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Letters

Giving thyroid hormones to clinically hypothyroid but biochemically euthyroid patients

BMJ 1997; 315 doi: https://doi.org/10.1136/bmj.315.7111.813 (Published 27 September 1997) Cite this as: BMJ 1997;315:813

Supporting authors' views would be unwise

  1. G J Beckett, Senior lecturer, university department of clinical biochemistrya,
  2. A D Toft, President, British Thyroid Associationa
  1. a a Royal Infirmary NHS Trust, Edinburgh EH3 9YW
  2. b University Clinical Departments at Aintree, Fazakerley Hospital, Liverpool L9 7AL
  3. c ME Association, Stanford le Hope, Essex SS17 0HA

    Editor—Gordon R B Skinner and colleagues advocated that a diagnosis of hypothyroidism in patients with suggestive symptoms should not be excluded on the basis of “normal” hormone concentrations.1 Furthermore, they proposed that an incremental trial of thyroxine for three months is not unreasonable in these patients.

    The consensus is that patients with subclinical hypothyroidism in whom serum thyroid stimulating hormone concentrations are consistently above the usually quoted upper limit of the reference range of 5 mU/l should be treated with thyroxine; this is particularly so if the patients have antibodies to thyroid peroxidase, a history of treatment of thyrotoxicosis, or a goitre.2 Two double blind trials in patients with subclinical hypothyroidism have shown that, after treatment with thyroxine, target organ function may improve and there may be a greater sense of wellbeing in some patients, though by no means all.3 The most cogent reason for treatment, however, is the knowledge that a considerable proportion of patients will develop overt hypothyroidism in future years,4 and it makes sense for the disorder to be “nipped in the bud” rather than risk loss to follow up.

    Because autoimmune thyroid disease is common, it is possible that reference ranges were calculated from populations containing patients with a degree of thyroid failure and that the true upper limit for normal serum thyroid stimulating hormone concentrations may be slightly lower than 5 mU/l. There are, however, no studies of the effect of thyroxine in patients with non-specific symptoms and hormone concentrations below 5 mU/l, and, until there is objective evidence of benefit—which from clinical experience is unlikely—it would be unwise to support Skinner and colleagues' views. It is also likely that many patients would gain a placebo effect and, in the long term, “feel better” only with a dose of thyroxine that suppresses serum thyroid stimulating hormone5—a situation that may be associated with the development of osteoporosis or atrial fibrillation.

    References

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    Distinguishing hypothyroid symptoms from common non-specific complaints is difficult

    1. Gareth Williams, Professor of medicine (diabetes and endocrinology)b
    1. a a Royal Infirmary NHS Trust, Edinburgh EH3 9YW
    2. b University Clinical Departments at Aintree, Fazakerley Hospital, Liverpool L9 7AL
    3. c ME Association, Stanford le Hope, Essex SS17 0HA

      Editor—Gordon R B Skinner and colleagues propose the apparently empirical treatment of suspected hypothyroidism in patients in whom results of thyroid function tests that fall within the normal range1. Nobody would argue with the assertion that the symptomatology of hypothyroidism can be non-specific, that it can be an easy diagnosis to miss, or that the rewards of replacing thyroxine in patients with proved hypothyroidism can be spectacular.

      There are considerable risks, however, in the inappropriate prescription of thyroid hormone replacement to patients who do not warrant it. This has been a particular problem in the management of obesity, and correspondence with our local group of the ME Association indicates that thyroid hormone treatment is also being promoted for chronic fatigue. For this condition, certain medical practitioners are advocating the use of desiccated thyroid extract in preference to the pure thyroid hormones that are recommended in the British National Formulary, presumably to add an element of mystique to this unproved treatment.

      Given the difficulty of distinguishing hypothyroid symptoms from common non-specific complaints such as tiredness, lack of energy, and difficulty in concentrating, Skinner and colleagues need to reassure us that their “established criteria” stand up to objective scrutiny. I agree with them that a formal clinical trial might be justified but suggest that this would be of little use unless an objective physiological outcome can be measured. In the meantime, giving thyroid hormones to patients who are biochemically euthyroid must remain dubious and potentially dangerous on both scientific and medicolegal criteria.

      References

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      Long term treatment is being used

      1. Charles Shepherd, Medical directorc
      1. a a Royal Infirmary NHS Trust, Edinburgh EH3 9YW
      2. b University Clinical Departments at Aintree, Fazakerley Hospital, Liverpool L9 7AL
      3. c ME Association, Stanford le Hope, Essex SS17 0HA

        Editor—During the past six months I have become aware of an increasing number of patients with normal results of thyroid function tests who are being treated with a daily dose of up to 100 μg thyroxine—mainly as a result of publicity being given in the lay media1 to a hypothesis put forward by Gordon R B Skinner and colleagues.2 These biochemically euthyroid patients invariably have several symptoms that are compatible with a clinical diagnosis of hypothyroidism, but many of them also have agreed diagnostic criteria for the chronic fatigue syndrome, a condition that does involve dysfunction of the hypothalamic-pituitary axis but not hypothyroidism.

        Although a short trial of low dose thyroxine may be relatively safe in these circumstances, my experience is that almost all of these patients are continuing to be prescribed thyroxine. In some cases the dose is being progressively increased. Serious cardiovascular side effects cannot be ruled out in patients with the chronic fatigue syndrome with undetected abnormalities in cardiovascular function,3 and there is a further danger of an addisonian crisis being precipitated in those who have hypocortisolaemia. Long term unwarranted use of thyroxine will increase the likelihood of osteoporosis and lead to a risk of permanent disruption to the normal feedback mechanisms affecting the release of thyroid stimulating hormone.

        In the absence of any reputable evidence to support the hypothesis that clinical hypothyroidism can exist in biochemically euthyroid patients, I believe that this entirely speculative use of thyroxine should be restricted to a carefully supervised research project with normal ethical approval. In the meantime I have sent all my information to the Department of Health in an attempt to persuade the chief medical officer to issue clear guidelines on giving thyroxine to patients with normal results of thyroid function tests. Doctors who decide to prescribe thyroxine for such an unlicensed purpose may well find themselves involved in litigation should a mishap subsequently occur.

        References

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