The relationship between hyperthyrotropinemia and metabolic and cardiovascular risk factors in a large group of overweight and obese children and adolescents.

PURPOSE: Mild TSH elevations are frequently observed in obese patients, in the absence of any detectable thyroid disease. Our objective is to evaluate the relationship between the raised TSH levels and the biochemical and clinical consequences of obesity. METHODS: This is a retrospective cross-sectional study of a large population of obese children and adolescents. We evaluated 833 subjects (340 m, 493 f), aged 14.4 ± 2.5 (range 5.2-18.5) years, height SDS 0.27 ± 1.04 (-3.49-4.35), and BMI SDS 2.94 ± 0.59 (1.60-4.68). Body composition, free T4, TSH, anti-TPO antibodies, anti-TG antibodies, inflammation markers (total WBC and the subtypes, ultrasensitive C-reactive protein), and metabolic parameters [AST, ALT, γGT, ALP, glycaemia, insulin, total cholesterol (TC), HDL-cholesterol (HDL-C), and LDL-cholesterol (LDL-C), triglycerides (TG)] were measured, and oral disposition index (ODI) and cardiovascular risk factors (TC/HDL-C and TG/HDL-C) were calculated. After exclusion of the subjects showing anti-thyroid antibodies, the remaining 779 (325 m, 454 f) were then subdivided into two subgroups according to a TSH value below (group A) or above (group B) 4.5 mU/L. RESULTS: Clinical characteristics and hematological markers of patients with and without positive anti-thyroid antibodies were similar, with the exception of higher TSH levels in the latter group. Using analysis of covariance, the subjects of group B had significantly higher values of TC (170.3 ± 28.7 vs 163.3 ± 32.9 mg/dL; p < 0.05), systolic (125.8 ± 13.5 vs 124.5 ± 13.1 mm/Hg), and diastolic blood pressure (79.2 ± 8.0 vs 77.9 ± 8.2 mm/Hg) than subjects of group A. No difference was observed in body composition, ODI, and the cardiovascular risk factors between these two groups. CONCLUSION: TSH elevation in overweight and obese children and adolescents, being associated with a higher TC and blood pressure, might negatively influence the cardiac status. Longitudinal studies are requested, however, to confirm this hypothesis and, therefore, to conclude whether a substitutive treatment with l-thyroxine is really needed in these patients.

Drugs Delivery by Charities: A Possible Epidemiologic Indicator in Children of Undocumented Migrants.

Describing the health status of a population is difficult, especially in the case of irregular migrants who are now a growing population in western Countries. Data for children of these families are almost inexistent. In the absence of databases on this peculiar pediatric population, we analyzed drugs dispensation by a major Charity to have an insight into their health needs. This observational retrospective study was carried out during the entire 2015 and enrolled 628 undocumented children. A cohort of 8438 adult patients belonging to the same ethnic groups was used for comparison. Respiratory drugs were those most commonly prescribed, followed by those for skin and ocular diseases and by those for gastrointestinal disorders. Also in adults respiratory medications were the most dispensed, but almost in equal measure than cardiovascular drugs.To our knowledge this is the first study on the health needs of undocumented children residing in a western Country. The method we used seems to be a useful method for epidemiological analysis. As could be expected, respiratory and skin diseases ranked first, possibly owing to environmental factors.

The burden of chronic noncommunicable diseases in undocumented migrants: a 1-year survey of drugs dispensation by a non-governmental organization in Italy.

OBJECTIVES: This study was carried out with two objectives. The first one was to have an insight into the prevalence of chronic noncommunicable diseases (CNCD) in undocumented migrants, and the second one was to evaluate if differences existed among different ethnic groups. STUDY DESIGN: The study is based on the collection of data on drug dispensation by a non-governmental organization (NGO) providing free medical assistance to undocumented migrants in Milan, Italy. All the prescriptions to adult subjects from January 1 to December 31 2014 (total 8438) were recorded and analyzed. All the data available for the patients receiving prescriptions (age, gender and country of birth) were also collected in anonymous form. Ethical approval for the study was given by the Ethics Committee of the NGO. METHODS: Drugs were grouped according to the anatomical therapeutic chemical (ATC) classification and their quantities expressed as daily defined doses (DDDs)/1000 patients/day. The 56 ATC levels were divided into three groups according to their use for acute, chronic, or both acute and chronic diseases. The statistical analysis of drug dispensation was performed for the whole population and for the five ethnic groups into which it had been divided. RESULTS: Prescription of medicines for chronic conditions was significantly greater than for acute (154.2 ± 45.9 vs 51.3 ± 18.4 DDD/1000 patients/day, P < 0.02) and for both acute and chronic conditions (57.9 ± 12.8 DDD/1000 patients/day, P < 0.02). Five ATC classes accounted for 60% of all chronic prescriptions. They were differently distributed among the five ethnic groups (e.g., Asians required more antihypertensives and antidiabetics, East Europeans required more lipid modifying drugs, antihypertensives and antithrombotics). CONCLUSIONS: Our data show an important use of medicines for chronic diseases in a population of undocumented migrants. Though with some limitations, this could be an indicator of a high prevalence of CNCD in this population, with significant differences among different ethnic groups. This situation should be considered when planning health interventions, also in consideration of the fact that it could have an impact on European Health Services in a short time.

