***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 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Background — American College of Cardiology/American Heart Association guidelines for the diagnosis and management of heart failure recommend investigating exacerbating conditions such as thyroid dysfunction , but without specifying the impact of different thyroid-stimulation hormone ( TSH ) levels . Limited prospect i ve data exist on the association between sub clinical thyroid dysfunction and heart failure events . Methods and Results — We performed a pooled analysis of individual participant data using all available prospect i ve cohorts with thyroid function tests and subsequent follow-up of heart failure events . Individual data on 25 390 participants with 216 248 person-years of follow-up were supplied from 6 prospect i ve cohorts in the United States and Europe . Euthyroidism was defined as TSH of 0.45 to 4.49 mIU/L , sub clinical hypothyroidism as TSH of 4.5 to 19.9 mIU/L , and sub clinical hyperthyroidism as TSH < 0.45 mIU/L , the last two with normal free thyroxine levels . Among 25 390 participants , 2068 ( 8.1 % ) had sub clinical hypothyroidism and 648 ( 2.6 % ) had sub clinical hyperthyroidism . In age- and sex-adjusted analyses , risks of heart failure events were increased with both higher and lower TSH levels ( P for quadratic pattern < 0.01 ) ; the hazard ratio was 1.01 ( 95 % confidence interval , 0.81–1.26 ) for TSH of 4.5 to 6.9 mIU/L , 1.65 ( 95 % confidence interval , 0.84–3.23 ) for TSH of 7.0 to 9.9 mIU/L , 1.86 ( 95 % confidence interval , 1.27–2.72 ) for TSH of 10.0 to 19.9 mIU/L ( P for trend < 0.01 ) and 1.31 ( 95 % confidence interval , 0.88–1.95 ) for TSH of 0.10 to 0.44 mIU/L and 1.94 ( 95 % confidence interval , 1.01–3.72 ) for TSH < 0.10 mIU/L ( P for trend=0.047 ) . Risks remained similar after adjustment for cardiovascular risk factors . Conclusion — Risks of heart failure events were increased with both higher and lower TSH levels , particularly for TSH ≥10 and < 0.10 PURPOSE The role of thyroxine replacement in sub clinical hypothyroidism remains unclear . We performed a 6-month r and omized , double-blind , placebo-controlled trial to evaluate the effects of thyroxine treatment for mild sub clinical hypothyroidism , defined as a serum thyroid-stimulating hormone level between 5 to 10 microU/mL with a normal serum free thyroxine level ( 0.8 - 16 ng/dL ) . SUBJECTS AND METHODS We r and omly assigned 40 women with mild sub clinical hypothyroidism who had presented to their family practitioners to either thyroxine treatment ( n = 23 ; 50 to 100 microg daily ) or placebo ( n = 17 ) .  Health-related quality of life ( Hospital Anxiety and Depression scale , 30-item General Health Question naire ) , fasting lipid profiles , body weight , and resting energy expenditure were measured at baseline and 6 months . RESULTS The most common presenting symptoms were fatigue ( n = 33 [ 83 % ] ) and weight gain ( n = 32 [ 80 % ] ) . At presentation , 20 women ( 50 % ) had elevated anxiety scores and 22 ( 56 % ) had elevated scores on the General Health Question naire .  Thirty-five women completed the study . There were no significant differences in the changes from baseline to 6 months between women in the thyroxine group and the placebo group for any of the metabolic , lipid , or anthropometric variables measured , expressed as the mean change in the thyroxine group minus the mean change in the placebo group : body mass index , -0.3 kg/m(2 ) ( 95 % confidence interval [ CI ] : -0.9 to 0.4 kg/m(2 ) ) ; resting energy expenditure , -0.2 kcal/kg/24 h ( 95 % CI : -1.3 to 1.0 kcal/kg/24 h ) ; and low-density lipoprotein cholesterol , -4 mg/dL ( 95 % CI : -23 to 15 mg/dL ) . There was a significant worsening in anxiety scores in the thyroxine group ( scores increased in 8 of 20 women and were unchanged in 2 