Nocturnal Growth Hormone Research Articles

OR14-4 Acute sleep disruption does not diminish pulsatile growth hormone secretion in pubertal children

Abstract Context: Growth hormone (GH) plays a critical role in glucose homeostasis and linear growth during childhood. GH secretion is controlled by multiple neurotransmitters and hormones. Sleep is also a powerful stimulus for GH secretion. In children, GH pulses occur after sleep onset in association with slow-wave sleep (SWS), but it is unclear if undisrupted sleep is required for normal GH secretion. Given the rising incidence of pediatric sleep disorders such as obstructive sleep apnea (OSA) that cause sleep fragmentation, it is critical to determine whether sleep fragmentation during childhood may dysregulate the somatotropic axis. Objective To quantify how undisrupted vs fragmented sleep affects GH secretion in children. Methods Pubertal subjects (10 M, 9 F; 9.1-14.4 yrs) were randomized to two overnight polysomnographic studies with frequent blood sampling (q10min) to measure GH: fourteen were healthy subjects studied with or without SWS disruption via auditory stimuli (3 sec, 1500 Hz tones, 40-100 dB followed by 18 sec of a 75 dB noise simulating a knock on the door) and five were subjects with OSA studied with or without prescribed continuous positive airway pressure (CPAP); the latter condition was expected to have sleep fragmentation due to untreated OSA. GH pulses were identified using sparse deconvolution. Studies without auditory stimuli or when using CPAP were combined and analyzed as 'undisrupted sleep'. The relationship between GH pulse rate per hour and sleep stage was evaluated using Poisson generalized estimating equations. Results In SWS disruption studies, an average of 77.51 ± 13.61 (range 23-190) auditory stimuli were delivered, causing a 40.02 ± 7.78% decrease in SWS in favor of lighter sleep stages. In subjects with OSA, CPAP withdrawal caused a slight increase in the apnea hypopnea index (1.08 ± 0.10 vs. 2.20 ± 1.70 events/hour of sleep, p=0.07) with no change in sleep stage durations. During undisrupted sleep, subjects had an average of 0.91 ± 0.067 GH pulses/hour with a mean pulse amplitude of 10.03 ± 1.00 ng/mL and mean basal secretion rate of 0.26 ± 0.10 ng/ml per min. GH pulses occurred more frequently during SWS (2.3 pulses/hour SWS, amplitude 9.92 ± 2.59 ng/mL) than during any other sleep stage (P < 0.001). Neither form of sleep disruption affected the distribution of GH pulses across sleep stages, GH pulse amplitude and frequency, nor basal GH secretion. Conclusion In children, nocturnal GH pulses are temporally associated with SWS. However, neither acute fragmentation of SWS nor nocturnal arousals from OSA altered basal or pulsatile GH secretion, indicating that somatotrophic axis activity is preserved in the face of acute sleep disruption in children. Presentation: Sunday, June 12, 2022 11:45 a.m. - 12:00 p.m.

Effect of long-acting growth hormone treatment on endogenous growth hormone secretion in prepubertal patients with idiopathic short stature: A preliminary study

Long-acting growth hormone (LAGH) is emerging to be a new preparation for treatment of short stature. We aimed to determine whether 12-month treatment with LAGH in patients with idiopathic short stature has an effect on the nocturnal endogenous growth hormone (GH) secretion and metabolic consequences and efficacy. Participants included 10 GH-naïve prepubertal children with idiopathic short stature (ISS). One patient was withdrawn due to own decline during study. Participants were randomized on a 1:1 ratio to receive either a daily GH (0.37 mg/kg/week) or once-weekly LAGH (0.7 mg/kg/week) over a 12-month period. Nocturnal endogenous GH secretory profiles obtained from 12-h blood samplings at 30-min interval were assessed at baseline and 2 weeks after the completion of GH treatment. Post-treatment changes in height velocity, height standard deviation score (SDS), metabolic parameters, and adverse events were measured. A total of 4 patients received LAGH, and 5 patients received daily GH. Nocturnal endogenous GH secretory profiles, such as mean serum GH concentrations, frequency, amplitude, interpulse interval of spontaneous GH secretory bursts, and mass of GH released per secretory burst were similar at baseline and after 12-month treatment in both groups. The efficacy and safety after LAGH treatment for 12 months were similar to those of daily GH. In conclusions, these findings indicated that LAGH does not suppress endogenous GH secretion, and can be used for treatment of non-GH deficient short stature with similar efficacy and safety compared to daily GH. These may contribute to define and develop treatment and follow-up protocols for LAGH use in ISS patients.

