A Systematic Review and Meta-Analysis of Patient Preferences for Combination Thyroid Hormone Treatment for Hypothyroidism
Background: The standard of care in management of hypothyroidism is treatment with levothyroxine (L-T4). Sometimes patients are dissatisfied with L-T4 and the combination of levo-triiodothyronine (L-T3) with L-T4 is considered.Methods: We performed a systematic review and meta-analysis of blinded ra...
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doaj-db907060ea064abca2867506b65f3b842020-11-25T02:35:43ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922019-07-011010.3389/fendo.2019.00477466604A Systematic Review and Meta-Analysis of Patient Preferences for Combination Thyroid Hormone Treatment for HypothyroidismAmit Akirov0Amit Akirov1Amit Akirov2Rouhi Fazelzad3Shereen Ezzat4Lehana Thabane5Anna M. Sawka6Department of Endocrine Oncology, Princess Margaret Cancer Centre, Toronto, ON, CanadaInstitute of Endocrinology, Beilinson Hospital, Petach Tikva, IsraelSackler School of Medicine, Tel Aviv University, Tel Aviv, IsraelPrincess Margaret Cancer Centre, University Health Network Library and Information Services, Toronto, ON, CanadaDepartment of Endocrine Oncology, Princess Margaret Cancer Centre, Toronto, ON, CanadaDepartment of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, CanadaDivision of Endocrinology, University Health Network and University of Toronto, Toronto, ON, CanadaBackground: The standard of care in management of hypothyroidism is treatment with levothyroxine (L-T4). Sometimes patients are dissatisfied with L-T4 and the combination of levo-triiodothyronine (L-T3) with L-T4 is considered.Methods: We performed a systematic review and meta-analysis of blinded randomized controlled trials (RCTs), reporting how often hypothyroid patients prefer combination L-T3/L-T4 treatment to L-T4 alone. We also explored for explanatory factors for combination therapy preference in sensitivity analyses examining trial, patient, and disease characteristics. Potential dose-response relationships were explored using meta-regression analyses. We searched 9 electronic databases (from inception until February, 2019), supplemented with a hand-search. Two reviewers independently screened abstracts and citations and reviewed full-text papers, with consensus achieved on the included studies. Two reviewers independently critically appraised the quality of included studies and abstracted the data. Random effects meta-analyses were reported for the percentage of patients preferring combination L-T3/T-T4 therapy over L-T4 alone. A binomial distribution of choices (i.e., preference of combination therapy or no preference for combination therapy) was assumed.Results: We included 7 blinded RCTs including 348 hypothyroid individuals in the primary meta-analysis. The pooled prevalence rate for preference of combination therapy over L-T4 was 46.2% (95% confidence interval 40.2%, 52.4%) (p = 0.231 for the difference from chance). There was no significant statistical heterogeneity among study results (Q = 7.32, degrees of freedom = 6, p = 0.293, I2 = 18.0%). In sensitivity analyses, combination treatment preference was explained in part by treatment effects on TSH concentration, mood and symptoms, but not quality of life nor body weight. In a secondary dose-response meta-regression analyses, a statistically significant association of treatment preference was identified for total daily L-T3 dose, but not L-T3:L-T4 dose ratio.Conclusions: In conclusion, in RCTs in which patients and investigators were blinded to treatment allocation, approximately half of participants reported preferring combination L-T3 and L-T4 therapy compared to L-T4 alone; this finding was not distinguishable from chance. An observed potential positive L-T3 dose effect on treatment preference deserves further study, with careful consideration of thyroid biochemical indices and patient reported outcomes.https://www.frontiersin.org/article/10.3389/fendo.2019.00477/fullhypothyroidismthyroid hormonelevothyroxinetriiodothyroninesystematic reviewmeta-analysis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Amit Akirov Amit Akirov Amit Akirov Rouhi Fazelzad Shereen Ezzat Lehana Thabane Anna M. Sawka |