of 20 ) compared with the placebo group ( scores increased in 1 of 14 women and were unchanged in 6 of 14 ; P = 0.03 ) . CONCLUSIONS ; We observed no clinical ly relevant benefits from 6 months of thyroxine treatment in women with mild sub clinical hypothyroidism Sub clinical hypothyroidism ( sHT ) is associated with dyslipidemia and enhanced cardiovascular risk . We assessed carotid artery intima-media thickness ( IMT , high-resolution ultrasonography ) and lipoprotein profile in 45 sHT patients ( aged 37 + /- 11 yr ) at baseline and after 6 months of r and omized , placebo-controlled L-T(4 ) replacement .  In comparison with 32 age- and sex-matched controls , sHT patients had elevated total and low-density lipoprotein ( LDL ) cholesterol and ApoB levels ( P = 0.002 , P = 0.0007 , and P = 0.01 , respectively ) and higher mean-IMT values ( P < 0.0001 ) . In stepwise regression analysis , mean-IMT was positively related ( r(2 ) = 0.71 , P < 0.0001 ) to age , TSH , and LDL cholesterol . L-T(4 ) replacement significantly reduced both total and LDL cholesterol ( P < 0.0001 for both ) and mean-IMT ( by 11 % , P < 0.0001 ) . The decrement in IMT was directly related to the decrements of both total cholesterol and TSH ( P = 0.02 and P = 0.0001 , respectively ) . We conclude that early carotid artery wall alterations are present in sHT patients . Whether such IMT increase is related to an early atherosclerotic involvement of the arterial wall can not be clearly decided on the basis of the present results . However , the fact that L-T(4 ) replacement therapy was able to improve both the atherogenic lipoprotein profile and intima-media thickening suggests that lipid infiltration of arterial wall may represent a major mechanism underlying IMT increase in sub clinical hypothyroidism OBJECTIVE To evaluate the effects of physiologic doses of levothyroxine replacement on the lipoprotein profile in patients with sub clinical hypothyroidism ( SCH ) . METHODS In a prospect i ve , double-blind , placebo-controlled study , we enrolled 120 patients --mostly , but not exclusively , premenopausal women -- with SCH . Patients were r and omly assigned to either a levothyroxine-treated group ( n = 60 ) or a placebo ( control ) group ( n = 60 ) .  Total cholesterol ( TC ) , low-density lipoprotein cholesterol ( LDL-C ) , high-density lipoprotein cholesterol ( HDL-C ) , and triglycerides ( TG )  were measured before and 52 weeks after assignment to either group . RESULTS In the levothyroxine-treated group , the lipoprotein mean values before and after the 52-week study were as follows : TC , 5.05 + /- 0.98 mmol/L versus 4.74 + /- 0.87 mmol/L ( P<.0001 ) ; LDL-C , 3.30 + /- 0.90 mmol/L versus 2.89 + /- 0.59 mmol/L ( P<.01 ) ; TG , 1.18 + /- 0.71 mmol/L versus 0.95 + /- 0.53 mmol/L ( P<.002 ) ; and HDL-C , 1.20 + /- 0.33 mmol/L versus 1.19 + /- 0.32 mmol/L ( P = .29 ) . In the control group , TC , HDL-C , and TG values remained unchanged after 52 weeks in comparison with baseline , but LDL-C mean values increased from 2.79 + /- 0.60 mmol/L to 3.11 + /- 0.77 mmol/L , a change that was statistically significant ( P<.001 ) . At the end of the study , the lipid profile changes between levothyroxine-treated and control groups were compared . Total cholesterol and LDL-C were significantly lower in the levothyroxine-receiving group ( P<.029 and P<.0001 , respectively ) in comparison with the control group . The difference did not reach statistical significance for TG and HDL-C values . CONCLUSION In premenopausal women , SCH has a negative effect on the lipoprotein profile and may translate into a sizable cardiovascular risk if left untreated BACKGROUND : Previous studies have suggested an association between sub clinical hypothyroidism and coronary artery disease that could be related to changes in serum lipids or endothelial dysfunction . METHODS : Thirty-two female