Energy expenditure and body composition in growth hormone deficient adults on exogenous growth hormone

OBJECTIVES We assessed whether the obesity observed in growth hormone deficient adults is maintained by a reduction in energy expenditure. We studied the effects of exogenous growth hormone on energy expenditure and body composition. DESIGN We performed an open study with growth hormone administered at 0 5 units per kilogram ideal body weight per week for 3 months. PATIENTS Seven growth hormone deficient adults were studied. Thirty-eight healthy volunteers had their resting metabolic rate measured, with seven of them proceeding to have their total energy expenditure assessed. MEASUREMENTS Total energy expenditure was measured by the doubly labelled water method (D₂0¹⁸), resting metabolic rate by ventilated hood indirect calorimetry, and fat free mass from the dilution volume of oxygen-18. Body composition and components of energy expenditure were assessed before, at 2 weeks and at the end of the 3-month treatment period on exogenous growth hormone. RESULTS Growth hormone deficient adults did not have a low total energy expenditure compared to healthy controls (13 12 vs 12 75 MJ/24 h) with only one patient expending less than 10 MJ/24 h. None had a resting metabolic rate lower than the 95% confidence limits of normality. The amount of energy expended on physical activity and thermogenesis was significant (6 54 MJ/24 h) and was similar to healthy controls (6 47 MJ/24 h). Resting metabolic rate increased by 15 9% after 14 days on exogenous growth hormone and was elevated 12-1% after 3 months treatment but the ratio to fat-free mass remained unaltered. Total energy expenditure increased by 13 4% after 14 days therapy. Fat-free mass increased significantly after 3 months treatment by (mean) 4 5 kg with no change in fat mass and no loss in body weight. CONCLUSIONS Obesity maintenance in growth hormone deficient adults is not a consequence of reduced total energy expenditure or a reduced exercise energy output. There was also no evidence for an energy sparing mechanism. Energy expenditure was increased by exogenous growth hormone but was not associated with a loss in fat mass or body weight suggesting the need for dietetic advice for those already obese at the outset of therapy.     

Long-term growth hormone treatment in growth hormone deficient adults.

Growth hormone treatment in GH-deficient adults has proved beneficial in recent short-term trials, but long-term results have not yet been reported. Thirteen GH-deficient adults (4 females, 9 males; mean (SEM) age 26.4 (1.7) years), who had completed 4 months of GH therapy in a double-blind placebo-controlled cross-over study were followed, for further 16.1 (0.8) months of uninterrupted GH therapy in an open design. A significant mean increase of 1.3 cm in linear height was recorded, whereas body mass index remained unchanged. Mean muscle volume of the thigh, estimated by computerised tomography, increased significantly compared with that of the initial placebo period (p = 0.01), and a slight decrease was recorded in adipose tissue volume of the thigh (p = 0.10) and subscapular skinfold thickness (p = 0.10). Still, the muscle to fat ratio of the thigh was significantly lower compared with that of normal subjects (72.6/27.4 vs 77.9/22.1) (p less than 0.01). The mean isometric strength of the quadriceps muscles increased significantly during long-term GH therapy (p less than 0.01), but remained lower compared with that of normal subjects (1.66 (0.10) vs 2.13 (0.11) Nm/kg body weight). Exercise capacity performed on a bicycle ergometer increased significantly after long-term therapy (p less than 0.05), but still did not reach the values seen in normal subjects (22.5 (3.4) vs 37.4 (4.2) watt.min.kg-1. No adverse reactions were recorded during long-term therapy and hemoglobin A1c remained unchanged. These data suggest that long-term GH replacement therapy in GH-deficient adults has beneficial effects on several physiological features which are subnormal in these patients.     

Changes in skeletal muscle and body composition after discontinuation of growth hormone treatment in growth hormone deficient young adults

