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Third of patients on levothyroxine have no reason to take the drug, claim researchers

UK researchers claim that up to a third of patients in primary care taking levothyroxine could be prescribed the drugs ‘without an accepted indication’.

The Cardiff University team found many patients were prescribed levothyroxine at TSH levels below 10.0 mIU/L, but with thyroxine (T4) levels in the reference range and no hypothyroidism symptoms.

The researchers looked at UK Clinical Practice Research Datalink records for over 50,000 patients prescribed levothyroxine between 2001 and 2009, and found there had been a 30% increase in the likelihood of treatment being started at TSH levels below 10.0 mIU/L – the usual cut-off for diagnosing overt hypothyroidism – over this time.

Among the 67% of patients who also had free T4 data available, around 30% had levothyroxine prescribed at a TSH level below 10.0 mIU/L and with T4 levels in the reference range, indicating subclinical hypothyroidism, despite having no classic hypothyroidism symptoms or cardiovascular risk factors.

The researchers said their results showed an increasing trend towards prescribing levothyroxine in patients with subclinical hypothyroidism, where the evidence base is weak and the risks might outweigh the benefits.

Overall, the researchers found older people were the most likely to be started on levothyroxine at borderline TSH levels of between 4.0 and 10.0 mIU/L, even with normal T4 levels, which they said was concerning because ‘treatment of subclinical hypothyroidism in individuals older than 70 years has less cardiovascular benefit than that in younger persons, and overtreatment in older patients may cause net harm’.

Even marginal overtreatment with levothyroxine can lead to low TSH levels, putting elderly patients at risk of osteoporotic fractures and atrial fibrillation, the researchers noted.

The team concluded in JAMA Internal Medicine this month: ‘In the United Kingdom, 1.6 million individuals are on long-term levothyroxine regimens, most of whom have been prescribed it for primary hypothyroidism. If current practice continues, up to 30% of persons receiving levothyroxine may have been prescribed it without an accepted indication and with the potential for net harm if they develop even a low thyrotropin level.’

Professor Simon Pearce, professor of endocrinology at Newcastle University, commented: ‘In contrast to the lack of prognostic benefits of levothyroxine therapy for subclinical hypothyroidism, there is known to be an excess of fractures in those taking levothyroxine who have a suppressed TSH (<0.05 mU/l), and in patients over 70 years taking larger doses of levothyroxine (>100 mcg daily).

‘There is also a small excess risk of cardiac events and atrial fibrillation in those with a fully suppressed TSH (<0.05 mU/l).’

He added: ‘The take-home message should be that many older patients without symptoms of subclinical hypothyroidism would have been safer living with a serum TSH in the 4 to 10mU/l range than being over-treated to a suppressed TSH level.’

Professor Pearce said optimal practice would be to simply monitor these untreated patients once or twice yearly for the development of symptoms and for progression to overt hypothyroidism, although the risk of progression is small, at less than 5% per year.

He said: ‘If levothyroxine treatment is started, the aims should be to alleviate symptoms (if present) and to keep the TSH in the reference interval. Nevertheless, and in contrast to what is generally believed, there is no hard evidence to show that patients who are slightly over-treated with levothyroxine as judged by a serum TSH in the 0.1-0.4mU/l range have any untoward outcomes.’

Readers' comments (14)

  • This has been recommended by an ENDOCRINOLOGIST for some of my patients-which rather puts me in a tricky position.

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  • I have several patients like this. All started by endocrinologists or psychiatrists in the private sector.

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  • Most Western countries don't set a ridiculous cutoff point of 10 which makes British thyroid guidelines the laughing stock of the international medical world.

    Other countries are aware of the fact that: "reference ranges were derived from cross-sectional studies of populations uncorrected for any underlying or occult disease '
    http://jcem.endojournals.org/content/90/9/5483.full.pdf

    Other countries are aware of the risks to patients of NOT treating patients suffering with hypothyroidism whereas the UK endocrine establishment ignores the deleterious effects of untreated hypothyroidism.

    Doctors in other countries are capable of recognising and treating hypothyroid symptoms when they see them. Whereas the UK endocrine establishment would inexplicably rather treat these symptoms with orlistat, statins, SSRIs, wigs, movicol, CBT, inappropriate referrals etc.

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  • Firstly, I had atrial fibrilliation constantly for many years UNTIL I was put on thyroxine a year ago.

    Secondly a TSH of 10+ only indicates PRIMARY hypothyroidism. Secondary hypothyroidism is not and cannot be diagnosed using TSH alone.