sub clinical hypothyroidism patients were r and omly assigned to 12 months of L-thyroxine replacement or no treatment . Endothelial function was measured by the flow-mediated vasodilatation of the brachial artery , as well as mean carotid artery intima-media thickness , and lipid profiles were studied at baseline and after 12 months of follow-up . RESULTS : The mean ( ±SD ) serum thyroid-stimulating hormone levels in the L-thyroxine replacement and control groups were 6.09±1.32 and 6.27±1.39 µUI/ml , respectively . No relationship between carotid artery intima-media thickness or brachial flow-mediated vasodilatation and free T4 and serum thyroid-stimulating hormone was found . The median L-T4 dose was 44.23±18.13 µg/day . After 12 months , there was a significant decrease in the flow-mediated vasodilatation in the sub clinical hypothyroidism control group ( before : 17.33±7.88 to after : 13.1±4.75 % , p = 0.03 ) , but there were no significant differences in flow-mediated vasodilatation in the L-thyroxine treated group ( before : 16.81±7.0 to after : 18.52±7.44 % , p = 0.39 ) . We did not find any significant change in mean carotid intima-media thickness after 12 months of L-thyroxine treatment . CONCLUSION : Replacement therapy prevents a decline in flow-mediated vasodilatation with continuation of the sub clinical hypothyroidism state . Large prospect i ve multicenter placebo-controlled trials are necessary to investigate endothelial physiology further in sub clinical hypothyroidism patients and to define the role of L-thyroxine therapy in improving endothelial function in these patients The indications for treating patients with sub clinical hypothyroidism ( normal serum thyroxine and free thyroxine levels , but elevated serum thyrotrophin levels ) are poorly defined . In this study , 33 patients with sub clinical hypothyroidism were r and omly assigned in a double-blind manner to receive placebo or L-thyroxine therapy and were followed for 1 year with thyroid function tests , serum lipid measurements , basal metabolic rate and systolic time interval determinations , and a question naire on hypothyroid symptoms . The placebo group showed no changes in thyroid function or peripheral indices of thyroid hormone action . In the thyroxine-treated group , serum lipids and the mean systolic time interval did not change , but the systolic time intervals became normal in the 5 patients with the most abnormal baseline values . Symptoms improved in 8 of 14 patients receiving thyroxine and in 3 of 12 patients receiving placebo ( p less than 0.05 ) . L-Thyroxine therapy may be useful for patients with sub clinical hypothyroidism with abnormal myocardial contractility or symptoms consistent with mild hypothyroidism , or both Twenty women , who had been r and omly selected from women with sub clinical hypothyroidism identified in a population study were treated with l‐thyroxine and placebo in a double‐blind cross‐over design during 2·6 months . Three women did not complete the study , one because she moved to another part of the country , and two because of nervousness and sense of tachycardia . None of these ‘ drop‐outs ’ had any objective signs of overtreatment ; they had normal pulse rate and a serum T3 concentration within the reference interval . During l‐thyroxine  treatment serum procollagen‐III‐peptide concentration increased in 13 women out of the 17 women completing the study and at the end of treatment the mean concentration was significantly raised ( P>0·001 ) . Serum concentrations of procollagen‐III‐pept 
    Output:
    
Thyroid screening could identify persons with sub clinical as well as undiagnosed overt thyroid dysfunction who could potentially benefit from treatment to reduce the risk for adverse health outcomes .
Does treating screen-detected overt or sub clinical thyroid dysfunction improve : a ) mortality and morbidity ?