***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: Biondi , Fazio , and colleagues recently reported that long term T4 treatment to suppress serum TSH markedly affects cardiac function . T4-treated patients had more symptoms [ 12.2 + /- 3.9 ( + /-SD ) vs. 4.2 + /- 2.3 by quantitative question naire ] , higher mean heart rate , increased incidence of atrial extrasystoles , increased interventricular septal thickness and left ventricular mass index ( LVMi ) , and significant diastolic dysfunction . The severity of cardiac abnormalities was highly correlated with scores of a rating scale used for assessing symptoms of thyrotoxicosis . We have duplicated their studies in 17 athyreotic patients ( mean age , 45 + /- 10 yr ; range , 27 - 63 yr ) without heart disease or hypertension whose dose of T4 was titrated to suppress serum TSH to less than 0.01 microU/mL. The mean duration of T4 treatment was 9.2 + /- 5.4 yr . Controls were healthy volunteers matched for sex and age ( + /-3 yr ) . The mean T4 dose was 2.8 + /- 0.9 micrograms/kg ( 0.192 + /- 0.058 mg/day ) . By question naire , patients had minimal symptoms , although their symptom score was significantly greater than the control value ( 4 + /- 3 vs. 2 + /- 1 ; P < 0.05 ; maximum score , 36 ) . No differences in mean heart rate or in atrial or ventricular extrasystoles were noted . In patients , indexes of systolic and diastolic function and interventricular septal thickness were similar to control values . The mean LVMi was normal in both groups . However , the mean LVMi in patients ( 117 + /- 35 g/m2 ) was higher than that in controls ( 92 + /- 31 ; P < 0.05 ) . In conclusion , patients were minimally affected by TSH-suppressive doses of T4 . They had few symptoms and no increase in extrasystoles or basal heart rate . Based on current knowledge , the increase in LVMi observed in patients without associated significant systolic or diastolic abnormalities does not have clinical or prognostic importance . Therefore , in the absence of symptoms of thyrotoxicosis , patients treated with TSH-suppressive doses of L-T4 may be followed clinical ly without specific cardiac laboratory studies CONTEXT Previous studies of the effects of levothyroxine ( LT(4 ) ) therapy on bone and bone metabolism have provided conflicting results . OBJECTIVE This study evaluated the potential effects and dose-response relationship of LT(4 ) therapy on bone mineral density ( BMD ) as well as bone and muscle strength . DESIGN AND SETTING We conducted a prospect i ve , nonr and omized , controlled cohort study with 1.1 ± 0.2-yr follow-up at an academic outpatient clinic in Germany . PARTICIPANTS Ninety-seven men and premenopausal women were enrolled in the study after thyroidectomy and radioiodine remnant ablation for well-differentiated thyroid carcinoma ( DTC ) or strumectomy for nontoxic goiter . Patients were matched with 89 healthy controls . INTERVENTIONS Twenty-eight men and 46 women on TSH-suppressive doses of LT(4 ) had DTC  , and 23 women were on LT(4 ) replacement therapy for nontoxic goiter . MAIN OUTCOME MEASURE This study assessed total and trabecular volumetric BMD ( vBMD ) as well as bone strength at the ultradistal radius , areal BMD at the lumbar spine and both hips , and the grip strength of the nondominant forearm . The dependent variables were annualized rates of change . RESULTS LT(4 ) therapy did not impair the areal BMD , bone strength , or grip strength of patients compared with controls . Women with DTC showed a significant loss of total vBMD , whereas men with DTC developed marginally less bone strength than women . Carboxy-terminal telopeptide indicated greater bone resorption in DTC patients compared with controls . CONCLUSIONS There was little evidence of adverse LT(4 ) effects on bone ; however , premenopausal women with DTC might be at risk for reduced vBMD in their ultradistal radii Data on co-morbidity in patients with postsurgical hypoparathyroidism ( HypoPT ) are sparse . We aim ed to assess risk of fractures , spinal stenosis , cataract , neuropsychiatric diseases , cancer , and infections within the historic cohort of patients with postsurgical HypoPT due to non-malignant