OBJECTIVES: The aim of this study was to determine whether there are any changes in skeletal muscle strength and size and body composition following growth hormone (GH) withdrawal in GH deficient young adults. DESIGN: A longitudinal, 1-year, open, uncontrolled study of the changes in skeletal muscle and body composition following GH withdrawal was performed. Endocrine status was reassessed at the end of the study period during an insulin tolerance test. Some measurements were repeated after 2 years of treatment. PATIENTS: Twelve (11 male, one female; age range 14-21) patients who had been diagnosed during childhood as growth hormone deficient took part in the study. Four of the 12 patients were found to have a normal GH response on retesting at the end of the study and their results were analysed as a separate group. MEASUREMENTS: Quadriceps and forearm flexor maximum voluntary isometric strength, body fat content and serum IGF-1 were measured at 3-monthly intervals over 1 year. Every 6 months muscle size was measured from computerized tomography scans and fibre area from quadriceps needle biopsy samples. RESULTS: For the growth hormone deficient group the 12 month quadriceps strength, size and fibre areas were 94.0% +/- 8.5 (mean +/- SD), 94.5% +/- 6.3 and 85.6% +/- 17.7 respectively of control (baseline) values. Forearm flexor strength and size were 101.4% +/- 7.9 and 92.0% +/- 9.2 of control. Body fat percentage had increased from 19.5% +/- 8.6 to 24.1% +/- 9.5. No change was seen in the non-growth hormone deficient group. CONCLUSIONS: Although the changes measured were relatively small they suggest a role for GH in the maintenance of muscle integrity and body composition in the young adult with growth hormone deficiency.     

Abnormal body composition and reduced bone mass in growth hormone deficient hypopituitary adults*

OBJECTIVES The role of growth hormone in maintaining normal body composition and bone strength In adults has attracted much interest recently. We have assessed body composition and bone mass in GH deficient hypopituitary adults on conventional replacement therapy and compared them with matched controls. DESIGN AND SUBJECTS A cross-sectional Study Of 64 growth hormone deficient hypopituitary adults (29 males and 35 females) on conventional replacement therapy and a large number of healthy control subjects matched for age, sex and body mass index (BMI). MEASUREMENTS Skinfold thicknesses at two sites (triceps and subscapular), waist and hip girth circumferences were assessed by standard methods. Body composition was assessed using total body potassium (TBK), bioelectrical impedance analysis (BIA) and dual-energy X-ray absorptiometry (DEXA). Bone mineral mass was assessed at the lumbar spine and the total body by DEXA. Not every patient and control participated In every measurement. RESULTS Obesity was common in the hypopituitary patients; BMI (mean±SD) was 27·5 ± 4·6 kg/m² and body weight was 111·8 ±185% of the maximal ideal for height (P< 0·001). The sum of subscapular and triceps skinfolds was significantly higher in hypopituitary patients than in controls (men 46+15 vs 37±14mm, P<0·05; women 55±13 vs 47±17mm, P<0·05). Waist to hip circumference ratio was significantly greater In female hypopituitary patients than in matched controls but was not significantly different in men (men 0·94± 0·07 vs 0·91 ± 0·07, NS; women 0·84±0·09 vs 0·77±0·05, P < 0·001). The difference between patients and controls in the sum of skinfolds and the waist to hip ratio were present In non-obese (BMI < 26 kg/m²) subjects (21 patients and 32 controls). TBK corrected for body weight was significantly lower In hypopituitary patients (n= 44) than in controls (n= 31) (men 43·±5.6 vs 50·1 ± 5·9 mmollkg, P < 0·003; women: 34·0 ± 3.2 vs 40·6 ± 5·3 mmol/kg, P < 0.0001). BIA-derived body water content (corrected for body weight) was significantly lower In hypopituitary patients (n= 56) than in controls (n= 57) (0·492 ± 0·064 vs 0·545 ± 0·067 1/kg, P < 0.0004). Percentage body fat derived from ail the three methods was significantly higher in hypopituitary patients than in normal controls In both sexes (from TBK men 34·7 ± 94 vs 28·8 ± 7·0%, P < 0·05; women 37·8 ± 8·7 vs 30·4 ± 9·7%, P < 0·01; from BIA men 29·3 ± 8·5 vs 23·2 ± 8·4%, P < 0·01; women 34·6 ± 8.1 vs 29·3 ± 9·1%P < 0·01; and from DEXA: men 24·8 ± 6·8 vs 20·4 ± 6·1 %, P < 0·05; women 38·9 ± 7·9 vs 32·5 ± 9·8%, P < 0·01). There was a significant difference between non-obese patients and controls in BIA-derived percentage fat in both sexes and in TBK-derived percentage fat In females only. Bone mineral density (BMD) of the lumbar spine in the L2-L4 region was lower in hypopituitary patients than in controls (men 1·116±0·129 vs 1·311 ± 0·131 g/cm², P <0·0001; women 1·001 ±0·122 vs 1·131 ±0·138g/cm², P < 0·001). Spine BMD was also reduced in hypopituitary patients compared to the young adult and age and weight matched reference data. Total body BMD was significantly lower in patients than In controls (men 1·186 ± 0·102 vs 1·250 ± 0·080 g/cm², P < 0·05; women 1·080 ± 0·077 vs 1·149 ± 0·073 g/cm², P < 0·005). CONCLUSIONS Hypopituitary adults on conventional therapy have abnormal body composition with increased fat content, reduced body water content and reduced bone mineral mass     