Unaltered ratio of circulating levels of growth hormone/GH isoforms in adults with Prader-Willi syndrome after GHRH plus arginine administration.

Human growth hormone (GH) is a heterogeneous protein hormone consisting of several isoforms, the most abundant being 22 kDa- and 20 kDa-GH. The availability of analytical methods to measure these GH isoforms might represent a valuable diagnostic tool to investigate GH hyposecretory states, including Prader-Willi syndrome (PWS), one of the most common causes of syndromic obesity. The aim of the present study was to measure circulating levels of 22 kDa- and 20 kDa-GH in PWS adults (n=14; M/F: 5/9; genotype DEL15/UPD15: 12/2; age: 19.0±3.7 years; BMI: 29.9±8.7 kg/m2) after combined GH releasing hormone (GHRH) plus arginine (ARG) administration. The results were analysed subdividing the study population in obese vs. nonobese (6/8) and GH deficient vs. nonGH deficient (GHD) (6/8) subjects, according to appropriate BMI-related diagnostic cut-off limits of GH peak response to the provocative test. Circulating levels of 22 kDa-GH were measured by a chemiluminescent method based on a detection monoclonal antibody targeting an epitope in the loop connecting helix 1 and 2 of GH, which is missing in 20 kDa-GH; the 20 kDa-GH was measured using a time resolved fluorescence assay based on two monoclonal antibodies with no cross-reactivity to 22-kDa GH. GHRH plus ARG significantly stimulated the secretions of 22 kDa- and 20 kDa-GH in nonobese (at 30, 45, 60 and 90 min and at 45, 60, 90 and 120 min vs. 0 min, p<0.05, with GH peaks of 15.8±10.3 ng/ml and 2.7±1.2 ng/ml, respectively) and in nonGHD PWS (at 30, 45 and 60 min and at 45, 60 and 90 min vs 0 min, p<0.05, with GH peaks of 12.5±9.0 ng/ml and 2.0±1.8 ng/ml, respectively). No significant GHRH plus ARG-induced changes in 22 kDa- and 20 kDa-GH were observed in obese or GHD PWS patients, the only exception being the increase of 22 kDa-GH (p<0.05) 60 min after the stimulus administration in GHD group (with GH peaks of 6.9±4.7 ng/ml and 0.8±0.6 ng/ml in obese subjects and 8.5±6.0 ng/ml and 1.2±1.0 ng/ml in GHD subjects for 22 kDa- and 20 kDa-GH, respectively). The GH responses for both isoforms were significantly higher in nonobese than in obese PWS patients (at 45 and 60 min for 22 kDa-GH and at 45, 60, 90 and 120 min for 20 kDa-GH, p<0.05), while no differences were detected between GHD vs. nonGHD groups. As previously reported in healthy subjects, the ratios of circulating levels of 22 kDa- to 20 kDa-GH remained constant after GHRH plus ARG both in obese/non-obese and GHD/non-GHD groups, thus suggesting the preservation of a normal balance in GH isoforms in PWS.

Does segmental body composition differ in women with Prader-Willi syndrome compared to women with essential obesity?

