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Antonio C Bianco - One of the best experts on this subject based on the ideXlab platform.
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comparative effectiveness of levothyroxine desiccated Thyroid Extract and levothyroxine liothyronine in hypoThyroidism
The Journal of Clinical Endocrinology and Metabolism, 2021Co-Authors: Thanh D Hoang, Vinh Q Mai, Mohamed K M Shakir, Antonio C Bianco, Daniel I Brooks, Elizabeth A Mcaninch, Tatiana L FonsecaAbstract:INTRODUCTION Studies comparing levothyroxine (LT4) therapy with LT4 + liothyronine (LT3) or desiccated Thyroid Extract (DTE) did not detect consistent superiority of either treatment. Here, we investigated these therapies, focusing on the whole group of LT4-treated hypoThyroid patients, while also exploring the most symptomatic patients. METHODOLOGY Prospective, randomized, double-blind, crossover study of 75 hypoThyroid patients randomly allocated to 1 of 3 treatment arms, LT4, LT4 + LT3, and DTE, for 22 weeks. The primary outcomes were posttreatment scores on the 36-point Thyroid symptom questionnaire (TSQ-36), 12-point quality of life general health questionnaire (GHQ-12), the Wechsler memory scale-version IV (VMS-IV), and the Beck Depression Inventory (BDI). Secondary endpoints included treatment preference, biochemical and metabolic parameters, etiology of hypoThyroidism, and Thr92Ala-DIO2 gene polymorphism. Analyses were performed with a linear mixed model using subject as a random factor and group as a fixed effect. RESULTS Serum TSH remained within reference range across all treatment arms. There were no differences for primary and secondary outcomes, except for a minor increase in heart rate caused by DTE. Treatment preference was not different and there were no interferences of the etiology of hypoThyroidism or Thr92Ala-DIO2 gene polymorphism in the outcomes. Subgroup analyses of the 1/3 most symptomatic patients on LT4 revealed strong preference for treatment containing T3, which improved performance on TSQ-36, GHQ-12, BDI, and visual memory index (VMS-IV component). CONCLUSIONS As a group, outcomes were similar among hypoThyroid patients taking DTE vs LT4 + T3 vs LT4. However, those patients that were most symptomatic on LT4 preferred and responded positively to therapy with LT4 + LT3 or DTE.
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desiccated Thyroid Extract versus synthetic lt4 t3 combination versus lt4 monotherapy in the treatment of primary hypoThyroidism with special attention to the thr92alad2 polymorphism with special attention to the gene polymorphism
Journal of the Endocrine Society, 2021Co-Authors: Thanh Duc Hoang, Vinh Q Mai, Antonio C Bianco, Daniel I Brooks, Elizabeth A Mcaninch, Tatiana L Fonseca, Mohamed K M ShakirAbstract:Introduction: Before the availability of levothyroxine (LT4), patients were treated with desiccated Thyroid Extract (DTE). When switching from DTE to LT4, despite adequate dosing based on serum TSH levels, some patients still feel unwell with fatigue, mental fogginess, weight gain etc. A recent randomized, crossed over study between DTE vs. LT4 conducted in our department showed that once-daily DTE caused modest weight loss and possible improvement in mental health scores without appreciable adverse effects; also, nearly half of the study patients preferred DTE over LT4. A few studies have shown that LT4/T3 combination had beneficial effects in improving quality of life relative to LT4 alone. Furthermore, it has been reported that patients with CC genotype in the deiodinase type 2 polymorphism responded more favorably with LT4/T3 combination than T4 monotherapy. Hypothesis: This study investigated the efficacy and effectiveness of DTE vs. LT4/T3 combination vs. LT4 monotherapy in hypoThyroid patients based on genotypic differences of deiodinase type 2. Methodology: This was a prospective, randomized, double-blind, crossover study. 75 subjects completed the study. There were 3 arms: DTE, LT4+T3 combination, and LT4 alone. Each subject was randomly allocated to one of these 3 arms for 12 weeks randomly. The study was powered to detect the primary outcome. The primary endpoint was post-treatment score on the 36-point Thyroid symptom questionnaire. Secondary endpoints were weight, general health questionnaire, the Beck depression inventory, Wechsler Memory testing, lipid panels and Thyroid function tests. Analysis was performed with a linear mixed model using subject as a random factor and group as a fixed effect. Results: There was no significant difference between the 3 arms on the Thyroid symptom questionnaire (p=.32), and the secondary outcomes showed no between group differences. Auditory memory index (p=.008), and visual working memory index (p=.02) were higher in the Hashimoto’s than non-Hashimoto’s group. There was no significant primary or secondary outcome difference among various genotypes of deiodinase 2. There was no relationship between Hashimoto’s vs. non-Hashimoto’s based on genotypes or likelihood of carrying Thr92AlaD2 polymorphism. Though there was no statistically significant preference for any treatment, numerically more patients with Hashimoto’s preferred DTE and LT4/T3 combination than LT4-monotherapy. Conclusions: There was no significant difference between hypoThyroid patients taking DTE vs. LT4/T3 combination vs. LT4 monotherapy. Numerically, Hashimoto’s patients tended to prefer DTE and LT4/T3 combination. Also, there was no observed relationship between Hashimoto’s and polymorphism. Further studies with more patients may be needed.