Effects of growth hormone replacement on physical performance and body composition in GH deficient adults

OBJECTIVES: Adults with GH deficiency complain frequently of low energy levels resulting in a low perceived quality of life. Body composition is altered, with increased fat mass and decreased lean body mass, and muscle strength is reduced. The aims of this study were to determine the effects of GH replacement on physical performance and body composition in GH deficient (GHD) adults. STUDY DESIGN: The study consisted of a 6-month randomised, double-blind, placebo controlled study of the administration of GH (0.25 IU/Kg/week (0.125 IU/kg/week for the first four weeks)) followed by a 6-month open phase of GH therapy. PATIENTS: Thirty-five GHD adults (17F), mean age 39.8 years (range 21.1-59.9), on conventional replacement therapy as required. METHODS: Maximum aerobic capacity was measured using an incremental walking test to volitional exhaustion on a motorized treadmill. Quadriceps muscle strength was assessed by measuring maximum voluntary contractions and body composition by dual energy X-ray absorptiometry (DEXA). RESULTS: There were no statistically significant changes in quadriceps muscle strength between the GH and placebo groups. In both groups, there was a significant increase in quadriceps muscle strength compared to baseline during the double-blind period (GH group: P = 0.016; placebo group: P = 0.048). Compared to baseline, muscle strength was further improved in the GH treatment group after 12 months of treatment (P = 0.007). No further improvement was noted in the placebo group after 6 months on open GH treatment. In the placebo group, maximum aerobic capacity decreased during the placebo period (P = 0.017). No significant change was observed in the GH group. During open GH treatment the previously placebo treated group had a significant increase of maximum aerobic capacity (P < 0.049) whereas no significant improvement could be seen in the GH group. In the GH group there was a significant increase in lean body mass (P = 0.001) and a significant decrease in fat mass (P < 0.001). No statistically significant changes were noted in the placebo group: the differences in these changes between treatment groups were statistically significant (lean body mass: P = 0.009; fat mass: P < 0.001). The changes in body composition in the GH group during the 6 month placebo-controlled period were maintained during continued open treatment. Similar changes in body composition to those observed in the GH group during the 6 month placebo-controlled period were also seen in the placebo group once the patients received GH treatment. CONCLUSIONS: Our data show that GH replacement in GH deficient adults is associated with favourable changes in body composition, which could be important in the long term health outcome and physical activity of GH deficient patients. Our data support the concept that GH therapy alone, in the absence of some form of exercise programme, may increase the amount of lean tissue but not the quality or functional capacity of this tissue and it may be that training, in addition to GH therapy, may be necessary to significantly increase physical performance in these patients. We suggest that future trials with GH therapy and general approaches to the treatment of GH deficiency should include a planned activity programme as an approach to health improvement in these patients.     

Short and long-term cardiovascular effects of growth hormone therapy in growth hormone deficient adults

OBJECTIVE Since GH substitution therapy is now available for adult GH deficient patients, information on the cardiovascular effects of GH substitution has assumed major clinical interest. We have therefore assessed cardiovascular effects of short and long-term growth hormone substitution therapy in these patients. PATIENTS AND MEASUREMENTS Doppler echocardiography was performed in 21 GH deficient patients after 4 months placebo and 4 months GH therapy, in a double blind cross-over study. In an open design study, 13 patients were reinvestigated following 16 months and 9 patients following 38 months of GH therapy. Twenty-one age and sex-matched normal control subjects were also investigated. RESULTS Heart rate was increased in placebo treated patients as compared to controls. After 4 months of GH treatment, heart rate showed a further Increase (10%, P<0·01) and seemed to remain elevated after 16 months of OH therapy. Systolic and diastolic blood pressures were significantly lower in placebo treated patients than in controls, and did not change significantly after OH treatment. The left ventricular diastolic diameter was reduced in patients as compared to controls, but increased after 4 months GH therapy (P>0·05) and seemed to increase further during prolonged GH treatment. Cardiac index was at the same level in controls and in placebo-treated patients, but increased by 20% following OH therapy and remained elevated after 16 and 38 months (P < 0·05) of GH substitution. CONCLUSION Following GH substitution in GH deficient adult patients, left ventricular diastolic dimensions increased and seemed to normalize, while heart rate and cardiac output were found to be increased to supra-normal levels.     