BACKGROUND: Subjects with Prader-Willi syndrome (PWS) have a higher fat mass and a lower fat-free mass compared to subjects with essential obesity. However, few data are presently available on the segmental body composition (BC) of PWS subjects. AIM: To evaluate whether women with PWS and women with essential obesity, matched for age and percent body fat, differ in segmental fat distribution and surrogate markers of cardiometabolic disease (CMD). SUBJECTS AND METHODS: 35 women with PWS and 50 women with essential obesity were matched for age and percent body fat using coarsened exact matching. BC was measured by dual-energy X-ray absorptiometry. Oral glucose tolerance testing and measurements of cholesterol, triglycerides, C-reactive protein, and blood pressure were performed. Comparisons between PWS and obese women were performed using generalized linear models. RESULTS: Trunk fat was lower in PWS than in obese women on both absolute [-7.3 (95% confidence interval -9.4 to -5.2) kg] and relative [-4.1 (-6.9 to -1.4)% of body fat] grounds. PWS and obese women had similar surrogate markers of CMD, with the exception of HDL-cholesterol, which was higher in PWS women. CONCLUSION: Trunk fat is lower in obese women with PWS than in those with essential obesity. Surrogate markers of CMD are, however, mostly similar in the two groups.

The GHRH + arginine stimulated pituitary GH secretion in children and adults with Prader-Willi syndrome shows age- and BMI-dependent and genotype-related differences.

OBJECTIVE: The quantitative and qualitative aspects of the pituitary response in children and adults with Prader-Willi syndrome (PWS) are compared in order to verify the possible age-dependent and genotype-related differences in terms of GH secretion. DESIGN: 29 young subjects (21 males and 8 females) and 65 adults (24 males and 41 females) with PWS were studied. All subjects underwent a standard GH Releasing Hormone (GHRH 1-29, 1 µg/kg as i.v. bolus at 0 minutes)+arginine (0.5 g/kg) test. Peak GH values, standard GH area under the curve (AUC), AUC of the instantaneous secretion rate (ISR), and secretion response analysis (i.e. half-secretion time) were evaluated. A regression analysis was performed to investigate which are the patient characteristics that affect the amplitude and shape of the GH secretion response. RESULTS: Peak GH values and AUCGH were significantly higher in PWS children than in PWS adults, these differences being also significant both in PWS DEL15 (only peak GH value) and PWS UPD15. Moreover, PWS children showed significantly lower half secretion time than PWS adults, this delayed response being present both in PWS DEL15 and PWS UPD15. Significant negative correlations between AUCGH and BMISDS were observed in the two groups (adults and children), as well as in adults and children DEL15, but not in adults and children PWS UPD15. A regression analysis performed on the whole dataset showed that for PWS DEL15 the statistically significant variable explaining GH responsiveness was BMISDS (p<0.0001), while for UPD15 no statistically significant covariate was found. Conversely, when the delay of the secretion response was considered, the regression model yielding the best performances was the one with only age as a regressor (p<0.001). CONCLUSIONS: The quantitative and qualitative analyses of GH responsiveness to GHRH+arginine highlight relevant differences between PWS children and PWS adults and genotype-related traits. The negative influence of BMISDS on GH secretion reinforces the need for an early start of life-long weight management in PWS subjects.

Comparison of dual-energy X-ray absorptiometry, air displacement plethysmography and bioelectrical impedance analysis for the assessment of body composition in morbidly obese women.

BACKGROUND/OBJECTIVES: We evaluated the agreement of air displacement plethysmography (ADP) and bioelectrical impedance analysis (BIA) with dual-energy X-ray absorptiometry (DXA) for the assessment of percent fat mass (%FM) in morbidly obese women. SUBJECTS/METHODS: Fifty-seven women aged 19-55 years and with a body mass index (BMI) ranging from 37.3 to 55.2 kg/m(2) were studied. Values of %FM were obtained directly from ADP and DXA, whereas for BIA we estimated fat-free mass (FFM) from an equation for morbidly obese subjects and calculated %FM as (weight-FFM)/weight. RESULTS: The mean (s.d.) difference between ADP and DXA for the assessment of %FM was -2.4% (3.3%) with limits of agreement (LOA) from -8.8% to 4.1%. The mean (s.d.) difference between BIA and DXA for the assessment of %FM was 1.7% (3.3%) with LOA from -4.9% to 8.2%. CONCLUSION: ADP-DXA and BIA-DXA are not interchangeable methods for the assessment of body composition in morbidly obese women.

GH responses to two consecutive bouts of respiratory muscle endurance training in healthy adults.

