Peak Stimulated Growth Hormone Research Articles

Optimal final adult height achieved by low-dose recombinant human growth hormone therapy.

Thailand has been administering the recombinant human growth hormone (rhGH) treatment for >20 years. Due to limited resources being available, efforts have been directed toward utilizing rhGH at the lowest feasible dose. However, there is currently a lack of evidence in terms of the efficacy and outcomes. To evaluate the auxological outcomes of growth hormone (GH) treatment and the GH secretion ability after reaching final adult height (FAH) and discontinuing rhGH. Data of 40 patients were retrospectively reviewed. The clinical characteristics, auxological data, and results of biochemical and endocrine investigations before and during rhGH treatment were evaluated. In addition, GH retesting was performed in 24 patients using the insulin tolerance test. Twenty patients (50%) had complete growth hormone deficiency (GHD), defined as peak stimulated GH level <5 ng/mL, and the remaining patients had partial GHD. Most patients were male (n = 25, 62.5%). The mean age at which rhGH was initiated was 8.9 years. Patients with partial GHD received a higher dose of rhGH than those with complete GHD (30.9 µg/kg/d vs. 26.2 µg/kg/d, P = 0.02). Patients with complete and partial GHD reached FAH at height standard deviation scores (SDSs) of -0.65 and -1.47, respectively. The factors associated with obtaining a good clinical response in terms of height gain included peak-stimulated GH level, age of puberty, and age of discontinuing rhGH. After completing the rhGH treatment, 13 of the 24 patients showed normal GH secretion. Patients with multiple pituitary hormone deficiency (MPHD) were likely to have persistent GHD through adulthood (n = 8, 88.9%). This study has demonstrated that the use of low-dose rhGH could result in healthy populations achieving optimal FAHs. Patients with MPHD might not require retesting as they were likely to have persistent GHD. The results obtained in this research highlight the benefits of the treatment. This treatment can be applied in resource-limited countries.

Evaluation of the Relationship Between Peak Growth Hormone Response to Growth Hormone Stimulation Tests and Body Mass Index

Objective: A contrary relationship between body mass index (BMI) and growth hormone (GH) secretion has been demonstrated in adults. BMI-specific cutoff levels are suggested for identifying growth hormone deficiency (GHD) in adulthood. However, specific values for BMI and growth hormone stimulation test responses in the childhood age group are not certain. In this research, our purpose was to investigate the relationship between GH peak response and BMI in children who underwent GHST with a pre-diagnosis of GHD. Material and Methods: This was a retrospective study of stimulative GH testing with clonidine and L-dopa performed in 150 children 2–18 year-old with short stature (&lt; -2 SDS) in the Pediatric Endocrinology Unit at Bakırçay University Çiğli Training and Research Hospital from the years of 2018 to 2023. Anthropometric measurements, insulin-like growth factor-1 (IGF-I) and IGFBP- 3 levels, especially peak-stimulated GH, were evaluated. Results: A total of 150 patients [98 boys (65.3%) and 52 girls (34.7%)] were included in the study. The mean age of the individuals during testing was 10.26 ± 3.37 years, mean height standard deviation score (SDS) was -2.64 ± 0.89, mean weight SDS was -1.85 ± 1.01 and mean body mass index (BMI) SDS was -0.47 ± 1.07. Ninety-two of the patients (63%) were prepubertal. The mean value for maximum growth hormone serum level (GHmax) clonidine collected during the growth hormone stimulation test was 4.46 ± 2.83 ng/mL, while the mean value in L-dopa test was 3.29 ± 2.57 ng/mL. There was no statistical distinction in terms of both test responses. The correlation between peak GH and BMI-SDS, in terms of clonidine and L-dopa tests, was significantly negative [β = -0.257 (p = 0.010), β = -0.283 (p = 0.004), respectively]. Age, gender and puberty were not significantly associated with peak GH value. In terms of L-dopa peak GH level, the GH level in group 4 (&gt;1 SDS) was revealed to be statistically lower than that in group 1 (&lt; -1 SDS), nevertheless, similar relationship was not detected for clonidine. Conclusion: In our study, a negative correlation was found between GHmax and BMI-SDS in terms of clonidine and L-dopa tests. Therefore, keeping BMI-SDS in mind when evaluating growth hormone stimulation tests performed in short children may be guiding. Still, future studies are needed to make it a determining factor when deciding on treatment.

