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Beate
Inscrit le: 10.10.00 Messages: 50593Carcinome papillaire... 60+ |
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Posté le: 15. Aoû 2008, 13:44
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Bonjour,
en me baladant sur le site américain NCBI - PubMed , j'ai trouvé les "abstracts", résumés, de quelques études intéressantes qui comparaissaient le traitement "T4 seule" au traitement combiné T4 + T3.
Il y en a même eu une concernant le traitement combiné après cancer de la thyroïde, en 2007, que je ne connaissais pas encore (les autres, on en parle régulièrement lors de divers congrès, le premier qui s'est intéressé à ce sujet fût Bunevicius en 1999) - mais même si apparemment, dans pratiquement toutes ces études, les PATIENTS préféraient le traitement combiné, il n'y a toujours pas de véritable consensus là-dessus dans le monde médical, car les résultats sont trop "subjectifs", pas suffisamment "mesurables" ...  - et il est vrai que la T3 n'est pas sans risques, si elle est mal utilisée (car très puissante et très rapide, elle peut donc être beaucoup plus dangéreuse, notamment pour le coeur, en cas de surdosage ou d'introduction trop rapide), donc la plupart des médecins restent très prudents, le lévothyrox est "tellement plus simple", avec sa longue demi-vie ...
Voilà donc les différents articles, par ordre chronologique (j'ai dû faire plusieurs messages, apparemment on ne peut faire qu'un nombre limité de citations par message) :
| Citation: | N Engl J Med. 1999 Feb 11;340(6):424-9.
Comment in:
Ann Intern Med. 2005 Oct 4;143(7):543; author reply 543-4.
N Engl J Med. 1999 Feb 11;340(6):469-70.
Effects of thyroxine as compared with thyroxine plus triiodothyronine in patients with hypothyroidism.
Bunevicius R, Kazanavicius G, Zalinkevicius R, Prange AJ Jr.
Institute of Endocrinology, Kaunas Medical University, Lithuania.
BACKGROUND: Patients with hypothyroidism are usually treated with thyroxine (levothyroxine) only, although both thyroxine and triiodothyronine are secreted by the normal thyroid gland. Whether thyroid secretion of triiodothyronine is physiologically important is unknown. METHODS: We compared the effects of thyroxine alone with those of thyroxine plus triiodothyronine (liothyronine) in 33 patients with hypothyroidism. Each patient was studied for two five-week periods. During one period, the patient received his or her usual dose of thyroxine. During the other, the patient received a regimen in which 50 microg of the usual dose of thyroxine was replaced by 12.5 microg of triiodothyronine. The order in which each patient received the two treatments was randomized. Biochemical, physiologic, and psychological tests were performed at the end of each treatment period. RESULTS: The patients had lower serum free and total thyroxine concentrations and higher serum total triiodothyronine concentrations after treatment with thyroxine plus triiodothyronine than after thyroxine alone, whereas the serum thyrotropin concentrations were similar after both treatments. Among 17 scores on tests of cognitive performance and assessments of mood, 6 were better or closer to normal after treatment with thyroxine plus triiodothyronine. Similarly, among 15 visual-analogue scales used to indicate mood and physical status, the results for 10 were significantly better after treatment with thyroxine plus triiodothyronine. The pulse rate and serum sex hormone-binding globulin concentrations were slightly higher after treatment with thyroxine plus triiodothyronine, but blood pressure, serum lipid concentrations, and the results of neurophysiologic tests were similar after the two treatments. CONCLUSIONS: In patients with hypothyroidism, partial substitution of triiodothyronine for thyroxine may improve mood and neuropsychological function; this finding suggests a specific effect of the triiodothyronine normally secreted by the thyroid gland. |
| Citation: | Endocrine. 2002 Jul;18(2):129-33.
Thyroxine vs thyroxine plus triiodothyronine in treatment of hypothyroidism after thyroidectomy for Graves' disease.
Bunevicius R, Jakubonien N, Jurkevicius R, Cernicat J, Lasas L, Prange AJ Jr.
Institute of Endocrinology, Clinic of the Kaunas Medical University, Lithuania.
