Spontaneous Growth Hormone Secretion Research Articles

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.

Effects of Toremifene, a Selective Estrogen Receptor Modulator, on Spontaneous and Stimulated GH Secretion, IGF-I, and IGF-Binding Proteins in Healthy Elderly Subjects.

Context:Estrogens amplify spontaneous and stimulated growth hormone (GH) secretion, whereas they diminish GH-dependent insulin-like growth factor (IGF)-I in a dose-dependent manner. Selective estrogen receptor modulators (SERMs), including tamoxifen and toremifene, are widely adjunctively used in breast and prostate cancer. Although some endocrine effects of tamoxifen are known, few data are available for toremifene.Objective:To explore sex-dependent effects of toremifene on spontaneous 10-hour overnight GH secretion, followed by GH-releasing hormone–ghrelin stimulation. Additionally, effects on IGF-I, its binding proteins, and sex hormone–binding globulin (SHBG) were quantified.Participants and Design:Twenty men and 20 women, within an allowable age range of 50 to 80 years, volunteered for this double-blind, placebo-controlled prospective crossover study. Ten-minute blood sampling was done for 10 hours overnight and then for 2 hours after combined GH-releasing hormone–ghrelin injection.Main Outcome Measures:Pulsatile GH and stimulated GH secretion, and fasting levels of IGF-I, IGF-binding protein (IGFBP)1, IGFBP3, and SHBG.Results:Toremifene did not enhance pulsatile or stimulated GH secretion, but decreased IGF-I by 20% in men and women. IGFBP3 was unchanged, whereas while IGFBP1 and SHBG increased in both sexes to a similar extent.Conclusions:The expected rise in spontaneous and stimulated GH secretion under the diminished negative feedback restraint of powered IGF-I favors a central inhibitory antiestrogenic effect of toremifene. Estrogenic effects of toremifene on the liver were present, as evidenced by increased IGFBP1 and SHBG levels. Men and women responded to this SERM comparably.

A pilot study of the effects of niacin administration on free fatty acid and growth hormone concentrations in children with obesity

Children with obesity have low spontaneous growth hormone (GH) secretion. High circulating free fatty acid (FFA) concentration is believed to inhibit GH secretion in those with obesity. In adults, lipolytic inhibition with niacin lowers FFA and increases GH, but there are no prior studies in children with obesity. The objective of the study was to determine the dose and frequency of niacin administration required to lower FFA and stimulate GH in children with obesity. Dose-finding study of nondiabetic children ages 6-12 years with body mass index (BMI) ≥ 95th percentile given niacin 250 mg q2h × 3 doses (n = 2), 500 mg q2h × 3 doses (n = 5) or 500 mg q1h × 4 doses (n = 5). Eight boys and four girls (age 9.7 ± 1.8 years; BMI 26.4 ± 3.1 kg m-2 ; BMIz 2.2 ± .25) were studied. Percentage of serum FFA values that were below 0.2 mEq L-1 . GH, insulin and glucose were also measured serially. FFA decreased as the dose and frequency of niacin increased (p = .01). Niacin 500 mg q1h 4 doses suppressed FFA < 0.2 mEq L-1 and significantly increased GH (p = .04). Adverse effects were flushing/warmth (100%), tingling (60%) and GI complaints (20-40%). Niacin 500 mg q1h significantly lowered serum FFA and increased GH. These pilot data suggest that high FFA is an important suppressor of GH secretion in children with obesity.

Prader-Willi syndrome and growth hormone deficiency.

Prader-Willi syndrome (PWS) is a rare multisystem genetic disorder demonstrating great variability with changing clinical features during patient’s life. It is characterized by severe hypotonia with poor sucking and feeding difficulties in early infancy, followed by excessive eating and gradual development of morbid obesity in later infancy or early childhood. The phenotype is most probably due to hypothalamic dysfunction which is also responsible for growth hormone (GH) and thyroid-stimulating hormone (TSH) deficiencies, central adrenal insufficiency and hypogonadism. The multidimensional problems of patients with PWS can be managed with multidisciplinary approach. Reduced GH secretion, low peak GH response to stimulation, decreased spontaneous GH secretion and low serum IGF-1 levels in PWS patients have been documented in many studies. GH therapy has multiple beneficial effects on growth and body composition, motor and mental development in PWS patients. The recommended dosage for GH is 0.5-1 mg/m2/day. GH therapy should not be started in the presence of obstructive sleep apnea syndrome, adenotonsillar hypertrophy, severe obesity and diabetes mellitus. GH treatment should be considered for patients with genetically confirmed PWS in conjunction with dietary, environmental and life-style measures.

