human
***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: The present study was design ed as a r and omized , double-blind placebo (Plc)-controlled study to determine the effect of 2 wk of growth hormone administration ( GH-adm . ) on energy expenditure ( EE ) and substrate oxidation in healthy humans . Sixteen young healthy men were divided into two groups . The study consisted of two 24-h measurements ( indirect calorimetry ) , separated by 2 wk of either Plc or GH injections ( 6 IU/day ) . At baseline , no significant differences were observed between the two groups in any of the measured anthropometric , hormonal , or metabolic parameters , neither did the parameters change over time in the Plc group . GH-adm . result ed in a 4.4 % increase in 24-h EE ( P < 0.05 ) and an increase in fat oxidation by 29 % ( P < 0.05 ) . However , a decrease in the respiratory quotient was only observed in the postabsorptive phase after an overnight fast ( 0.84 + /- 0.1 to 0.79 + /- 0.1 , P < 0.05 ) . Furthermore , lean body mass ( LBM ) was increased by GH-adm . only [ 62.8 + /- 2.5 kg ( baseline ) vs. 64.7 + /- 2.4 kg ( after ) , P < 0.001 ] . In conclusion , GH-adm . increases 24-h EE , which may be partly explained by increased LBM . Furthermore , GH-adm . stimulates fat combustion , especially in the postabsorptive state GH is being used by elite athletes to enhance sporting performance . To examine the hypothesis that exogenous 22-kDa recombinant human GH ( rhGH ) administration could be detected through suppression of non-22-kDa isoforms of GH , we studied seventeen aerobically trained males ( age , 26.9 + /- 1.5 yr ) r and omized to rhGH or placebo treatment ( 0.15 IU/kg/day for 1 week ) . Subjects were studied at rest and in response to exercise ( cycle-ergometry at 65 % of maximal work capacity for 20 min ) . Serum was assayed for total GH ( Pharmacia IRMA and pituitary GH ) , 22-kDa GH ( 2 different 2-site monoclonal immunoassays ) , non-22-kDa GH ( 22-kDa GH-exclusion assay ) , 20-kDa GH , and immunofunctional GH . In the study , 3 h after the last dose of rhGH , total and 22-kDa GH concentrations were elevated , reflecting exogenous 22-kDa GH . Non-22-kDa and 20-kDa GH levels were suppressed . Regression of non-22-kDa or 20-kDa GH against total or 22-kDa GH produced clear separation of treatment groups . In identical exercise studies repeated between 24 and 96 h after cessation of treatment , the magnitude of the responses of all GH isoforms was suppressed ( P < 0.01 ) , but the relative proportions were similar to those before treatment . We conclude : 1 ) supraphysiological doses of rhGH in trained adult males suppressed exercise-stimulated endogenous circulating isoforms of GH for up to 4 days ; 2 ) the clearest separation of treatment groups required the simultaneous presence of high exogenous 22-kDa GH and suppressed 20-kDa or non-22-kDa GH concentrations ; and 3 ) these methods may prove useful in detecting rhGH abuse in athletes In a r and omized , double-blind , placebo-controlled , cross-over study , we examined the effects of 14 days of growth hormone ( GH ) administration ( 12 IU/d subcutaneously ) on  energy expenditure ( EE ) , respiratory exchange ratio ( RER ) , and thyroid function in 14 normal adults of normal weight ( eight men and six women ) .  EE ( kcal/24 h ) was significantly elevated after GH administration ( 2,073 + /- 392 , [ GH ] , 1,900 + /- 310 , [ placebo ] , P = .01 ) . RER was significantly lowered during GH administration ( 0.73 + /- 0.04 v 0.78 + /- 0.06 , P = .02 ) , reflecting increased oxidation of lipids . Total triiodothyronine ( TT3 ) ( nmol/L ) and free T3 ( FT3 ) ( pmol/L ) increased significantly during GH ( TT3 : 1.73 + /- 0.06 [ GH ] , 1.48 + /- 0.08 [ placebo ] , P = .01 ; FT3 : 6.19 + /- 0.56 [ GH ] , 5.49 + /- 0.56 [ placebo ] , P = .01 ) . Concomitantly , an insignificant decrease in reverse T3 ( rT3 ) ( nmol/L ) was observed ( 0.07 + /- 0.01 [ GH ] , 0.15 + /- 0.01 [ placebo ] , P = .08 ) . GH caused a highly significant increase in T3/thyroxine ( T4 ) ( x 100 ) ratio ( 1.84 + /- 0.12 [ GH ] , 1.37 + /- 0.06 [ placebo ] ) . Serum thyrotropin ( TSH ) was not significantly changed by GH . No changes in total thyroxine ( TT4 ) ( nmol/L ) ( 98 + /- 6 [ GH ] , 111 + /- 8 [ placebo ] , P = .40 ) and free thyroxine ( FT4 ) ( pmol/L ) ( 17.4 + /- 1.3 [ GH ] , 18.6 + /- 1.1 [ placebo ] , P = .37 ) after 14 days of GH administration were observed . In conclusion , 2 weeks of GH administration increases EE and lipidoxidation . This finding may partly be mediated by an increase in peripheral T4 to T3 conversion Adults with hypopituitarism receive therapy that replaces cortisol , thyroid hormone , and gonadal steroids , but growth hormone replacement has typically been reserved for children with growth hormone deficiency . However , several observations suggest that growth hormone may have an important role in maintaining bone density and body composition in adults .  