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liothyronine and desiccated Thyroid Extract in the treatment of hypoThyroidism
Thyroid, 2020Co-Authors: Thaer Idrees, Scott Bradley Palmer, Rui M B Maciel, Antonio C BiancoAbstract:Background: The basis for the treatment of hypoThyroidism with levothyroxine (LT4) is that humans activate T4 to triiodothyronine (T3). Thus, while normalizing serum thyrotropin (TSH), LT4 doses should also restore the body's reservoir of T3. However, there is evidence that T3 is not fully restored in LT4-treated patients. Summary: For patients who remain symptomatic on LT4 therapy, clinical guidelines recommend, on a trial basis, therapy with LT4+LT3. Reducing the LT4 dose by 25 mcg/day and adding 2.5-7.5 mcg liothyronine (LT3) once or twice a day is an appropriate starting point. Transient episodes of hypertriiodothyroninemia with these doses of LT4 and LT3 are unlikely to go above the reference range and have not been associated with adverse drug reactions. Trials following almost a 1000 patients for almost 1 year indicate that similar to LT4, therapy with LT4+LT3 can restore euThyroidism while maintaining a normal serum TSH. An observational study of 400 patients with a mean follow-up of ∼9 years did not indicate increased mortality or morbidity risk due to cardiovascular disease, atrial fibrillation, or fractures after adjusting for age when compared with patients taking only LT4. Desiccated Thyroid Extract (DTE) is a form of combination therapy in which the LT4/LT3 ratio is ∼4:1; the mean daily dose of DTE needed to normalize serum TSH contains ∼11 mcg T3, but some patients may require higher doses. The DTE remains outside formal FDA oversight, and consistency of T4 and T3 contents is monitored by the manufacturers only. Conclusions: Newly diagnosed hypoThyroid patients should be treated with LT4. A trial of combination therapy with LT4+LT3 can be considered for those patients who have unambiguously not benefited from LT4.
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the history and future of treatment of hypoThyroidism
Annals of Internal Medicine, 2016Co-Authors: Elizabeth A Mcaninch, Antonio C BiancoAbstract:Thyroid hormone replacement has been used for more than a century to treat hypoThyroidism. Natural Thyroid preparations (Thyroid Extract, desiccated Thyroid, or thyroglobulin), which contain both thyroxine (T4) and triiodothyronine (T3), were the first pharmacologic treatments available and dominated the market for the better part of the 20th century. Dosages were adjusted to resolve symptoms and to normalize the basal metabolic rate and/or serum protein-bound iodine level, but thyrotoxic adverse effects were not uncommon. Two major developments in the 1970s led to a transition in clinical practice: 1) The development of the serum Thyroid-stimulating hormone (TSH) radioimmunoassay led to the discovery that many patients were overtreated, resulting in a dramatic reduction in Thyroid hormone replacement dosage, and 2) the identification of peripheral deiodinase-mediated T4-to-T3 conversion provided a physiologic means to justify l-thyroxine monotherapy, obviating concerns about inconsistencies with desiccated Thyroid. Thereafter, l-thyroxine monotherapy at doses to normalize the serum TSH became the standard of care. Since then, a subgroup of Thyroid hormone-treated patients with residual symptoms of hypoThyroidism despite normalization of the serum TSH has been identified. This has brought into question the inability of l-thyroxine monotherapy to universally normalize serum T3 levels. New research suggests mechanisms for the inadequacies of l-thyroxine monotherapy and highlights the possible role for personalized medicine based on deiodinase polymorphisms. Understanding the historical events that affected clinical practice trends provides invaluable insight into formulation of an approach to help all patients achieve clinical and biochemical euThyroidism.
