***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: OBJECTIVE : The objective of this study was to compare various parameters in patients with hypothyroidism receiving either monotherapy with L-Thyroxine ( L-T4 ) or combination therapy with L-T4 and L-Triiodothyronine ( L-T3 ) .  DESIGN : We conducted a r and omized , controlled trial in 36 premenopausal women with hypothyroidism . The patients were divided into two groups : Group A ( n=20 ) received only L-T4 , while Group B received the combination L-T4 and L-T3 . The treatment period lasted for 6 months . RESULTS : At baseline , the various parameters examined did not differ in the two groups . No significant difference between monotherapy and combined therapy was demonstrated on TSH level , ECG monitoring , densitometry , or thyroid symptoms score . The lipid profile was better during combined treatment compared to L-T4 alone ; in Group A during treatment with L-T4 the levels of cholesterol and Low Density Lipoprotein ( LDL ) Cholesterol were unchanged , while in group B total cholesterol and LDL decreased ( p<0.05 ) . The changes in osteocalcin levels did not differ in the two groups , whereas the levels of urine deoxypyridinoline at the end of therapy were higher in the group with combination therapy , compared to monotherapy . CONCLUSION : Compared with L-T4 alone , replacement therapy with the combination of L-T4+L-T3 shows favourable changes in serum lipid profile , but higher activation of bone resorption CONTEXT St and ard 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 R and omized , 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 ) question naire , 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 question naire 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 question naire , and st and ard measures of cognitive performance A -double-blind crossover trial of a combined preparation of triiodothyronine and thyroxine ( 1:4 ratio ) compared with thyroxine alone was conducted with 99 patients previously stabilized on . thyroxine as treatment for hypothyroidism . Four patients were excluded during the trial and eight afterwards owing to gross deficiencies in taking the tablets . Of the remaining 87 patients 42 ( 48 % ) had no -preference for either medication , 29 ( 33 % ) preferred thyroxine alone , and 16 ( 18 % ) the combination . A high incidence of unpleasant symptoms was experienced during the two months ' treatment with the combined preparation . The serum protein-bound iodine levels were lowered ( mean reduction 1·8 μg./100 ml . ) on the combination , but the labelled T3-resin sponge uptake values were not altered and remained in the normal range . on both treatments It was recently demonstrated that treatment with levorotatory thyroxine ( T4 ) plus triodotthyronine ( 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 µg of T3 for 50 µg 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 st and ard 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 Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more 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 , r and omized , 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 ) . R and omization 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 question naires 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 question naires 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 INTRODUCTION Some patients on levothyroxine replacement  display significant impairment in psychological well-being , compared with sex- and age-matched controls . Levothyroxine-treated patients can be assumed to derive T3 exclusively from deiodination of T4 , which , in the central nervous system , is regulated by type II deiodinase ( DII ) . OBJECTIVE We investigated whether two recently identified polymorphisms in the DII gene ( DII-ORFa-Gly3Asp and DII-Thr92Ala ) are determinants of well-being and neurocognitive functioning and associated with a preference for replacement with a combination of T3 and T4 . METHODS Genotypes for both polymorphisms were determined in 141 patients with primary autoimmune hypothyroidism , adequately treated with levothyroxine monotherapy and participating in a r and omized clinical trial comparing T4 therapy with T4/T3 combination therapy .  Question naires on well-being and neurocognitive tests were performed at baseline . RESULTS Allele frequencies in patients with primary hypothyroidism were similar to those of healthy blood bank donors ( 32.0 vs. 33.9 % for DII-ORFa-Gly3Asp and 40.4 vs. 38.8 % for DII-Thr92Ala ) . DII polymorphisms were not associated with measures of well-being , neurocognitive functioning , or preference for combined T4/T3 therapy . CONCLUSION The DII-ORFa-Gly3Asp and DII-Thr92Ala polymorphisms do not explain differences in well-being , neurocognitive functioning , or appreciation of T4/T3 combination  therapy in patients treated for hypothyroidism Context Studies comparing the outcomes of treatment of hypothyroidism  with l-thyroxine alone versus with a combination of l-thyroxine and liothyronine have had conflicting results . Some experts believe the conflicting results occurred because some studies used supraphysiologic doses of liothyronine . Contribution This crossover trial compared l-thyroxine with a combina-tion of physiologic doses of l-thyroxine and liothyronine and found no objective advantages of combination therapy . Implication s Treatment of hypothyroidism with l-thyroxine alone is sufficient . The Editors The recommended treatment for hypothyroidism is oral l-thyroxine sodium . This treatment is administered with the aim of restoring clinical euthyroidism and well-being and maintaining normal serum levels of thyroid-stimulating hormone ( TSH ) ( 1 ) . However , triiodothyronine is the most active thyroid hormone because its affinity for the nuclear thyroid hormone receptor is 10- to 20-fold that of thyroxine ( 2 , 3 ) . The current practice of using l-thyroxine alone as replacement therapy for hypothyroidism assumes that peripheral conversion of thyroxine into triiodothyronine is able to restore normal triiodothyronine concentrations in target tissues . However , no experimental data support this assumption . On the contrary , we found that infusion of thyroxine alone into thyroidectomized rats was not able to restore euthyroidism ( 4 ) ; this was possible only by infusing combinations of thyroxine and triiodothyronine in proportions similar to those secreted by the rat thyroid gl and ( 5 ) . An early study in hypothyroid patients compared treatment with the usual daily l-thyroxine dose , consisting of two or three 100-g tablets , versus the same number of tablets , each containing 80 g of l-thyroxine and 20 g of liothyronine(6 ) . Although patients were probably overtreated throughout the study , adverse events were more frequent during treatment with the l-thyroxineliothyronine combination ( 6 ) , probably because of the excessive amount of liothyronine administered . More recently , several studies have evaluated combined levothyroxineliothyronine treatment using a triiodothyronine substitution approach , in which a small yet supraphysiologic amount of liothyronine , ranging from 10 g/d to 15 g/d , was substituted for 50 g of the total l-thyroxine dose ( 7 - 10 ) . Bunevicius and colleagues ( 7 , 8) reported that triiodothyronine substitution result ed in marked improvements in several items of the Profile of Mood States ( POMS ) and in a few indexes of psychometric function and quality of life , especially in athyreotic patients with thyroid cancer ( 8) . Recent studies , however , have failed to confirm any beneficial effects of triiodothyronine substitution on quality of life ( 9 , 10 ) . Even in selected hypothyroid patients presenting with depress 
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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 .
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 .