Impact of the growth hormone replacement on bone status in growth hormone deficient adults

IntroductionGrowth hormone deficiency (GHD) is associated with reduced bone mineral density (BMD). GH replacement has positive effect on BMD but the magnitude of this effect and its mechanism are debated.ObjectivesThe objectives of this study was first, to assess the effect of GH replacement on BMD, and second, to evaluate the effect of GH treatment on bone turnover and microarchitecture and to assess the factors influencing the effect of the therapy on BMD.Patients and MethodsAdult GHD (AO-GHD) and childhood onset GHD (CO-GHD) patients treated with GH using IGF-I normalization GH replacement regimen were prospectively followed during 2 years. Lumbar spine (L1–L4) and total femur BMD by Hologic discovery, in the subset of patients also bone turnover markers; osteocalcin and carboxy-terminal collagen crosslinks (CTx) were assessed at baseline and at months 3, 6, 12 and 24, respectively. The trabecular bone score (TBS) derived from lumbar spine DXA by the iNsight® software was assessed in a subset of study population at baseline and months 12 and 24.ResultsIn total, 147 GHD patients (age 35.1 years, 84 males/63 females, 43 of childhood onset GHD/104 AO-GHD) were included. BMD of lumbar spine and femur increased significantly during the treatment (14% and 7% increase at 2 years, respectively; p < 0.0001).Bone markers increased during the first 12 months of treatment with subsequent decrease of CTx. At month 24, significant increase in TBS was observed (4%, p = 0.02).BMD increase was significantly higher in males (15% increase in males vs. 10% in females, p = 0.037) and childhood onset GHD (CO-GHD) patients (13% increase in CO-GHD, p = 0.004).ConclusionGH supplementation leads to an increase of BMD with corresponding changes in bone turnover markers and changes in microarchitecture as assessed by trabecular bone score. Positive effect of GH on bone status is more pronounced in males and CO-GHD adults.     

Metabolic effects of growth hormone administered subcutaneously once or twice daily to growth hormone deficient adults

OBJECTIVE The aim of this study was to compare the metabolic effects of GH administered subcutaneously either once or twice daily. The actions of GH might depend upon a pulsatlle pattern of serum GH. Pulsatile and continuous intravenous delivery of GH, however, induce similar short-term metabolic effects in GH deficient patients. An improved growth response is obtained in GH deficient children when a fixed weekly GH dose Is administered by dally subcutaneous injections instead of twice or thrice-weekly intramuscular injections. A more pulsatile pattern and serum GH levels above zero might be achieved by further increasing the Injection frequency. Increased daytime GH levels might, however, adversely affect the circadian patterns of metabolic indices, whlch have been demonstrated to be more successfully reproduced by evening compared with morning GH administration. DESIGN AND MEASUREMENTS In a cross-over study, 8 GH deficient patients (age 16–43 years) were treated with 3IU/m²/24h of human GH. The dose was injected in the evening for 4 weeks and for another 4 weeks two-thirds was injected in the evening and one-third in the morning. At the end of each period the patients were admitted to the hospital for 37 hours. Steady-state profiles of GH, IGF-I, IGF binding proteins 1 and 3, Insulin, glucose, lipid Intermediates and metabolites were obtained following administration of 3IU/m² of GH (at 1900 h (one injection) and at 1900 and 0800 h (two injections). RESULTS Similar mean integrated levels of serum GH (mUII) were obtained (7·46 ± 0·84 (one injection) vs 6·46 ±0·62 (two Injections) (P = 0·15). Mean levels ± SEM of serum IGF-I (μg/I) were significantly increased (P < 0·01) following two daily GH Injections (330·3±48·1 (one Injection) vs 399·1±53·0 (two injections). Serum IGFBP-3 levels were not signlflcantly different on the two occasions, while levels of the GH Independent IGFBP-1 (μg/l) were slightly but significantly lower following twice-dally GH injections (1·61±0·42 vs 1·13 ±0·56, respectively (P < 0·04). The pattern of IGFBP-1 was opposite to that of insulin. Similar levels of insulin and glucose were obtained with both GH regimens, while levels of non-esterlfied fatty acids were significantly higher following once-dally GH injection (P < 0·001). CONCLUSIONS Twice-dally GH injections, apart from producing a more physiological serum GH profile, were superior to one Injection in increasing serum IGF-I and decreasing IGFBP-1 levels. Both of these changes tend to amplify the effects of the administered GH. Twice-daily Injections, however, resulted Ln lower night-time levels of lipid Intermediates.     