Repetition of voluntary exercise bouts and of different pharmacological GH-releasing stimuli at 2-h intervals is associated with a complete abolishment of GH responsiveness. By contrast, a different pattern is observed after repeated neuromuscular electrostimulation, which is characterized by preservation of GH responsiveness. Aim of the study was to evaluate GH responses to repeated bouts of respiratory muscle endurance training (RMET) by mean of a specific commercially available device (Spiro Tiger®). Eight healthy men underwent an incremental progressive RMET protocol of 11 daily sessions. Blood samplings for GH, cortisol and lactate (LA) determinations were collected during the 12th session, which was composed of two consecutive bouts of RMET (of identical intensity and duration: 1 min at a respiration rate of 28 acts/min, 5 min at 32 acts/min, 5 min at 34 acts/min, 4 min at 36 acts/min) at a 2 h interval. Baseline GH levels (mean: 0.9±0.4 ng/ml) significantly (p<0.01) increased after the first bout of RMET (peak: 15.7±4.0 ng/ml). The administration of the second bout of RMET resulted in a significantly lower (p<0.05) GH increase (peak: 3.9±0.8 ng/ml) in comparison with the first one. Baseline LA levels (mean: 1.2±0.1 mmol/l) significantly increased (p<0.001) after the first bout of RMET (peak: 2.3±0.2 mmol/l). The administration of the second RMET bout resulted in a comparable LA increase (from a basal value of 1.2±0.1 mmol/l up to a peak of 2.0±0.1 mmol/l, p<0.001). The first bout of RMET caused a significant increase of cortisol levels (p<0.01), starting from a basal mean value of 142.9±9.4 ng/ml up to a peak of 188.8±10.3 ng/ml. By contrast, the second bout of RMET did not induce any significant change of cortisol levels (basal: 149.1±9.0 ng/ml, peak: 168.5±5.1 ng/ml). In conclusion, a single bout of RMET is capable of stimulating GH and cortisol secretions and LA production. When a second bout is repeated after 2 h, there is a blunting of GH and cortisol responses with a preservation of LA release. Further studies are needed to schedule long-term RMET protocols capable of persistently stimulating GH-IGF-I release and to maximally enhance the ergogenic and metabolic benefits of this intervention either in normal subjects (e.g. athletes) or patients with an impairment of motor capabilities requested to perform normal daily activities (i.e. severely obese and elderly people).

Anorexigenic postprandial responses of PYY and GLP1 to slow ice cream consumption: preservation in obese adolescents, but not in obese adults.

OBJECTIVE: Eating slowly increases the postprandial responses of some anorexigenic gut hormones in healthy lean subjects. As the rate of food intake is positively associated with obesity, the aim of the study was to determine whether eating the same meal at different rates evokes different postprandial anorexigenic responses in obese adolescent and adult subjects. DESIGN AND METHODS: Eighteen obese adolescents and adults were enrolled. A test meal was consumed on two different sessions by each subject, meal duration taking either 5  min (fast feeding) or 30  min (slow feeding). Circulating levels of glucagon-like peptide 1 (GLP1), peptide YY (PYY), glucose, insulin, and triglycerides were measured over 210  min. Visual analog scales were used to evaluate the subjective feelings of hunger and satiety. RESULTS: fast feeding did not stimulate GLP1 release in obese adolescent and adults, whereas slow feeding increased circulating levels of GLP1 only in obese adolescents. Plasma PYY concentrations increased both in obese adolescents and in adults, irrespective of the eating rate, but slow feeding was more effective in stimulating PYY release in obese adolescents than in adults. simultaneously, slow feeding evoked a higher satiety only in obese adolescents compared with fast feeding but not in obese adults. in obese adolescents, slow feeding decreased hunger (only at 210 min). irrespective of the eating rate, postprandial responses of insulin and triglycerides were higher in obese adults than in obese adolescents. CONCLUSION: Slow feeding leads to higher concentrations of anorexigenic gut peptides and favors satiety in obese adolescents, but this physiological control of food intake is lost in obese adults.

Impact of percent body fat on oral glucose tolerance testing: a cross-sectional study in 1512 obese children.

BACKGROUND: Although an association between insulin resistance (IR) and body adiposity has been reported in obese children, this relationship has not been studied as thoroughly as in adults. AIM: We evaluated the association between oral glucose tolerance testing (OGTT) and percent body fat (PBF) in a sample of 1512 obese children followed at a Pediatric Obesity Clinic. SUBJECTS AND METHODS: Six hundred and twenty-eight male and 884 female obese children aged 6 to 18 yr were consecutively enrolled into the study. OGTT was performed with administration of 1.75 g of glucose per kg of body weight (up to 75 g). PBF was estimated through bioelectrical impedance analysis (BIA) using a population- specific formula recently published by our group. Multivariable median regression was used to evaluate the association between 4 outcomes [glucose area under the curve (AUC), insulin AUC, insulin sensitivity index (ISI), and insulinogenic index (IGI)] and gender, age or pubertal status and PBF. RESULTS: Median PBF was 52% (range 26 to 70%). After correction for age and gender, a 10% increase of PBF was associated with a decrease of -0.50 [95% confidence interval (CI): -0.65 to -0.35] units of ISI and an increase of 0.15 units of IGI (95%CI 0.07 to 0.24). CONCLUSIONS: In obese children, PBF is inversely associated with IR and directly associated to ß-cell response as detected by OGTT.