The GH/IGF-1 Axis Is Associated With Intrahepatic Lipid Content and Hepatocellular Damage in Overweight/Obesity.

Obesity is a state of relative growth hormone (GH) deficiency, and GH has been identified as a candidate disease-modifying target in nonalcoholic fatty liver disease (NAFLD) because of its lipolytic and anti-inflammatory properties. However, the GH/IGF-1 axis has not been well characterized in NAFLD. We aimed to investigate serum GH and IGF-1 levels in relation to intrahepatic lipid content (IHL) and markers of hepatocellular damage and fibrosis in NAFLD. This cross-sectional study included 102 adults (43% women; age 19-67; BMI ≥ 25 kg/m2) without type 2 diabetes. IHL was measured by magnetic resonance spectroscopy; NAFLD was defined by ≥ 5% IHL. Peak-stimulated GH in response to GH releasing hormone and arginine was assessed as was serum IGF-1 (LC/MS). There was no difference in mean age, BMI, or sex distribution in NAFLD vs controls. Mean (± SD) IHL was higher in NAFLD vs controls (21.8 ± 13.3% vs 2.9 ± 1.1%, P < 0.0001). Mean peak-stimulated GH was lower in NAFLD vs controls (9.0 ± 6.3 vs 15.4 ± 11.2 ng/mL, P = 0.003), including after controlling for age, sex, visceral adipose tissue, and fasting glucose. In a stepwise model, peak-stimulated GH predicted 14.6% of the variability in IHL (P = 0.004). Higher peak-stimulated GH was also associated with lower ALT. Higher serum IGF-1 levels were associated with lower risk of liver fibrosis by Fibrosis-4 scores. Individuals with NAFLD have lower peak-stimulated GH levels but similar IGF-1 levels as compared to controls. Higher peak-stimulated GH levels are associated with lower IHL and less hepatocellular damage. Higher IGF-1 levels are associated with more favorable fibrosis risk scores. These data implicate GH and IGF-1 as potential disease modifiers in the development and progression of NAFLD.

Impact of BMI on Growth Hormone Stimulation Tests in Children and Adolescents: A Systematic Review and Meta-Analysis

Background: Peak stimulated growth hormone (GH) levels are known to decrease with increasing BMI, possibly leading to overdiagnosis of GH deficiency (GHD) in children with overweight and obesity. However, current guidelines do not provide guidance how to interpret peak GH values of these children, nor has this been assessed systematically. The aim of this systematic review and meta-analysis was to study the effect of BMI on stimulated peak GH values in children, and to quantify to which extent peak GH values in children with obesity are decreased. Methods: We searched the Medline, Embase, Cochrane, Web of Science, and Google Scholar databases (13 July 2020) for studies reporting impact of BMI on peak GH in children. Where possible, individual participant data was extracted and/or obtained from the authors. Primary outcome was the association between peak GH values and BMI standard deviation score (SDS). Pooled correlation coefficients were calculated under a random effects model, and exploratory moderator analyses and meta-regression were performed. Study heterogeneity was assessed using the I2 statistic. For studies with available individual participant data, linear mixed-models regression analysis was performed with BMI SDS as predictor and ln(peak GH) as outcome, accounting for used GH stimulation agent (fixed effect) and study (random effect). This systematic review was performed in accordance to the PRISMA guidelines. Results: In total, 56 studies were included, providing data on n=5100 children (1346 with individual participant data). Across all studies, a pooled r of -0.37 (95% CI -0.44 to -0.31, n=2785) was found. Study heterogeneity was large (I2=58%). Pubertal status, sex, presence of syndromic obesity, and mean age and BMI SDS of the population did not significantly moderate the pooled r (all p>0.05). Individual participant data analysis revealed a beta of -0.11 (95% CI -0.08 to -0.15, p<0.001), i.e., per 1 point increase in BMI SDS, peak GH decreases by 11% (95% CI 7 to 14%). In the 8 studies performed in children referred for short stature, obesity was present in 27/893 (3.02%) children without GHD and in 36/615 (5.85%) children with GHD (p=0.0069). This corresponds to a RR of 1.43 (95% CI 1.14 to 1.78, p=0.002) for a diagnosis of GHD in children with short stature with obesity compared to children without obesity. Discussion: To our knowledge, this is the first systematic review and meta-analysis to investigate the impact of BMI on peak GH values in children, showing a significant negative correlation and risk of overdiagnosis of GHD in children with obesity. All in all, with ever-rising prevalence of pediatric obesity, our study highlights the urgent need for BMI (SDS)-specific cut-off values for GH stimulation tests in children.