It was recently demonstrated that treatment with levorotatory thyroxine (T4) plus triiodothyronine (T3) compared with treatment with T4 alone improves psychologic functioning in hypothyroid patients with thyroid cancer or autoimmune thyroiditis. In the present double-blind crossover study, we again compared the effects of combined thyroid replacement vs monotherapy on psychologic function, endocrine function, cardiovascular function, and body composition. The patients were women who were hypothyroid after thyroidectomy for Graves' disease. The substitution of 10 microg of T3 for 50 microg of T4 caused a statistically significant decrease in free T4 concentration but no significant change in T3 or thyroid-stimulating hormone concentration. Symptoms of hypothyroidism and of hyperthyroidism tended to decrease on a standard symptom scale after combined treatment. With combined hormone replacement, mental state tended to improve on some mood scales but not on cognitive tests. We found alterations in left ventricular diastolic function but no change in body composition after the combined treatment regimen. These preliminary findings in a small group of patients with Graves' disease are consistent with earlier findings that thyroid replacement with T4-T3 combination improves mental functioning. |
| Citation: | J Clin Endocrinol Metab. 2003 Oct;88(10):4543-50
Combined thyroxine/liothyronine treatment does not improve well-being, quality of life, or cognitive function compared to thyroxine alone: a randomized controlled trial in patients with primary hypothyroidism.
Walsh JP, Shiels L, Lim EM, Bhagat CI, Ward LC, Stuckey BG, Dhaliwal SS, Chew GT, Bhagat MC, Cussons AJ.
Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia. john.walsh@health.wa.gov.au
T(4) is standard treatment for hypothyroidism. A recent study reported that combined T(4)/liothyronine (T(3)) treatment improved well-being and cognitive function compared with T(4) alone. We conducted a double-blind, randomized, controlled trial with a crossover design in 110 patients (101 completers) with primary hypothyroidism in which liothyronine 10 micro g was substituted for 50 micro g of the patients' usual T(4) dose. No significant (P < 0.05) difference between T(4) and combined T(4)/T(3) treatment was demonstrated on cognitive function, quality of life scores, Thyroid Symptom Questionnaire scores, subjective satisfaction with treatment, or eight of 10 visual analog scales assessing symptoms. For the General Health Questionnaire-28 and visual analog scales assessing anxiety and nausea, scores were significantly (P < 0.05) worse for combined treatment than for T(4) alone. Serum TSH was lower during T(4) treatment than during combined T(4)/T(3) treatment (mean +/- SEM, 1.5 +/- 0.2 vs. 3.1 +/- 0.2 mU/liter; P < 0.001), a potentially confounding factor; however, subgroup analysis of subjects with comparable serum TSH concentrations during each treatment showed no benefit from combined treatment compared with T(4) alone. We conclude that in the doses used in this study, combined T(4)/T(3) treatment does not improve well-being, cognitive function, or quality of life compared with T(4) alone. |
| Citation: | JAMA. 2003 Dec 10;290(22):2952-8
Combined levothyroxine plus liothyronine compared with levothyroxine alone in primary hypothyroidism: a randomized controlled trial.
Clyde PW, Harari AE, Getka EJ, Shakir KM.
Department of Endocrinology and Metabolism, Nation Naval Medical Center, Bethesda, Md 20889-5600, USA. pwclyde@mar.med.navy.mil
CONTEXT: Standard therapy for patients with primary hypothyroidism is replacement with synthetic thyroxine, which undergoes peripheral conversion to triiodothyronine, the active form of thyroid hormone. Within the lay population and in some medical communities, there is a perception that adding synthetic triiodothyronine, or liothyronine, to levothyroxine improves the symptoms of hypothyroidism despite insufficient evidence to support this practice. OBJECTIVE: To evaluate the benefits of treating primary hypothyroidism with levothyroxine plus liothyronine combination therapy vs levothyroxine monotherapy. DESIGN, SETTING, AND PATIENTS: Randomized, double-blind, placebo-controlled trial conducted from May 2000 to February 2002 at a military treatment facility that serves active duty and retired military personnel and their family members. The trial included a total of 46 patients aged 24 to 65 years with at least a 6-month history of treatment with levothyroxine for primary hypothyroidism. INTERVENTION: Patients received either their usual dose of levothyroxine (n = 23) or combination therapy (n = 23), in which their usual levothyroxine dose was reduced by 50 micro g/d and substituted with liothyronine, 7.5 micro g, taken twice daily for 4 months. MAIN OUTCOME MEASURES: Scores on a hypothyroid-specific health-related quality-of-life (HRQL) questionnaire, body weight, serum lipid levels, and 13 neuropsychological tests measured before and after treatment. RESULTS: Serum thyrotropin levels remained similar and within the normal range in both treatment groups from baseline to 4 months. Body weight and serum lipid levels did not change. The HRQL questionnaire scores improved significantly in both the control group (23%; P<.001) and the combination therapy group (12%; P =.02), but these changes were statistically similar (P =.54). In 12 of 13 neuropsychological tests, outcomes between groups were not significantly different; the 1 remaining test (Grooved Peg Board) showed better performance in the control group. CONCLUSION: Compared with levothyroxine alone, treatment of primary hypothyroidism with combination levothyroxine plus liothyronine demonstrated no beneficial changes in body weight, serum lipid levels, hypothyroid symptoms as measured by a HRQL questionnaire, and standard measures of cognitive performance. |
| Citation: | Clin Endocrinol (Oxf). 2004 Jun;60(6):750-7
Replacement therapy with levothyroxine plus triiodothyronine (bioavailable molar ratio 14 : 1) is not superior to thyroxine alone to improve well-being and cognitive performance in hypothyroidism.