The cholestyramine-induced decrease of PYY postprandial response is negatively correlated with fat mass in obese women.

Obese patients have decreased fasting and postprandial levels of peptide YY (PYY), an anorexigenic peptide produced by the L cells of the gastrointestinal mucosa. Fatty nutrients are the most powerful stimulus for PYY release. Cholestyramine, an anion exchanger which adsorbs bile salts, reduces digestion of lipids. The aim of the present study was to investigate the effects of cholestyramine or placebo on PYY secretion in obese women administered a high-fat meal [n=8; age: 30.9±2.7 years; BMI: 47.3±3.3 kg/m2]. Postprandial PYY levels in obese women given placebo significantly increased in plasma at 30, 60, 90, and 120 min after meal ingestion. Cholestyramine administration significantly reduced postprandial PYY response at 15, 30, and 60 min. Percent fat mass (FM%) was negatively correlated with the percent increment of plasma PYY concentrations induced by meal administration at 30 min; conversely, there was a positive correlation between FM% and the percent decrement of plasma PYY concentrations induced by cholestyramine at the same time interval. These correlations failed to reach statistical significance when related to BMI. This study implies that in the obese state the altered PYY response to food consumption is a consequence of a dysfunction of L cells, which become less sensitive to the positive feedback effect of lipids.

Growth hormone and lactate responses induced by maximal isometric voluntary contractions and whole-body vibrations in healthy subjects.

BACKGROUND: In contrast with maximal voluntary resistance exercise, which is allegedly considered a potent GH stimulus in young subjects, evaluation of GH response to whole-body vibrations (WBV) has yielded conflicting results. METHODS: The acute effects of WBV alone (test A), maximal voluntary isometric contractions (MVC) (test B), and combination of WBV and MVC (test C) on serum GH and blood lactate (LA) levels were studied in 9 healthy adult males. Muscle soreness was assessed 24 and 48 h after exercise by a visual analogue scale. RESULTS: GH responses were significantly higher after tests B and C than after test A (GH peaks: 18.8 ± 9.5 ng/ml or 20.8 ± 13.7 ng/ml, respectively, vs 4.3 ± 3.5 ng/ml; p<0.05), with no difference between tests B and C. LA concentrations significantly increased after tests A, B, and C, being significantly higher after tests B and C than after test A (LA peaks: 2.0 ± 0.5 mmol/l or 6.7 ± 2.3 mmol/l, respectively, vs 7.6 ± 0.9 mmol/l; p<0.05). Peak LA values were significantly correlated to GH peaks in the 3 tests (r=0.48; p<0.05). Muscle soreness was significantly higher 24-48 h after tests B and C than after test A, no significant differences being present between tests B and C. CONCLUSIONS: WBV stimulates GH secretion and LA production, with no additive effect when combined with repeated isometric voluntary contractions. Optimization of protocols based on WBV seems important to maximize the positive effects of this intervention on the somatotropic function.

GH responses to two consecutive bouts of whole body vibration, maximal voluntary contractions or vibration alternated with maximal voluntary contractions administered at 2-h intervals in healthy adults.

BACKGROUND: Pharmacological or exercise stimuli repeated at a short interval (but not electrical muscle stimulation) are associated with a blunting of GH responsiveness. AIM: To compare GH responses to repeated bout of three different GH-releasing stimuli. METHODS: The effects of two consecutive bouts (with a 2-h interval) of whole body vibrations (WBV), maximal voluntary contractions alone (MVC), or alternated with WBV (MVC-WBV) on blood GH and lactate (LA) were assessed in nine young males. RESULTS: Baseline levels of both GH and LA increased significantly after the first bout of all the tested stimuli, and were significantly lower after WBV than after MVC or MVC alternated with WBV, no difference being detected between these last. The administration of a second bout resulted in significantly lower GH increases than those elicited in the first bout in the three different tests; significantly lower LA responses were recorded after the second bout of MVC and MVC-WBV when compared with those obtained after the first bout, while no significant differences were observed after the two WBV bouts for LA. All responses after the second bout of MVC and MVC-WBV were significantly higher than those observed after WBV alone. GH concentrations were significantly correlated with LA after all stimuli, although LA concentrations after the second bout were associated with markedly lower GH levels. CONCLUSIONS: A significant blunting of GH responsiveness ensues after a second bout of different GH-releasing stimuli, independent from the amount of GH released after the first bout. This is a pattern also observed for other pharmacological stimuli and exercise modalities, and suggests a common mechanism underlying different GH-releasing stimuli.