Clinical and Biochemical Phenotype of Indian Children with Different Types of Idiopathic Growth Hormone Deficiency and their Association with Pituitary Height on MRI.

Background and Objectives:Differentiation of growth hormone deficiency (GHD) into various types has been made based on peak stimulated growth hormone levels and other hormone axis involvement. The data regarding how this classification is associated with variation in clinical and biochemical phenotype and how these findings associate with pituitary morphology remains sparse, especially in the Indian population. Therefore, we aimed to ascertain the differences in the pattern of auxological, clinical features including pituitary hypoplasia, and endocrinological profile among patients with severe GHD, partial GHD, and MPHD in the Indian population and to evaluate the association of pituitary height with various clinical and hormonal parameters.Materials and Methods:We conducted a cross-sectional study in 100 patients with idiopathic GHD. Patients were grouped into severe GHD, partial GHD, and MPHD to observe the differences in clinical, biochemical, and MRI findings. The pituitary height findings were correlated clinical and biochemical presentation.Results:MPHD subjects had a significantly higher frequency of breech delivery, neonatal jaundice, neonatal hypoglycemia, and micropenis. A significant difference was observed in the chronological age, bone age retardation (CA-BA), height SDS, weight SDS, peak GH response, IGF-1, IGF-1 SDS, and prevalence of pituitary hypoplasia, pituitary height, and pituitary height SDS among these three groups. In the composite population of GHD, pituitary height SDS was correlated with peak GH, basal IGF-I SDS, and body height SDS.Conclusion:The clinical and biochemical phenotype differs significantly among the various types of GHD. Pituitary height correlates with these findings and is helpful in further assessment of these patients.

MON-286 Peak Stimulated Growth Hormone Is Lower in Subjects with Nonalcoholic Fatty Liver Disease Than Controls of Similar Sex, Age and BMI

