Thyroxine treatment in patients with symptoms of hypothyroidism but thyroid function tests within the reference range: randomised double blind placebo controlled crossover trial
Open accessAbstract
Objectives: To determine whether thyroxine treatment is effective in patients with symptoms of hypothyroidism but with thyroid function tests within the reference range, and to investigate the effect of thyroxine treatment on psychological and physical wellbeing in healthy participants. Design: Randomised double blind placebo controlled crossover trial. Setting: Outpatient clinic in a general hospital. Participants: 25 patients with symptoms of hypothyroidism who had thyroid function tests within the reference range, and 19 controls. Methods: Participants were given thyroxine 100 µg or placebo to take once a day for 12 weeks. Washout period was six weeks. They were then given the other to take once a day for 12 weeks. All participants were assessed physiologically and psychologically at baseline and on completion of each phase. Main outcome measures: Thyroid function tests, measures of cognitive function and of psychological and physical wellbeing. Results: 22 patients and 19 healthy controls completed the study. At baseline, patients' scores on 9 out of 15 psychological measures were impaired when compared with controls. Patients showed a significantly greater response to placebo than controls in 3 out of 15 psychological measures. Healthy participants had significantly lower scores for vitality when taking thyroxine compared to placebo (mean (SD) 60 (17) v 73 (16), P<0.01). However, patients' scores from psychological tests when taking thyroxine were no different from those when taking placebo except for a poorer performance on one visual reproduction test when taking thyroxine. Serum concentrations of free thyroxine increased and those of thyroid stimulating hormone decreased in patients and controls while they were taking thyroxine, confirming compliance with treatment. Although serum concentrations of free triiodothyronine increased in patients and controls taking thyroxine, the difference between the response to placebo and to thyroxine was significant only in the controls. Conclusions: Thyroxine was no more effective than placebo in improving cognitive function and psychological wellbeing in patients with symptoms of hypothyroidism but thyroid function tests within the reference range. Thyroxine did not improve cognitive function and psychological wellbeing in healthy participants. What is already known on this topic: Recent anecdotal accounts suggest that patients with symptoms of hypothyroidism but who are biochemically euthyroid may benefit from thyroxine treatment No controlled trials in this area have been reported What this study adds: This study suggests that thyroxine is no more effective than placebo in improving psychological and physical wellbeing in patients who show symptoms of being clinically hypothyroid but whose thyroid function tests are within the reference range Thyroxine replacement did not improve psychological and physical wellbeing in healthy participants
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Symptoms consistent with hypothyroidism in euthyroid individuals do not respond to LT4 and should not be treated with LT4.
“It seems clear that symptoms consistent with hypothyroidism in euthyroid individuals do not respond to (nor should they be treated with) LT4.”
From Pharmacodynamic and Therapeutic Actions of Levothyroxine (2021) · cites this paper as [88]
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- Authors
- Pollock, M. A., Sturrock, A., Marshall, K., Davidson, K. M., Kelly, C. J. G., McMahon, A. D., & McLaren, E. H.
- Affiliations
- Stobhill Hospital (GB)
- Gartnavel General Hospital (GB)
- University of Glasgow (GB)
- Corresponding author
- Pollock, M Anne
- Venue
- BMJ
- Publisher
- BMJ
- Published
- 2001-10-20
- Volume
- 323
- Issue
- 7318
- Pages
- 891-895
- ISSN
- 0007-1447 (ISSN-L)
- 0959-8138
- 1468-5833
- PMC
- PMC58535
- OpenAlex
- W2087859267
- Cited by
- 98
- References
- 11
- Citations by year
- 2025: 3 · 2024: 1 · 2023: 1 · 2022: 3 · 2021: 7 · 2020: 4 · 2019: 11 · 2018: 6 · 2017: 1 · 2016: 5 · 2015: 2 · 2014: 5 · 2013: 3 · 2012: 4
- FWCI
- 3.91
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- www.bmj.com/company/legal-information/terms-conditions/legal-information/tdm-licencepolicy (tdm)
- Locations
- BMJ (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
- Keywords
- thyroxine, hypothyroidism symptoms, euthyroid patients, placebo response, cognitive function, psychological well-being, physical well-being, vitality, free triiodothyronine, thyroid-stimulating hormone, free thyroxine, medication adherence, healthy volunteers, crossover trial
- MeSH terms
- Antibodies, Cholesterol, Double-Blind Method, Ferritins, Humans, Hypothyroidism, Iodide Peroxidase, Prolactin, Psychological Tests, Thyroid Function Tests, Thyroid Gland, Thyrotropin, Thyrotropin-Releasing Hormone, Thyroxine, Treatment Failure, Cross-Over Studies
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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