Changes in plasma levels of ghrelin, leptin, and other hormonal and metabolic parameters following standardized breakfast, lunch, and physical exercise before and after a multidisciplinary weight-reduction intervention in obese adolescents.

OBJECTIVE: To investigate in severely obese adolescents the effects of a 3-week multidisciplinary weight-reduction intervention involving moderate energy restriction, individualised physical activity and behavior therapy on the response of some hormonal and metabolic parameters to meals and exercise. DESIGN: Clinical longitudinal study on inpatients in a specialised institution. SUBJECTS: A total of 20 obese adolescents (10 boys and 10 girls) aged 12-17 yr [body mass index (BMI): 37.7±6.1 kg/m2; fat mass (FM): 44.8±13.2 kg]. MEASUREMENTS: The changes in plasma concentration of leptin, ghrelin, GH, IGF-I, insulin, glucose, and non-esterified fatty acids (NEFA) in response to standardised meals and exercise bouts were measured before and after the weight-reduction intervention. At the same times, body composition was assessed by bioelectrical impedance as well as appetite sensations using a visual analog scale. RESULTS: At the end of the intervention, the adolescents had lost body weight and FM (expressed both in kg and %) (p<0.05), without any significant fat-free mass loss (in % terms). In response to both meals and exercise, after the 3-week intervention, plasma leptin concentration decreased significantly (p<0.05), whereas the other hormones (insulin, ghrelin, GH, and IGF-I) and metabolic parameters (glucose and NEFA) did not change. Interestingly, appetite was not affected by the intervention. CONCLUSION: This 3-week multidisciplinary intervention in obese adolescents induced a significant body weight loss with beneficial changes in body composition. However, despite there being no change in metabolic parameters and ghrelin in response to meals and exercise after the intervention, plasma concentrations of leptin were decreased. The failure of ghrelin levels to increase by this approach might explain the good control of appetite observed at the end of the study.

GH responses to two consecutive bouts of neuromuscular electrical stimulation in healthy adults.

BACKGROUND: It is well established that repeated GHRH administration or repeated voluntary exercise bouts are associated with a complete blunting of GH responsiveness when the administration of the second stimulus follows the first one after a 2-h interval. AIM: To evaluate GH responses to neuromuscular electrical stimulation (NMES) in healthy adults. METHODS: Six volunteers (mean age+/-s.d. 31.7+/-5.5 years) were studied before and after two consecutive bouts of NMES exercise (a series of 20 contractions at the maximum of individual tolerance, frequency: 75 Hz, pulse duration: 400 mus, on-off ratio: 6.25-20 s) administered at a 2-h interval. RESULTS: Baseline GH levels (mean: 0.3+/-0.2 ng/ml) significantly increased after the first NMES (peak: 4.2+/-3.7 ng/ml), with a complete normalization after 120 min (0.3+/-0.3 ng/ml). The administration of the second bout of NMES of comparable characteristics also resulted in a significant GH increase (peak: 5.2+/-3.2 ng/ml), which was comparable with that observed after the previous one. GH net incremental area under the curve after the first and second bouts of NMES were not significantly different (155.1+/-148.5 and 176.9+/-123.3 ng/ml per h, P=0.785). CONCLUSIONS: Unlike repeated pharmacological stimuli and voluntary exercise bouts, subsequent sessions of NMES administered at a 2-h interval appear to circumvent feedback mechanisms and to re-induce the GH responses, thus indicating a possible different underlying mechanism elicited by different GH-releasing stimuli.

Exercise-induced effects on growth hormone levels are associated with ghrelin changes only in presence of prolonged exercise bouts in male athletes.