Bone density is reduced in patients with growth hormone deficiency that develops during childhood or adulthood [ 1 - 3 ] . In vitro , growth hormone binds to growth hormone receptors on rat osteoblast-like cells and produces a mitogenic response mediated by local synthesis and action of insulin-like growth factor 1 ( IGF-1 ) [ 4 , 5 ] . Administration of growth hormone to adults with growth hormone deficiency increases serum and urine markers of bone turnover [ 6 - 10 ] . In adults with childhood-onset growth hormone deficiency ( in whom osteopenia probably results from a failure to reach peak bone mass ) , growth hormone therapy increases bone density [ 3 , 8 , 10 , 11 ] . However , the effects of growth hormone replacement on bone density in adult-onset growth hormone deficiency are largely unknown . In addition to having an increased risk for fracture , adults with growth hormone deficiency have an excess risk for cardiovascular-related death that may be attributed to increased central fat mass [ 12 - 17 ] . Growth hormone therapy reduces body fat and increases lean mass in adults with growth hormone deficiency , primarily those in whom the deficiency developed during childhood [ 6 - 9 , 18 - 20 ] . However , previous studies of growth hormone replacement in adults have several important limitations . First , most of these studies used pharmacologic rather than physiologic doses of growth hormone . Second , most have focused on childhood-onset growth hormone deficiency . Third , effects of growth hormone on bone density in patients with adult-onset growth hormone deficiency have not been examined in a controlled study . Because of these limitations , the critical question of whether long-term growth hormone therapy is beneficial in patients with adult-onset growth hormone deficiency has not been definitively answered . We sought to determine whether long-term growth hormone replacement therapy , given at a dose adjusted according to IGF-1 levels , improves bone density , bone turnover , body composition , and several variables associated with quality of life in patients with adult-onset growth hormone deficiency . Methods Patients Thirty-two men ( median age , 51 years ; range , 24 to 62 years ) with a history of pituitary disease were recruited from the Massachusetts General Hospital Neuroendocrine Clinical Center and from surrounding communities . Growth hormone secretion profiles in 23 of these patients have been reported elsewhere [ 21 ] . All patients met the following inclusion criteria : 1 ) normal growth and development , 2 ) benign sellar neoplasm , pituitary apoplexy , or idiopathic hypopituitarism diagnosed after age 18 years , and 3 ) peak serum growth hormone levels less than 5 mg/L after receipt of two pharmacologic stimuli on separate mornings . The 13 patients younger than 50 years of age received intravenous insulin , 0.1 U/kg of body weight , and oral clonidine , 0.15 mg . The 18 patients 50 years of age or older received oral clonidine , 0.15 mg , and intravenous arginine , 30 g ; these patients were given arginine rather than insulin to avoid potential cardiovascular complications of hypoglycemia . Patients were excluded if they had a history of acromegaly or diabetes mellitus ; were taking drugs ( such as phenytoin or etidronate ) known to affect bone density ; were not receiving st and ard thyroid or adrenal hormone replacement therapy  if the patient was deficient in those hormones ; or had begun receiving adrenal , gonadal , or thyroid hormone replacement therapy within 6 months before study enrollment . Growth hormone deficiency was caused by a clinical ly nonfunctioning pituitary adenoma in 12 patients , prolactinoma in 9 patients , craniopharyngioma in 9 patients , pituitary apoplexy in 4 patients , Cushing disease in 1 patient , and adult-onset idiopathic hypopituitarism in 1 patient . Twenty-one patients were deficient in adrenocorticotropin , thyroid-stimulating hormone , and gonadotropins .  