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Management of primary hypothyroidism: statement by the British Thyroid Association Executive Committee

Open access
Okosieme, Onyebuchi, Gilbert, Jackie, Abraham, Prakash, Boelaert, Kristien, Dayan, Colin, Gurnell, Mark, Leese, Graham, McCabe, Christopher +4 more·2016·Clinical Endocrinology
DOI 10.1111/cen.12824
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Abstract

Summary: The management of primary hypothyroidism with levothyroxine (L‐T4) is simple, effective and safe, and most patients report improved well‐being on initiation of treatment. However, a proportion of individuals continue to suffer with symptoms despite achieving adequate biochemical correction. The management of such individuals has been the subject of controversy and of considerable public interest. The American Thyroid Association (ATA) and the European Thyroid Association (ETA) have recently published guidelines on the diagnosis and management of hypothyroidism. These guidelines have been based on extensive reviews of the medical literature and include sections on the role of combination therapy with L‐T4 and liothyronine (L‐T3) in individuals who are persistently dissatisfied with L‐T4 therapy. This position statement by the British Thyroid Association (BTA) summarises the key points in these guidelines and makes recommendations on the management of primary hypothyroidism based on the current literature, review of the published positions of the ETA and ATA, and in line with best principles of good medical practice. The statement is endorsed by the Association of Clinical Biochemistry, (ACB), British Thyroid Foundation, (BTF), Royal College of Physicians (RCP) and Society for Endocrinology (SFE).

Integrity signals

Registry

Crossref · 10.1111/cen.12824

Cites

29 of 29 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 16 cited sources checked · 0 supported · 0 flagged

  • Findingnone given

    Short-term outcome data in hypothyroid patients suggest that thrice-daily synthetic L-T3 may improve parameters such as weight and lipids.

    “Although short-term outcome data in hypothyroid patients suggest that thrice daily synthetic L-T3 may be associated with beneficial effects on parameters such as weight and lipids, longer term controlled clinical trials using a longer acting form of L-T3 are needed, before considering the endorsement of synthetic L-T3 therapy for routine clinical use”
    Quote in the paperSubstantial claim
  • Findingcitation

    In older people, higher serum TSH and lower free T4 within the euthyroid range are associated with a lower risk of multiple adverse events, including mortality.

    “recent evidence suggests that in older people, higher serum TSH and lower free T4 concentrations within the euthyroid range are associated with lower risk of multiple adverse events including mortality.18”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [18] source

      Not checked in the free run.

  • Findingnone given

    Data are lacking on the sensitivity and specificity of established instruments for measuring hypothyroid symptoms in everyday clinical practice.

    “Of the established instruments used to measure hypothyroid symptoms, data are lacking regarding their sensitivity and specificity in the 'everyday' clinical setting to recommend their routine clinical use.”
    Quote in the paperNot a substantial claim
  • Findingcitation

    Randomized controlled trials of thyroid hormone treatment for subclinical hypothyroidism have given inconsistent evidence of benefit.

    “The evidence for benefit in randomized controlled trials of thyroid hormone treatment in subclinical hypothyroidism is inconsistent and further studies are needed.3,15”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [3] source

      Not checked in the free run.

    • cites [15] source

      Not checked in the free run.

  • Findingcitation

    Epidemiological studies have linked subclinical hypothyroidism to coronary heart disease in people younger than 65 years or with TSH above 10 mU/l.

    “Although epidemiological studies have shown an association between subclinical hypothyroidism and coronary heart disease in younger people (<65 years) 16 or those with high TSH (>10 mU/l), 17”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [16] source

      Not checked in the free run.

    • cites [17] source

      Not checked in the free run.

  • Classified as probably not a substantial claim. 25
  • May combine two claims. 11

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingcitation

    In the United States, 3.6% of endocrinologists report that they would prescribe L-T3 to hypothyroid patients with persistent symptoms and normal biochemical thyroid status.

    “In the United States, 3Á6% of endocrinologists report that they would give L-T3 to patients with hypothyroidism with persistent symptoms and normal biochemical thyroid status.24”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingnone given

    The clinical significance of discordance between pituitary and other tissue thyroid status is unknown.

    “The clinical significance of this is not known”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    Tissue biomarkers of thyroid hormone action are not sensitive, specific, readily available, or standardized.

    “Tissue biomarkers of thyroid hormone action are not recommended for routine clinical use, outside of the research setting, as these parameters are not sensitive, specific, readily available or standardized 2/+00”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Findingnone given

    In some specific instances, the thyroid status of the pituitary gland, as reflected by serum TSH, appears discordant with the thyroid status of other tissues as indicated by biomarkers.