AIM: The aim of this study was to evaluate growth hormone (GH) and ghrelin levels in response to physical exercise in athletes. METHODS: Two different exercise workloads were administered in two different groups of athletes. Group A athletes (19 males, 18 females; mean age +/- standard deviation: 25+/-6.7 years), performing a 60-90 min training session at approximately 80% of VO2max, were sampled for GH and ghrelin determinations before and immediately at the end of a training session on-the-field. Group B athletes (4 males; mean age: 28.2+/-7.2 years) performed two consecutive 30-min cycling sessions at 80% of individual VO2max at different time intervals between bouts (2 and 6 h) in two different days. GH and ghrelin concentrations were determined in blood samples collected at 15-min intervals during exercise and following 1 h of recovery. RESULTS: In group A athletes, GH levels increased after the training session (P<0.0001), with no differences between males and females. In male athletes, ghrelin levels significantly decreased after the training session (from 1 506.4+/-859 to 1 254.8+/-661.7 pg/mL, P<0.05), while no significant changes were found in females. No correlations were observed between GH and ghrelin levels at rest and after training. In group B athletes, GH levels significantly increased after the first exercise bouts (peak: 26.8+/-11.2 and 17.3+/-3.5 ng/mL, respectively), while the pattern of GH response was different after the second bout of exercise performed at 2-h or 6-h interval. In fact, peak GH concentration in response to the second bout (4.3+/-1.6 ng/mL) was lower (P<0.01) than that of the first bout when the interval elapsed was only 2 h, while a recovery of GH responsiveness was evident after the 6-h interval between the two exercise bouts (11.9+/-3.3 ng/mL). As far as ghrelin levels are concerned, no significant changes were observed during and after the two exercise bouts performed at the different time intervals. CONCLUSION: GH responses to prolonged exercise bouts (60-90 min) are associated with changes in ghrelin levels only in male athletes, while repeated exercise bouts of lower duration (30 min), capable to determine marked GH responses, are divorced from changes in ghrelin concentrations.

Prediction of resting energy expenditure in severely obese Italian males.

The objectives of the present study were to develop and cross-validate new equations for predicting resting energy expenditure (PREE) in severely obese Italian males, and to compare their accuracy with those of the Harris-Benedict, WHO/ FAO/UNU, Huang, Owen, Mifflin, Livingston, Nelson, Bernstein, and Cunnimgham equations in order to predict resting energy expenditure (REE), using the Bland-Altman method. One hundred and sixty-four severely obese males [mean body mass index (BMI): 45.4 kg/m2; 50.2% fat mass), aged 20 to 65 yr participated in this study. REE was measured by indirect calorimetry and body composition by bioelectrical analysis. Equations were derived by stepwise multiple regression analysis using a calibration group and tested against the validation group. Two new specific equations, based on anthropometric [REE=Weight x 0.048 + Height x 4.655 - age x 0.020 - 3.605 (R2=0.68, SE=1.14 MJ/d)] or body composition parameters [REE=fat free mass (FFM) x 0.081 + fat mass (FM) x 0.049 - age x 0.019 - 2.194 (R2=0.65, SE=1.15 MJ/d)], were generated. Mean PREE were not different from the mean measured REE (MREE) (<1%, p<0.001), REE being predicted accurately (95-105% of MREE) in 66 and 62% of subjects, respectively. The Harris-Benedict, WHO/FAO/UNU, Huang and Owen equations showed mean differences lower than 5% and PREE was accurate in less than 30% of subjects. The Mifflin, Livingston, and Nelson equations showed a mean PREE underestimation >7% (p<0.001) and PREE was accurate in less than 25% of subjects. The Bernstein and Cunningham equations showed a greater PREE underestimation (>22%, p<0.001) in more than 85% of subjects. The new prediction equations allow an accurate estimation of REE in groups of severely obese males and result in lower mean differences and lower limits of agreement between PREE and MREE than the commonly used equations.

A follow-up of GH-dependent biomarkers during a 6-month period of the sporting season of male and female athletes.