Mohamed K M Shakir - One of the best experts on this subject based on the ideXlab platform.
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comparative effectiveness of levothyroxine desiccated Thyroid Extract and levothyroxine liothyronine in hypoThyroidism
The Journal of Clinical Endocrinology and Metabolism, 2021Co-Authors: Thanh D Hoang, Vinh Q Mai, Mohamed K M Shakir, Antonio C Bianco, Daniel I Brooks, Elizabeth A Mcaninch, Tatiana L FonsecaAbstract:INTRODUCTION Studies comparing levothyroxine (LT4) therapy with LT4 + liothyronine (LT3) or desiccated Thyroid Extract (DTE) did not detect consistent superiority of either treatment. Here, we investigated these therapies, focusing on the whole group of LT4-treated hypoThyroid patients, while also exploring the most symptomatic patients. METHODOLOGY Prospective, randomized, double-blind, crossover study of 75 hypoThyroid patients randomly allocated to 1 of 3 treatment arms, LT4, LT4 + LT3, and DTE, for 22 weeks. The primary outcomes were posttreatment scores on the 36-point Thyroid symptom questionnaire (TSQ-36), 12-point quality of life general health questionnaire (GHQ-12), the Wechsler memory scale-version IV (VMS-IV), and the Beck Depression Inventory (BDI). Secondary endpoints included treatment preference, biochemical and metabolic parameters, etiology of hypoThyroidism, and Thr92Ala-DIO2 gene polymorphism. Analyses were performed with a linear mixed model using subject as a random factor and group as a fixed effect. RESULTS Serum TSH remained within reference range across all treatment arms. There were no differences for primary and secondary outcomes, except for a minor increase in heart rate caused by DTE. Treatment preference was not different and there were no interferences of the etiology of hypoThyroidism or Thr92Ala-DIO2 gene polymorphism in the outcomes. Subgroup analyses of the 1/3 most symptomatic patients on LT4 revealed strong preference for treatment containing T3, which improved performance on TSQ-36, GHQ-12, BDI, and visual memory index (VMS-IV component). CONCLUSIONS As a group, outcomes were similar among hypoThyroid patients taking DTE vs LT4 + T3 vs LT4. However, those patients that were most symptomatic on LT4 preferred and responded positively to therapy with LT4 + LT3 or DTE.