Siegmund W, Spieker K, Weike AI, Giessmann T, Modess C, Dabers T, Kirsch G, Sänger E, Engel G, Hamm AO, Nauck M, Meng W.
Department of Clinical Pharmacology of the Peter Holtz Research Centre of Pharmacology and Experimental Therapeutics, Ernst Moritz Arndt University, Greifswald, Germany.
OBJECTIVES: There is evidence from recent controlled clinical studies that replacement therapy of hypothyroidism with T4 in combination with a small amount of T3 may improve the well-being of the patients. As the issue is still the subject of controversial discussion, our study was assigned to confirm the superiority of a physiological combination of thyroid hormones (absorbed molar ratio 14 : 1) over T4 alone with regard to mood states and cognitive functioning. DESIGN AND PATIENTS: After a run-in period with the T4 study medication for 4 weeks, a controlled, randomized, double-blind, two-period (each 12 weeks), cross-over study without washout between the treatment periods was performed in 23 hypothyroid patients (three males, 20 females, age 23-69 years, 21 subjects after surgery/radioiodine, two with autoimmune thyroiditis) to compare the effects of the previous individual T4 dose (100-175 micro g) with a treatment in which 5% of the respective T4 dose was substituted by T3. MEASUREMENTS: Standard hormonal characteristics and standardized psychological tests to quantify mood and cognitive performance were measured after the run-in period and at the end of each treatment period. In 12 subjects, the concentration-time profiles of fT3 and fT4 were compared after the last administration of the respective study medication. TSH, fT3 and fT4 were measured with immunological assays. CLINICAL RESULTS: Replacement therapy with T4 and T4/T3 was not different in all steady-state hormonal, metabolic and cardiovascular characteristics except for TSH, which was more suppressed after T4/T3. The efficacy of replacement therapy with the T4/T3 combination was not different from the T4 monotherapy with regard to all psychological test scores describing mood and cognitive functioning of the patients. Mood was even significantly impaired by the T4/T3 combination in eight subjects, with TSH < 0.02 mU/l, compared to patients with normal TSH (Beck Depression Inventory: 8.25 +/- 5.01 vs. 4.07 +/- 5.60, P = 0.026). PHARMACOKINETIC RESULTS: The area under the concentration-time curve (AUC(0-8h)) of fT3 was significantly higher after T4/T3 compared to the T4 monotherapy (42.8 +/- 9.03 pmol x h/l vs. 36.3 +/- 8.50 pmol x h/l, P < 0.05) and was significantly correlated to serum TSH (r(s) = -0.609, P < 0.05). After T4/T3, patients with a history of Graves' disease or autoimmune thyroiditis had significantly higher serum trough levels of fT3 whereas the fT4 concentrations were significantly lower in patients with a nonautoimmune background. CONCLUSION: Replacement therapy of hypothyroidism with T4 plus T3 does not improve mood and cognitive performance compared to the standard T4 monotherapy. There is even a higher risk of signs of subclinical hyperthyroidism associated with impaired well-being of the patients, which is clearly caused by significant fluctuations in the steady-state fT3 serum concentrations. |
Beate
Dernière édition par Beate le 15. Aoû 2008, 13:53; édité 1 fois |
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Beate
Inscrit le: 10.10.00 Messages: 50593Carcinome papillaire... 60+ |
Message: (p167933)
Posté le: 15. Aoû 2008, 13:45
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| Citation: | Hormones (Athens). 2005 Apr-Jun;4(2):101-7.
TSH and thyroid hormones concentrations in patients with hypothyroidism receiving replacement therapy with L-thyroxine alone or in combination with L-triiodothyronine.
Fadeyev VV, Morgunova TB, Sytch JP, Melnichenko GA.
