Combination Therapy for Hypothyroidism: Rationale, Therapeutic Goals, and Design
Hypothyroidism is a common condition with a wide spectrum of etiologies and clinical manifestations. While the majority of patients affected by hypothyroidism respond well to levothyroxine, some patients do not and complain of symptoms despite adequate replacement. There is evidence in experimental...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-07-01
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| Series: | Frontiers in Endocrinology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fendo.2020.00371/full |
| _version_ | 1818554585538625536 |
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| author | Ritu Madan Francesco S. Celi |
| author_facet | Ritu Madan Francesco S. Celi |
| author_sort | Ritu Madan |
| collection | DOAJ |
| description | Hypothyroidism is a common condition with a wide spectrum of etiologies and clinical manifestations. While the majority of patients affected by hypothyroidism respond well to levothyroxine, some patients do not and complain of symptoms despite adequate replacement. There is evidence in experimental models of hypothyroidism that levothyroxine alone may not be able to deliver an adequate amount of T3 to all the tissues targeted by the hormonal action, while liothyronine/levothyroxine combination therapy can. The results of clinical studies directed to assess the effectiveness of liothyronine/levothyroxine combination therapy on the amelioration of hypothyroid symptoms have been disappointing. Most of the trials have been short and underpowered, with several shortcomings in the study design. There is consensus that an adequately powered clinical trial should be developed to prove or disprove the efficacy and effectiveness of therapies other than LT4 alone for the treatment of hypothyroidism, and to assess which group of patients would benefit from them. Here we present some considerations on the technical aspects and necessary tradeoffs in designing such a study with a particular focus on study population selection, choice of endpoints, and study drugs formulation and regimen. |
| first_indexed | 2024-12-12T09:41:54Z |
| format | Article |
| id | doaj.art-bec809bb63cd48f19cdc8d972fa3cdfc |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-12-12T09:41:54Z |
| publishDate | 2020-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-bec809bb63cd48f19cdc8d972fa3cdfc2022-12-22T00:28:32ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922020-07-011110.3389/fendo.2020.00371539806Combination Therapy for Hypothyroidism: Rationale, Therapeutic Goals, and DesignRitu MadanFrancesco S. CeliHypothyroidism is a common condition with a wide spectrum of etiologies and clinical manifestations. While the majority of patients affected by hypothyroidism respond well to levothyroxine, some patients do not and complain of symptoms despite adequate replacement. There is evidence in experimental models of hypothyroidism that levothyroxine alone may not be able to deliver an adequate amount of T3 to all the tissues targeted by the hormonal action, while liothyronine/levothyroxine combination therapy can. The results of clinical studies directed to assess the effectiveness of liothyronine/levothyroxine combination therapy on the amelioration of hypothyroid symptoms have been disappointing. Most of the trials have been short and underpowered, with several shortcomings in the study design. There is consensus that an adequately powered clinical trial should be developed to prove or disprove the efficacy and effectiveness of therapies other than LT4 alone for the treatment of hypothyroidism, and to assess which group of patients would benefit from them. Here we present some considerations on the technical aspects and necessary tradeoffs in designing such a study with a particular focus on study population selection, choice of endpoints, and study drugs formulation and regimen.https://www.frontiersin.org/article/10.3389/fendo.2020.00371/fullhypothyroidismliothyroninelevothyroxinecombination therapypharmacokinetics |
| spellingShingle | Ritu Madan Francesco S. Celi Combination Therapy for Hypothyroidism: Rationale, Therapeutic Goals, and Design Frontiers in Endocrinology hypothyroidism liothyronine levothyroxine combination therapy pharmacokinetics |
| title | Combination Therapy for Hypothyroidism: Rationale, Therapeutic Goals, and Design |
| title_full | Combination Therapy for Hypothyroidism: Rationale, Therapeutic Goals, and Design |
| title_fullStr | Combination Therapy for Hypothyroidism: Rationale, Therapeutic Goals, and Design |
| title_full_unstemmed | Combination Therapy for Hypothyroidism: Rationale, Therapeutic Goals, and Design |
| title_short | Combination Therapy for Hypothyroidism: Rationale, Therapeutic Goals, and Design |
| title_sort | combination therapy for hypothyroidism rationale therapeutic goals and design |
| topic | hypothyroidism liothyronine levothyroxine combination therapy pharmacokinetics |
| url | https://www.frontiersin.org/article/10.3389/fendo.2020.00371/full |
| work_keys_str_mv | AT ritumadan combinationtherapyforhypothyroidismrationaletherapeuticgoalsanddesign AT francescosceli combinationtherapyforhypothyroidismrationaletherapeuticgoalsanddesign |