Discordance Between Stimulated and Spontaneous Growth Hormone Levels in Short Children Is Dependent on Cut-Off Level and Partly Explained by Refractoriness.

BackgroundA growth hormone (GH) stimulation test is the recommended method for evaluating GH levels in children with possible GH deficiency (GHD). However, serial measurements of nocturnal spontaneous GH secretion are also performed. Divergent results from these tests have been reported, but with variable frequencies.ObjectivesTo investigate whether performing one or two GH tests is associated with the probability to diagnose a child with GHD; the frequency of divergent results in the arginine-insulin tolerance test (AITT) and the nocturnal spontaneous test using different cut-off levels, and whether refractoriness may explain some of the discordance.MethodsIn a population-based setting, the medical records of all short children evaluated for possible GHD during January 1993–February 2017 were reviewed. Twenty-one patients had been evaluated with one GH test only and 102 children had been evaluated with a spontaneous nocturnal GH test followed immediately by a complete AITT. Divergent results were defined as having a pathological response on only one of the tests when using 3, 5, 7, and 10 µg/L as cut-offs for peak GH on both tests, 1.1 and 3.3 µg/L for mean nocturnal values and receiver operating characteristic curves-derived cut-offs for nocturnal values.ResultsChildren evaluated with one test only were more often diagnosed with GHD compared with children evaluated with both tests (48 vs. 19%, p = 0.019). Divergent results were found in 6–42% of the patients, with higher frequencies seen when higher cut-offs were applied. A higher proportion of patients with stimulated peak values ≤ 7 and ≤ 5 µg/L had a spontaneous peak within 2 h before the start of the AITT compared with patients with higher stimulated peak values (68 vs. 45%, p = 0.026, and 77 vs. 48%, p = 0.033, respectively).ConclusionsDivergent results between AITT and nocturnal spontaneous secretion are common in short children, dependent on the cut-offs applied and partly due to refractoriness. Performing both tests decreases the risk of over diagnosing GHD in short children.

Strong Positive Correlation between TSH and Ghrelin in Euthyroid Non-Growth Hormone-Deficient Children with Short Stature.

The growth processes in children depend on the proper functioning of some hormones and growth factors. Recently, a positive correlation between ghrelin and TSH (thyroid stimulating hormone) in patients with hyper- and hypothyroidism was proved. Moreover, in hypothyroid rats with high ghrelin concentration, growth hormone (GH) and insulin-like growth factor I (IGF-I) secretion was suppressed. We analyzed these relationships in euthyroid prepubertal children with idiopathic short stature (ISS). The analysis comprised concentration of ghrelin, GH in stimulating tests and during the night, as well as IGF-I, TSH, free thyroxine (FT4) and free triiodothyronine (FT3) in 85 children with ISS (36 girls, 49 boys) aged 9.65 ± 3.02 years (mean ± SD). A strong positive correlation between ghrelin and TSH was confirmed (r = +0.44, p < 0.05). A higher ghrelin but lower nocturnal GH and lower IGF-I were observed in children with higher normal TSH concentration than those in children with lower normal TSH. Interestingly, alterations of TSH level were without any impact on FT4 and FT3 concentrations. Summing up, in ISS prepubertal euthyroid children, ghrelin and TSH secretion are closely related. On the other hand, the higher the TSH, the lower the nocturnal GH and IGF-I levels. The contribution of the above findings in deterioration of growth processes requires further studies.

P1.03: Intravenous glucose nocturnal infusion reduces growth hormone secretion in children on total parenteral nutrition