Background: Nonalcoholic fatty liver disease (NAFLD), fatty infiltration of the liver in the absence of alcohol use, is a prevalent and serious complication of obesity. Obesity is a state of relative growth hormone (GH) deficiency, and GH has been identified as a candidate disease-modifying target in NAFLD because of its lipolytic and anti-inflammatory properties. However, it is not known whether individuals with NAFLD phenotyped by proton magnetic resonance spectroscopy (1H-MRS), the gold standard imaging modality for assessment of intrahepatic lipid (IHL) content, have lower peak stimulated GH levels as compared to those of similar age, sex and BMI without NAFLD. Methods: We studied 99 generally healthy adults without diabetes or significant alcohol use, ages 19-67 y and BMI >25 kg/m2. All subjects underwent 1H-MRS for assessment of IHL content. Using a cutoff of >5.5%, 65 subjects had NAFLD and 34 did not (controls). GHRH-arginine stimulation testing was performed. GH was measured by immunoassay and IGF-1 by LC/MS/MS (Quest Diagnostics, CA, USA). Visceral and subcutaneous adipose tissue (VAT/SAT) were assessed by cross-sectional CT at L4. Results are reported as mean ±SD. Results: There was no difference between NAFLD vs controls in mean age (48±12 vs 45±14 y, p=0.30), BMI (33±4 vs 33±7 kg/m2, p=0.96), sex (43% vs 44% female, p=0.90) or premenopausal status (50% vs 60%, p=0.50). Mean IHL was 21.8±13.3% (range 5.5-57.8%) and 2.9±1.1% (range 1.0-4.9%) in the NAFLD and control groups, respectively (p<0.0001). NAFLD subjects had higher ALT, total cholesterol, triglycerides, VLDL, LDL and lower HDL than controls. Fasting glucose was statistically but not clinically significantly higher in NAFLD vs controls (90±9 vs 86±7 mg/dL, p=0.03), and mean HbA1c did not differ significantly. There was a trend towards a higher mean VAT in the NAFLD vs controls (157±70 vs 131±67 g, p=0.07) but no difference in SAT. Mean peak stimulated GH was significantly lower in NAFLD vs controls (9.0±6.3 vs 15.4±11.2 ng/mL, p=0.003) which remained significant after controlled for age, BMI, sex and VAT. In a stepwise model including peak stimulated GH, VAT, age, BMI and sex, peak stimulated GH predicted 8% of the variability in IHL (p=0.004); no other variables were significant predictors of IHL. Mean IGF-1 (149±53 vs 151±49 ng/mL, p=0.80) and IGF-1 Z-score (-0.03±0.61 vs -0.03±0.68, p=0.90) were not significantly different between the groups. Conclusion: Subjects with NAFLD have lower peak stimulated GH but similar IGF-1 levels compared to non-NAFLD controls of similar age, BMI and sex. Additionally, lower peak stimulated GH was predictive of higher IHL, independent of age, BMI, sex and VAT. This suggests that the relative GH deficiency of obesity may be an independent contributor to the development of NAFLD and that the GH axis and downstream signaling pathways may be a therapeutic target for this disease where few currently exist.

Impact of BMI on peak growth hormone responses to provocative tests and therapeutic outcome in children with growth hormone deficiency

This study investigated the relationship between peak stimulated growth hormone (GH) and body mass index (BMI), as well as the impact of BMI on therapeutic response in patients with GH deficiency (GHD). A total of 460 patients were enrolled in the study. The patients were divided into four groups as per the etiology and peak GH values: idiopathic (n = 439), organic (n = 21), complete (n = 114), and partial (n = 325) GHD groups. Subsequently, they were classified as normal, overweight, or obese based on their BMI. There was no difference in BMI between complete and partial GHD. A significant negative relationship between peak GH and BMI were found. Moreover, obese GHD children had a considerably better therapeutic response in height increase and BMI decrease during 2 years of GH treatment compared to non-obese children with GHD. There was no difference between peak GH and type of GH stimulation test (GHST), except the clonidine test, which showed a much lower peak GH in obese GHD children. In conclusion, BMI had a negative impact on peak GH response, and therapeutic outcome was more favorable in the obese group. Despite no difference in GH response by type of GHST, the degree of obesity differentially affected the results.

Reduced peak stimulated growth hormone is associated with hyperuricemia in obese children and adolescents

The purpose of the study is to investigate whether reduced peak GH response to arginine-levodopa test is associated with hyperuricemia in obese children and adolescents. The study population consisted of a total sample of 78 obese and 30 normal-weight children and adolescents without known hypopituitarism. All participants underwent clinical examination and GH stimulation testing. IGF-1, lipid profile and other metabolic markers were assessed. The obese subjects were then divided into two groups according to the serum levels of uric acid. Results show that obese subjects had significantly lower peak GH, lower IGF-1 and similar height SDS than those in the control group. Children with hyperuricemia had significantly lower peak stimulated GH compared with non-hyperuricemia obese subjects. Results from logistic regression model showed that peak GH were negatively associated with hyperuricemia after controlling for age, gender, tanner stage, BMI SDS, IGF-1, blood pressure, HOMA-IR, lipids status. These data indicate that lower peak GH is positively associated with hyperuricemia in obese children and adolescents without known hypothalamic/pituitary disease after controlling BMI and insulin resistance, as well as other cardiometabolic risk factors.