IGF-1 and IGFBP 3 in Growth Hormone Deficiency Role of Insulin Like Growth Factor-1 (IGF-1) and IGF Binding Protein 3 in the Diagnosis of Growth Hormone Deficiency: Changing Paradigm

GH stimulation tests are widely used in the diagnosis of GH deficiency (GHD), although they are associated with a high false positive rate. Serum IGF-I levels are monitored during GH replacement treatment in subjects with GH deficiency (GHD) to guide GH dose adjustment and to minimize occurrence of GHrelated side-effects. The need for reliance on provocative testing is based on evidence that the evaluation of spontaneous growth hormone (GH) secretion over 24 hours and the measurement of IGF-I and IGFBP-3 levels do not distinguish between normal and GHD subjects. Regarding IGF-I, it has been demonstrated that very low levels in patients highly suspected for GHD (i.e., patients with childhood-onset, severe GHD, or with multiple hypopituitarism acquired in adulthood) may be considered definitive evidence for severe GHD obviating the need for provocative tests. However, normal IGF-I levels do not rule out severe GHD and therefore adults suspected for GHD and with normal IGF-I levels must undergo a provocative test of GH secretion. We hereby review the various literatures at disposal justifying the use of IGF-1 and IGBP3 for diagnosis of growth hormone deficiency.Data Source: We searched PUBMED and MEDLINE database for relevant articles including key words. References of each article were further reviewed for final synthesis of the manuscript.J Nepal Paediatr Soc 2012;32(2):154-162 doi: http://dx.doi.org/10.3126/jnps.v32i2.5342

Endocrine Dysfunction following Traumatic Brain Injury in Children

To identify the incidence of endocrine dysfunction in children following traumatic brain injury (TBI). This was a prospective evaluation of 31 children after TBI. Inclusion criteria included Glasgow Coma Scale score ≤ 12 and age 1.5-18 years. We evaluated thyroid function, insulin-like growth factor I, insulin-like growth factor-binding protein 3, and cortisol at 1, 3, 6, and 12 months after injury, and assessed prolactin at 3 and 6 months. At 6 months, we also assessed overnight spontaneous growth hormone secretion, nocturnal thyrotropin surge, adrenal reserve, and serum and urine osmolarity. The average patient age was 11.6 years, and mean Glascow Coma Scale score was 6. The incidence of endocrine dysfunction was 15% at 1 month, 75% at 6 months, and 29% at 12 months. At 12 months after injury, 14% had precocious puberty, 9% had hypothyroidism, and 5% had growth hormone deficiency. Endocrine dysfunction at 1 year did not correlate with the severity of injury. Endocrine dysfunction after TBI is common in children, but most cases resolve by 1 year. We recommend endocrine surveillance at both 6 and 12 months following moderate or severe TBI to ensure early intervention for persistent or late-occurring endocrine sequelae.

A super-agonist of growth hormone–releasing hormone causes rapid improvement of nutritional status in patients with chronic kidney disease

Chronic kidney disease is frequently associated with protein-energy wasting related to chronic inflammation and a resistance to anabolic hormones such as insulin and growth hormone (GH). In this study, we determined whether a new GH-releasing hormone super-agonist (AKL-0707) improved the anabolism and nutritional status of nondialyzed patients with stage 4-5 chronic kidney disease randomized to twice daily injections of the super-agonist or placebo. After 28 days, this treatment significantly increased 24-h GH secretion by almost 400%, without altering the frequency or rhythmicity of secretory bursts or fractional pulsatile GH release, and doubled the serum insulin-like growth factor-1 level. There was a significant change in the Subjective Global Assessment from 'mildly to moderately malnourished' to 'well-nourished' in 6 of 9 patients receiving AKL-0707 but in none of 10 placebo-treated patients. By dual-energy X-ray absorptiometry, both the mean fat-free mass and the body mineral content increased, but fat mass decreased, all significantly. In the AKL-0707-treated group, both serum urea and normalized protein equivalent of nitrogen appearance significantly decreased with no change in dietary protein intake, indicating a protein anabolic effect of treatment. Thus, our study shows that stimulation of endogenous GH secretion by AKL-0707 overcomes uremic catabolism of patients with advanced chronic kidney disease.