Introduction: Most children with intestinal failure (IF) benefit from home parenteral nutrition (HPN). It allows a familial life with normal children activities such as going to school, sports, and being at home. In order to do so, PN is provided with cyclic infusion at night. Children with IF on HPN should have normal growth. However, some children grow under their genetic target height and present with decreased height velocity. Methods: We report the case of two children on HPN who presented with decreased height velocity while their weight gain was normal. After ruling out usual etiology (insufficient protein intake, acidosis, sodium deficiency, IFALD…), growth hormone (GH) deficiency was considered. Extensive testings were performed such as IgF1 levels, GH secretion stimulation test and nocturnal GH secretion. PN dependency was assessed using the PN/REE index (parenteral nutrition non-protein energy intake divided by resting energy expenditure calculated using Schofield equation, expressed in percentage). Results: These two children needed extremely high PN caloric intake to achieve a normal weight gain with a PN dependency index of 163% and 150%. Table 1 shows their clinical characteristics. Table 2 shows the results of the biological testings. These two children showed a normal GH peak under stimulation, but a low nocturnal GH secretion meaning they were able to produce GH under stimulation, but their nocturnal physiological secretion was inhibited. Their mean glycemia during PN perfusion was high compared to fasting glycemia which should normally be observed at night in children. Hyperglycemia is a well known inhibitor of GH secretion. Conclusion: Children with very high PN dependency are at risk of developing reduced height. In some children, GH secretion seems to be inhibited by nocturnal high glucose infusion. A longer PN infusion time can be proposed and/or a decrease in glucose intake with an increase in lipid intake. Also, growth hormone supplementation might be discussed and should be evaluated in this setting.

Aromatized Estrogens Amplify Nocturnal Growth Hormone Secretion in Testosterone-Replaced Older Hypogonadal Men.

Testosterone (T) increases GH secretion in older men with a relative lack of T, in hypogonadal men of all ages, and in patients undergoing sex reassignment. The role of estradiol (E2) in men is less well defined. To assess the contribution of aromatization of T to spontaneous nocturnal and stimulated GH secretion. Four groups of healthy older men (N = 74, age range 57 to 77 years) were studied. The gonadotropic axis was clamped with the gonadotropin-releasing hormone antagonist degarelix. Three groups received T and one group placebo addback. Two T-replaced groups were treated with anastrozole (an aromatase inhibitor) and either placebo or E2 addback. Ten-minute GH concentration profiles were quantified by deconvolution analysis, after overnight (2200 to 0800 hours) sampling, and after combined IV injection of GHRH (0.3 µg/kg) and GHRH-2 (0.3 µg/kg) and withdrawal of a 2-hour somatostatin infusion (1 µg/kg/h). E2 addback during aromatase inhibition increased basal (P = 0.046), pulsatile (P = 0.020), and total (P = 0.018) GH secretion by 60% to 70%. E2 did not potentiate GH secretory stimuli. Logarithmically transformed pulsatile GH secretion correlated strongly and positively with concurrent E2 concentrations overall (P = 0.028) and under anastrozole treatment (P = 0.005). E2 administration in older men transdermally stimulates overnight pulsatile GH secretion. The exact site of E2 action cannot be ascertained from these experiments but may include hypothalamic loci involved in GH regulation, especially because GH secretagogue effects on somatotrope pituitary cells were not affected.

Pilot study: an acute bout of high intensity interval exercise increases 12.5h GH secretion.

The purpose of this study was to test the hypothesis that high‐intensity interval exercise (HIE) significantly increases growth hormone (GH) secretion to a greater extent than moderate‐intensity continuous exercise (MOD) in young women. Five young, sedentary women (mean ± SD; age: 22.6±1.3 years; BMI: 27.4±3.1 kg/m2) were tested during the early follicular phase of their menstrual cycle on three occasions. For each visit, participants reported to the laboratory at 1700 h, exercised from 1730–1800 h, and remained in the laboratory until 0700 h the following morning. The exercise component consisted of either 30‐min of moderate‐intensity continuous cycling at 50% of measured peak power (MOD), four 30‐s “all‐out” sprints with 4.5 min of active recovery (HIE), or a time‐matched sedentary control using a randomized, cross‐over design. The overnight GH secretory profile of each trial was determined from 10‐min sampling of venous blood from 1730–0600 h, using deconvolution analysis. Deconvolution GH parameters were log transformed prior to statistical analyses. Calculated GH AUC (0–120 min) was significantly greater in HIE than CON (P = 0.04), but HIE was not different from MOD. Total GH secretory rate (ng/mL/12.5 h) was significantly greater in the HIE than the CON (P = 0.05), but MOD was not different from CON or HIE. Nocturnal GH secretion (ng/mL/7.5 h) was not different between the three trials. For these women, in this pilot study, a single bout of HIE was sufficient to increase 12.5 h pulsatile GH secretion. It remains to be determined if regular HIE may contribute to increased daily GH secretion.