Department of Endocrinology of Moscow Medical Academy, Moscow, 119992, Russia. walfad@nccom.ru
The aim of this study was to evaluate parameters of thyroid function in patients with primary hypothyroidism receiving either monotherapy with L-T4 or combination L-T4+L-T3. Fifty-eight women with primary hypothyroidism receiving L-T4 were enrolled in the study. The patients were randomised into two groups: Group 1 (n=42) patients continued monotherapy with L-T4, and Group 2 (n=16) patients were switched to combined therapy with L-T4+L-T3 (25 microg L-T4 was replaced with 12.5 microg L-T3). The final examination was carried out 6 months thereafter. There was also a third group of 20 healthy women (control group). Under monotherapy with L-T4, serum FT4 levels were higher (p < 0.05) and FT3 lower (p < 0.05) than in the control group, while the monotherapy subgroup of patients with low-normal TSH had serum FT4 levels higher than in the control group (p < 0.05). Serum FT4 under combined therapy was significantly lower than in both control and monotherapy groups. FT3 levels did not differ between the two groups of combined and monotherapy subjects; the highest FT3 levels were in the control group. L-T4 replacement therapy is associated with non-physiologically high FT4 and low FT3 levels. Therapy with L-T3 once a day does not simulate the normal production of T3 by the thyroid. |
| Citation: | Ann Intern Med. 2005 Mar 15;142(6):412-24.Links
Thyroid hormone replacement therapy in primary hypothyroidism: a randomized trial comparing L-thyroxine plus liothyronine with L-thyroxine alone.
Escobar-Morreale HF, Botella-Carretero JI, Gómez-Bueno M, Galán JM, Barrios V, Sancho J.
Department of Endocrinology, Hospital Ramón y Cajal, Madrid, Spain. hescobarm.hrc@salud.madrid.org
BACKGROUND: Substituting part of the dose of l-thyroxine with small but supraphysiologic doses of liothyronine in hypothyroid patients has yielded conflicting results. OBJECTIVE: To evaluate combinations of L-thyroxine plus liothyronine in hypothyroid patients that match the proportions present in normal secretions of the human thyroid gland. DESIGN: Randomized, double-blind, crossover trial. SETTING: Academic research hospital. PARTICIPANTS: 28 women with overt primary hypothyroidism. INTERVENTION: Crossover trial comparing treatment with l-thyroxine, 100 microg/d (standard treatment), versus treatment with L-thyroxine, 75 microg/d, plus liothyronine, 5 microg/d (combination treatment), for 8-week periods. All patients also received L-thyroxine, 87.5 microg/d, plus liothyronine, 7.5 microg/d (add-on combination treatment), for a final 8-week add-on period. MEASUREMENTS: Primary outcomes included serum thyroid hormone levels, results of quality-of-life and psychometric tests, and patients' preference. Multiple biological thyroid hormone end points were studied as secondary outcomes. RESULTS: Compared with standard treatment, combination treatment led to lower free thyroxine levels (decrease, 3.9 pmol/L [95% CI, 2.5 to 5.3 pmol/L]), slightly higher serum levels of thyroid-stimulating hormone (increase, 0.62 mU/L [CI, 0.01 to 1.23 mU/L]), and unchanged free triiodothyronine levels. No improvement was observed in the other primary and secondary end points after combination treatment, with the exception of the Digit Span Test, in which the mean backward score and the mean total score increased slightly (0.6 digit [CI, 0.1 to 1.0 digit] and 0.8 digit [CI, 0.2 to 1.4 digits], respectively). The add-on combination treatment resulted in overreplacement. Levels of thyroid-stimulating hormone decreased by 0.85 mU/L (CI, 0.27 to 1.43 mU/L) and serum free triiodothyronine levels increased by 0.8 pmol/L (CI, 0.1 to 1.5 pmol/L) compared with standard treatment; 10 patients had levels of thyroid-stimulating hormone that were below the normal range. Twelve patients preferred combination treatment, 6 patients preferred the add-on combination treatment, 2 patients preferred standard treatment, and 6 patients had no preference (P = 0.015). LIMITATIONS: Treatment with L-thyroxine, 87.5 microg/d, plus liothyronine, 7.5 microg/d, was an add-on regimen and was not randomized. CONCLUSIONS: Physiologic combinations of L-thyroxine plus liothyronine do not offer any objective advantage over l-thyroxine alone, yet patients prefer combination treatment. |
Article complèt : http://www.annals.org/cgi/reprint/142/6/412.pdf
| Citation: | Endocr Pract. 2005 Jul-Aug;11(4):223-33.
Substitution of liothyronine at a 1:5 ratio for a portion of levothyroxine: effect on fatigue, symptoms of depression, and working memory versus treatment with levothyroxine alone.
Rodriguez T, Lavis VR, Meininger JC, Kapadia AS, Stafford LF.
College of Nursing, Texas Woman's University, Institute of Health Sciences, Houston, Texas 77030, USA.