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desiccated Thyroid Extract versus synthetic lt4 t3 combination versus lt4 monotherapy in the treatment of primary hypoThyroidism with special attention to the thr92alad2 polymorphism with special attention to the gene polymorphism
Journal of the Endocrine Society, 2021Co-Authors: Thanh Duc Hoang, Vinh Q Mai, Antonio C Bianco, Daniel I Brooks, Elizabeth A Mcaninch, Tatiana L Fonseca, Mohamed K M ShakirAbstract:Introduction: Before the availability of levothyroxine (LT4), patients were treated with desiccated Thyroid Extract (DTE). When switching from DTE to LT4, despite adequate dosing based on serum TSH levels, some patients still feel unwell with fatigue, mental fogginess, weight gain etc. A recent randomized, crossed over study between DTE vs. LT4 conducted in our department showed that once-daily DTE caused modest weight loss and possible improvement in mental health scores without appreciable adverse effects; also, nearly half of the study patients preferred DTE over LT4. A few studies have shown that LT4/T3 combination had beneficial effects in improving quality of life relative to LT4 alone. Furthermore, it has been reported that patients with CC genotype in the deiodinase type 2 polymorphism responded more favorably with LT4/T3 combination than T4 monotherapy. Hypothesis: This study investigated the efficacy and effectiveness of DTE vs. LT4/T3 combination vs. LT4 monotherapy in hypoThyroid patients based on genotypic differences of deiodinase type 2. Methodology: This was a prospective, randomized, double-blind, crossover study. 75 subjects completed the study. There were 3 arms: DTE, LT4+T3 combination, and LT4 alone. Each subject was randomly allocated to one of these 3 arms for 12 weeks randomly. The study was powered to detect the primary outcome. The primary endpoint was post-treatment score on the 36-point Thyroid symptom questionnaire. Secondary endpoints were weight, general health questionnaire, the Beck depression inventory, Wechsler Memory testing, lipid panels and Thyroid function tests. Analysis was performed with a linear mixed model using subject as a random factor and group as a fixed effect. Results: There was no significant difference between the 3 arms on the Thyroid symptom questionnaire (p=.32), and the secondary outcomes showed no between group differences. Auditory memory index (p=.008), and visual working memory index (p=.02) were higher in the Hashimoto’s than non-Hashimoto’s group. There was no significant primary or secondary outcome difference among various genotypes of deiodinase 2. There was no relationship between Hashimoto’s vs. non-Hashimoto’s based on genotypes or likelihood of carrying Thr92AlaD2 polymorphism. Though there was no statistically significant preference for any treatment, numerically more patients with Hashimoto’s preferred DTE and LT4/T3 combination than LT4-monotherapy. Conclusions: There was no significant difference between hypoThyroid patients taking DTE vs. LT4/T3 combination vs. LT4 monotherapy. Numerically, Hashimoto’s patients tended to prefer DTE and LT4/T3 combination. Also, there was no observed relationship between Hashimoto’s and polymorphism. Further studies with more patients may be needed.
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desiccated Thyroid Extract compared with levothyroxine in the treatment of hypoThyroidism a randomized double blind crossover study
The Journal of Clinical Endocrinology and Metabolism, 2013Co-Authors: Thanh D Hoang, Cara H Olsen, Vinh Q Mai, Patrick W Clyde, Mohamed K M ShakirAbstract:Context: Patients previously treated with desiccated Thyroid Extract (DTE), when being switched to levothyroxine (l-T4), occasionally did not feel as well despite adequate dosing based on serum TSH levels. Objective: Our objective was to investigate the effectiveness of DTE compared with l-T4 in hypoThyroid patients. Design and Setting: We conducted a randomized, double-blind, crossover study at a tertiary care center. Patients: Patients (n = 70, age 18–65 years) diagnosed with primary hypoThyroidism on a stable dose of l-T4 for 6 months were included in the study. Intervention: Patients were randomized to either DTE or l-T4 for 16 weeks and then crossed over for the same duration. Outcome Measures: Biochemical and neurocognitive tests at baseline and at the end of each treatment period were evaluated. Results: There were no differences in symptoms and neurocognitive measurements between the 2 therapies. Patients lost 3 lb on DTE treatment (172.9 ± 36.4 lb vs 175.7 ± 37.7 lb, P < .001). At the end of the ...
Thanh D Hoang - One of the best experts on this subject based on the ideXlab platform.
