Sustained Release T3 Therapy: Animal Models and Translational Applications

Idrees, Thaer; Price, John; Piccariello, T.; Bianco, Antonio C.

doi:10.3389/fendo.2019.00544

Cited by 21 publications

(19 citation statements)

References 59 publications

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“…Of the 14 combination therapy trials that have been completed, 10 employed once-daily LT3 administration [23, 46, 47, 49, 51, 52, 59, 71, 78, 79], 4 employed twice-daily LT3 therapy [17, 48, 53, 60], and none used three times a day LT3 therapy. Assuming that three times daily LT3 administration is too onerous to be used in future trials [75, 76], and considering that a sustained-release preparation is not yet available for clinical use [80-83], twice a day therapy may be the most reasonable option. Given that twice-daily LT3 therapy, although not ideal with respect to the T3 fluctuations produced, is likely to be the best compromise, modeling studies provide information about potential twice-daily LT3 doses that could be utilized [67, 77].…”

Section: Results: Topics Summaries Summary Statements and Consensusmentioning

confidence: 99%

“…There should not be a clinically meaningful difference in TSH between groups to be able to make a meaningful comparison of the outcomes between the two therapies. As long as a new sustained-release T3 product is not being utilized [80][81][82][83], the outcome measures do not need to be selected with Food and Drug Administration approval in mind. The most important consideration for choice of outcome measure is whether this outcome is responsive to LT3 therapy within the range of acceptable T3 levels or T3 tissue actions.…”

Section: Outcomes To Be Considered In Future Combination Therapy Trialsmentioning

confidence: 99%

See 1 more Smart Citation

Evidence-Based Use of Levothyroxine/Liothyronine Combinations in Treating Hypothyroidism: A Consensus Document

et al. 2021

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Background: Fourteen clinical trials have not shown a consistent benefit of combination therapy with levothyroxine (LT4) and liothyronine (LT3). Despite the publication of these trials, combination therapy is widely used and patients reporting benefit continue to generate patient and physician interest in this area. Recent scientific developments may provide insight into this inconsistency and guide future studies. Methods: The American Thyroid Association (ATA), British Thyroid Association (BTA), and European Thyroid Association (ETA) held a joint conference on November 3, 2019 (live-streamed between Chicago and London) to review new basic science and clinical evidence regarding combination therapy with presentations and input from 12 content experts. After the presentations, the material was synthesized and used to develop Summary Statements of the current state of knowledge. After review and revision of the material and Summary Statements, there was agreement that there was equipoise for a new clinical trial of combination therapy. Consensus Statements encapsulating the implications of the material discussed with respect to the design of future clinical trials of LT4/LT3 combination therapy were generated. Authors voted upon the Consensus Statements. Iterative changes were made in several rounds of voting and after comments from ATA/BTA/ETA members. Results: Of 34 Consensus Statements available for voting, 28 received at least 75% agreement, with 13 receiving 100% agreement. Those with 100% agreement included studies being powered to study the effect of deiodinase and thyroid hormone transporter polymorphisms on study outcomes, inclusion of patients dissatisfied with their current therapy and requiring at least 1.2 µg/kg of LT4 daily, use of twice daily LT3 or preferably a slow-release preparation if available, use of patient-reported outcomes as a primary outcome (measured by a tool with both relevant content validity and responsiveness) and patient preference as a secondary outcome, and utilization of a randomized placebo-controlled adequately powered double-blinded parallel design. The remaining statements are presented as potential additional considerations. Discussion: This article summarizes the areas discussed and presents Consensus Statements to guide development of future clinical trials of LT4/LT3 combination therapy. The results of such redesigned trials are expected to be of benefit to patients and of value to inform future thyroid hormone replacement clinical practice guidelines treatment recommendations.

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Section: Results: Topics Summaries Summary Statements and Consensusmentioning

confidence: 99%

Section: Outcomes To Be Considered In Future Combination Therapy Trialsmentioning

confidence: 99%

Evidence-Based Use of Levothyroxine/Liothyronine Combinations in Treating Hypothyroidism: A Consensus Document

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Of the 14 combination therapy trials that have been completed, 10 employed once-daily LT3 administration (23,46,47,49,51,52,59,71,78,79), 4 employed twice-daily LT3 therapy (17,48,53,60), and none used three times a day LT3 therapy. Assuming that three times daily LT3 administration is too onerous to be used in future trials (75,76), and considering that a sustained-release preparation is not yet available for clinical use (80)(81)(82)(83), twice a day therapy may be the most reasonable option. Given that twice-daily LT3 therapy, although not ideal with respect to the T3 fluctuations produced, is likely to be the best compromise, modeling studies provide information about potential twice-daily LT3 doses that could be utilized (67,77).…”

Section: Summary Statementsmentioning

confidence: 99%

“…There should not be a clinically meaningful difference in TSH between groups to be able to make a meaningful comparison of the outcomes between the two therapies. As long as a new sustained-release T3 product is not being utilized (80)(81)(82)(83), the outcome measures do not need to be selected with Food and Drug Administration approval in mind. The most important consideration for choice of outcome measure is whether this outcome is responsive to LT3 therapy within the range of acceptable T3 levels or T3 tissue actions.…”