OBJECTIVE: To attempt to confirm a previous report of superior effectiveness of using two thyroid hormones rather than one hormone to treat hypothyroidism. METHODS: This trial attempted to replicate prior findings, which suggested that substituting 12.5 microg of liothyronine (LT(3)) for 50 microg of levothyroxine (LT(4)) might improve mood, cognition, and physical symptoms in patients with primary hypothyroidism. Additionally, this trial aimed to extend the previous findings to fatigue and to assess for differential effects in subjects with low fatigue and high fatigue at baseline. A randomized, double-blind, two-period, crossover design was used. At an endocrinology and diabetes clinic, 30 adult subjects with primary hypothyroidism stabilized on LT(4) were recruited. Patients randomly assigned to treatment sequence 1 received their standard LT(4) dose in one capsule and placebo in another. Patients assigned to sequence 2 received their usual LT(4) dose minus 50 microg in one capsule and 10 microg of LT(3) in the other. At the end of the first 6 weeks, subjects were crossed over to receive the other treatment. Carryover and treatment effects were assessed by t tests. RESULTS: Of the 30 enrolled study subjects, 27 completed the trial. The mean LT(4) dose was 121 +/- 26 microg/day at baseline. No significant differences in fatigue and symptoms of depression were found between treatments. Measures of working memory were unchanged. During substitution treatment, the free thyroxine index was reduced by 0.7 (P<0.001), total serum thyroxine was reduced by 3.0 microg/dL (P<0.001), and total serum triiodothyronine was increased by 20.5 ng/dL (P = 0.004). CONCLUSION: With regard to the outcomes measured, substitution of LT(3) at a 1:5 ratio for a portion of baseline LT(4) yielded no better results than did treatment with the original dose of LT(4) alone. |
| Citation: | J Clin Endocrinol Metab. 2005 May;90(5):2666-74. Epub 2005 Feb 10.
Combined therapy with levothyroxine and liothyronine in two ratios, compared with levothyroxine monotherapy in primary hypothyroidism: a double-blind, randomized, controlled clinical trial.
Appelhof BC, Fliers E, Wekking EM, Schene AH, Huyser J, Tijssen JG, Endert E, van Weert HC, Wiersinga WM.
Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, F5-161, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands. b.c.appelhof@amc.uva.nl
Controversy remains about the value of combined treatment with levothyroxine (LT4) and liothyronine (LT3), compared with LT4 alone in primary hypothyroidism. We compared combined treatment with LT4 and LT3 in a ratio of 5:1 or 10:1 with LT4 monotherapy. We conducted a double-blind, randomized, controlled trial in 141 patients (18-70 yr old) with primary autoimmune hypothyroidism, recruited via general practitioners. Inclusion criteria included: LT4 treatment for 6 months or more, a stable dose for 6 wk or more, and serum TSH levels between 0.11 and 4.0 microU/ml (mU/liter). Randomization groups were: 1) continuation of LT4 (n = 48); 2) LT4/LT3, ratio 10:1 (n = 46); and 3) LT4/LT3, ratio 5:1 (n = 47). Subjective preference of study medication after 15 wk, compared with usual LT4, was the primary outcome measure. Secondary outcomes included scores on questionnaires on mood, fatigue, psychological symptoms, and a substantial set of neurocognitive tests. Study medication was preferred to usual treatment by 29.2, 41.3, and 52.2% in the LT4, 10:1 ratio, and 5:1 ratio groups, respectively (chi2 test for trend, P = 0.024). This linear trend was not substantiated by results on any of the secondary outcome measures: scores on questionnaires and neurocognitive tests consistently ameliorated, but the amelioration was not different among the treatment groups. Median end point serum TSH was 0.64 microU/ml (mU/liter), 0.35 microU/ml (mU/liter), and 0.07 microU/ml (mU/liter), respectively [ANOVA on ln(TSH) for linear trend, P < 0.01]. Mean body weight change was +0.1, -0.5, and -1.7 kg, respectively (ANOVA for trend, P = 0.01). Decrease in weight, but not decrease in serum TSH was correlated with increased satisfaction with study medication. Of the patients who preferred combined LT4/LT3 therapy, 44% had serum TSH less than 0.11 microU/ml (mU/liter). Patients preferred combined LT4/LT3 therapy to usual LT4 therapy, but changes in mood, fatigue, well-being, and neurocognitive functions could not satisfactorily explain why the primary outcome was in favor of LT4/LT3 combination therapy. Decrease in body weight was associated with satisfaction with study medication. |
| Citation: | J Clin Endocrinol Metab. 2005 Aug;90(8):4946-54. Epub 2005 May 31.
REVIEW: Treatment of hypothyroidism with combinations of levothyroxine plus liothyronine.
Escobar-Morreale HF, Botella-Carretero JI, Escobar del Rey F, Morreale de Escobar G.
Department of Endocrinology, Hospital Ramón y Cajal, Madrid, Spain.