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comparative effectiveness of levothyroxine desiccated Thyroid Extract and levothyroxine liothyronine in hypoThyroidism
The Journal of Clinical Endocrinology and Metabolism, 2021Co-Authors: Thanh D Hoang, Vinh Q Mai, Mohamed K M Shakir, Antonio C Bianco, Daniel I Brooks, Elizabeth A Mcaninch, Tatiana L FonsecaAbstract:INTRODUCTION Studies comparing levothyroxine (LT4) therapy with LT4 + liothyronine (LT3) or desiccated Thyroid Extract (DTE) did not detect consistent superiority of either treatment. Here, we investigated these therapies, focusing on the whole group of LT4-treated hypoThyroid patients, while also exploring the most symptomatic patients. METHODOLOGY Prospective, randomized, double-blind, crossover study of 75 hypoThyroid patients randomly allocated to 1 of 3 treatment arms, LT4, LT4 + LT3, and DTE, for 22 weeks. The primary outcomes were posttreatment scores on the 36-point Thyroid symptom questionnaire (TSQ-36), 12-point quality of life general health questionnaire (GHQ-12), the Wechsler memory scale-version IV (VMS-IV), and the Beck Depression Inventory (BDI). Secondary endpoints included treatment preference, biochemical and metabolic parameters, etiology of hypoThyroidism, and Thr92Ala-DIO2 gene polymorphism. Analyses were performed with a linear mixed model using subject as a random factor and group as a fixed effect. RESULTS Serum TSH remained within reference range across all treatment arms. There were no differences for primary and secondary outcomes, except for a minor increase in heart rate caused by DTE. Treatment preference was not different and there were no interferences of the etiology of hypoThyroidism or Thr92Ala-DIO2 gene polymorphism in the outcomes. Subgroup analyses of the 1/3 most symptomatic patients on LT4 revealed strong preference for treatment containing T3, which improved performance on TSQ-36, GHQ-12, BDI, and visual memory index (VMS-IV component). CONCLUSIONS As a group, outcomes were similar among hypoThyroid patients taking DTE vs LT4 + T3 vs LT4. However, those patients that were most symptomatic on LT4 preferred and responded positively to therapy with LT4 + LT3 or DTE.
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desiccated Thyroid Extract compared with levothyroxine in the treatment of hypoThyroidism a randomized double blind crossover study
The Journal of Clinical Endocrinology and Metabolism, 2013Co-Authors: Thanh D Hoang, Cara H Olsen, Vinh Q Mai, Patrick W Clyde, Mohamed K M ShakirAbstract:Context: Patients previously treated with desiccated Thyroid Extract (DTE), when being switched to levothyroxine (l-T4), occasionally did not feel as well despite adequate dosing based on serum TSH levels. Objective: Our objective was to investigate the effectiveness of DTE compared with l-T4 in hypoThyroid patients. Design and Setting: We conducted a randomized, double-blind, crossover study at a tertiary care center. Patients: Patients (n = 70, age 18–65 years) diagnosed with primary hypoThyroidism on a stable dose of l-T4 for 6 months were included in the study. Intervention: Patients were randomized to either DTE or l-T4 for 16 weeks and then crossed over for the same duration. Outcome Measures: Biochemical and neurocognitive tests at baseline and at the end of each treatment period were evaluated. Results: There were no differences in symptoms and neurocognitive measurements between the 2 therapies. Patients lost 3 lb on DTE treatment (172.9 ± 36.4 lb vs 175.7 ± 37.7 lb, P < .001). At the end of the ...
Vinh Q Mai - One of the best experts on this subject based on the ideXlab platform.
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comparative effectiveness of levothyroxine desiccated Thyroid Extract and levothyroxine liothyronine in hypoThyroidism
The Journal of Clinical Endocrinology and Metabolism, 2021Co-Authors: Thanh D Hoang, Vinh Q Mai, Mohamed K M Shakir, Antonio C Bianco, Daniel I Brooks, Elizabeth A Mcaninch, Tatiana L FonsecaAbstract:INTRODUCTION Studies comparing levothyroxine (LT4) therapy with LT4 + liothyronine (LT3) or desiccated Thyroid Extract (DTE) did not detect consistent superiority of either treatment. Here, we investigated these therapies, focusing on the whole group of LT4-treated hypoThyroid patients, while also exploring the most symptomatic patients. METHODOLOGY Prospective, randomized, double-blind, crossover study of 75 hypoThyroid patients randomly allocated to 1 of 3 treatment arms, LT4, LT4 + LT3, and DTE, for 22 weeks. The primary outcomes were posttreatment scores on the 36-point Thyroid symptom questionnaire (TSQ-36), 12-point quality of life general health questionnaire (GHQ-12), the Wechsler memory scale-version IV (VMS-IV), and the Beck Depression Inventory (BDI). Secondary endpoints included treatment preference, biochemical and metabolic parameters, etiology of hypoThyroidism, and Thr92Ala-DIO2 gene polymorphism. Analyses were performed with a linear mixed model using subject as a random factor and group as a fixed effect. RESULTS Serum TSH remained within reference range across all treatment arms. There were no differences for primary and secondary outcomes, except for a minor increase in heart rate caused by DTE. Treatment preference was not different and there were no interferences of the etiology of hypoThyroidism or Thr92Ala-DIO2 gene polymorphism in the outcomes. Subgroup analyses of the 1/3 most symptomatic patients on LT4 revealed strong preference for treatment containing T3, which improved performance on TSQ-36, GHQ-12, BDI, and visual memory index (VMS-IV component). CONCLUSIONS As a group, outcomes were similar among hypoThyroid patients taking DTE vs LT4 + T3 vs LT4. However, those patients that were most symptomatic on LT4 preferred and responded positively to therapy with LT4 + LT3 or DTE.