spellingShingle |
Amit Akirov Amit Akirov Amit Akirov Rouhi Fazelzad Shereen Ezzat Lehana Thabane Anna M. Sawka A Systematic Review and Meta-Analysis of Patient Preferences for Combination Thyroid Hormone Treatment for Hypothyroidism Frontiers in Endocrinology hypothyroidism thyroid hormone levothyroxine triiodothyronine systematic review meta-analysis |
author_facet |
Amit Akirov Amit Akirov Amit Akirov Rouhi Fazelzad Shereen Ezzat Lehana Thabane Anna M. Sawka |
author_sort |
Amit Akirov |
title |
A Systematic Review and Meta-Analysis of Patient Preferences for Combination Thyroid Hormone Treatment for Hypothyroidism |
title_short |
A Systematic Review and Meta-Analysis of Patient Preferences for Combination Thyroid Hormone Treatment for Hypothyroidism |
title_full |
A Systematic Review and Meta-Analysis of Patient Preferences for Combination Thyroid Hormone Treatment for Hypothyroidism |
title_fullStr |
A Systematic Review and Meta-Analysis of Patient Preferences for Combination Thyroid Hormone Treatment for Hypothyroidism |
title_full_unstemmed |
A Systematic Review and Meta-Analysis of Patient Preferences for Combination Thyroid Hormone Treatment for Hypothyroidism |
title_sort |
systematic review and meta-analysis of patient preferences for combination thyroid hormone treatment for hypothyroidism |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Endocrinology |
issn |
1664-2392 |
publishDate |
2019-07-01 |
description |
Background: The standard of care in management of hypothyroidism is treatment with levothyroxine (L-T4). Sometimes patients are dissatisfied with L-T4 and the combination of levo-triiodothyronine (L-T3) with L-T4 is considered.Methods: We performed a systematic review and meta-analysis of blinded randomized controlled trials (RCTs), reporting how often hypothyroid patients prefer combination L-T3/L-T4 treatment to L-T4 alone. We also explored for explanatory factors for combination therapy preference in sensitivity analyses examining trial, patient, and disease characteristics. Potential dose-response relationships were explored using meta-regression analyses. We searched 9 electronic databases (from inception until February, 2019), supplemented with a hand-search. Two reviewers independently screened abstracts and citations and reviewed full-text papers, with consensus achieved on the included studies. Two reviewers independently critically appraised the quality of included studies and abstracted the data. Random effects meta-analyses were reported for the percentage of patients preferring combination L-T3/T-T4 therapy over L-T4 alone. A binomial distribution of choices (i.e., preference of combination therapy or no preference for combination therapy) was assumed.Results: We included 7 blinded RCTs including 348 hypothyroid individuals in the primary meta-analysis. The pooled prevalence rate for preference of combination therapy over L-T4 was 46.2% (95% confidence interval 40.2%, 52.4%) (p = 0.231 for the difference from chance). There was no significant statistical heterogeneity among study results (Q = 7.32, degrees of freedom = 6, p = 0.293, I2 = 18.0%). In sensitivity analyses, combination treatment preference was explained in part by treatment effects on TSH concentration, mood and symptoms, but not quality of life nor body weight. In a secondary dose-response meta-regression analyses, a statistically significant association of treatment preference was identified for total daily L-T3 dose, but not L-T3:L-T4 dose ratio.Conclusions: In conclusion, in RCTs in which patients and investigators were blinded to treatment allocation, approximately half of participants reported preferring combination L-T3 and L-T4 therapy compared to L-T4 alone; this finding was not distinguishable from chance. An observed potential positive L-T3 dose effect on treatment preference deserves further study, with careful consideration of thyroid biochemical indices and patient reported outcomes. |
topic |
hypothyroidism thyroid hormone levothyroxine triiodothyronine systematic review meta-analysis |
url |
https://www.frontiersin.org/article/10.3389/fendo.2019.00477/full |
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