Five patients had two of these deficiencies , 5 patients had one , and 1 patient had none . Twenty-five patients were treated surgically ( 16 of the 25 were also treated with radiation or bromocriptine , or both ) . Five patients received bromocriptine with or without radiation therapy , and 2 were treated with hormonal replacement only . The Subcommittee on Human Studies of the Massachusetts General Hospital approved the study , and all patients gave written informed consent . Protocol Patients were r and omly assigned to receive recombinant human growth hormone ( Nutropin , Genentech , Inc. , South San Francisco , California ) at a daily dose of 10 g/kg subcutaneously or a placebo . The computerized r and omization , done by statisticians at Genentech , Inc. , stratified patients to assure balance between the groups with respect to age . Staff at Genentech , Inc. , informed the primary investigator of treatment assignment by telephone ; the study physician kept the information in a private computer data base . Only the study physician was aware of the treatment assignment . Patients were admitted to the General Clinical Research Center for measurements of bone mineral density of the lumbar spine , femoral neck , and proximal radius . Body mass index , lean body mass , and percentage of body fat were also measured . Patients had echocardiography and were tested for strength and exercise capacity . Urine was collected for 24 hours for measurement of pyridinoline , deoxypyridinoline , calcium , and creatinine excretion . Fasting blood sample s were drawn at 0900 hours for measurement of IGF-1 , glucose , insulin , lipids , and hemoglobin A1c values . Patients returned at 1 week , 1 month , and 3 months for outpatient measurement of serum IGF-1 , glucose , insulin , lipid ( at 1 and 3 months ) , and hemoglobin A1c ( at 3 months only ) values . Patients were readmitted at 6 , 12 , and 18 months so that the baseline evaluation could be repeated . Echocardiography and tests of strength and exercise capacity were repeated only at the 18-month visit . The growth hormone dose was reduced by 25 % if the patient 's serum IGF-1 level was found to be elevated at the 6- or 12-month visit ; serum IGF-1 levels were remeasured approximately 1 month after the dose was decreased . The dose was further adjusted if necessary . To maintain patient blinding , each placebo recipient was asked to reduce his dose by 25 % during the first 6 months of the study . Bone Density Bone mineral density of the lumbar spine , femoral neck , radius , and total body was determined by dual-energy x-ray absorptiometry ( Hologic QDR-2000 , Waltham , Massachusetts ) . Density of the nondominant radius was measured at the junction of the proximal two third 
    Output:
    
agent
Some have suggested that growth hormone is a wonder drug ( 16 ) that results in ripped muscle ( 17 ) and provides stamina-increasing properties ( 18 ) .
***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: The present study was design ed as a r and omized , double-blind placebo (Plc)-controlled study to determine the effect of 2 wk of growth hormone administration ( GH-adm . ) on energy expenditure ( EE ) and substrate oxidation in healthy humans . Sixteen young healthy men were divided into two groups . The study consisted of two 24-h measurements ( indirect calorimetry ) , separated by 2 wk of either Plc or GH injections ( 6 IU/day ) . At baseline , no significant differences were observed between the two groups in any of the measured anthropometric , hormonal , or metabolic parameters , neither did the parameters change over time in the Plc group . GH-adm . result ed in a 4.4 % increase in 24-h EE ( P < 0.05 ) and an increase in fat oxidation by 29 % ( P < 0.05 ) . However , a decrease in the respiratory quotient was only observed in the postabsorptive phase after an overnight fast ( 0.84 + /- 0.1 to 0.79 + /- 0.1 , P < 0.05 ) . Furthermore , lean body mass ( LBM ) was increased by GH-adm . only [ 62.8 + /- 2.5 kg ( baseline ) vs. 64.7 + /- 2.4 kg ( after ) , P < 0.001 ] . In conclusion , GH-adm . increases 24-h EE , which may be partly explained by increased LBM . Furthermore , GH-adm . stimulates fat combustion , especially in the postabsorptive state GH is being used by elite athletes to enhance sporting performance . To examine the hypothesis that exogenous 22-kDa recombinant human GH ( rhGH ) administration could be detected through suppression of non-22-kDa isoforms of GH , we studied seventeen aerobically trained males ( age , 26.9 + /- 1.5 yr ) r and omized to rhGH or placebo treatment ( 0.15 IU/kg/day for 1 week ) . Subjects were studied at rest and in response to exercise ( cycle-ergometry at 65 % of maximal work capacity for 20 min ) . Serum was assayed for total GH ( Pharmacia IRMA and pituitary GH ) , 22-kDa GH ( 2 different 2-site monoclonal immunoassays ) , non-22-kDa GH ( 22-kDa GH-exclusion assay ) , 20-kDa GH , and immunofunctional GH . In the study , 3 h after the last dose of rhGH , total and 22-kDa GH concentrations were elevated , reflecting exogenous 22-kDa GH . Non-22-kDa and 20-kDa GH levels were suppressed . Regression of non-22-kDa or 20-kDa GH against total or 