The Effect of Adenotonsillectomy on Growth in Prepubertal Children

Adenotonsillar hypertrophy (ATH) is the most common cause of obstructive sleep apnea syndrome in children,1 and the prevalence of obstructive sleep apnea syndrome (OSAS) were at least 1–3% in children.2 Sleep disordered breathing (SDB) is often associated with loud snoring, daytime sleepiness, and daytime mouth breathing. Complications of SDB may include failure to thrive, nocturnal enuresis, sweating during sleep, reduced neurocognition, behavioral problem, and school performances.3-5 Several possible mechanisms for failure to thrive have been assessed. Interruption of the insulin-like growth factor-I axis secondary to abnormal nocturnal growth hormone secretion,6 low caloric intake caused by poor appetite and dysphagia,7 recurrent tonsillitis,8 and high energy expenditure as a consequence of increased work of breathing during sleep9 had been proposed as causes. Also many studies had suggested and proved that growth failures were improved after adenotonsillectomy in children with ATH.10-12 On the other hand, obesity could be one of the risk factor for SDB in children.13 There were few studies about the effect of adenotonsillectomy in obesity children, instead it was reported that children who undergo adenotonsillectomy could be at risk to develop overweight in the years after surgery.14 The effect of SDB and adenotonsillectomy on children might be different according to the growth status, but little is known in this aspect. Received: June 8, 2016 Revised: June 17, 2016 Accepted: June 20, 2016

Effect of Growth Hormone on Dawn Phenomenon in Healthy Adults

The purpose of this study was to investigate the involvement of growth hormone in the diurnal variation of insulin sensitivity in healthy adults. Afternoon (16:00 hr) or night (23:00 hr) pretreatment with a subcutaneous injection of normal saline, human growth hormone to mimic the normal nocturnal rise in growth hormone, or octreotide to inhibit endogenous growth hormone secretion to create a state of relative nocturnal growth hormone deficiency, was given 16 hours before undergoing the modified insulin suppression test in healthy subjects. The morning and evening experiments were separated by an interval of at least 3 days. Thus, each subject was tested on six separate occasions arranged in a random order. A higher value of the steady-state plasma glucose (SSPG) is indicative of lower insulin sensitivity. Plasma glucose, serum insulin, insulin-like growth factor-1, nonesterified fatty acids (NEFA), and metabolic clearance rate of insulin (MCRI) were measured. In the normal saline and human growth hormone groups, SSPG levels were lower in the morning than in the evening. Evening SSPG levels, MCRI, and NEFA concentrations were higher in the participants treated with normal saline and growth hormone than in the octreotide group. Differences in SSPG levels between the morning and evening values were higher in the participants pretreated with normal saline and growth hormone than in those treated with octreotide. A diurnal variation in insulin sensitivity existed in healthy subjects. These results provided direct evidence that the role of growth hormone in regulating insulin sensitivity might be related to changes in the MCRI and the metabolism of NEFA in healthy subjects.

Hypopituitarism in Pediatric Survivors of Inflicted Traumatic Brain Injury

Endocrine dysfunction is common after accidental traumatic brain injury (TBI). Prevalence of endocrine dysfunction after inflicted traumatic brain injury (iTBI) is not known. The aim of this study was to examine endocrinopathy in children after moderate-to-severe iTBI. Children with previous iTBI (n=14) were evaluated for growth/endocrine dysfunction, including anthropometric measurements and hormonal evaluation (nocturnal growth hormone [GH], thyrotropin surge, morning and low-dose adrenocorticotropin stimulated cortisol, insulin-like growth factor 1, IGF-binding protein 3, free thyroxine, prolactin [PRL], and serum/urine osmolality). Analysis used Fisher's exact test and Wilcoxon's rank-sum test, as appropriate. Eighty-six percent of subjects had endocrine dysfunction with at least one abnormality, whereas 50% had two or more abnormalities, significantly increased compared to an estimated 2.5% with endocrine abnormality in the general population (p<0.001). Elevated prolactin was common (64%), followed by abnormal thyroid function (33%), short stature (29%), and low GH peak (17%). High prolactin was common in subjects with other endocrine abnormalities. Two were treated with thyroid hormone and 2 may require GH therapy. In conclusion, children with a history of iTBI show high risk for endocrine dysfunction, including elevated PRL and growth abnormalities. This effect of iTBI has not been well described in the literature. Larger, multi-center, prospective studies would provide more data to determine the extent of endocrine dysfunction in iTBI. We recommend that any child with a history of iTBI be followed closely for growth velocity and pubertal changes. If growth velocity is slow, PRL level and a full endocrine evaluation should be performed.