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.

Spontanes Wachstumshormonsekretionsprofil

Growth hormone neurosecretory dysfunction (NSD) can only be diagnosed by the analysis of a spontaneous growth hormone (GH) secretion profile over a defined period of time. Since the procedure is not regulated uniformly, examination periods of 2-24 h with blood withdrawal intervals of 10-30 min can be encountered. To answer the question of whether the analysis of spontaneous GH secretion over 2.6 h after falling asleep is comparable to that over 10 h, we recalculated the datasets of 60 children with a diagnosis of GH deficiency (GHD, n=20), NSD (n=20) and idiopathic short stature (ISS, n=20). We analysed GH values in blood specimens taken every 20 min from 8 pm to 6 am. All calculations were made using PULSAR program. All children with GHD had a pathological GH secretion values, whereas children with NSD had significantly higher GH values after 2.6 h than after 10 h. The analysis of spontaneous GH secretion over a period of 2.6 h after falling asleep seems to be insufficient for the diagnosis of NSD. This complex diagnostic procedure should be left to hospitals which have the prerequisites to perform a GH secretion profile over at least 10 h.

Growth hormone, menopause and ageing: no definite evidence for 'rejuvenation' with growth hormone

Estrogens regulate growth hormone (GH) secretion and modulate the tissue responsiveness to GH. After the menopause, and during ageing, a decline in GH secretion (somatopause) is physiologically observed. This article (i) provides a brief overview of the different regulators of GH secretion, (ii) reviews the mechanisms involved in age-related changes in GH concentrations, with particular emphasis on the interrelationships between menopause and GH, and (iii) discusses the interventions aimed at the restoration of GH and insulin-like growth factor (IGF-1) circulating levels. A systematic literature search was conducted in the PubMed database using the search terms 'Growth Hormone', 'Somatopause' and 'Menopause'. The search included full English articles covering the period 1972-2008. We selected 234 relevant citations. We also included three chapters from books. Estrogen deficiency may contribute, through its action on GH, to the complex physical and metabolic alterations of menopause. Several attempts have been made to restore the GH and IGF-1 levels within the young adult range. There is no definite evidence that elderly subjects really benefit from treatment with GH or GH secretagogues. Strategies aimed at enhancing spontaneous GH secretion such as sleep and exercise are safer and certainly less expensive than GH supplementation regimen.

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.

Usefulness of Growth Hormone (GH) Stimulation Tests and IGF-1 Concentration Measurement in GH Deficiency Diagnosis

The diagnosis of growth hormone (GH) deficiency (GHD) is still problematic for the clinician. There is no gold standard for estimating GH secretion. The aim of this study was to compare the diagnostic usefulness of spontaneous GH secretion test, pharmacological tests with insulin, clonidine, L-dopa, and glucagon, and IGF-1 measurement in GHD. We studied 180 prepubertal, short children. Predictive values were calculated for different GH cutoff levels for each diagnostic test. ROC curves were used to estimate the diagnostic usefulness of the tests. The results show that sleep is the strongest stimulatory agent for GH secretion. The estimation of GH secretion after onset of sleep can be used as a screening test in GHD diagnosis. The insulin test has the highest discrimination. A combination of insulin test with another provocative test allows high discrimination and accuracy for standard cut-off GH level. Measurement of IGF -I is characterized by low predictive values. IGF-1 level below the mean according to age indicates high probability of GHD. Auxological parameters should be the most important factor in diagnosing GHD.

Is there a relationship between spontaneous GH secretion, anthropometric parameters and exercise capacity in healthy men over 50 years?