In order to verify the effects of the sporting season (entailing periods of training, competition, recovery, resting) on GH-dependent parameters in male and female athletes from different sporting disciplines, 47 male and female athletes (3 rowers, 5 swimmers, 7 alpine skiers, 3 soccer players, 7 middle distance runners, 14 sprinters, 4 triathletes, 1 road walker, 3 cyclists) were followed-up for a period of 6 months. Blood samples were taken every two months for the evaluation of IGF-I, N-terminal propeptide of type III procollagen (PIIINP) and C-terminal cross-linked telopeptide of type I collagen (ICTP). Abnormal IGF-I, PIIINP and ICTP levels were observed during the follow-up period in 7/100 (7%), 9/100 (9.0%) and 8/100 (8%) samples of the male group, respectively, and in 9/88 (10.2%), 1/88 (1.1%) and 0/88 (0%) samples of the female group, respectively. Abnormal levels appeared to be randomly distributed over the different periods of the sporting season and within male and female subjects, with the large majority of abnormal values being found in the younger athletes. Taking into account all the tests done during the 6-month period (no. 564), individual markers falling outside the normal range (for age) were observed in a small number of instances (34/564 tests done, 24/300 for males and 10/264 for females). When our method for the detection of exogenous recombinant GH (rhGH) administration, based on the concomitant determination of these three peripheral GH-dependent markers and on the attribution of specific scores, was applied in the same athlete at a given time point of the 6-month period, the prevalence of a positive score was extremely low (ie, 3/188 samples or 1.6%). Total positive scores were actually recorded in only three male athletes (2 swimmers and 1 skier, aged <21 yr) at one occasion during the 6-month period considered. In contrast, no total positive scores were found in female athletes (ie, 0/88 samples). In conclusion, the concentrations of IGF-I, PIIINP and ICTP were stable and not significantly modified during 6 months of a sporting season (entailing periods of training, competition, recovery, resting) in athletes from different sporting disciplines. Therefore our method, based on the concomitant determination of three peripheral GH-dependent biomarkers appears safe, acceptable, relatively inexpensive and repeatable (in case of positive or suspected values) immediately or at different intervals of the sporting season. Further additional studies are requested to precise the cut-off values for narrower age-class subdivisions in both genders in order to improve the proposed method.

Elite volunteer athletes of different sport disciplines may have elevated baseline GH levels divorced from unaltered levels of both IGF-I and GH-dependent bone and collagen markers: a study on-the-field.

Seventy-seven Italian eliteathletes(42 M, 35 F, mean age +/- SE: 24.4-0.7 yr, age range: 17-47 yr) of different sport disciplines (sprinters, triathletes, middle-distance runners, road-walkers, cyclists, rowing athletes, skiers, roller hockey players, swimmers) were sampled on-the-field (before a training session) for the determination of basal GH, IGF-I, C-terminal cross-linked telopeptide of type I collagen (ICTP) and amino-terminal propeptide of type III procollagen (PIIINP) levels, two GH-dependent peripheral markers of bone and collagen turnover, respectively. Basal GH concentrations were significantly higher (p<0.001) in female (5.8 +/- 1.0 ng/ml) vs male athletes (1.8 +/- 0.5 ng/ml), with a large spread of values in either gender. Mean GH levels of athletes were significantly higher than those recorded in age-matched sedentary controls (females: 2.5 +/- 0.5 ng/ml, p<0.001; males: 0.5 +/- 0.2 ng/ml, p<0.05). Among female athletes, 7/35 had basal GH values higher than the upper limit of control values (>9.5 ng/ml), while among males 7/42 had values higher than the upper limit of male sedentary controls (>3.6 ng/ml). No significant differences in basal GH concentrations were found between females taking oral contraceptives (OC) and those who did not receive this treatment (5.0 +/- 2.1 vs 6.0 +/- 1.2 ng/ml). IGF-I levels (236.4 +/- 7.8 ng/ml) were in the normal range for age in all athletes (except for 1 athlete with slightly increased levels), no significant correlation being found between GH and IGF-I levels (R2=0.0393). Mean ICTP (4.6 +/- 0.2 ng/ml) and PIIINP (4.4-0.1 ng/ml) concentrations of elite athletes were not significantly different from those recorded in age and matched healthy sedentary subjects; 4 athletes showed increased PIIINP levels and 2 had increased ICTP levels. ICTP and PIIINP levels were positively correlated with chronological age (p<0.001), a positive correlation being also found between the two markers (p<0.001). On the contrary, no significant correlation was found between basal GH/IGF-I levels and ICTP/PIIINP levels. In conclusion, the present study demonstrates that: 1) elite athletes (particularly females), which have frequently increased basal GH on-the-field, have actually normal IGF-I levels; 2) ICTP and PIIINP levels of athletes are similar to those recorded in healthy sedentary, being significantly higher in younger subjects of both groups; 3) the presence of increased basal GH levels, being associated with normal IGF-I, ICTP and PIIINP levels, is probably the result of a transient GH peak in this study group. Further additional studies are requested to verify the possible use of these peripheral GH-dependent markers for detecting exogenous chronic administration of recombinant GH in athletes.