CONTEXT: Combined infusion of levothyroxine plus liothyronine, as opposed to levothyroxine alone, is the only way of restoring the concentrations of circulating TSH, T4, and T3 as well as those of both T4 and T3 in all tissues of thyroidectomized rats. Considering the substantial differences in thyroid hormone secretion, transport, and metabolism between rats and humans, whether or not combined levothyroxine plus liothyronine replacement therapy has advantages over treatment with levothyroxine alone in hypothyroid patients is still questioned. EVIDENCE ACQUISITION: We conducted a systematic review of all the published controlled studies comparing treatment with levothyroxine alone with combinations of levothyroxine plus liothyronine in hypothyroid patients, identified through the Entrez-PubMed search engine. EVIDENCE SYNTHESIS: Nine controlled clinical trials were identified that compared treatment with levothyroxine alone and treatment with combinations of levothyroxine plus liothyronine and included a sufficient number of adult hypothyroid patients to yield meaningful results. In only one study did the combined therapy appear to have beneficial effects on the mood, quality of life, and psychometric performance of the patients over levothyroxine alone. These results have not been confirmed by later studies using either T3 substitution protocols or approaches with fixed combinations of levothyroxine plus liothyronine, including those based on the physiological proportion in which T3 and T4 are secreted by the human thyroid. However, in some of these studies the patients preferred levothyroxine plus liothyronine combinations, for reasons not explained by changes in the psychological and psychometric tests employed. Yet patients' preference should be balanced against the possibility of adverse events resulting from the addition of liothyronine to levothyroxine, even in the small doses used in these studies. CONCLUSIONS: Until clear advantages of levothyroxine plus liothyronine are demonstrated, the administration of levothyroxine alone should remain the treatment of choice for replacement therapy of hypothyroidism. |
| Citation: | J Clin Endocrinol Metab. 2006 Jul;91(7):2624-30. Epub 2006 May 2.
Small changes in thyroxine dosage do not produce measurable changes in hypothyroid symptoms, well-being, or quality of life: results of a double-blind, randomized clinical trial.
Walsh JP, Ward LC, Burke V, Bhagat CI, Shiels L, Henley D, Gillett MJ, Gilbert R, Tanner M, Stuckey BG.
Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Western Australia. john.walsh@health.wa.gov.au
CONTEXT: In patients with primary hypothyroidism, anecdotal evidence suggests that well-being is optimized by fine adjustment of T(4) dosage, aiming for a serum TSH concentration in the lower reference range. This has not been tested in a clinical trial. OBJECTIVE: Our objective was to test whether adjustment of T(4) dosage aiming for a serum TSH concentration less than 2 mU/liter improves well-being compared with a serum TSH concentration in the upper reference range. DESIGN: We conducted a double-blind, randomized clinical trial with a crossover design. PARTICIPANTS: Fifty-six subjects (52 females) with primary hypothyroidism taking T(4) (>/=100 microg/d) with baseline serum TSH 0.1-4.8 mU/liter participated. INTERVENTIONS: Each subject received three T(4) doses (low, middle, and high in 25-microg increments) in random order. OUTCOME MEASURES: Outcome measures included visual analog scales assessing well-being (the primary endpoint) and hypothyroid symptoms, quality of life instruments (General Health Questionnaire 28, Short Form 36, and Thyroid Symptom Questionnaire), cognitive function tests, and treatment preference. RESULTS: Mean (+/- sem) serum TSH concentrations were 2.8 +/- 0.4, 1.0 +/- 0.2, and 0.3 +/- 0.1 mU/liter for the three treatments. There were no significant treatment effects on any of the instruments assessing well-being, symptoms, quality of life, or cognitive function and no significant treatment preference. CONCLUSIONS: Small changes in T(4) dosage do not produce measurable changes in hypothyroid symptoms, well-being, or quality of life, despite the expected changes in serum TSH and markers of thyroid hormone action. These data do not support the suggestion that the target TSH range for the treatment of primary hypothyroidism should differ from the general laboratory range. |
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Beate
Inscrit le: 10.10.00 Messages: 50593Carcinome papillaire... 60+ |
Message: (p167934)
Posté le: 15. Aoû 2008, 13:46
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| Citation: | Exp Clin Endocrinol Diabetes. 2007 Apr;115(4):261-7.
Twenty-four hour hormone profiles of TSH, Free T3 and free T4 in hypothyroid patients on combined T3/T4 therapy.
Saravanan P, Siddique H, Simmons DJ, Greenwood R, Dayan CM.
Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Bristol, UK.