Circadian variation in the pharmacokinetics of steady state continuous subcutaneous infusion of growth hormone in adult growth hormone deficient patients

BackgroundPrevious studies in growth hormone (GH)-deficient (GHD) patients have indicated a possible diurnal variation in the pharmacokinetics (PK) of GH after subcutaneous (sc) GH administration. Thus, higher GH levels were observed during the night with continuous sc infusion, and increased GH bioavailability was reported following daily sc injections in the evening compared to morning. ObjectiveThe aim was to study whether diurnal variability in the PK of sc administered exogenous GH can be reproduced under standard conditions for all study participants, e.g. supine rest. Design and methodsEight male GHD patients (59.8±8years, body mass index 29.7±4.9kg/m2) received a continuous sc infusion of GH (3mg/24h) for 60h on two different occasions. Diurnal variation in PK of GH was studied during steady state in the last 24h of the infusion period. ResultsMedian GH levels were higher at night time (23:00h–07:00h) than during the day (10:00h–18:00h) for visit 1 [5.1 (4.5–7.2ng/ml/0.5h) vs. 4.6 (3.7–5.7ng/ml/0.5h); p<0.05], and reproducible results of diurnal GH variation were obtained during visit 2 [5.7 (4.6–7.4) ng/ml/0.5h vs. 4.6 (3.8–6.0) ng/ml/0.5h, p<0.05]. Reproducible results between days 1 and 2 were also obtained during 08:30h–20:30h and 20:30h–08:30h, respectively. ConclusionsPrevious findings of higher nocturnal GH levels were confirmed during steady state continuous sc GH infusion under standard conditions. The underlying mechanisms, e.g. whether GH absorption, distribution or elimination is primarily affected need to be further elucidated.

Detailed studies of growth hormone secretion in cystinosis patients

Cystinosis is an autosomal recessive disorder characterized by intralysosomal cystine accumulation. Growth retardation is more pronounced in cystinosis than in other chronic kidney diseases and is mostly not corrected by cysteamine. Growth was evaluated in nine cystinosis patients, all treated with cysteamine, both after cysteamine and recombinant human growth hormone (rhGH) therapy initiation. Growth hormone (GH) secretion was studied by nocturnal GH measurements in four of nine patients and by glucagon test in four of nine patients. RhGH was administered to seven of nine patients. At rhGH initiation, height was below -2 SDS in five of seven patients, final height was above -2 SDS in six of seven. In two patients not treated with rhGH, final height remained below -4 SDS despite cysteamine treatment being started at the age of 6.1 and 8.1 years, respectively. Nocturnal GH secretion was normal in all patients. Glucagon tests revealed GH deficiency in one patient; two of four patients had abnormal GH peak timing. We present the first reported case of GH deficiency in cystinosis. Although no overt GH deficiency was detected in other patients, abnormal GH peak timing can indicate a subclinical GH secretion problem. RhGH significantly improved growth in cystinosis patients and should be initiated early in life.

Decreased nocturnal growth hormone secretion and sleep fragmentation in combat-related posttraumatic stress disorder; potential predictors of impaired memory consolidation

Healthy sleep facilitates the consolidation of newly acquired memories. Although patients with posttraumatic stress disorder (PTSD) often complain of sleep disturbances and memory deficits, the interrelatedness of these symptoms is not well understood. Sleep may be disturbed in PTSD by increased awakenings during sleep, which has been associated with decreased growth hormone (GH) secretion. We conducted a controlled study in which we assessed sleep fragmentation, nocturnal secretion of GH, and memory consolidation in patients with PTSD. While sleep EEG was being monitored, 13 veterans with PTSD, 15 trauma controls (TC) and 15 healthy controls (HC) slept with an iv catheter, through which blood was collected every 20 min from 23:00 h to 08:00 h. Declarative memory encoding was assessed with the 15 word task before sleep, and consolidation was assessed the next morning by a free recall. Sleep was more fragmented in patients with PTSD, with more awakenings in the first half of the night (p<0.05). Plasma levels of GH during the night were significantly decreased in PTSD compared with HC (p<0.05). Furthermore, GH secretion and awakenings were independent predictors for delayed recall, which was lower in PTSD compared to HC (p<0.05). These data show that PTSD is associated with increased awakenings during sleep and decreased nocturnal GH secretion. Furthermore, decreased GH secretion may be related to sleep fragmentation and both variables may exert a negative effect on sleep dependent memory consolidation.