Development of additional pituitary hormone deficiencies in pediatric patients originally diagnosed with isolated growth hormone deficiency due to organic causes

To determine characteristics of children initially diagnosed with isolated growth hormone deficiency (IGHD) of organic aetiology, who later developed multiple pituitary hormone deficiencies (MPHD). Data were analysed for 716 growth hormone-treated children with organic IGHD, who were growth hormone-naïve at baseline in the multinational, observational Genetics and Neuroendocrinology of Short Stature International Study. Development of MPHD was ascertained from investigator-provided diagnoses, adverse events and concomitant medications. Analyses were performed for all patients and separately for those who developed MPHD within 4.5 years or had >3.5 years follow-up and continued to have IGHD (4-year cohort). MPHD developed in 71/716 (9.9%) children overall, and in 60/290 (20.7%) in the 4-year cohort. The most frequent additional deficiencies were thyroid-stimulating hormone (47 patients) and gonadotropins (23 patients). Compared with those who remained with IGHD, children who developed MPHD had more severe GHD at study entry, significantly lower baseline insulin-like growth factor1, peak stimulated growth hormone, and more frequent diagnosis of intracranial tumour or mutation of gene(s) controlling hypothalamic-pituitary development and/or function. Multivariate logistic regression analyses identified female gender, longer follow-up, higher baseline age and lower peak stimulated growth hormone as predictors of MPHD development. MPHD is more likely to develop in patients with severe organic IGHD, especially those with history of intracranial tumour or mutation of gene(s) controlling hypothalamic-pituitary development and/or function. Older baseline age, female gender and longer follow-up duration were also associated with higher incidence of MPHD. Long-term monitoring of pituitary function is recommended, irrespective of the aetiology of GHD.

The Relationship between Subnormal Peak-Stimulated Growth Hormone Levels and Auxological Characteristics in Obese Children.

Context: The hypothesis that obese children are overdiagnosed with growth hormone deficiency (GHD) has not been adequately investigated in the context of adiposity-related differences in auxology.Aim: To investigate the differences in auxological parameters between short, prepubertal, obese children, and normal-weight peers who underwent growth hormone stimulation testing (GHST).Hypothesis: Over-weight/obese children with GHD [peak growth hormone (GH) < 10 μg/L] will have higher values for growth velocity (GV) standard deviation score (SDS), bone age minus chronological age (BA − CA), and child height SDS minus mid-parental height (MPTH) SDS when compared to normal-weight GHD peers.Subjects and Methods: A retrospective review of anthropometric and provocative GHST data of 67 prepubertal, GH-naïve children of age 10.21 ± 2.56 years (male n = 45, age 10.8 ± 2.60 years; female n = 22, age 8.94 ± 2.10). Inclusion criteria: GHST using arginine and clonidine. Exclusion criteria: hypopituitarism, abnormal pituitary magnetic resonance imaging scan, syndromic obesity, or syndromic short stature. Data were expressed as mean ± SD.Results: The over-weight/obese children with peak GH of <10 μg/L had significantly lower value for natural log (ln) peak GH (1.45 ± 0.09 vs. 1.83 ± 0.35, p = 0.022), but similar values for GV SDS, insulin-like growth factor-I, insulin-like growth factor binding protein-3, bone age, BA − CA, MPTH, and child height SDS minus MPTH SDS compared to normal-weight peers with GHD. After adjusting for covariates, the over-weight/obese children (BMI ≥ 85th percentile) were >7 times more likely than normal-weight subjects (BMI < 85th percentile) to have a peak GH of <10 μg/L, and 23 times more likely to have a peak GH of <7 μg/L (OR = 23.3, p = 0.021). There was a significant inverse relationships between BMI SDS and the ln of peak GH (β = −0.40, r2 = 0.26, p = 0.001), but not for BMI SDS vs. GV SDS, ln peak GH vs. BA, or ln peak GH vs. GV SDS.Conclusion: Subnormal peak GH levels in obese prepubertal children are not associated with unique pre-GHST auxological characteristics.