The benefits of using thyroxine (T4) plus triiodothyronine (T3) in combination in thyroid hormone replacement are unproven but many individuals continue to be treated with this regime. When T3 is used alone for hypothyroidism, it results in wide fluctuations of thyroid hormone levels. However, only limited data exists on combined T3/T4 therapy. In this study, we have compared 24-hour profiles of thyroid stimulating hormone (TSH), free T4 (fT4) and free T3 (fT3) and cardiovascular parameters in 10 hypothyroid patients who had been on once daily combined T3/T4 therapy for more than 3 months with 10 patients on T4 alone. Twenty patients, who were part of a larger study, investigating the long-term benefits of combined T3/T4 therapy, were recruited into this sub-study. Over 24-hours, 12 samples were taken for thyroid hormones. Their 24-hour pulse and BP is also monitored on a separate occasion. On T4 alone, a modest 16% rise in fT4 with no change in fT3 was seen in the first 4-hours post-dose. In contrast, on combined treatment, fT3 levels showed a marked rise of 42% within the first 4-hours post-dose (T3/T4:T4=6.24: 4.63 mU/L, p<0.001). Mean exposure to fT3 calculated by area under the curve (AUC) was higher (T3/T4:T4=1148:1062, p<0.0001) on T3. Circadian rhythm of TSH was maintained on both treatments. No difference in pulse or blood pressure over the 24-hours was seen between the groups. Our data suggests that despite chronic combined T3/T4 therapy, wide peak-to-trough variation in fT3 levels persists. Although no immediate cardiovascular effects were seen, the long-term consequences for patients on combined therapy are unknown. |
| Citation: | Thyroid. 2007 Apr;17(4):323-31.
Effects of either LT4 monotherapy or LT4/LT3 combined therapy in patients totally thyroidectomized for thyroid cancer.
Regalbuto C, Maiorana R, Alagona C, Paola RD, Cianci M, Alagona G, Sapienza S, Squatrito S, Pezzino V.
Division of Endocrinology, Department of Internal and Specialistic Medicine, University of Catania, Italy. segmeint@unict.it
After total thyroidectomy all thyroid cancer patients require lifelong treatment with thyroid hormones; the treatment of choice is synthetic levothyroxine (LT4). The question of whether these patients might benefit from the combined LT4 and liothyronine (LT3) treatment has been addressed with conflicting conclusions. The aim of the present study was to compare the effects of combined low LT4/LT3 molar ratio therapy versus LT4 monotherapy on various target organs and tissues in patients thyroidectomized for thyroid cancer. Urine collection (24 hour), a fasting blood sample for laboratory examinations, thyroid function clinical score, and cardiovascular, neurological, and neuropsychological evaluations were obtained. Clinical parameters and peripheral markers of thyroid function were measured during the two different treatment regimens in 20 patients. Mean serum aspartate aminotransferase, alanine aminotransferase, sex hormone binding globulin, and osteocalcin values were significantly higher during the combined treatment. No significant differences in the clinical score, the systolic and diastolic performance, and the neurological and neuropsychological evaluations were observed between the two treatment regimens. Moreover, no alteration due to subclinical hyperthyroidism or to the fluctuations in serum T3 concentrations during the combined therapy was observed. In conclusion, we found no evidence that combined therapy with a low LT4/LT3 molar ratio resulted in improved well-being and cognitive function or in increased thyroid hormone action on peripheral tissues in respect to LT4 monotherapy. Until future large, blind, randomized, and controlled trials prove otherwise, LT4 should remain the standard treatment for thyroid cancer patients. |
Tout ça ne nous avance pas des masses ... mais bon, ça montre au moins qu'il y a plein de gens qui travaillent là-dessus, même s'ils n'arrivent apparemment pas à se mettre d'accord ! La seule chose qu'ils disent TOUS, c'est qu'il faut "davantage d'études à grande échelle, standardisées et en double-aveugle" ...
Voyons ce qu'on va nous en dire cette année, au congrès international de la thyroïde de l'ETA en Grèce (septembre 2008), et au congrès de la société française d'endocrinologie, SFE (Lille, octobre 2008) ? Je vous tiendrai au courant bien sûr !
Voir aussi l'intéressant article  La substitution parfaite : Un rêve impossible ?
Bon courage à tous !
Beate |
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Beate
Inscrit le: 10.10.00 Messages: 50593Carcinome papillaire... 60+ |
Message: (p167939)
Posté le: 15. Aoû 2008, 14:28
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J'ai aussi trouvé quelques COMMENTAIRES intéressants, notamment celui-ci, de 2005, concernant les travaux de Bunevicius (et les études qui ont suivi et qui ont tenté d'infirmer ses constatations, notamment Escobar) - en plus, il vient d'un médecin français ...
