Management of Patients Symptomatically Unresponsive to Levothyroxine:
                    Natural Desiccated Thyroid Extract or the Combination of Levothyroxine and
                    Liothyronine? A Research Priority

Heald, Adrian; Livingston, Mark; Hughes, Dyfrig

doi:10.1055/a-1062-6167

Cited by 4 publications

(6 citation statements)

References 23 publications

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“…At present, it remains to be seen what proportion of these will benefit from liothyronine either in its current form or in the form of newer longer acting preparations currently under development. Certainly, recent evidence has shown that a small but significant proportion of people treated for hypothyroidism remain actively symptomatic 18,19 . Interestingly, it is noteworthy that even in the 1970s it was recognized that some patients did not feel well on levothyroxine monotherapy and seemed to prefer liothyronine being used in combination with levothyroxine 20 …”

Section: Discussionmentioning

confidence: 99%

“…Certainly, recent evidence has shown that a small but significant proportion of people treated for hypothyroidism remain actively symptomatic. 18,19 Interestingly, it is noteworthy that even in the 1970s it was recognized that some patients did not feel well on levothyroxine monotherapy and seemed to prefer liothyronine being used in combination with levothyroxine. 20 Decisions concerning the formulary restriction, deprescribing or…”

Section: Costmentioning

confidence: 99%

See 1 more Smart Citation

Trends in costs and prescribing for liothyronine and levothyroxine in England and wales 2011–2020

Stedman¹,

Taylor

Premawardhana

et al. 2021

Clinical Endocrinology

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Section: Discussionmentioning

confidence: 99%

Section: Costmentioning

confidence: 99%

Trends in costs and prescribing for liothyronine and levothyroxine in England and wales 2011–2020

Stedman¹,

Taylor

Premawardhana

et al. 2021

Clinical Endocrinology

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“…Published clinical trials and systematic reviews 9 16 were assessed for relevant data on the clinical effectiveness of liothyronine/levothyroxine combination therapy. None of the trials restricted their inclusion criteria to (or performed a subgroup analysis of) the population of interest and were therefore not considered relevant to inform the decision problem.…”

Section: Methodsmentioning

confidence: 99%

“…Clinical guidelines acknowledge the limited evidence-base for liothyronine. While 13 trials of combination versus levothyroxine monotherapy therapy have been reported,9 the majority are underpowered, some are unlikely to have tested the correct dose of liothyronine, and none restricted recruitment to patients who did not feel significantly better on levothyroxine alone 3 9–12. This latter point could explain why liothyronine/levothyroxine combination therapy has not demonstrated superiority, even in the larger trials.…”

Section: Introductionmentioning

confidence: 99%

Liothyronine for hypothyroidism: a candidate for disinvestment or in need of further research? A value of information analysis

et al. 2021

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ObjectiveMedicines with limited evidence of effectiveness are prime candidates for disinvestment. However, investment in further research may be preferable to deimplementation, given that the absence of evidence is not evidence of absence, and research can inform formulary decisions. A case in point is liothyronine, which is sometimes prescribed to levothyroxine-treated patients who continue to experience hypothyroid symptoms. It is a putative low value medicine, associated with uncertainties in both clinical and cost-effectiveness. The aim was to assess the cost-effectiveness of liothyronine in this context, and estimate the value of conducting further research.DesignCost utility and value of information analyses.SettingPrimary care within the National Health Service in the UK.ParticipantsFifty-four levothyroxine-treated patients with persistent symptoms of hypothyroidism.InterventionsLiothyronine plus levothyroxine versus levothyroxine alone.Primary and secondary outcome measuresIncremental cost per quality-adjusted life year (QALY) gained, and the expected monetary value of sample information.Results20/54 (37%) of patients who responded to the survey reported severe problems in carrying out usual activities of everyday living and 12/54 (22%) reported severe anxiety or depression symptoms. Mean (SD) utility was 0.53 (0.23). The differences in expected total, 10-year costs and QALYs between a treatment strategy of liothyronine/levothyroxine combination therapy, and levothyroxine alone, was £12 053 and 1.014, respectively. The incremental cost-effectiveness ratio of £11 881 per QALY gained was sensitive to the price of liothyronine. The probability of liothyronine/levothyroxine combination therapy being cost effective at a threshold of £20 000 per QALY was 0.56. The value of reducing uncertainty in the efficacy of treatment was £3.64 m per year in the UK.ConclusionsA definitive clinical trial to confirm clinical effectiveness may be preferable to immediate disinvestment, and would be justified given the value of the information gained far exceeds the cost.

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“…It has been found that 5-10% of hypothyroid patients receiving LT4 continue to experience disabling symptoms such as fatigue, depression, and impaired cognition, despite being adequately replaced biochemically, affecting their quality of life [4]. In a study that aimed to evaluate satisfaction and quality of life (QOL) in 969 hypothyroid patients through a survey, it was found that 77.6% were dissatisfied, and the scores of QOL were low.…”

Section: Introductionmentioning

confidence: 99%

Liothyronine use in primary hypothyroidism — current concepts

Concepción-Zavaleta¹,

Ildefonso-Najarro

Paz-Ibarra

et al. 2021

Endokrynologia Polska

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Hypothyroidism is an endocrine disorder whose management raises many challenges in clinical practice. Its standard treatment is levothyroxine (LT4). The goal of the treatment is to normalize signs and symptoms, as well as to achieve thyroid-stimulating hormone (TSH) concentrations within the reference range, on an individual basis. It is known that 5-10% of hypothyroid patients remain symptomatic, despite achieving the target TSH levels, which, in turn, affects their quality of life. After ruling out other causes of non-thyroid origin for this persistence, it is suggested that these patients could benefit from the use of liothyronine (LT3), added to LT4, especially if polymorphism of the deiodinase 2 (D2) genes is documented. There exist a variety of LT3 preparations, whose concentrations vary from 5 to 50 ug, with the recommended LT4/LT3 ratio of 13:1-20:1. The goals of combination therapy should be to achieve a physiological ratio of free triiodothyronine/free thyroxine (FT3/FT4) and non-suppression of TSH. Because there is currently no guide that makes evidence-based recommendations on the use of LT3 in primary hypothyroidism, more clinical studies are needed to be able to identify hypothyroid patients who may benefit from the use of LT3, by identifying new biomarkers.

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Management of Patients Symptomatically Unresponsive to Levothyroxine: Natural Desiccated Thyroid Extract or the Combination of Levothyroxine and Liothyronine? A Research Priority

Cited by 4 publications

References 23 publications

Trends in costs and prescribing for liothyronine and levothyroxine in England and wales 2011–2020

Trends in costs and prescribing for liothyronine and levothyroxine in England and wales 2011–2020

Liothyronine for hypothyroidism: a candidate for disinvestment or in need of further research? A value of information analysis

Liothyronine use in primary hypothyroidism — current concepts

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