Section: Summary Statementsmentioning

confidence: 99%

Evidence-Based Use of Levothyroxine/Liothyronine Combinations in Treating Hypothyroidism: A Consensus Document

Jonklaas

Bianco

Cappola

et al. 2021

Thyroid

Self Cite

110

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Background: Fourteen clinical trials have not shown a consistent benefit of combination therapy with levothyroxine (LT4) and liothyronine (LT3). Despite the publication of these trials, combination therapy is widely used and patients reporting benefit continue to generate patient and physician interest in this area. Recent scientific developments may provide insight into this inconsistency and guide future studies. Methods: The American Thyroid Association (ATA), British Thyroid Association (BTA), and European Thyroid Association (ETA) held a joint conference on November 3, 2019 (live-streamed between Chicago and London) to review new basic science and clinical evidence regarding combination therapy with presentations and input from 12 content experts. After the presentations, the material was synthesized and used to develop Summary Statements of the current state of knowledge. After review and revision of the material and Summary Statements, there was agreement that there was equipoise for a new clinical trial of combination therapy. Consensus Statements encapsulating the implications of the material discussed with respect to the design of future clinical trials of LT4/ LT3 combination therapy were generated. Authors voted upon the Consensus Statements. Iterative changes were made in several rounds of voting and after comments from ATA/BTA/ETA members. Results: Of 34 Consensus Statements available for voting, 28 received at least 75% agreement, with 13 receiving 100% agreement. Those with 100% agreement included studies being powered to study the effect of deiodinase and thyroid hormone transporter polymorphisms on study outcomes, inclusion of patients dissatisfied with their current therapy and requiring at least 1.2 lg/kg of LT4 daily, use of twice daily LT3 or preferably a slow-release preparation if available, use of patient-reported outcomes as a primary outcome (measured by a tool with both relevant content validity and responsiveness) and patient preference as a secondary outcome, and utilization of a randomized placebo-controlled adequately powered double-blinded parallel design. The remaining statements are presented as potential additional considerations. Discussion: This article summarizes the areas discussed and presents Consensus Statements to guide development of future clinical trials of LT4/LT3 combination therapy. The results of such redesigned trials are expected to be of benefit to patients and of value to inform future thyroid hormone replacement clinical practice guidelines treatment recommendations.

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“…This knowledge gap highlights the need for more sophisticated and well-designed RCTs, large studies that allow for subgroup analysis to identify which patients benefit with DTE compared to LT4, and studies incorporating patient-reported and patient-important outcomes, to elucidate the physiological support responsible for combined therapy preference in this subset of patients. On the other hand, research efforts could be directed to evaluate the effect of synthetic slow-release preparations of thyroid hormones [37] in humans and the development of dose-consistent DTE preparations.…”

Section: Implications For Future Researchmentioning

confidence: 99%

Patient Experiences and Perceptions Associated with the Use of Desiccated Thyroid Extract

et al. 2020

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Background and objectives: It is unclear why many patients with hypothyroidism prefer the use of desiccated thyroid extract (DTE) as a thyroid hormone replacement formulation over levothyroxine (LT4) treatment, as recommended by clinical practice guidelines. We analyzed patient-reported information from patient online forums to better understand patient preferences for and attitudes toward the use of DTE to treat hypothyroidism. Materials and Methods: We conducted a mixed-methods study by evaluating the content of online posts from three popular hypothyroidism forums from patients currently taking DTE (n = 673). From these posts, we extracted descriptive information on patient demographics and clinical characteristics and qualitatively analyzed posts’ content to explore patient perceptions on DTE and other therapies further. Results: Nearly half (46%) of the patients reported that a clinician initially drove their interest in trying DTE. Patients described many reasons for switching from a previous therapeutic approach to DTE, including lack of improvement in hypothyroidism-related symptoms (58%) and the development of side effects (22%). The majority of patients described DTE as moderately to majorly effective overall (81%) and more effective than the previous therapy (77%). The most frequently described benefits associated with DTE use were an improvement in symptoms (56%) and a change in overall well-being (34%). One-fifth of patients described side effects related to the use of DTE. Qualitative analysis of posts’ content supported these findings and raised additional issues around the need for individualizing therapy approaches for hypothyroidism (e.g., a sense of each patient has different needs), as well as difficulties obtaining DTE (e.g., issues with pharmacy availability). Conclusions: Lack of individualized treatment and a feeling of not been listened to were recurrent themes among DTE users. A subset of patients may prefer DTE to LT4 for many reasons, including perceived better effectiveness and improved overall well-being, despite the risks associated with DTE.

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Sustained Release T3 Therapy: Animal Models and Translational Applications

Cited by 21 publications

References 59 publications

Evidence-Based Use of Levothyroxine/Liothyronine Combinations in Treating Hypothyroidism: A Consensus Document

Evidence-Based Use of Levothyroxine/Liothyronine Combinations in Treating Hypothyroidism: A Consensus Document

Evidence-Based Use of Levothyroxine/Liothyronine Combinations in Treating Hypothyroidism: A Consensus Document

Patient Experiences and Perceptions Associated with the Use of Desiccated Thyroid Extract

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