    Thirdly. Patients are not being put on thyroxine because they don't have symptoms. Doctors are prescribing it to patients who exhibit often blatantly overt symptoms but whose TSH doesn't reach the giddy heights of 10 in an attempt to help their patients.

    TSH is a pointless test, but it's cheap. The test that is required is Free T3. This is the hormone that the body needs and this is the hormone that needs measuring.

    Fourthly. ME/CFS were invented after the introduction of the TSH test to get rid of all those patients who were no longer being treated. I know - I've been ill for 37 years. Last year I took matters in to my own hands after a GP grudgingly admitted my thyroid as "slightly underactive". I was prescribed thyroxine to shut me up.

    Fifthly - thryoid hormones are only part of the picture. Other factors need to be optimised before thyroid hormones work effectively. These include, but are not limited to, Vit D, Vit B12, iron, folate, ferritin and adrenal function.

    The NHS only acknowledges adrenal failure. If your adrenal tests come back only one point above the cut off point for failure you are pronounced normal. Treating the adrenals appropriately in many cases either increases the effectiveness of thyroid meds or reduces the need for them.

    There is no disclosure that I can see on who funded this study. It is important to know that if it is to have any credibility.

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  • This study can have no credibility since a large part of the data was collected before the current guidelines came into force in 2006. A more useful study would have been to identify how may patients experienced severe thyroid illness long before they reached a TSH of 10mlU/L

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  • Many diagnostic tests are known to be imperfect. In general, over time, efforts are made to improve them. One relevant (though seemingly fairly rare) example is that macro-TSH can cause elevation of TSH results. Test manufacturers have tried to isolate the result from such interference. This very process of improvement to the tests means that, over periods of years, results will change.

    https://www.jstage.jst.go.jp/article/endocrj/56/3/56_K08E-361/_article

    Against that background, and the fairly modest reduction of the TSH level at initiation of therapy (from 8.7 to 7.9 mIU/L), how much of the reported change comes from improvement to the actual tests, rather than in the actual hypothyroidism of the patients?

    Further, if initiation of levothyroxine therapy is inappropriate (as implied), what action should be taken? It is all too easy to take the inference that there should be none. It seems to be rare that any other possibilities are even considered, so what else should the patient expect?

    I declare an interest. Diagnosed after a series of steadily rising TSH results over a couple of years or so. With a TSH just over 5. And feeling very much better in so many ways on 100 micrograms of levothyroxine and last TSH at 1.6.

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  • Treat the person not the lab results.
    Secondary hypothyroidism is grossly under-diagnosed in the UK.
    But treating it can get you in trouble with the GMC...
    so only do it covertly.

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  • "But treating it can get you in trouble with the GMC... "

    Patients do NOT report a doctor to the GMC for treating their thyroid symptoms. It is doctors who report other doctors... that is where the problem lies.

    It is also nonsense that a suppressed TSH is 'dangerous' or affects bone mineral density. Where is the evidence?

    J Affect Disord. 2012 Jan;136(1-2):e89-94. doi: 10.1016/j.jad.2011.06.011. Epub 2011 Jul 14.
    Long-term treatment with supraphysiological doses of thyroid hormone in affective disorders - effects on bone mineral density.
    Ricken R, Bermpohl F, Schlattmann P, Bschor T, Adli M, Mönter N, Bauer M.
    http://www.ncbi.nlm.nih.gov/pubmed/21757236

    Are biochemical tests of thyroid function of any value in monitoring patients receiving thyroxine replacement?
    W D Fraser, E M Biggart, D S O'Reilly, H W Gray, J H McKillop, and J A Thomson http://www.ncbi.nlm.nih.gov/pubmed/21757236

    Thyroid hormone replacement: an iatrogenic problem.O'Reilly DS.
    Source Department of Clinical Biochemistry, Royal Infirmary, Glasgow, UK. Denis.O'Reilly@ggc.scot.nhs.uk
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1341585/

    A TSH test will also NOT detect Hashimoto's, or patients who are unable to convert the inactive prohormone thyroxine (T4) into the active hormone triiodothyronine (T3) at a peripheral cellular level in the BODY and FREE T3 Deficiency IN THE BODY (not the thyroid GLAND) or Low Free T3 Syndrome which requires the hormone Liothyronine (T3).