22-kDa GH produced clear separation of treatment groups . In identical exercise studies repeated between 24 and 96 h after cessation of treatment , the magnitude of the responses of all GH isoforms was suppressed ( P < 0.01 ) , but the relative proportions were similar to those before treatment . We conclude : 1 ) supraphysiological doses of rhGH in trained adult males suppressed exercise-stimulated endogenous circulating isoforms of GH for up to 4 days ; 2 ) the clearest separation of treatment groups required the simultaneous presence of high exogenous 22-kDa GH and suppressed 20-kDa or non-22-kDa GH concentrations ; and 3 ) these methods may prove useful in detecting rhGH abuse in athletes In a r and omized , double-blind , placebo-controlled , cross-over study , we examined the effects of 14 days of growth hormone ( GH ) administration ( 12 IU/d subcutaneously ) on  energy expenditure ( EE ) , respiratory exchange ratio ( RER ) , and thyroid function in 14 normal adults of normal weight ( eight men and six women ) .  EE ( kcal/24 h ) was significantly elevated after GH administration ( 2,073 + /- 392 , [ GH ] , 1,900 + /- 310 , [ placebo ] , P = .01 ) . RER was significantly lowered during GH administration ( 0.73 + /- 0.04 v 0.78 + /- 0.06 , P = .02 ) , reflecting increased oxidation of lipids . Total triiodothyronine ( TT3 ) ( nmol/L ) and free T3 ( FT3 ) ( pmol/L ) increased significantly during GH ( TT3 : 1.73 + /- 0.06 [ GH ] , 1.48 + /- 0.08 [ placebo ] , P = .01 ; FT3 : 6.19 + /- 0.56 [ GH ] , 5.49 + /- 0.56 [ placebo ] , P = .01 ) . Concomitantly , an insignificant decrease in reverse T3 ( rT3 ) ( nmol/L ) was observed ( 0.07 + /- 0.01 [ GH ] , 0.15 + /- 0.01 [ placebo ] , P = .08 ) . GH caused a highly significant increase in T3/thyroxine ( T4 ) ( x 100 ) ratio ( 1.84 + /- 0.12 [ GH ] , 1.37 + /- 0.06 [ placebo ] ) . Serum thyrotropin ( TSH ) was not significantly changed by GH . No changes in total thyroxine ( TT4 ) ( nmol/L ) ( 98 + /- 6 [ GH ] , 111 + /- 8 [ placebo ] , P = .40 ) and free thyroxine ( FT4 ) ( pmol/L ) ( 17.4 + /- 1.3 [ GH ] , 18.6 + /- 1.1 [ placebo ] , P = .37 ) after 14 days of GH administration were observed . In conclusion , 2 weeks of GH administration increases EE and lipidoxidation . This finding may partly be mediated by an increase in peripheral T4 to T3 conversion Adults with hypopituitarism receive therapy that replaces cortisol , thyroid hormone , and gonadal steroids , but growth hormone replacement has typically been reserved for children with growth hormone deficiency . However , several observations suggest that growth hormone may have an important role in maintaining bone density and body composition in adults .  Bone density is reduced in patients with growth hormone deficiency that develops during childhood or adulthood [ 1 - 3 ] . In vitro , growth hormone binds to growth hormone receptors on rat osteoblast-like cells and produces a mitogenic response mediated by local synthesis and action of insulin-like growth factor 1 ( IGF-1 ) [ 4 , 5 ] . Administration of growth hormone to adults with growth hormone deficiency increases serum and urine markers of bone turnover [ 6 - 10 ] . In adults with childhood-onset growth hormone deficiency ( in whom osteopenia probably results from a failure to reach peak bone mass ) , growth hormone therapy increases bone density [ 3 , 8 , 10 , 11 ] . However , the effects of growth hormone replacement on bone density in adult-onset growth hormone deficiency are largely unknown . In addition to having an increased risk for fracture , adults with growth hormone deficiency have an excess risk for cardiovascular-related death that may be attributed to increased central fat mass [ 12 - 17 ] . Growth hormone therapy reduces body fat and increases lean mass in adults with growth hormone deficiency , primarily those in whom the deficiency developed during childhood [ 6 - 9 , 18 - 20 ] . However , previous studies of growth hormone replacement in adults have several important limitations . First , most of these studies used pharmacologic rather than physiologic doses of growth hormone . Second , most have focused on childhood-onset growth hormone deficiency . Third , effects of growth hormone on bone density in patients with adult-onset growth hormone deficiency have not been examined in a controlled study . Because of these limitations , the critical question of whether long-term growth hormone therapy is beneficial in patients with adult-onset growth hormone deficiency has not been definitively answered . We sought to determine whether long-term growth hormone replacement therapy , given at a dose adjusted according to IGF-1 levels , improves bone density , bone turnover , body composition , and several variables associated with quality of life in patients with adult-onset growth hormone deficiency . Methods Patients Thirty-two men ( median age , 51 years ; range , 24 to 62 years ) with a history of pituitary disease were recruited from the Massachusetts General Hospital Neuroendocrine Clinical Center and from surrounding communities . Growth hormone secretion profiles in 23 of these patients have been reported elsewhere [ 21 ] . All patients met the following inclusion criteria : 1 ) normal growth and development , 2 ) benign sellar neoplasm , pituitary apoplexy , or idiopathic hypopituitarism diagnosed after age 18 years , and 3 ) peak serum growth hormone levels less than 5 mg/L after receipt of two pharmacologic stimuli on separate mornings . The 13 patients younger than 50 years of age received intravenous insulin , 0.1 U/kg of body weight , and oral clonidine , 0.15 mg . The 18 patients 50 years of age or older received oral clonidine , 0.15 mg , and intravenous arginine , 30 g ; these patients were given arginine rather than insulin to avoid potential cardiovascular complications of hypoglycemia . Patients were excluded if they had a history of acromegaly or diabetes mellitus ; were taking drugs ( such as phenytoin or etidronate ) known to affect bone density ; were not receiving st and ard thyroid or adrenal hormone replacement therapy  if the patient was deficient in those hormones ; or had begun receiving adrenal , gonadal , or thyroid hormone replacement therapy within 6 months before study enrollment . Growth hormone deficiency was caused by a clinical ly nonfunctioning pituitary adenoma in 12 patients , prolactinoma in 9 patients , craniopharyngioma in 9 patients , pituitary apoplexy in 4 patients , Cushing disease in 1 patient , and adult-onset idiopathic hypopituitarism in 1 patient . Twenty-one patients were deficient in adrenocorticotropin , thyroid-stimulating hormone , and gonadotropins .  Five patients had two of these deficiencies , 5 patients had one , and 1 patient had none . Twenty-five patients were treated surgically ( 16 of the 25 were also treated with radiation or bromocriptine , or both ) . Five patients received bromocriptine with or without radiation therapy , and 2 were treated with hormonal replacement only . The Subcommittee on Human Studies of the Massachusetts General Hospital approved the study , and all patients gave written informed consent . Protocol Patients were r and omly assigned to receive recombinant human growth hormone ( Nutropin , Genentech , Inc. , South San Francisco , California ) at a daily dose of 10 g/kg subcutaneously or a placebo . The computerized r and omization , done by statisticians at Genentech , Inc. , stratified patients to assure balance between the groups with respect to age . Staff at Genentech , Inc. , informed the primary investigator of treatment assignment by telephone ; the study physician kept the information in a private computer data base . Only the study physician was aware of the treatment assignment . Patients were admitted to the General Clinical Research Center for measurements of bone mineral density of the lumbar spine , femoral neck , and proximal radius . Body mass index , lean body mass , and percentage of body fat were also measured . Patients had echocardiography and were tested for strength and exercise capacity . Urine was collected for 24 hours for measurement of pyridinoline , deoxypyridinoline , calcium , and creatinine excretion . Fasting blood sample s were drawn at 0900 hours for measurement of IGF-1 , glucose , insulin , lipids , and hemoglobin A1c values . Patients returned at 1 week , 1 month , and 3 months for outpatient measurement of serum IGF-1 , glucose , insulin , lipid ( at 1 and 3 months ) , and hemoglobin A1c ( at 3 months only ) values . Patients were readmitted at 6 , 12 , and 18 months so that the baseline evaluation could be repeated . Echocardiography and tests of strength and exercise capacity were repeated only at the 18-month visit . The growth hormone dose was reduced by 25 % if the patient 's serum IGF-1 level was found to be elevated at the 6- or 12-month visit ; serum IGF-1 levels were remeasured approximately 1 month after the dose was decreased . The dose was further adjusted if necessary . To maintain patient blinding , each placebo recipient was asked to reduce his dose by 25 % during the first 6 months of the study . Bone Density Bone mineral density of the lumbar spine , femoral neck , radius , and total body was determined by dual-energy x-ray absorptiometry ( Hologic QDR-2000 , Waltham , Massachusetts ) . Density of the nondominant radius was measured at the junction of the proximal two third 
    Output:
    