Administration of recombinant human growth hormone on alternate days is sufficient to increase whole body protein synthesis and lipolysis in growth hormone deficient adults

OBJECTIVE: At present, the duration of the effect of recombinant human growth hormone (rhGH) on the rates of protein synthesis and lipolysis in GH deficient (GHD) adults is unknown. This study was designed to establish the frequency of rhGH administration necessary to provide the beneficial metabolic effects of the hormone in GHD adults. DESIGN AND PATIENTS: Two different studies (A and B) were performed in two groups of five GHD men. In study A, whole body protein and lipid kinetics was determined in the basal state (Bas), 12 (GH12h) and 36 (GH36h) h after the last of seven injections of rhGH (3.3 microg/kg), given at bedtime on alternate days. In study B, the same parameters were determined in the basal state (Bas), 60 (GH60h) and 84 (GH84h) h after the last of seven injections of rhGH (3.3 microg/kg), given at bedtime at 3 day intervals. MEASUREMENTS: The rates of protein metabolism were estimated by infusing [1-13C]leucine, and those of lipolysis by infusing [1,1,2,3, 3-D5]glycerol. RESULTS: Leucine oxidation decreased (P < 0.01) by approximately 30% after GH12h and GH36h but did not change after GH60h and GH84h. Non-oxidative leucine disposal increased after GH12h and GH36h by approximately 13% (P < 0.05) whereas it did not change after GH60h and GH84h. Glycerol appearance increased (P < 0. 01) by approximately 45% after GH12h and GH36h but did not change after GH60h and GH84h. CONCLUSIONS: The effects on protein and lipid metabolism following the injection of rhGH last longer than 36 and less than 60 h. In fact, rhGH administration on alternate days induced a sustained increase in the rates of protein synthesis and lipolysis of GHD adults, whereas a longer interval of administration (3 days) had no effect by 60 h.     

Increased body fat mass and decreased extracellular fluid volume in adults with growth hormone deficiency

OBJECTIVE Growth hormone deficiency in adults with hypopituitarism has previously received little attention. Recent data, however, suggest that GH deflciency might be essential for the long-term prognosis of these patients. Earlier studies have documented that GH regulates body composition; in this, body composition in adult patients with hypopituitarism including GH deficiency was studied. DESIGN A follow-up study of patients with hypopituitarism on routine replacement therapy with l-thyroxine, cortisone acetate and sex steroids. PATIENTS One hundred and six patients (69 males, mean age 52.5 years and 37 females, mean age 53.4 years) diagnosed as having growth hormone deficiency on the basis of low IGF-I concentration or a maximum GH-response less than 5 mU/I after an insulin/glucagon tolerance test. MEASUREMENTS Body composition was estimated from body weight, total body water and total body potassium and the results were compared with values predicted from height, weight, age and sex, using data from a large number of healthy subjects. RESULTS The total body water was slgnificantly lower than that predicted from the observed body weight (P >0.001), as was the extracellular water (P >0.001) and the extracellular/intracellular water quotient (P >0.001). On average, the body cell mass was similar to the predicted value, but the observed/predicted body cell mass ratio correlated positively with age at follow-up. The body cell mass was lower than predicted in subjects below the age of 50 years (P >0.01). The body fat was higher than predicted (P >0.001); the increase was also noted in lean subjects. The observed body weight in male subjects was 7.5 kg higher (P >0.001) than that predicted from healthy subjects of the same body height, a difference explained by an average increase of 6 6 kg in the body fat (P >0.001) and 1.6 kg in the body cell mass, with a simultaneous reduction of 0.7 kg in the extracellular water (NS). Male patients suffering from untreated androgen deficiency had lower body cell mass than those on androgen treatment. Female subjects weighed 3.6 kg (NS) more on average than healthy women, a difference explained by an increase in the body fat of 6.0 kg (P >0.001) with a simultaneous decrease of 2.4 kg in the extracellular water (P >0.001). The body cell mass was similar to that seen in the controls. CONCLUSIONS Adult patients with growth hormone deficiency have an increased body weight compared to normals of the same age, sex and height, due to an increment of the body fat with a simultaneous reduction in the total body water.     