Publié dans les "Annals of Internal Medecine", Volume 143, Number 7, Octobre 2005
http://www.annals.org/cgi/reprint/143/7/543.pdf
| Citation: | L-Thyroxine plus Liothyronine in Hypothyroidism
TO THE EDITOR:
Although hypothyroid patients have been treated for decades with desiccated thyroid extracts, L-thyroxine is now considered the only therapy. However, several studies have demonstrated differences between the effects of L-thyroxine and liothyronine, and liothyronine has been used in some heart and muscular conditions.
Deiodination abnormalities could be induced by casual events, such as selenium deficiency, or by chronic disease.
Bunevicius and colleagues (1) demonstrated that hypothyroid patients feel better when they receive combination therapy with Lthyroxine and liothyronine. Escobar-Morreale and colleagues (2) seem to support this patient preference but conclude with arguments that “physiologic combinations of L-thyroxine plus liothyronine do not offer any objective advantage over L-thyroxine alone.”
Before making an abrupt conclusion about a treatment that probably concerns fewer than 10% of hypothyroid patients, it would seem wise to have information on important variables. For example, clinical and biological muscular investigations should be performed to determine why abnormalities persist several months after thyroxine treatment begins (3). Also, exploration of antioxidant status could determine why increased peroxidation is observed several years after the beginning of treatment (4), although such studies can be difficult to perform and interpret.
Despite the opinions of some pharmaceutical firms and scientists, liothyronine therapy (with the usual caution, low dosages, and appropriate adjustment) cannot be rejected when L-thyroxine does not yield satisfying clinical improvement.
Jean Eisinger, MD
Centre Hospitalier de Toulon
F83056 Toulon, France
References
1. Bunevicius R, Kazanavicius G, Zalinkevicius R, Prange AJ Jr. Effects of thyroxine as compared with thyroxine plus triiodothyronine in patients with hypothyroidism. N Engl J Med. 1999;340:424-9. [PMID: 9971866].
2. Escobar-Morreale HF, Botella-Carretero JI, Gomez-Bueno M, Galan JM, Barrios V, Sancho J. Thyroid hormone replacement therapy in primary hypothyroidism: a randomized trial comparing L-thyroxine plus liothyronine with L-thyroxine alone. Ann Intern Med. 2005;142:412-24. [PMID: 15767619]
3. Khaleeli AA, Gohil K, McPhail G, Round JM, Edwards RH. Muscle morphology and metabolism in hypothyroid myopathy: effects of treatment. J Clin Pathol. 1983; 36:519-26. [PMID: 6841646]
4. Eisinger J, Marie PA, Fontaine G, Calendini C, Ayavou T. Métabolisme énergétique et statut antioxydant au cours de myalgies. I-Hypothyroïdie. Lyon Mediterr Med Med Sud Est. 1966;32:2167-70. |
Ce commentaire me semble plein de bon sens, et ce Dr Eisinger très sympathique ... je pense que je vais tenter de le contacter, pour discuter avec lui ? Il semble surtout s'intéresser à la fibromyalgie, et a publié beaucoup de travaux à ce sujet, voir ici ... mais son point de vue sur la T3 me semble très intéressant, aussi ... Apparemment, il participe au site infomyalgie.com, et a pris sa retraite en 2006 ... il aurait peut-être un peu de temps pour nous conseiller, nous aussi ?
Beate
Beate |
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crichine 
Inscrit le: 01.07.04 Messages: 4070 |
Message: 
(p167966)
Posté le: 15. Aoû 2008, 18:30
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très intéressant, je relirai à tête reposée. A première vue, ils font des essais "scientifiques" 1 groupe de référence, ceux avec T4 seule et ceux avec T4 et T3. A première vue c'est insatisfaisant. Il me semble qu'il faudrait étudier à part le cas de ceux qui transforment mal la T4 en T3. Je vais essayer d'être claire :
pour ceux qui transforment bien, il n'est pas étonnant que l'adjonction de T3 ne donne pas de résultat flagrant. En est-il de même avec ceux qui transforment mal ?
D'autre part, ils répètent assez souvent que leurs résultats ne sont pas flagrants dans le sens de l'amélioration. Je pense à moi : mal avec de la T4 seule et mal avec la combinaison. Conclusion ? La T3 n'est pas une panacée, mais ça, nous ici on le sait. Il y a bien d'autres facteurs qui entre en jeu. Mais lesquels ? Pourquoi depuis 2003 on ne trouve pas le bon dosage ?
Une autre réflexion : leurs dosages sont standardisés. Or, personne n'est pareil que levoisin.... ça apporte un sérieux bémol aux résultats.
Bien sûr qu'on a besoin d'études sérieuses et scientifiques. Mais en médecine et en hormonologie en particulier, il n'y a pas de science exacte. Dur dur de nous faire entrer dans un moule.
Bises
_________________
Crichine
Rejoignez l'association ! Toutes les explications Sujet |
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