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desiccated Thyroid Extract versus synthetic lt4 t3 combination versus lt4 monotherapy in the treatment of primary hypoThyroidism with special attention to the thr92alad2 polymorphism with special attention to the gene polymorphism
Journal of the Endocrine Society, 2021Co-Authors: Thanh Duc Hoang, Vinh Q Mai, Antonio C Bianco, Daniel I Brooks, Elizabeth A Mcaninch, Tatiana L Fonseca, Mohamed K M ShakirAbstract:Introduction: Before the availability of levothyroxine (LT4), patients were treated with desiccated Thyroid Extract (DTE). When switching from DTE to LT4, despite adequate dosing based on serum TSH levels, some patients still feel unwell with fatigue, mental fogginess, weight gain etc. A recent randomized, crossed over study between DTE vs. LT4 conducted in our department showed that once-daily DTE caused modest weight loss and possible improvement in mental health scores without appreciable adverse effects; also, nearly half of the study patients preferred DTE over LT4. A few studies have shown that LT4/T3 combination had beneficial effects in improving quality of life relative to LT4 alone. Furthermore, it has been reported that patients with CC genotype in the deiodinase type 2 polymorphism responded more favorably with LT4/T3 combination than T4 monotherapy. Hypothesis: This study investigated the efficacy and effectiveness of DTE vs. LT4/T3 combination vs. LT4 monotherapy in hypoThyroid patients based on genotypic differences of deiodinase type 2. Methodology: This was a prospective, randomized, double-blind, crossover study. 75 subjects completed the study. There were 3 arms: DTE, LT4+T3 combination, and LT4 alone. Each subject was randomly allocated to one of these 3 arms for 12 weeks randomly. The study was powered to detect the primary outcome. The primary endpoint was post-treatment score on the 36-point Thyroid symptom questionnaire. Secondary endpoints were weight, general health questionnaire, the Beck depression inventory, Wechsler Memory testing, lipid panels and Thyroid function tests. Analysis was performed with a linear mixed model using subject as a random factor and group as a fixed effect. Results: There was no significant difference between the 3 arms on the Thyroid symptom questionnaire (p=.32), and the secondary outcomes showed no between group differences. Auditory memory index (p=.008), and visual working memory index (p=.02) were higher in the Hashimoto’s than non-Hashimoto’s group. There was no significant primary or secondary outcome difference among various genotypes of deiodinase 2. There was no relationship between Hashimoto’s vs. non-Hashimoto’s based on genotypes or likelihood of carrying Thr92AlaD2 polymorphism. Though there was no statistically significant preference for any treatment, numerically more patients with Hashimoto’s preferred DTE and LT4/T3 combination than LT4-monotherapy. Conclusions: There was no significant difference between hypoThyroid patients taking DTE vs. LT4/T3 combination vs. LT4 monotherapy. Numerically, Hashimoto’s patients tended to prefer DTE and LT4/T3 combination. Also, there was no observed relationship between Hashimoto’s and polymorphism. Further studies with more patients may be needed.