Low-dose growth hormone replacement lowers plasma leptin and fat stores without affecting body mass index in adults with growth hormone deficiency

OBJECTIVE  The ob gene product, leptin, is considered to be a marker of adipose tissue mass and a possible homeostatic regulator of body mass. Our objective was to examine the effect of GH replacement on adipose tissue stores and leptin in adult hypopituitarism.
SUBJECTS  Twenty adults, mean age 47 years (range 20–69) with proven GH deficiency were randomly allocated to either GH (up to 0.25 U/kg/week in daily doses) or placebo for 3 months before cross-over to the opposite treatment.
MEASUREMENTS  Body composition was measured by dual-energy X-ray absorptiometry (DEXA) in the whole body, trunk and limbs. Plasma leptin was measured by radioimmunoassay at baseline and +2, +4, +8 and +12 weeks in each treatment arm.
RESULTS  Total body tissue fat (mean±SE) was 30.1±2.2% after GH compared with 31.9±2.2% after placebo, P <0.001 (ANOVA). There were no significant changes in BMI (kg/m²), 29.1±1.3 after placebo vs 28.8±1.2 after GH; or waist to hip ratio (WHR), 0.91±0.01 after both placebo and GH. Baseline plasma leptin showed a significant correlation with baseline BMI, r =0.67, P <0.005 and baseline percentage total body fat, R =0.89, P <0.001. Plasma leptin (adjusted by using baseline percentage total body fat as a covariate) showed a significant linear decrease with time on GH compared with placebo ( P =0.03 ANOVA).
CONCLUSIONS  Plasma leptin and total body fat fall promptly in response to low-dose replacement of GH in GH-deficient subjects. Hormone-induced changes in leptin can occur in humans in the absence of change in body mass index.     

Glucose and fat metabolism in adults with growth hormone deficiency

OBJECTIVE Adults with long-standing GH deficiency have a decreased lean body mass and an increased fat mass. We investigated the effects of the abnormal body composition on glucose turnover and fuel metabolism. DESIGN Cross-sectional analysis. PATIENTS Twenty-four adults with acquired GH deficiency and a wide range of adiposity (body mass index from 18·8 to 42·3 kg/m²). MEASUREMENTS In the post-absorptive state glucose turnover was measured following intravenous injection of 3-³H-glucose and leucine oxidation was assessed following intravenous injection of 1-¹⁴C-leuclne. Glucose and fat oxidation were calculated from indirect calorimetry using protein oxidation derived from leucine oxidation. RESULTS Total glucose turnover was 692 ± 146 μmol/min (mean ± SD) and Increased with height (r= 0·70, P= 0·0003) and with lean body mass (LBM) (r= 0·80, P < 0·0001). Glucose turnover expressed per kg LBM was in the published normal range (14·2 ± 2·1 pmol/kg LBM min). Glucose oxidation was 47 ± 27% of glucose turnover and increased with LBM (r= 0·59, P= 0·008) but not with height (r= 0·32, NS). Glucose turnover increased with increasing fat oxidation (r= 0·61, P= 0·006). The non-oxidative part of glucose turnover was positively correlated with fat oxidation (r= 0·82, P= 0·0001) and inversely with the respiratory quotient (r= -0·81, P < 0·0001). Ketone body concentration (r= 0·55, P= 0·03), but not free fatty acid levels (r= 0·21, NS), correlated with fat oxidation. Fasting plasma glucagon levels were elevated (35 ± 13 vs 9 ± 19pmol/l (published controls) and inversely related to lean body mass (r= -0·44, P= 0·04). CONCLUSIONS Adults with GH deficiency studied after an overnight fast have changes In glucose and fuel metabolism seen In normal subjects after more prolonged fasting suggesting that adults with hormone deficiency have reduced carbohydrate stores.     