    Doctors should be aware that the lack of T3 in the body are often misdiagnosed as psychiatric/mental health disorders. If the brain is lacking T3, the patient will have concentration problems,personality changes, tearfulness, depression, brain fog, increased allergies, hair loss, dry skin and countless other symptoms including increased sweating and muscle weakness. These patients are normally prescribed many different medication to treat each symptom when what they really need is the appropriate thyroid hormone, mainly Liothyronine (T3) at doses MUCH higher than recommended in the BNF, or BOTH thyroxine and liothyronine. When taking ANY form of T3, the TSH will automatically be suppressed.

    Dr Utiger states it in his 1965 research paper the TSH HAS to be suppressed when taking T3 to get results.

    What doctors really want to see is for results to be nicely within the test result confidence interval, but they take little note of presenting symptoms and signs.

    When a hypothyroid patient (whose circulating pool of TSH is too low) starts taking exogenous Thyroid Hormone (TH), a negative feedback system reduces the pituitary gland's output of TSH. This decreases the thyroid gland's output of endogenous TH and despite the patient's exogenous TH’s contribution to their total circulating thyroid pool, that pool does not increase until the TSH is suppressed and the thyroid gland is contributing no more thyroid hormone to the total circulating pool. At that point, adding more exogenous TH will finally increase the circulating pool of thyroid hormone. The increase must occur for thyroid hormone therapy to be effective. The patient's suppressed TSH, then, does NOT indicate that the patient is over-treated with TH; instead, it indicates that the patient's low total thyroid hormone pool will finally rise to potentially adequate levels.

    The ‘Warmingham Hypothesis’ is clear: In general, if doctors deny their patient more exogenous TH because their TSH level is suppressed, they are denying the patient sufficient thyroid hormone to increase the circulating pool of the hormone to a level adequate for maintaining normal TH-driven CELLULAR metabolic processes. But if a doctor continues to increase the patient's TH dosage, based on relevant measures of physiological function, such as the basal temperature, then the patient's health will be properly served despite their suppressed TSH level. This hypothesis is of supreme importance to the proper treatment and health and well-being of patients suffering hypothyroid symptoms and should be taken into consideration, but unfortunately, and to the detriment of patients continuing to suffer symptoms, neither the Royal College of Physicians Teaching Curriculum or the General Medical Council Endocrine Curriculum take this into account. This is HARMING patients.

    1. Warmingham, P.: Effect of exogenous thyroid hormone intake on the interpretation of serum TSH test results. Thyroid Science, 5(7)1-6, 201
    http://www.thyroidscience.com/hypotheses/warmingham.2010/warmingham.intro.7.2010.htm

    2. Igoe, D., Duffy, M.J., and McKenna, T.J.: TSH as an index of L-thyroxine replacement and suppression therapy. Ir. J. Med. Sci., 161(12):684-686, 1992

    3. "Radioimmunoassay of Human Plasma Thyrotropin”, published in the Journal of Clinical Investigation in 1965 The publication came from http://www.jci.org/articles/view/105234 / http://www.jci.org/articles/view/105234/pdf : The paper even mentions about a patient having 500mcg of T3 and the plasma HTSH levels halved within 4 hours and a maximum reduction within 24 hours. Pages 1284-5 are the outcome and summary.

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  • I agree with you in your clinical presentation.
    But just to qualify, the statistics shows that the GMC does not respond to patient complaints, but always to PCT and such, and sometimes to groups of doctors.

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  • Dear Caroline Price,

    Over a year ago my hair started falling out. I've lost 50% on my hair. A few months later my eyelashes and eyebrows started to fall out. It's left me devastated. I used to be a confident person..that went. During this time my TSH went from 1.14 to 5.09. It's never been that high. The symptoms got worse; sleeping 10 hours a night but still tired, going from being slim to putting on half a stone every week. Having to starve myself. Feeling cold and having anaemia. Hoarse voice. Feeling of a lump in my throat. Swelling where the thyroid is. Puffy eyes. Depression. Anxiety. Mood swings. I nearly got sectioned. Migranes. Eczema. Spots. Constipation. The list goes on. I could no longer work, and moved back home so my parents could look after me.

    Had a TPO (antibodies) test that came back positive.

    My GP didn't put me on a trial of thyroxine. The GPs who are putting patients on thyroxine when they have symptoms and have a TSH under 10 are doing the RIGHT thing. We should be encouraging these GPs. This article discourages them.

    After a sucide attempt I got my thyroid medication, still not from my GP, and so far my weight is stable, my mental health is getting a bit better. It's early days.

    We should encourage GPs to treat patients who have hypothyroid symptoms when there TSH is under 10.

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