causes that we previously have characterized . Patients were identified through the Danish National Patient Registry and regional prescription data bases , with subsequent validation of their individual hospital records . Identified cases were matched with three age- ( ± 2 yr ) and gender-matched controls from the general background population . Compared with controls , patients did not have an increased risk of cataract ( p = 0.52 ) , spinal stenosis ( p = 0.59 ) , or any fracture ( p = 0.98 ) . However , the risk of fractures at the upper extremities was significantly decreased in patients ( HR 0.69 , 95 % CI 0.49 - 0.97 ) . Compared with controls , patients had a significantly increased risk of hospitalization due to infections ( HR 1.42 , 95 % CI 1.20 - 1.67 ) and depression/bipolar affective disorders ( HR 1.99 , 95 % CI 1.14 - 3.46 ) . The risk of malignant diseases did not differ between groups although the risk of gastrointestinal cancers was significantly lower in patients compared with controls ( HR 0.63 , 95 % CI 0.44 - 0.93 ) . In conclusion , HypoPT is associated with an increased risk of depression and other types of neuropsychiatric diseases as well as infections , whereas patients seem to be protected against fractures at the upper extremities and gastrointestinal malignancies OBJECTIVE To evaluate if a supervised exercise training program improves the quality of life ( QoL ) of differentiated thyroid carcinoma ( DTC ) patients on TSH-suppressive therapy with levothyroxine ( L-T4 ) . SUBJECTS AND METHODS Initially , a cross-sectional study was performed to compare the QoL and the health-related quality of life ( HRQoL ) between sub clinical hyperthyroidism ( SCH ) patients ( n = 33 ) and euthyroid subjects ( EU ; n = 49 ) . In the prospect i ve phase of the study , SCH patients were r and omized in a non-blinded fashion to either participate ( SCH-Tr = trained patients ; n = 16 ) or not ( SCH-Sed = untrained patients ; n = 17 ) in a supervised exercise training program . The exercise program consisted of 60 minutes of aerobic and stretching exercises , twice a week , during twelve weeks . The QoL was assessed by the application of the WHOQOL-Bref , and the SF-36 was used to assess the HRQoL. RESULTS SCH patients had statistically lower scores than EU on the " physical " domain of WHOQOL-Bref , besides " physical function " , " role-physical " , " bodily pain " , " general health " , " vitality " , " role-emotional " , and " mental-health " domains of SF-36 . After three months , SCH-Tr patients showed improvement in the " physical " and " psychological " domains of WHOQOL-Bref ( p < 0.05 ) , and in the " physical function " , " role-physical " , " bodily pain " , " vitality " and " mental health " domains of SF-36 . CONCLUSION Patients on TSH-suppressive therapy with L-T4 for DTC had impaired QoL and HRQoL compared to EU , but it was improved after 3-months of an exercise training program . Exercise seems to play an important role in the follow-up of DTC patients , since it seems to minimize the adverse effects of the treatment on QoL and To determine the effect of suppressive doses of thyroxine ( T4 ) on bone mass , we studied 50 women on suppressive doses of T4 for 3 - 27 years ( mean of 11 years ) . Twenty-five had nontoxic goiter and 25 had well-differentiated thyroid carcinoma . Fifty controls were matched for age , menopausal status , and body mass index . Bone mineral density ( BMD ) was measured in the lumbar spine ( LS ) , femoral neck ( FN ) , trunk ( TK ) , and extremities ( EXT ) by dual-energy X-ray absorptiometry ( DXA ) . In addition , the trunk area was measured by neutron activation analysis and recorded as a calcium bone index ( CaBI ) . Twenty-one patients were restudied with DXA measurements at a mean of 1.5 + /- 0.5 ( 1 SD ) years . The total population of 50 patients showed no difference in bone mass from controls . In patients with nontoxic goiter , there was no evidence of any loss in bone mass . Cancer patients showed insignificant reductions of 2 - 5 % in BMD of LS , FN , and TK and a significant 5 % reduction in BMD of EXT , compared to controls , and a 12 % reduction in CaBI compared to goiter patients . Cancer patients had a slightly higher ( p < 0.001 ) mean daily dose of T4 than goiter patients ( 0.23 vs 0.15 mg/day ) but had a similar degree of TSH suppression . BMD and CaBI values did not correlate with free T4 index ) with the daily T4 dose , accumulative dose , or with duration of T4 therapy . There were no significant changes in bone mass in either goiter or cancer patients restudied after a mean of 1.5 years . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND The influence of thyrotropin ( thyroid-stimulating hormone [ TSH ] ) suppressive therapy on bone mineral density ( BMD ) remains contentious . We have conducted a r and omized controlled trial evaluating the effects of postoperative TSH suppressive therapy on disease-free survival for papillary thyroid carcinoma ( PTC ) since 1996 , while prospect ively verifying the effects of TSH suppression on BMD . METHODS Lumbar spine BMD as expressed by T-score was examined annually in female patients r and omly assigned to receive TSH suppressive therapy ( group A ; n = 144 ) or no therapy ( group B ; n = 127 ) . RESULTS The mean TSH level was 0.07 ± 0.10 mU/L in group A and 3.14 ± 1.69 mU/L in group B. Group B did not show any significant decrease in T-score until 5 years postoperatively , whereas group A had a significant deterioration from 1 year postoperatively . Among group A patients , significant decreases in T-score within 1 year were seen in patients ≥ 50 years of age , but not in those < 50 years of age . After 5 years of TSH suppression , 20 patients had T-scores below -2.0 and 100 patients did not . These former patients were significantly older and had lower preoperative BMD measurements than the latter . CONCLUSION This prospect i ve controlled trial suggests that TSH suppression after surgery for PTC has adverse effects on BMD in women ≥ 50 years of age OBJECTIVE To address the influence of thyroid hormones on circulating markers of cell-mediated immune response in an in vivo human model . SUBJECTS AND DESIGN Twenty-two patients with stage I differentiated thyroid carcinoma were studied on the last day of thyroxine suppressive treatment , 4 - 7 days after withdrawal , and the day before whole body scanning .  Three patients were excluded because of residual disease . Twenty euthyroid individuals served as controls .  Serum thyrotrophin and thyroid hormones were measured by an immunometric assay , circulating cytokines by enzyme-linked immuno-sorbent assay and lymphoid population s by flow cytometry . RESULTS Thyroid function in patients changed from sub clinical or mild hyperthyroidism at the first visit , to a situation of normal circulating levels of free thyroxine and triiodothyronine at the second , ending in a state of overt hypothyroidism . Thyroxine suppressive treatment in patients increased serum interleukin-18 concentrations ( IL-18 , mean+/-s.d . , 280+/-122 vs 183+/-106 pg/ml , F = 3.192 , P = 0.029 ) , soluble interleukin-2 receptor levels ( sIL-2R , 4368+/-1480 vs 2564+/-846 pg/ml , F = 21.324 , P < 0.001 ) , and the percentage of natural killer ( NK ) cells in peripheral blood ( 15.9+/-8.6 vs 10.5+/-3.6 % , F = 4.977 , P = 0.004 ) compared with controls . After thyroxine withdrawal , serum levels of IL-18 , sIL-2R and the percentage of NK cells decreased progressively . CONCLUSION Our present results suggest that thyroid hormones modulate the cell-mediated immune response in humans Abstract . This study was carried out in order to investigate the possible detrimental effects on bone of levothyroxine ( l-T4 ) suppressive therapy in female patients who had undergone surg 
    Output:
    
Skeletal effects were more marked in postmenopausal women .
There was no evidence of increased fracture risk , and only little data were available on hypoparathyroidism .
There was little difference in basic physiological parameters and limited literature regarding symptoms or significant events .
Impaired glucose metabolism and prothrombotic states were also found in DTC patients .
CONCLUSION There is limited literature regarding long-term DTC treatment-related morbidity , particularly regarding the effects of long-term hypocalcemia .