Effect of sodium oxybate on growth hormone secretion in narcolepsy patients and healthy controls

Hypocretin deficiency causes narcolepsy and may affect neuroendocrine systems and body composition. Additionally, growth hormone (GH) alterations my influence weight in narcolepsy. Symptoms can be treated effectively with sodium oxybate (SXB; γ-hydroxybutyrate) in many patients. This study compared growth hormone secretion in patients and matched controls and established the effect of SXB administration on GH and sleep in both groups. Eight male hypocretin-deficient patients with narcolepsy and cataplexy and eight controls matched for sex, age, BMI, waist-to-hip ratio, and fat percentage were enrolled. Blood was sampled before and on the 5th day of SXB administration. SXB was taken two times 3 g/night for 5 consecutive nights. Both groups underwent 24-h blood sampling at 10-min intervals for measurement of GH concentrations. The GH concentration time series were analyzed with AutoDecon and approximate entropy (ApEn). Basal and pulsatile GH secretion, pulse regularity, and frequency, as well as ApEn values, were similar in patients and controls. Administration of SXB caused a significant increase in total 24-h GH secretion rate in narcolepsy patients, but not in controls. After SXB, slow-wave sleep (SWS) and, importantly, the cross-correlation between GH levels and SWS more than doubled in both groups. In conclusion, SXB leads to a consistent increase in nocturnal GH secretion and strengthens the temporal relation between GH secretion and SWS. These data suggest that SXB may alter somatotropic tone in addition to its consolidating effect on nighttime sleep in narcolepsy. This could explain the suggested nonsleep effects of SXB, including body weight reduction.

Normal growth hormone secretion in overweight young adults with Down syndrome

Down syndrome (DS) is associated with short stature and obesity. Adults with DS have several features in common with growth hormone (GH) deficient adult subjects. The aim of this study was to investigate GH secretion in young adults with DS and its relation to body composition as well as glucose and lipid metabolism. Ten young adults with DS (aged 24–32 years; 5 F) and ten controls matched for age and sex were examined regarding spontaneous nocturnal GH secretion and body composition. Stable isotope tracers were used to study glucose and lipid metabolism in the DS subjects. There was no difference in secretion of GH between the DS subjects and controls. The DS subjects had a higher BMI, fat mass proportion and HOMA (homeostasis model assessment) index compared with the controls. The rates of production of glucose and glycerol (reflecting lipolysis) in the DS subjects were increased (15.5 ± 5.07 and 3.5 ± 1.68 μmol/kg/min, respectively). The DS subjects showed normal GH secretion despite increased BMI and fat mass. The increased HOMA index and high rate of glucose production indicate peripheral and hepatic insulin resistance in adult DS subjects.

Overtrained horses alter their resting pulsatile growth hormone secretion

The influence of intensified and reduced training on nocturnal growth hormone (GH) secretion and elimination dynamics was studied in young (1.5 yr) Standardbred geldings to detect potential markers indicative for early overtraining. Ten horses trained on a treadmill for 32 wk in age-, breed-, and gender-matched fixed pairs. Training was divided into four phases (4, 18, 6, and 4 wk, respectively): 1) habituation to high-speed treadmill trotting, 2) normal training, in which speed and duration of training sessions were gradually increased, 3) in this phase, the horses were divided into 2 groups: control (C) and intensified trained (IT) group. In IT, training intensity, duration, and frequency were further increased, whereas in control these remained unaltered, and 4) reduced training (RT). At the end of phases 2, 3, and 4, blood was sampled overnight every 5 min for 8 h for assessment of GH secretory dynamics using pulse detection, deconvolution analysis, and approximate entropy (ApEn). Intensified training induced overtraining (performance decreased by 19% compared with C), which was associated with an increase in concentration peaks number (3.6 vs. 2.0, respectively), a smaller peak secretion pattern with a prolonged half-life (15.2 vs. 7.3 min, respectively), and an increased ApEn (0.89 vs. 0.49, respectively). RT did not lead to full recovery for the overtrained horses. The increased irregularity of nocturnal GH pulsatility pattern is indicative of a loss of coordinated control of GH regulation. Longer phases of somatostatin withdrawal are hypothesized to be the underlying mechanism for the observed changes in GH pulsatility pattern.