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desiccated Thyroid Extract compared with levothyroxine in the treatment of hypoThyroidism a randomized double blind crossover study
The Journal of Clinical Endocrinology and Metabolism, 2013Co-Authors: Thanh D Hoang, Cara H Olsen, Vinh Q Mai, Patrick W Clyde, Mohamed K M ShakirAbstract:Context: Patients previously treated with desiccated Thyroid Extract (DTE), when being switched to levothyroxine (l-T4), occasionally did not feel as well despite adequate dosing based on serum TSH levels. Objective: Our objective was to investigate the effectiveness of DTE compared with l-T4 in hypoThyroid patients. Design and Setting: We conducted a randomized, double-blind, crossover study at a tertiary care center. Patients: Patients (n = 70, age 18–65 years) diagnosed with primary hypoThyroidism on a stable dose of l-T4 for 6 months were included in the study. Intervention: Patients were randomized to either DTE or l-T4 for 16 weeks and then crossed over for the same duration. Outcome Measures: Biochemical and neurocognitive tests at baseline and at the end of each treatment period were evaluated. Results: There were no differences in symptoms and neurocognitive measurements between the 2 therapies. Patients lost 3 lb on DTE treatment (172.9 ± 36.4 lb vs 175.7 ± 37.7 lb, P < .001). At the end of the ...
Elizabeth A Mcaninch - One of the best experts on this subject based on the ideXlab platform.
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comparative effectiveness of levothyroxine desiccated Thyroid Extract and levothyroxine liothyronine in hypoThyroidism
The Journal of Clinical Endocrinology and Metabolism, 2021Co-Authors: Thanh D Hoang, Vinh Q Mai, Mohamed K M Shakir, Antonio C Bianco, Daniel I Brooks, Elizabeth A Mcaninch, Tatiana L FonsecaAbstract:INTRODUCTION Studies comparing levothyroxine (LT4) therapy with LT4 + liothyronine (LT3) or desiccated Thyroid Extract (DTE) did not detect consistent superiority of either treatment. Here, we investigated these therapies, focusing on the whole group of LT4-treated hypoThyroid patients, while also exploring the most symptomatic patients. METHODOLOGY Prospective, randomized, double-blind, crossover study of 75 hypoThyroid patients randomly allocated to 1 of 3 treatment arms, LT4, LT4 + LT3, and DTE, for 22 weeks. The primary outcomes were posttreatment scores on the 36-point Thyroid symptom questionnaire (TSQ-36), 12-point quality of life general health questionnaire (GHQ-12), the Wechsler memory scale-version IV (VMS-IV), and the Beck Depression Inventory (BDI). Secondary endpoints included treatment preference, biochemical and metabolic parameters, etiology of hypoThyroidism, and Thr92Ala-DIO2 gene polymorphism. Analyses were performed with a linear mixed model using subject as a random factor and group as a fixed effect. RESULTS Serum TSH remained within reference range across all treatment arms. There were no differences for primary and secondary outcomes, except for a minor increase in heart rate caused by DTE. Treatment preference was not different and there were no interferences of the etiology of hypoThyroidism or Thr92Ala-DIO2 gene polymorphism in the outcomes. Subgroup analyses of the 1/3 most symptomatic patients on LT4 revealed strong preference for treatment containing T3, which improved performance on TSQ-36, GHQ-12, BDI, and visual memory index (VMS-IV component). CONCLUSIONS As a group, outcomes were similar among hypoThyroid patients taking DTE vs LT4 + T3 vs LT4. However, those patients that were most symptomatic on LT4 preferred and responded positively to therapy with LT4 + LT3 or DTE.