    “There are specific instances in which there appears to be discordance between the thyroid status of the pituitary gland, as reflected by the serum TSH, and the thyroid status of other tissues as indicated by various biomarkers.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingcitation

    Up to one-quarter of healthy people may have symptoms such as lethargy and weight gain that are often labelled hypothyroid.

    “It is recognized that up to one-quarter of the healthy normal population may have 'hypothyroid' symptoms such as lethargy and weight gain.14”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [14] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingcitation

    Subclinical hypothyroidism is common in community studies of healthy people, found in 5-10% of the population, more often in women, and increases with age.

    “Subclinical hypothyroidism is common in studies of healthy people in the community and is found in 5-10% of the population, being more common in women and increasing with age.9”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [9]

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Wider consultations were held with representatives of the SFE, ACB, RCP, and the British Thyroid Foundation.

    “Wider consultations were then held with representatives of the SFE, ACB and RCP, as well as with the BTF, the patient support charity for thyroid disorders.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    A systematic PubMed search was performed, and additional references were found through the reference lists of individual articles.

    “Furthermore, a systematic search of PubMed was undertaken, and additional references were sourced through references of individual articles.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    No external funding was received from the BTA or individual members for developing this statement.

    “No external funding was received, either by the BTA or by individual members, for the development of this statement, and all conflict of interests are declared.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    All conflicts of interest are declared.

    “No external funding was received, either by the BTA or by individual members, for the development of this statement, and all conflict of interests are declared.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationnone given

    The case for narrowing the serum TSH reference range is not convincing and would not justify the resulting large increase in healthy people needing investigation.

    “The evidence in favour of narrowing the serum TSH reference range is not convincing and cannot justify the large increase in the number of healthy people that would require investigation (1/++0).”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisenone given

    A key feature of both the ETA and ATA guidelines is recognition of the subset of L-T4-treated patients with persistent symptoms despite adequate biochemical thyroid status.

    “A key feature of both guidelines is the acknowledgement of the subset of L-T4-treated patients who suffer persistent symptoms despite adequate biochemical thyroid status.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    The current ETA and ATA guidelines can be viewed as adding to, rather than departing from, the 2011 RCP position.

    “Thus, the current ETA and ATA guidelines can be seen as an addition rather than a departure from this position.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductreasoning

    The document was finalized after feedback from each body and agreement from all authors.

    “The document was finalized following feedback from each of these bodies, and agreement from all authors was reached on the final statement.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    The statement was developed after consultation within the BTA and with relevant stakeholder groups.

    “The statement has been developed following consultation within the BTA and with relevant stakeholder groups.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Both the ETA and ATA guidelines strongly recommend L-T4 as the therapy of choice and do not support routine L-T4/L-T3 combination therapy because of insufficient controlled-trial evidence, lack of long-term L-T3 safety data, and absence of L-T3 formulations that mimic natural physiology.

    “Both guidelines strongly recommend that L-T4 remains the therapy of choice in hypothyroidism and do not support the routine use of L-T4/L-T3 combination therapy due to insufficient evidence from controlled trials, lack of long-term L-T3 safety data, and unavailability of L-T3 formulations that mirror natural physiology.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [26] source

      Not checked in the free run.

    • cites [27] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisereasoning

    The ETA and ATA guidelines differ in scope, but their key recommendations on diagnosis and management of hypothyroidism are comparable.

    “The ETA and ATA guidelines differ in scope although the key recommendations on the diagnosis and management of hypothyroidism are comparable.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    The 2011 RCP statement did not specifically address management strategies for L-T4-treated patients with persistent symptoms after nonthyroid causes are excluded.

    “The 2011 RCP statement concluded that L-T3 'should be reserved for use by accredited endocrinologists in individual patients' but did not specifically address management strategies for L-T4-treated patients with persistent symptoms after nonthyroid causes are excluded.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [25]

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    All authors are members of the BTA executive committee with expertise in thyroid disease management and research.

    “All authors are members of the BTA executive committee with expertise in thyroid disease management and research.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Interpretationnone given

    The evidence is insufficient to support monitoring serum T3 as a therapeutic target in hypothyroidism.

    “There is insufficient evidence to recommend monitoring serum T3 as a therapeutic target in hypothyroidism (Table 3).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Consensus on the recommendations was reached through discussion.

    “Consensus on recommendations was reached through discussions.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    The balance of clinical evidence on monotherapy versus combination therapy supports the need for further well-designed randomized controlled trials.