Background: The use of growth hormone (GH) in deficient adults has already been demonstrated to result in several benefits regarding metabolic parameters, body composition and quality of life. Due to the similarities between GH deficiency in adults and the aging process, the concept of somatopause has emerged. Objectives: Correlate the GH secretion profile in healthy men older than 50 years with anthropometric parameters and exercise capacity. Patients and methods: Twenty-nine healthy male were selected, with a mean age of 57.9 ± 4.2 years (range 50–66). After hospital admission, body mass index (BMI), body composition (fat mass) and abdominal circumference, 24-h GH profile, GH peak and basal IGF-I were evaluated, and all the patients underwent a treadmill stress testing to estimate exercise capacity with the Bruce protocol, with evaluation of the maximum oxygen peak, maximum heart rate and METs. All the results are shown as mean ± Std deviation: BMI −26.5 ± 4.9 kg/m 2, percent fat mass −27.1 ± 6.2%, abdominal circumference −92.1 ± 10.1 cm, 24 h GH profile −0.3 ± 0.2 ng/dl, peak GH −2.5 ± 2.0 ng/dl, IGF-I −202.4 ± 72.4 ng/dl, maximum oxygen peak −31.9 ± 6.8 L, maximum heart rate – 161.4 ± 7.5 bpm and METs – 9.1 ± 1.9. After regression analysis using the GH secretion profile (mean GH in 24 h, spontaneous peak GH and basal IGF-I) as dependent variable, no correlations were found between these and the other evaluated parameters.

Growth hormone (GH) secretion and response to GH therapy after total body irradiation and haematopoietic stem cell transplantation during childhood

In January 1997 we introduced a protocol for the treatment with GH of children with impaired growth after unfractionated total body irradiation (TBI). This study is an evaluation of that protocol. Between January 1997 and July 2005, 66 patients (48 male) treated for haematological malignancies had at least two years of disease-free survival after TBI-based conditioning for stem cell transplantation (SCT). Stimulated and/or spontaneous GH secretion was decreased in 8 of the 29 patients tested because of impaired growth. Treatment with GH (daily dose 1.3 mg/m2 body surface area) was offered to all 29 patients and initiated in 23 of them (17 male). The main outcome measure was the effect of GH therapy on height standard deviation scores (SDS) after onset of GH therapy, estimated by random-effect modelling with corrections for sex, age at time of SCT and puberty (data analysed on intention-to-treat basis). At time of analysis, median duration of therapy was 3.2 years; median follow-up after start of GH therapy was 4.2 years. The estimated effect of GH therapy, modelled as nonlinear (logit) curve, was +1.1 SD after 5 years. Response to GH therapy did not correlate to GH secretion status. GH therapy has a positive effect on height SDS after TBI, irrespective of GH secretion status.

The advantage of measuring spontaneous growth hormone (GH) secretion compared with the insulin tolerance test in the diagnosis of GH deficiency in young adults

Reassessment of GH status after the attainment of adult height has important clinical implications in the diagnosis and prognosis of GH deficiency (GHD) in adulthood. The current GH threshold for biochemical definition of GHD in young adults is still a subject of debate. To investigate the role of pharmacological stimulation tests compared with spontaneous 12-h nocturnal GH secretion in the diagnosis of permanent GHD in young adults with childhood-onset GHD. Forty-five young adults (25 males, 20 females) with childhood-onset GHD, height standard deviation score (SDS) -1.1 +/- 1.3 and body mass index (BMI) SDS 1.0 +/- 1.6, were re-evaluated at the age of 19.8 +/- 2.7 years. Sixteen subjects showed a normal pituitary gland on magnetic resonance imaging (MRI), while in 29, consistent structural hypothalamic-pituitary abnormalities were found. GH secretion was assessed by means of an insulin tolerance test (ITT) and a 12-h spontaneous nocturnal profile as well as by IGF-I assessment. The results were compared with those of 43 healthy controls. Mean 12-h spontaneous nocturnal GH secretion was < 3.1 microg/l (the lowest limit of the normal range) in 36 (80%) of the subjects and > 3.1 microg/l in nine (20%). Of these 36 patients, 29 (80%) had abnormal MRI findings and 20 (55%) had multiple pituitary hormone deficiencies (MPHD). All nine subjects with mean spontaneous GH secretion > 3.1 microg/l had a normal pituitary MRI, isolated GHD and a peak GH response to ITT > 5 microg/l. There was a discordance in 14 patients (31%), who showed a peak GH response to ITT > 5 microg/l but a reduced spontaneous GH secretory capacity; 10 had structural hypothalamic-pituitary abnormalities on MRI. Although the ITT provides valuable information and proves to be a sensitive index of permanent GHD, the results of this study emphasize the potential diagnostic value of assessment of 12-h spontaneous GH secretion in young adults with childhood-onset GHD.