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desiccated Thyroid Extract versus synthetic lt4 t3 combination versus lt4 monotherapy in the treatment of primary hypoThyroidism with special attention to the thr92alad2 polymorphism with special attention to the gene polymorphism
Journal of the Endocrine Society, 2021Co-Authors: Thanh Duc Hoang, Vinh Q Mai, Antonio C Bianco, Daniel I Brooks, Elizabeth A Mcaninch, Tatiana L Fonseca, Mohamed K M ShakirAbstract:Introduction: Before the availability of levothyroxine (LT4), patients were treated with desiccated Thyroid Extract (DTE). When switching from DTE to LT4, despite adequate dosing based on serum TSH levels, some patients still feel unwell with fatigue, mental fogginess, weight gain etc. A recent randomized, crossed over study between DTE vs. LT4 conducted in our department showed that once-daily DTE caused modest weight loss and possible improvement in mental health scores without appreciable adverse effects; also, nearly half of the study patients preferred DTE over LT4. A few studies have shown that LT4/T3 combination had beneficial effects in improving quality of life relative to LT4 alone. Furthermore, it has been reported that patients with CC genotype in the deiodinase type 2 polymorphism responded more favorably with LT4/T3 combination than T4 monotherapy. Hypothesis: This study investigated the efficacy and effectiveness of DTE vs. LT4/T3 combination vs. LT4 monotherapy in hypoThyroid patients based on genotypic differences of deiodinase type 2. Methodology: This was a prospective, randomized, double-blind, crossover study. 75 subjects completed the study. There were 3 arms: DTE, LT4+T3 combination, and LT4 alone. Each subject was randomly allocated to one of these 3 arms for 12 weeks randomly. The study was powered to detect the primary outcome. The primary endpoint was post-treatment score on the 36-point Thyroid symptom questionnaire. Secondary endpoints were weight, general health questionnaire, the Beck depression inventory, Wechsler Memory testing, lipid panels and Thyroid function tests. Analysis was performed with a linear mixed model using subject as a random factor and group as a fixed effect. Results: There was no significant difference between the 3 arms on the Thyroid symptom questionnaire (p=.32), and the secondary outcomes showed no between group differences. Auditory memory index (p=.008), and visual working memory index (p=.02) were higher in the Hashimoto’s than non-Hashimoto’s group. There was no significant primary or secondary outcome difference among various genotypes of deiodinase 2. There was no relationship between Hashimoto’s vs. non-Hashimoto’s based on genotypes or likelihood of carrying Thr92AlaD2 polymorphism. Though there was no statistically significant preference for any treatment, numerically more patients with Hashimoto’s preferred DTE and LT4/T3 combination than LT4-monotherapy. Conclusions: There was no significant difference between hypoThyroid patients taking DTE vs. LT4/T3 combination vs. LT4 monotherapy. Numerically, Hashimoto’s patients tended to prefer DTE and LT4/T3 combination. Also, there was no observed relationship between Hashimoto’s and polymorphism. Further studies with more patients may be needed.
-
the history and future of treatment of hypoThyroidism
Annals of Internal Medicine, 2016Co-Authors: Elizabeth A Mcaninch, Antonio C BiancoAbstract:Thyroid hormone replacement has been used for more than a century to treat hypoThyroidism. Natural Thyroid preparations (Thyroid Extract, desiccated Thyroid, or thyroglobulin), which contain both thyroxine (T4) and triiodothyronine (T3), were the first pharmacologic treatments available and dominated the market for the better part of the 20th century. Dosages were adjusted to resolve symptoms and to normalize the basal metabolic rate and/or serum protein-bound iodine level, but thyrotoxic adverse effects were not uncommon. Two major developments in the 1970s led to a transition in clinical practice: 1) The development of the serum Thyroid-stimulating hormone (TSH) radioimmunoassay led to the discovery that many patients were overtreated, resulting in a dramatic reduction in Thyroid hormone replacement dosage, and 2) the identification of peripheral deiodinase-mediated T4-to-T3 conversion provided a physiologic means to justify l-thyroxine monotherapy, obviating concerns about inconsistencies with desiccated Thyroid. Thereafter, l-thyroxine monotherapy at doses to normalize the serum TSH became the standard of care. Since then, a subgroup of Thyroid hormone-treated patients with residual symptoms of hypoThyroidism despite normalization of the serum TSH has been identified. This has brought into question the inability of l-thyroxine monotherapy to universally normalize serum T3 levels. New research suggests mechanisms for the inadequacies of l-thyroxine monotherapy and highlights the possible role for personalized medicine based on deiodinase polymorphisms. Understanding the historical events that affected clinical practice trends provides invaluable insight into formulation of an approach to help all patients achieve clinical and biochemical euThyroidism.