Dataset Information

Combination Therapy for Hypothyroidism: Rationale, Therapeutic Goals, and Design.

ABSTRACT: 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.

SUBMITTER: Madan R

PROVIDER: S-EPMC7360670 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Combination Therapy for Hypothyroidism: Rationale, Therapeutic Goals, and Design.

Madan Ritu R Celi Francesco S FS

Frontiers in endocrinology 20200708

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 t ...[more]

PMID: 32733377

Similar Datasets

Project description:BackgroundThrombolysis with intravenous rt-PA is currently the only approved acute therapy for ischemic stroke. Re-occlusion after initial recanalization occurs in up to 34% in patients treated with rt-PA, probably caused by platelet activation. In acute myocardial infarction, the combination of thrombolysis and antiplatelet therapy leads to a greater reduction of mortality compared to thrombolysis alone. In patients with acute ischemic stroke, several studies showed that patients already on antiplatelet treatment prior to thrombolysis had an equal or even better outcome compared to patients without prior antiplatelet treatment, despite an increased risk of intracerebral bleeding. Based on the fear of intracerebral haemorrhage, current international guidelines recommend postponing antiplatelet therapy until 24 hours after thrombolysis. Remarkably, prior use of antiplatelet therapy is not a contra-indication for thrombolysis. We hypothesize that antiplatelet therapy in combination with rt-PA thrombolysis will improve outcome by enhancing fibrinolysis and preventing re-occlusion.Methods/designARTIS is a randomised multi-center controlled trial with blind endpoint assessment. Our objective is to investigate whether immediate addition of aspirin to rt-PA thrombolysis improves functional outcome in ischemic stroke. Patients with acute ischemic stroke eligible for rt-PA thrombolysis are randomised to receive 300 mg aspirin within 1.5 hours after start of thrombolysis or standard care, consisting of antiplatelet therapy after 24 hours. Primary outcome is poor functional health at 3 months follow-up (modified Rankin Scale 3 - 6).DiscussionThis is the first clinical trial investigating the combination of rt-PA and acute aspirin by means of a simple and cheap adjustment of current antiplatelet regimen. We expect the net benefit of improved functional outcome will overcome the possible slightly increased risk of intracerebral haemorrhage.Trial registrationThe Netherlands National Trial Register NTR822. The condensed rationale of the ARTIS-Trial has already been published in Cerebrovascular Diseases.

Project description:ObjectivesHypothyroidism results in decreased mood and neurocognition, weight gain, fatigue, and many other undesirable symptoms. The American Association of Clinical Endocrinologists, the American Thyroid Association (ATA), and The Endocrine Society recommend levothyroxine (LT4) monotherapy as the treatment for hypothyroidism; however, after years of monotherapy, some patients continue to experience impaired quality of life. Combination LT4 and synthetic liothyronine (LT3) therapy or the use of desiccated thyroid extract (DTE), has not been suggested for this indication based on short-duration studies with no significant benefits. Our first observational study examined the role of combination therapy for 6 years in improving quality of life in a subset of a hypothyroid population without adverse effects and cardiac mortality.MethodsAn observational retrospective study examining patients prescribed thyroid replacements with serum triiodothyronine (FT3), LT4 with LT3 (synthetic therapy) or DTE (natural therapy), compared with LT4 alone in the United States from 2010 to 2016. Thyroid-stimulating hormone (TSH), serum thyroxine (FT4), and FT3 levels were documented for each patient in addition to any admissions of myxedema coma, thyrotoxicosis, or cardiovascular complications, such as arrhythmias, atrial fibrillation, and mortality. At the conclusion of the study, a cross-sectional interview assessed quality of life for each combination therapy through the Medical Outcomes Study Short Form-20 questionnaire.ResultsCompared with patients taking only LT4, 89.47% using synthetic therapy had therapeutic TSH (P < 0.05). Similarly, 96.49% using natural therapy had therapeutic TSH (P < 0.05). Less than 5% of patients had supratherapeutic FT3. None of the patients who had abnormally low TSH or elevated FT3 or FT4 levels had hospitalizations for arrhythmias or thyrotoxicosis. On the Medical Outcomes Study Short Form-20 questionnaire, >92% answered feeling "excellent, very good, or good" when questioned about their health while undergoing thyroid replacement compared with levothyroxine alone.ConclusionsThis is the only retrospective study reported to use long-term (mean 27 months) thyroid replacements with combination therapy and to compare between the two forms of therapy: synthetic and natural. For patients undergoing either therapy, we did not identify additional risks of atrial fibrillation, cardiovascular disease, or mortality in patients of all ages with hypothyroidism.

Dataset Information

Combination Therapy for Hypothyroidism: Rationale, Therapeutic Goals, and Design.

Publications

Combination Therapy for Hypothyroidism: Rationale, Therapeutic Goals, and Design.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets