt hypothyroidism each year; the rate of progression is higher in patients with thyroid autoantibodies and higher thyroid stimulating hormone levels. However, thyroid function normalises spontaneously in up to 40% cases. Only a small minority of patients with subclinical hypothyroidism have symptoms, and the evidence to support that levothyroxine ameliorate the symptoms in these patients is weak. Subclinical hypothyroidism in younger patients (<65 years) is associated with an increased risk of coronary heart disease, heart failure and cerebrovascular disease. The risk increases with increasing levels of thyroid stimulating hormone, and is particularly high in patients with TSH levels ≥10.0 mu/L. There is lack of evidence from randomised controlled trials as to whether levothyroxine treatment can prevent these risks, although a large observational study of the UK general practice research database has shown that levothyroxine may reduce the risk of coronary heart disease in younger patients (<70 years). Therefore, the decision whether to treat or not to treat subclinical hypothyroidism should be made after careful consideration of the patient's age, the presence of symptoms, the presence of thyroid antibodies and other risk factors such as cardiovascular disease.


Hypothyroidism; levothyroxine; thyroid; thyroid peroxidase antibodies; thyroid stimulating hormone

PMID: 28406057

DOI: 10.1177/2053369117705058

Like my son says...'Population control'!

I am not as clever as some here with understanding results but I managed to persuade my Doctor to increase from 100 to 125 levo recently although my blood test result was, according to him, satisfactory which I disagreed with. I had been reduced by another Doctor a year ago and I have been having certain symptoms. Aged 76 makes me wary as to dosages on offer but fortunately I am still corpus mentis! On the other hand I could receive all sorts of medications without any bother due to my age but at this moment in time always refuse preferring to go down the natural route where possible. What happens when we do not have the strength to fight I don't know but in the meantime grrrrrr.

That is the problem Joyia more often than not Hypo's don't have the strength to fight, that is why they get away with so much!

The long and short of it, is that the NHS has over prioritised cancer due to political pressure for many years. If they refuse a very expensive drug and immeidate campaign is started to embarrass them.

With relentless real term cuts from government combined with constant pressure from medics for wage rises out all of all comparison with the situation the rest of of face at work.

I short cancer patients get five star treatment even though it produces quite short extensioins in life span and they cut corners everywhere else. They describe living one or two years as 'surviving cancer' which sounds good but is not the truth.

The NHS director has recentely made this policy public and much more severe.

It suddenly occurred to me to wonder who paid for this research. I went to the NEJM link :

and noticed there was some supplementary material available.

The Protocol document :

makes it clear this was an NHS study. So it is unlikely it will be ignored.

There is also a Supplementary Appendix :

and Disclosures of Conflicts of Interest Forms for each of the authors :

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