Muscle strength and body composition during the transition phase in patients treated with recombinant GH to final height.

We assessed body composition and muscle strength during the transition phase in 18 growth hormone (GH) deficient males treated with recombinant GH to final height and 18 controls. According to peak-stimulated GH and basal insulin-like growth factor-1 (IGF-1) during the transition phase, patients were subdivided into GH deficient (GHD-TP, n=9) and GH sufficient (GHS-TP, n=9) groups. Assessments included lean and fat body mass and bone mineral density (BMD), all measured by dual-energy X-ray absorptiometry, and dynamic knee muscle strength, assessed by isokinetic dynamometer. Total body and lumbar spine BMD and muscle strength were lower in GHD-TP patients when compared with GHS-TP and controls (all p<0.05), whereas lean and fat body mass were lower in both GHD-TP and GHS-TP patients when compared with controls (p<0.05). These findings suggest that administration of recombinant GH to final height is not sufficient to provide normal body composition and muscle strength in young male patients with GH deficiency.

Multiple pituitary hormone deficiency: beware of combined hormones deficiency

Multiple Pituitary Hormone Deficiency (MPHD) is an endocrine disorder due to combination of pituitary hormones deficiencies. Clinical manifestations vary due to the combination of individual hormone deficiencies. The diagnosis is established based on history, signs and symptoms, hormonal and radiological examination. MPHD should be managed by hormones replacement according hormone abnormalities. The objective is to present a case of multiple pituitary hormones deficiency in a child, focusing in diagnosis and management. A 14 years-old boy, come with main complaint of short stature and delayed puberty. The height was below the 3rd percentile for age. Patient also suffered from micropenis. Tanner stage was prepuberta. Laboratories showed peak stimulated growth hormone concentration test was below 10 ng/mL, low levels of IGF 1 and IGF-BP3; FT4: 5.99ng/dl (normal:4.6-11),TSH: 3.08 IU/mL (normal:0.4-7.0); non stimulated LH level: 0.23 mIU/µL (cut-off limit prepubertal-pubertal level was 0.6 IU/L), FSH: 1.6 mIU/µL; testosrone: <15 ng/dL (normal basal testosterone: 19 ng/L). Working diagnosis was GH deficiency and hypogonadotrophic hypogonadism. This patient treated with growth hormone and testosterone. The height increased 10 cm during 10 months growth hormone treatment and the penile length increased became normal range. This paper reported growth hormone deficiencies accompanied by hypogonadotrophic hypogonadism. Facing patient with pituitary hormone deficiency must be aware of the abnormality of other pituitary hormone.

Body Fat Mass is a Strong and Negative Predictor of Peak Stimulated Growth Hormone and Bone Mineral Density in Healthy Adolescents During Transition Period

The adipose tissue has detrimental effects on growth hormone secretion, even in the absence of obesity. The majority of previous studies have shown an inverse relationship between fat mass and the growth hormone response to several stimulation tests in adults and in children. The contribution of body fat mass on growth hormone response to provocative tests during the transition age is not known. We analyzed the GH-IGF1 axis by GHRH-arginine test in 30 healthy adolescents with normal stature during the transition period from 14 to 18 years. All subjects underwent body composition analysis by dual-energy X-ray absorptiometry (DXA). We found that total body fat mass was inversely correlated with peak GH to provocative test (r=-0.6, p=0.004). GH deficiency was shown in 2 of our healthy patients if diagnosis was based on GH peak below 19 μg/l. Both children who failed the GHRH-arginine were overweight (BMI for age above 85th percentile). However, their GH status was normal when assessed by insulin tolerance test. Multivariate analysis demonstrated strong correlation between peak stimulated GH and measures of body adiposity, including body mass index and fat mass index, with the latter showing the most important effect on GH secretion. Fat mass index alone explained 34.5% of the variability in peak GH. This study has shown for the first time that during the transition period, GH response to GHRH-arginine test is strongly influenced by body composition, and cutoff values appropriate for overweight and obese adolescents are needed.