Growth hormone levels in the diagnosis of growth hormone deficiency in adulthood

Current guidelines for the diagnosis of adult growth hormone deficiency (GHD) state that the diagnosis must be proven biochemically by provocative testing that is done within the appropriate clinical context. The need for reliance on provocative testing is based on evidence that the evaluation of spontaneous growth hormone (GH) secretion over 24 h and the measurement of IGF-I and IGFBP-3 levels do not distinguish between normal and GHD subjects. Regarding IGF-I, it has been demonstrated that very low levels in patients highly suspected for GHD (i.e., patients with childhood-onset, severe GHD, or with multiple hypopituitarism acquired in adulthood) may be considered definitive evidence for severe GHD obviating the need for provocative tests. However, normal IGF-I levels do not rule out severe GHD and therefore adults suspected for GHD and with normal IGF-I levels must undergo a provocative test of GH secretion. The insulin tolerance test (ITT) is the test of choice, with severe GHD being defined by a GH peak less than 3 microg/l, the cut-off that distinguishes normal from GHD adults. The ITT is contraindicated in the presence of ischemic heart disease, seizure disorders, and in the elderly. Other tests are as reliable as the ITT, provided they are used with appropriate cut-off limits. Glucagon stimulation, a classical test, and especially new maximal tests such as GHRH in combination with arginine or GHS (i.e., GHRP-6) have well-defined cut-off limits, are reproducible, are independent of age and gender, and are able to distinguish between normal and GHD subjects. The confounding effect of overweight or obesity on the interpretation of the GH response to provocative tests needs to be considered as the somatotropic response to all stimuli is negatively correlated with body mass index. Appropriate cut-offs for lean, overweight, and obese subjects must be used in order to avoid false-positive diagnoses of severe GHD in obese adults.

Apomorphine‐Induced Growth Hormone Response Is Attenuated by Ethanol but Not Dextromethorphan

Misuse of alcohol drinking is a major health problem. Alcohol decreases spontaneous growth hormone (GH) secretion, but the mechanism is unclear. The aim of this study was to test whether administration of alcohol (study 1) or a N-methyl d-aspartate (NMDA) receptor antagonist (study 2) attenuates the GH response to pharmacological dopaminergic stimulation. The 2-session repeated measures design was conducted at the endocrine laboratory at the Department of Psychiatry at the Free University Berlin. Twenty healthy Caucasian males aged 35+/-10 years without a history of alcohol use disorders were tested using the Apomorphine (APO) challenge test. In study 1, we injected APO (0.01 mg/kg s.c.) 1 hour after oral administration of 1 g/kg ethanol and placebo, respectively. In study 2, the APO challenge was conducted after 0.3 mg/kg dextromethorphan (DXM) and placebo. The main outcome measures were the peak serum GH concentration and area under the time/concentration curve up to 120 minutes after APO. The effects of ethanol and DXM were tested using the Wilcoxon signed-rank tests. Compared with placebo, alcohol significantly decreased the APO-induced GH release (mean and SEM peak GH concentration 19.9+/-3.2 vs 6.2+/-1.9 ng/mL, p=0.002). Dextromethorphan did not change APO-induced GH response (22.5+/-5.4 vs 21.0+/-5.8 ng/mL, p=0.105). A single intermediate alcohol dose markedly reduces GH response to dopaminergic stimulation. Although alcohol is thought to stimulate dopaminergic function in certain pathways, but not necessarily in the hypothalamus, our results are in line with the alcohol effect on baseline GH secretion. Growth hormone suppression appears not to be mediated by ethanol's NMDA-antagonistic properties.