    “The balance of clinical evidence regarding the efficacy of monotherapy vs combination therapy calls for further well-designed randomized controlled trials (Table 10).”
    • Also stated in: § Commentary · hedged
      “The authors further assert that the balance of clinical evidence on the benefits of combination therapy over L-T4 monotherapy would demand that further randomized controlled trials are indicated.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductcitation

    Recommendations in the BTA statement are rated as strong or weak, and evidence quality is rated using the GRADE system.

    “Recommendations made in the BTA statement are also rated as strong (1) or weak recommendations (2) and the quality of evidence rated as high (+++), moderate (++0), low (+00) or insufficient (000) according to the GRADE system classification for clinical practice recommendations.30,31”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [30]

      Not checked in the free run.

    • cites [31] source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    The 2011 Royal College of Physicians statement did not support thyroid extracts or L-T3 for hypothyroidism and said L-T3 should be reserved for accredited endocrinologists in individual patients.

    “This RCP statement, updated in 2011, did not support the use of thyroid extracts or L-T3 in the treatment of hypothyroidism and recommended that L-T3 'should be reserved for use by accredited endocrinologists in individual patients'.25”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [25]

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Interpretationnone given

    Levothyroxine therapy is a safe, rational, and simplified approach to correcting hypothyroidism.

    “Levothyroxine therapy offers a safe, rational and simplified approach to the correction of hypothyroidism”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    Unregulated use of unapproved therapies has potential for harm.

    “the potential for harm exists with unregulated use of unapproved therapies.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Premisenone given

    Clinical equipoise is disturbed only by well-designed randomized controlled trials with statistical power to settle efficacy between monotherapy and combination therapy or other therapies.

    “Clinical equipoise is disturbed only by the results of well-designed randomized controlled trials that have the statistical power to settle the question of efficacy between monotherapy and combination therapy, or other forms of therapy Ungraded”
    Quote in the paperNot a substantial claim
27 of 27

  • The paper relies on this without support.

    A significant proportion of healthy people in the community have asymptomatic chronic autoimmune thyroiditis.

    “A significant proportion of healthy subjects in the community have asymptomatic chronic autoimmune thyroiditis and a significant proportion have subclinical hypothyroidism.”

  • The paper relies on this without support.

    Spontaneous recovery occurs in some people with subclinical hypothyroidism.

    “Spontaneous recovery has been described in subjects with subclinical hypothyroidism.”

  • The paper relies on this without support.

    Spontaneous recovery from subclinical hypothyroidism is more likely in people with negative antithyroid antibodies and serum TSH below 10 mU/l, and within the first two years after diagnosis.

    “It is more likely in those with negative antithyroid antibodies and serum TSH levels less than 10 mU/l, and within the first 2 years after diagnosis.”

  • The paper relies on this without support.

    A higher serum TSH value increases the likelihood that overt hypothyroidism will develop.

    “The higher the serum TSH value, the greater the likelihood of development of overt”

  • The paper relies on this without support.

    The ETA and ATA guidelines are applicable to UK clinical practice.

    “Based on the current literature and following review of the published positions of the ETA and ATA, and in line with the best principles of good medical practice, the BTA, ACB, BTF, RCP and SFE have agreed the following statement:”

  • The paper relies on this without support.

    A proportion of patients on L-T4 have persistent symptoms despite normal serum TSH and are dissatisfied with therapy.

    “It is acknowledged that a proportion of individuals on L-T4 are not satisfied with therapy and have persistent symptoms despite a normal serum TSH.”

  • The paper relies on this without support.

    Rarely, patients require a specific brand of L-T4 due to intolerance of generic preparations.

    “Rarely, patients may require a specific brand of L-T4 to be prescribed due to intolerance of generic preparations.”
7 of 7

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The AACE, ATA, BTA, and NICE guidelines are not supportive of LT3 therapy for the treatment of hypothyroidism.

    “The AACE, ATA, BTA, and NICE guidelines are not supportive of LT3 therapy for the treatment of hypothyroidism (Table 1) (10,29,30,105).”

    From Liothyronine and Desiccated Thyroid Extract in the Treatment of Hypothyroidism (2020) · cites this paper as [29]

    The BTA Statement (items 10 and 14; page not provided) advises against routine LT4/LT3 combination therapy and finds no convincing evidence for routine LT3 monotherapy. But item 12 allows a supervised combination-therapy trial for selected patients who have not benefited from LT4, so describing the BTA position as unsupportive of LT3 therapy without qualification overstates it. This verdict concerns the BTA position, not the other guidelines cited in the sentence. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • The AACE, ATA, BTA, ETA, and NICE guidelines do not recommend the use of desiccated thyroid extract (DTE).