Treatment with Recombinant Human Growth Hormone during Childhood is Associated with Increased Intraocular Pressure

To evaluate the association between recombinant human growth hormone (rhGH) treatment and intraocular pressure (IOP) in children. This is an observational cohort study including comparison between children treated with rhGH for at least 12 months (treatment group), matched children prior to treatment (control group), and population age-adjusted normograms of IOP. All children underwent an ocular slit lamp assessment and Goldmann applanation tonometry. Charts were reviewed for cause of therapy, peak stimulated growth hormone level prior to therapy, treatment duration, insulin-like growth factor 1, and rhGH dosage. The treatment group included 55 children and the control group included 24 children. Mean age at examination was comparable at 11.4 ± 3.3 years and 10.3 ± 2.6 years, respectively (P = .13). Mean treatment duration was 37.5 ± 22.8 months and mean rhGH dose was 0.04 ± 0.01 mg/kg/d. Mean IOP was significantly increased in the treatment group compared with the control group and compared with age-matched normograms (16.09 ± 2.2 mm Hg, 13.26 ± 1.83 mm Hg and 14.6 ± 1.97 mm Hg, respectively, P < .001). IOP was positively correlated with treatment duration (r = 0.559, P < .001) and rhGH dosage (r = 0.274, P = .043). IOP in children treated with rhGH is increased compared with a similar population without treatment and compared with healthy population normograms. IOP is associated with longer treatment duration and higher dosages.

Reduced growth hormone secretion in obesity is associated with smaller LDL and HDL particle size

Reduced growth hormone (GH) secretion is observed in obesity and may contribute to increases in cardiovascular disease (CVD) risk. Lipoprotein characteristics including increased small dense low-density lipoprotein (LDL) particles are known independent risk factors for CVD. We hypothesized that reduced GH secretion in obesity would be associated with a more atherogenic lipid profile including increased small dense LDL particles. To evaluate this hypothesis, we studied 102 normal weight and obese men and women using standard GH stimulation testing to assess GH secretory capacity and performed comprehensive lipoprotein analyses including determination of lipoprotein particle size and subclass concentrations using proton NMR spectroscopy. Obese subjects were stratified into reduced or sufficient GH secretion based on the median peak-stimulated GH (≤6·25 μg/l). Obese subjects with reduced GH secretion (n = 35) demonstrated a smaller mean LDL and HDL particle size in comparison to normal weight subjects (n = 33) or obese subjects with sufficient GH (n = 34) by ANOVA (P < 0·0001). Univariate analyses demonstrated peak-stimulated GH was positively associated with LDL (r = 0·50; P < 0·0001) and HDL (r = 0·57; P < 0·0001), but not VLDL (P = 0·06) particle size. Multivariate regression analysis controlling for age, gender, race, ethnicity, tobacco, use of lipid-lowering medication, BMI and HOMA demonstrated peak-stimulated GH remained significantly associated with LDL particle size (β = 0·01; P = 0·01; R(2) = 0·42; P < 0·0001 for overall model) and HDL particle size (β = 0·008; P = 0·001; R(2) = 0·44; P < 0·0001 for overall model). These results suggest reduced peak-stimulated GH in obesity is independently associated with a more atherogenic lipoprotein profile defined in terms of particle size.

Growth hormone secretion in HIV-positive versus HIV-negative hemophilic males with abnormal growth and pubertal development. The Hemophilia Growth and Development Study.