Effects of Exercise Training Intensity on Nocturnal Growth Hormone Secretion in Obese Adults with the Metabolic Syndrome

Abdominal adiposity is associated with reduced spontaneous GH secretion, and an increased incidence of the metabolic syndrome, type 2 diabetes, and cardiovascular disease. Exercise training increases GH secretion, induces abdominal visceral fat loss, and has been shown to improve the cardiometabolic risk factor profile. However, little is known about the effects of endurance training intensity on spontaneous GH release in obese individuals. Our objective was to examine the effects of 16 wk endurance training on spontaneous 12-h overnight GH secretion in adults with the metabolic syndrome. This randomized, controlled exercise intervention was conducted at the University of Virginia. A total of 34 adults with the metabolic syndrome (mean +/- sem: age: 49.1 +/- 1.8 yr) participated. Participants were randomized to one of three groups for 16 wk: no exercise training (control), low-intensity exercise training, or high-intensity training. Change in nocturnal integrated GH area under the curve (AUC) was calculated. Both exercise training conditions augmented within-group nocturnal GH AUC pretrain to post-training (low-intensity exercise training approximately (upward arrow) 49%, P < 0.05; and high-intensity training approximately (upward arrow) 65%, P < 0.01), and these changes were also greater than the changes in the control group (P < 0.01). The change in nocturnal GH AUC was inversely associated with the change in fat mass across the entire sample (r = -0.34; P = 0.051; n=34) but was not significantly associated with the change in abdominal visceral fat (r = 0.02; P = 0.920; n = 34). Sixteen wk of supervised exercise training in adults with the metabolic syndrome increases spontaneous nocturnal GH secretion independent of exercise training intensity.

Growth and Factors Affecting it in Thalassemia Major

In our thalassemic (T) cohort, 45% of them had height standard deviation score (HtSDS) less than −2 and 56% of them had growth velocity standard deviation score (GVSDS) less than −1. Their mid-arm circumference and triceps skin-fold thickness were decreased versus normal controls. Their circulating insulin-like growth factor-I (IGF-I) concentrations were significantly lower than normal children. Growth hormone (GH) response to provocation with clonidine and glucagon was defective in half of the short T children (peak GH < 7 ng/dL). Some of the short T children, with normal GH response to provocation, had defective spontaneous nocturnal GH secretion. IGF-I generation after one GH injection was reduced in T children than those with GH deficiency (GHD) and constitutional delay of growth and puberty (CDGP). GH therapy for a year significantly increased IGF-I concentrations, GV, and HtSDS in T children but to a lower level compared to those with GHD or CDGP, suggesting partial GH insensitivity. Pubertal induction with human chorionic gonadotropin in T adolescents was associated with increased IGF-I concentrations, GV, and HtSDS.

Dinner Cancelling and its effect on nocturnal Growth-Hormone Kinetics

Dinner Cancelling and its effect on nocturnal Growth-Hormone Kinetics

The effect of mode of breathing on craniofacial growth--revisited

It has been maintained that because of large adenoids, nasal breathing is obstructed leading to mouth breathing and an 'adenoid face', characterized by an incompetent lip seal, a narrow upper dental arch, increased anterior face height, a steep mandibular plane angle, and a retrognathic mandible. This development has been explained as occurring by changes in head and tongue position and muscular balance. After adenoidectomy and change in head and tongue position, accelerated mandibular growth and closure of the mandibular plane angle have been reported. Children with obstructive sleep apnoea (OSA) have similar craniofacial characteristics as those with large adenoids and tonsils, and the first treatment of choice of OSA children is removal of adenoids and tonsils. It is probable that some children with an adenoid face would nowadays be diagnosed as having OSA. These children also have abnormal nocturnal growth hormone (GH) secretion and somatic growth impairment, which is normalized following adenotonsillectomy. It is hypothesized that decreased mandibular growth in adenoid face children is due to abnormal secretion of GH and its mediators. After normalization of hormonal status, ramus growth is enhanced by more intensive endochondral bone formation in the condylar cartilage and/or by appositional bone growth in the lower border of the mandible. This would, in part, explain the noted acceleration in the growth of the mandible and alteration in its growth direction, following the change in the mode of breathing after adenotonsillectomy.