Growth hormone versus placebo treatment for one year in growth hormone deficient adults: increase in exercise capacity and normalization of body composition

OBJECTIVE Studies with GH substitution in GH-deficient (GHD) adults lasting more than 6 months have so far been uncontrolled. End-points such as physical fitness and body composition may be subject to a considerable placebo effect which weakens the validity of open studies. We therefore tested GH (2 IU/m² per day) versus placebo treatment for 12 months. DESIGN Twenty-nine patients (mean age 45.5±2.0 years) with adult-onset GHD were studied in a double-blind, parallel design. Measurements of body composition by means of conventional anthropometry, bioelectrical impedance (BIA), CT scan and DEXA scan, exercise capacity, and isometric muscle strength were performed at baseline and after 12 months treatment. For body composition measurements a control group of 39 healthy, age and sex-matched subjects was included. RESULTS Sum of skinfolds (SKF) at 4 sites decreased significantly after GH treatment. Total body fat (TBF) as assessed by DEXA and BIA was elevated at baseline but normalized after GH. TBF assessed by SKF revealed significantly higher levels compared to DEXA and BIA, although all estimates intercorrelated closely. Visceral and subcutaneous abdominal fat decreased by 25 and 17%, respectively after GH (P<0.01) to levels no longer different from the control group. CT of the mid thigh revealed a significant reduction in fat tissue and a significant increase in muscle volume after GH treatment, both of which resulted in a normalization of the muscle : fat ratio (%) (placebo: 58 : 42 (baseline) vs 58 : 42 (12 months); GH: 66 : 34 (baseline) vs 72 : 28 (12 months) (P=0.002); normal subjects: 67 : 33 (P<0.05 when compared to 12 months placebo data)). Total body resistance and resistance relative to muscle volume decreased significantly after GH treatment suggesting over-hydration as compared to normal subjects. Exercise capacity (kJ) increased significantly after GH treatment (placebo: 54.7±9.8 (baseline) vs 51.6±8.2 (12 months); GH: 64.9±13.3 (baseline) vs 73.5±13.6 (12 months) (P<0.05)). Isometric quadriceps strength increased after GH but no treatment effect could be detected owing to a small increase in the placebo group. Serum IGF-I levels (μg/l) were low baseline and increased markedly after GH treatment to a level exceeding that of normal subjects (270±31 (12 months GH) vs 156±8 (normal subjects (P<0.01)). The levels of serum electrolytes and HbA1c remained unchanged. The number of adverse effects were higher in the GH group after 3 months, but not after 6 and 12 months. CONCLUSIONS (1) The reduction in excess visceral fat during GH substitution is pronounced and sustained; (2) beneficial effects on total body fat, muscle volume and physical fitness can be reproduced during prolonged placebo-controlled conditions; (3) uncontrolled data on muscle strength must be interpreted with caution; (4) a daily GH substitution dose of 2 IU/m² seems too high in many adult patients.     

Comparison of ultrasonographic and anthropometric methods to assess body fat in childhood obesity

BACKGROUND: Pattern of fat distribution rather than obesity is of importance for cardiovascular morbidity and mortality. The accurate measurement of total and regional fat mass requires sophisticated and often expensive methods that have limited applicability in the clinical setting. OBJECTIVE: The aim of this study is to evaluate body fat distributions by ultrasound (US) as a gold standard method for measuring visceral, preperitoneal and subcutaneous fat layers and comparing with anthropometric results, and then to find the most reliable anthropometric measurement in childhood obesity. MATERIALS AND METHODS: Study group of 51 obese children (21 F, 30 M) (mean age+/-s.d.: 11.5+/-2.6 years) and control group of 33 non-obese children (17 F, 16 M) (mean age+/-s.d.: 12.2+/-2.7 years) were recruited for this study. Anthropometric measurements as body mass index (BMI), waist circumference (WC), waist/hip ratio (WHR), triceps and subscapular skinfold thicknesses were taken from all the participants. Abdominal preperitoneal (P), subcutaneous (S) fat at their maximum (max) and minimum (min) thickness sites, visceral (V), triceps (TrUS) and subscapular (SsUS) fat thicknesses were also measured ultrasonographically. RESULTS: In the obese group, BMI was significantly correlated with US measurements of fat thicknesses, except Pmin and SsUS, whereas in the control group, BMI was significantly correlated with all US fat measurements. The relation of US measurements with skinfold thickness and WC was more significant in the control than in the obese group. No relation between WHR and US fat thickness measurements was found in both groups. Multiple regression analysis, using V as the dependent variable and anthropometric parameters, gender and the group as the independent variables, revealed BMI was the best single predictor of V (R(2): 0.53). CONCLUSION: This study suggests that the validity of the anthropometric skinfold thickness in the obese children is low. Despite the limitations reported in the literature, in our study, BMI provides the best estimate of body fat. WHR in children and adolescents is not a good index to show intra-abdominal fat deposition.