Growth and pubertal development in hemophilic males, age 6-19 years at baseline, were evaluated over a 3.5-year period in 207 HIV-positive and 126 HIV-negative subjects as part of the Hemophilia Growth and Development Study. Thyroid function, insulin-like growth factor I (IGF-1) levels, bone age, cranial magnetic resonance image normality, CD4+ counts, and serum testosterone levels of study participants were measured at baseline. An extensive endocrine evaluation was performed in subjects who demonstrated declines in height for age (measurement <5th percentile with two pervious heights >10th percentile), who had not achieved Tanner stage 4 level of pubertal development by age 15 years or who had abnormal growth velocity, which included assessment of peak stimulated growth hormone response after clonidine stimulation, 12-hour growth hormone profiles, and serum beta carotene levels (triggered protocol). For almost the entire group (-99%), thyroid function tests were normal for age. IGF-1 levels were normal for 93% of the cohort. A total of 120 subjects, 89 HIV-positive and 31 HIV-negative, had an abnormality of growth, pubertal development, or both; 34 (11.1%) HIV-positive and 4 (3.6%) HIV-negative subjects had declines in height (p = .001), 20 (23.3%) HIV-positive and 5 (15.8%) HIV-negative subjects had not achieved Tanner stage 4 by 15 years of age (p = .372) and 59 (43.4%) HIV-positive and 23 (25.6) HIV-negative subjects had abnormal growth velocity (p < 0.001). Among subjects with abnormal height or growth velocity, the HIV-positive group had significantly lower mean age-adjusted testosterone levels than did the HIV-negative group (p = .030). Within the HIV-positive group, older subjects with abnormal height or growth velocity had significantly lower mean bone age than subjects of similar age without growth abnormalities (p = .0092). Extensive testing was done in 39 patients (32 HIV-positive, 7 HIV-negative). Half of the HIV-positive subjects had mean 12-hour growth hormone levels <3 ng/ml, 47% had peak stimulated levels <10 ng/ml, 28% had peak spontaneous values <10 ng/ml, and 38% had low levels of IGF-1. In the HIV-positive cohort, there was no difference in the rate of abnormalities of growth hormone secretion between those with CD4+ counts > or = or <200 cells/mm3 and between those subjects that met the 1987 Centers for Disease Control (CDC) surveillance definition of AIDS. In the subset of HIV-positive patients with abnormal peak growth hormone levels after clonidine stimulation, growth hormone response correlated positively with CD4+ count (r = .657, p = .0056) and beta carotene concentration (R = .596, p = .0192). The results of this longitudinal study suggest that abnormalities of growth and pubertal development, particularly an abnormal growth velocity, are common in HIV-infected hemophilic boys and adolescents. These abnormalities might serve as indicators of the presence of HIV infection in this at-risk population. Since thyroid function tests and IGF-1 levels were normal, the etiology of growth impairment in HIV infection does not appear to be secondary to inadequate caloric intake or acquisition, or severe illness such as that caused by recurrent or persistent infection. Rather, HIV infection appears to lead to diminished growth hormone production or release and decreased androgen secretion, even before the development of AIDS and immunocompromise. These results provide a rationale for trials of treatment with growth hormone or androgens in patients with abnormalities of endocrine function.

The relationship of growth rate, plasma growth hormone (GH) concentration, and GH-binding protein.

Growth hormone (GH)-binding protein (GHBP) and GH secretion are potential mediators of linear growth in children. To study the relationship between these variables, we measured GHBP activity, peak stimulated GH (PKGH), and 24-hour integrated GH concentration (ICGH) in 76 children referred for evaluation of growth. Linear growth was expressed as an age- and sex-specific growth rate standard deviation score (GRSD), which was calculated from sequential height measurements in the 6-month period immediately before GH testing. Using multiple regression models, we found that the relationship between GHBP and growth (GRSD) depended on height (height standard deviation [HGTSD] expressed as an age- and sex-specific z score) controlling for ICGH or PKGH. In further analysis of this relationship, we divided the subjects by HGTSD in subsequent analyses. In 19 children of normal stature (HGTSD > -2), GRSD increased with GH concentration (measured both as PKGH and ICGH: P <.013,R2 = .56) but decreased with higher levels of GHBP (P < .005,R2 = .62). In contrast, for 57 subjects with severe short stature (HGTSD < or = -2), GRSD could not be predicted from GHBP, GH secretion, HGTSD, or interaction involving these variables. These data suggest the hypothesis that under normal conditions, GHBP and GH level may be important predictors of growth rate in children.