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.

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.

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.

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).

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.

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.

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.

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.

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.

Growth hormone responses to growth hormone-releasing hormone and hexarelin in fed and fasted dogs: effect of somatostatin infusion or pretreatment with pirenzepine.

Using unanesthetized young male and female beagle dogs, before and after a 2-day fast, we studied the effect of an i.v. infusion of 0.9% saline (5 ml/h), somatostatin (SS, 4 or 8 micrograms/kg/h), or pretreatment with pirenzepine (PZ, 0.6 mg/kg i.v.), a muscarinic cholinergic antagonist which allegedly releases SS, on the GH release evoked by acute administration of GHRH (2 micrograms/kg i.v.), hexarelin (HEXA), a member of the GH-releasing peptide family (250 micrograms/kg i.v.) or GHRH plus HEXA. In fasted dogs, GHRH delivered during saline infusion induced a clear-cut rise in plasma GH levels, significantly higher than that which it induced in fed dogs. In contrast, HEXA, although very effective in causing the release of GH, only slightly increased GH secretion in fasted dogs over that which it induced in fed dogs. Co-administration of GHRH plus HEXA into fed dogs induced a synergic GH response that further increased with fasting. The action of GHRH in fed dogs was abolished by the lower dose of SS, whereas SS at either dose was ineffective in suppressing the GH-releasing effect during fasting. Infusion of the lower dose of SS failed to counter the action of HEXA, either before or during fasting, whilst the higher SS dose partially reduced it in both conditions. In contrast to SS, PZ reduced the GH-releasing effect of GHRH and HEXA, both in the fed state and, though to a lesser extent, during fasting. Pirenzepine only slightly reduced the robust GH rise elicited by GHRH plus HEXA in fed dogs. The suppressive effect of PZ on the GH response to combined administration of the peptides was lowest in fasted dogs. These data show that: (1) fasting augmented the GH response to GHRH and (to a lesser degree) to HEXA; (2) SS inhibited the GH response to GHRH in the fed state, but not in the fasted state; (3) only the higher dose of SS partially reduced the GH stimulation by HEXA in either the fed or the fasted state; (4) PZ lowered the GH response to GHRH and to HEXA in both the fed and (to a lesser degree) the fasted state; (5) PZ did not modify the GH release due to the combined administration of GHRH and HEXA. It is suggested that: (1) during fasting the greatly enhanced GH response to GHRH alone or GHRH plus HEXA probably reflects an augmented GHRH secretion; (2) somatotrope refractoriness to SS may contribute to the enhanced GH secretion in states of calorie deprivation; (3) in contrast to a general belief, muscarinic cholinergic antagonists, e.g. PZ, do not act exclusively via release of SS, but probably also through inhibition of GHRH function.

Six-week treatment with hexarelin in young dogs: evaluation of the GH responsiveness to acute hexarelin or GHRH administration, and of the orexigenic effect of hexarelin.

In this study we evaluated, in six young (5-7 year-old) beagle dogs, the effects of a 6-week administration of hexarelin (250 microg/kg s. c. twice daily) on the GH response to an acute challenge with hexarelin or GHRH (2 microg/kg i.v.), delivered before and after 3 and 6 weeks of treatment. The GH peak response to acute hexarelin or GHRH initially increased, with a maximum observed at the 3rd week, and then decreased to basal values (GHRH) or less (hexarelin) at the 6th week. These data would indicate that hexarelin initially primed the pituitary to acute administration of further hexarelin or of GHRH, followed by downregulation of the GH response to hexarelin and preservation of the response to GHRH. We then studied the rebound increase in GH secretion after withdrawal of an infusion of somatostatin (4 microg/kg per h for 1.5 h), a likely stimulus of endogenous GHRH function. The pattern obtained was similar to, though not superimposable upon, that ensuing after acute hexarelin or GHRH administration. Parallel evaluation of the acute orexigenic effect of hexarelin evinced a different time-course of the behavioural response, namely an acute feeding response to hexarelin that was abolished at the 3rd week and returned to normal at the 6th week. The differing timing of the neuroendocrine or behavioural response to hexarelin would suggest the existence of different subtypes of central nervous system GH-releasing peptide receptors.

Nitric oxide modulation of the growth hormone-releasing activity of Hexarelin in young and old dogs.

The growth hormone (GH)-releasing activity of Hexarelin, a potent GH-releasing peptide (GHRP) analog, was evaluated in eight young (aged 1 to 6 years) and five old (10 to 16 years) beagle dogs pretreated with erythrityl tetranitrate, a liposoluble nitric oxide (NO) donor, and/or indomethacin, an inhibitor of cyclooxygenase enzymes, and N-nitro-L- or N-nitro-D-arginine methylester (L-NAME and D-NAME), active and inactive NO synthase (NOS) inhibitors, respectively. Erythrityl tetranitrate (0.3 mg x kg(-1) oral [p.o.]) strikingly potentiated Hexarelin-stimulated GH secretion (31.25 microg x kg(-1) intravenous [i.v.]) in both young (area under the time-concentration curve at 0 to 90 minutes AUC(0-90)] 878.50 +/- 267.02 v 1,994.04 +/- 434.20 ng x mL(-1) x h, P < .01) and aged animals (314.82 +/- 117.11 v 1,314.12 +/- 484.75 ng x mL(-1) x h, P < .01). The NO donor alone did not modify baseline GH levels in either young dogs (188.68 +/- 85.24 ng x mL(-1) x h) or old dogs (120.49 +/- 22.03 ng x mL(-1) x h). L-NAME (5 mg x kg(-1) x 2 i.v.) suppressed GH release induced by the peptide in young dogs (1,367.68 +/- 251.87 v 411.12 +/- 68.49 ng x mL(-1) x h, P < .01), but potentiated it in old dogs (314.73 +/- 117.10 v 1,103.97 +/- 374.11 ng x mL(-1) x h, P < .01). D-NAME (5 mg x kg(-1) x 2 i.v.) did not affect the GH response to Hexarelin in either young (1,328.68 +/- 433.54 ng x mL(-1) x h) or aged (342.32 +/- 84.82 ng x mL(-1) x h) dogs. Indomethacin (1.5 mg x kg(-1) i.m.) abolished the NO-donor potentiation of the GH response induced by Hexarelin in both young dogs (1,627.25 +/- 260.90 v 1,163.37 +/- 334.84 ng x mL(-1) x h, P < .05) and old dogs (1,061.47 +/- 210.38 v 365.69 +/- 79.27 ng x mL(-1) x h, P < .01) without affecting the plasma GH peak evoked by the peptide alone (young dogs, 786.04 +/- 153.44 v 960.04 +/- 444.44 ng x mL(-1) x h, P = NS; old dogs, 474.55 +/- 47.30 v 490.82 +/- 144.86 ng x mL(-1) x h, P = NS). In conclusion, (1) NO donors are capable to further increase the strong GH-releasing activity of Hexarelin in both young and old dogs, although the site(s) and mechanism(s) of action of NO is still obscure; (2) the different GH response to the peptide after NOS inhibition in young and old dogs signifies in the latter an alteration of the somatotrope function; and (3) prostaglandins are the downstream effectors of the chain of events triggered by activation of the NO-ergic system.

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.

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.

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.