    “The American Association of Clinical Endocrinologist (AACE), ATA, BTA, ETA, and NICE guidelines do not recommend the use of DTE (Table 1) (9,10,11,29,30).”

    From Liothyronine and Desiccated Thyroid Extract in the Treatment of Hypothyroidism (2020) · cites this paper as [29]

    The Summary of ETA and ATA guidelines (page unavailable) says routine use of thyroid extracts is not recommended, supporting the claim for the guidance this paper summarizes. The Background (page unavailable) also reports that an earlier UK statement did not support thyroid extracts. Our copy does not establish a DTE recommendation from AACE or NICE, and it does not separately identify an ETA recommendation specifically about DTE. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • The AACE and Latin American Thyroid Society guidelines do not support the use of combination therapy as a form of thyroid hormone replacement in patients with primary hypothyroidism, while the ATA, BTA, ETA, and NICE guidelines recommend against routine use but recognize that a trial of LT4+LT3 can be attempted on a case-by-case basis for patients who remain symptomatic on LT4 alone.

    “At this time, the AACE and Latin American Thyroid Society guidelines do not support the use of combination therapy as a form of TH replacement in patients with primary hypothyroidism (105,130). At the same time, the ATA, BTA, ETA, and NICE guidelines take a more permissive stance. They recommend against the routine use of combination therapy but recognize that a trial of LT4+LT3 can be attempted”

    From Liothyronine and Desiccated Thyroid Extract in the Treatment of Hypothyroidism (2020) · cites this paper as [29]

    Split into 2 atoms — 0 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.

    Experimental — accuracy not yet measured

  • British Thyroid Association guidelines suggested that combination therapy could be prescribed and carefully monitored under certain circumstances.

    “subsequently published British Thyroid Association guidelines (20) have suggested that combination therapy could be prescribed and carefully monitored under certain circumstances.”

    From Short-Term Time Trends in Prescribing Therapy for Hypothyroidism: Results of a Survey of American Thyroid Association Members (2019) · cites this paper as [20]

  • BTA and ETA guidelines recognize that a trial with LT4+LT3 can be attempted in patients who have unambiguously not benefited from LT4.

    “the most recent clinical guidelines prepared by the British Thyroid Association (BTA) (29) and the European Thyroid Association (ETA) (9) explicitly recognize that a trial with LT4+LT3 can be attempted in patients who have unambiguously not benefited from LT4”

    From Liothyronine and Desiccated Thyroid Extract in the Treatment of Hypothyroidism (2020) · cites this paper as [29]

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Authors
Okosieme, O., Gilbert, J., Abraham, P., Boelaert, K., Dayan, C., Gurnell, M., Leese, G., McCabe, C., Perros, P., Smith, V., Williams, G., & Vanderpump, M.
Affiliations
  • Prince Charles Hospital (GB)
  • King's College Hospital (GB)
  • Aberdeen Royal Infirmary (GB)
  • University of Birmingham (GB)
  • Cardiff University (GB)
  • Addenbrooke's Hospital (GB)
  • University of Dundee (GB)
  • Royal Victoria Infirmary (GB)
  • Imperial College London (GB)
  • Royal Free London NHS Foundation Trust (GB)
Corresponding author
Vanderpump, Mark
ORCID
Venue
Clinical Endocrinology
Publisher
Wiley
Published
2015-06-25
Volume
84
Issue
6
Pages
799-808
ISSN
  • 0300-0664 (ISSN-L)
  • 1365-2265
DOI
10.1111/cen.12824
OpenAlex
W1936573764
Semantic Scholar
a97e5e52c9c87115cb9be0d0120b2aaef1b74393
Cited by
208
References
29
Citations by year
2026: 9 · 2025: 12 · 2024: 15 · 2023: 21 · 2022: 26 · 2021: 41 · 2020: 23 · 2019: 19 · 2018: 16 · 2017: 12 · 2016: 10 · 2015: 1 · 2014: 1
FWCI
1.95
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Clinical Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
  • Discovery Research Portal (University of Dundee) (submittedVersion)
  • ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
  • University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
  • Apollo (University of Cambridge) (submittedVersion)
  • Apollo
Funders
  • Society for Endocrinology
  • British Thyroid Foundation
  • Association for Clinical Biochemistry and Laboratory Medicine
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
primary hypothyroidism, levothyroxine, liothyronine, combination thyroid hormone therapy, treatment satisfaction, thyroid hormone replacement
MeSH terms
Drug Therapy, Combination, Humans, Hypothyroidism, Thyroxine, Triiodothyronine, Practice Guidelines as Topic, Disease Management

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