Bone mineral density and bone turnover in young adult survivors of childhood acute lymphoblastic leukaemia

Treatment for childhood leukaemia induces many risk factors for development of decreased bone mineral density (BMD). Physical activity is also known to affect BMD. The aim was to study BMD and markers of bone turnover in a well-defined group of survivors of acute lymphoblastic leukaemia (ALL) who had all reached final height as well as peak bone mass, taking both previous treatment and physical activity into consideration. All patients treated for ALL before the onset of puberty in the region of western Sweden, between 1973 and 1985, in first remission were included. Thirty-five out of forty-seven patients aged 20-32 years participated. Nineteen patients had received cranial radiotherapy, and the median follow-up time was 20 years. BMD was assessed using dual-energy X-ray absorptiometry (DEXA). Serum concentrations of markers of bone turnover were analysed. Physical performance was measured using a performance exercise capacity stress test. BMD was slightly reduced in lumbar spine (-0.4 SD), but not in femoral neck or total body. BMD in femoral neck was correlated to physical performance and dose of corticosteroid, but no correlation was found with spontaneous growth hormone (GH) secretion. Markers of bone turnover were also correlated to physical performance, but not to GH secretion. Physical fitness seems to be the most important factor in developing and preserving normal bone mineral density in ALL patients. We propose that lifestyle education promoting physical activity is encouraged from an early point in time for these patients.

Pubertal alterations in growth and body composition: IX. Altered spontaneous secretion and metabolic clearance of growth hormone in overweight youth

Deconvolution analysis was used to determine 12-hour spontaneous nocturnal growth hormone (GH) secretion and GH half-life in lean (body mass index, <85th percentile; n = 39) and overweight (body mass index, ≥85th percentile; n = 18) youth. The integrated GH concentration, GH burst mass, and half-life were lower ( P < .05) in overweight than in lean youth. For each unit increase in percentage of body fat, integrated serum GH concentrations, secretory burst mass, and half-life declined by 83.6 μg/L per minute ( r = −0.39, P < .01), 0.22 μg/L ( r = −0.28, P < .05), and 0.2 minute ( r = −0.38, P < .01), respectively. The effect of overweight on GH secretion was independent of pubertal status. Hierarchical regression models tested the hypothesis that altered GH secretion in youth is more related to total adiposity than abdominal visceral fat. When age, sex, fat-free mass, testosterone, and estradiol were held constant, the sequential addition of abdominal visceral fat did not increase R 2 for any GH secretion variable. Sequential addition of percentage of body fat increased R 2 ( P < .05) for integrated GH concentration, total secretory rate, secretory burst mass, and pulsatile production rate. We conclude that serum GH concentrations are reduced in overweight youth primarily because of reduced GH burst mass with no change in the number of secretory events and secondarily to reduced GH half-life. Based on the model that GH-releasing hormone predominantly increases GH pulse amplitude whereas somatostatin primarily controls GH pulse frequency, these results suggest that overweight in youth diminishes GH-releasing hormone stimulation resulting in truncated GH bursts but does not alter the number of somatostatin withdrawal intervals so that GH burst frequency is conserved.

Pioglitazone Treatment Increases Spontaneous Growth Hormone (GH) Secretion and Stimulated GH Levels in Polycystic Ovary Syndrome

Low GH levels, probably due to insulin resistance and increased abdominal fat mass, are well described in polycystic ovary syndrome (PCOS). GH acts as an important ovarian cogonadotropin, and GH disturbances may be an additional pathogenic factor in PCOS. Decreased abdominal fat mass and improved insulin sensitivity during pioglitazone treatment may affect GH secretion. The objective of the study was to investigate the effect of pioglitazone on GH levels in PCOS. Thirty insulin-resistant PCOS patients were randomized to either 16 wk pioglitazone (30 mg/d) or placebo treatment. Before and after intervention, levels of fasting insulin, GH, total IGF-I, free IGF-I, IGF binding protein-1, IGF-II, free fatty acids, testosterone, and SHBG were measured. Patients underwent whole-body dual x-ray absorptiometry scans, pyridostigmine-GHRH tests, and 24-h 20-min integrated blood sampling for measurement of GH. Peak GH and area under the curve for GH in pyridostigmine-GHRH tests and 24-h mean GH concentrations and pulsatile GH secretion significantly increased after pioglitazone treatment. No significant changes were observed in GH pulse frequency, pulse duration, approximate entropy levels, or basal GH release. Levels of IGF binding protein-1 significantly increased, whereas no significant differences were measured in total IGF-I and free IGF-I. Pioglitazone treatment significantly decreased fasting insulin and homeostasis model assessment levels. No significant changes were observed in Ferriman Gallwey score or androgen levels. Pioglitazone treatment significantly increased GHRH-stimulated GH levels and 24-h pulsatile GH secretion, probably directly or indirectly due to improved insulin sensitivity.