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Ibba, Anastasia, Francesca Corrias, Chiara Guzzetti, Letizia Casula, Mariacarolina Salerno, Natascia di Iorgi, Gianluca Tornese, et al. "IGF1 for the diagnosis of growth hormone deficiency in children and adolescents: a reappraisal." Endocrine Connections 9, no. 11 (November 2020): 1095–102. http://dx.doi.org/10.1530/ec-20-0347.
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A number of studies have evaluated the role of IGF1 measurement in the diagnosis of growth hormone deficiency (GHD). This study aimed to evaluate the accuracy and the best cut-off of IGF1 SDS in the diagnosis of GHD in a large cohort of short children and adolescents. One-hundred and forty-two children and adolescents with GHD ((63 organic/genetic (OGHD), 79 idiopathic (IGHD)) and 658 short non-GHD children (median age 10.4 years) were included in the analysis. The two groups were subdivided according to age (G1 <6, G2 6 <9, G3 9 <12, G4 ≥12) and to pubertal status. Serum IGFI was measured by the same chemiluminescence assay in all samples and expressed as age- and sex-based SDS. Receiver operating characteristic (ROC) analysis was used to evaluate the optimal IGF1 SDS cut-off and the diagnostic accuracy. Median IGF1 SDS was significantly lower in the GHD than in non-GHD patients. The area under the curve (AUC) was 0.69, with the best IGF1 cut-off of −1.5 SDS (sensitivity 67.61%, specificity 62.62%). The AUC was 0.75 for OGHD and 0.63 for IGHD. The accuracy was better in the pubertal (AUC = 0.81) than the prepubertal group (AUC = 0.64). In our cohort, IGF1 measurement has poor accuracy in discriminating GHD from non-GHD. Our findings confirm and reinforce the belief that IGF1 values should not be used alone in the diagnosis of GHD but should be interpreted in combination with other clinical and biochemical parameters.
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Kaplowitz, Paul B., Janna Manjelievskaia, Lorena Lopez-Gonzalez, Cynthia D. Marrow, Pisit Pitukcheewanont, and Alden Smith. "Economic Burden of Growth Hormone Deficiency in a US Pediatric Population." Journal of the Endocrine Society 5, Supplement_1 (May 1, 2021): A675. http://dx.doi.org/10.1210/jendso/bvab048.1376.
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Abstract Pediatric GHD is a rare disorder of short stature that is currently treated with daily injections of GH. In addition to short stature, GHD is associated with other comorbidities such as impaired musculoskeletal development, cardiovascular disease, and decreased quality of life. The objective of this study was to analyze GH utilization, adherence, and healthcare costs among children with GHD who had either Medicaid or commercial health insurance. Children (age <18 years) with a diagnosis of GHD between January 1, 2007, and December 31, 2017 were identified in the IBM Marketscan Commercial and Medicaid Databases. Children with GHD were direct matched (1:3) to controls without GHD (or other short stature-related disorder) on age, gender, plan type, region, and race (Medicaid only). The index date was set as the date of the first GHD diagnosis during the selection window for GHD patients and using random assignment for controls. Patients were followed for the 12 months prior to the index date until the end of continuous database enrollment or December 31, 2018. Baseline comorbidities and medications were measured during the 12 months pre-index. Treatment patterns and all-cause and GHD-related healthcare costs were measured during the variable follow-up period. Multivariable modeling was used to compare costs between GHD patients and controls and between GH treated and untreated GHD patients while adjusting for baseline characteristics. There were 6,820 Medicaid and 14,070 commercial patients with GHD who met the study inclusion criteria. Mean (SD) age at index was 9.5 (4.5) years for Medicaid patients and 11.1 (3.7) years for commercial patients. A majority of patients were male (>65%) and followed for at least 3.7 years. Overall, 63.2% of Medicaid and 68.4% of commercial patients were treated with GH during follow-up. Among Medicaid patients, the treatment rate was highest among white males and lowest among black females. Adherence, as measured by proportion of days covered, was low, with 18.4% of Medicaid patients and 32.3% of commercial patients considered “adherent” (PDC ≥ 0.8). Nearly half (49.1%) of treated Medicaid patients and 24.3% of commercial patients discontinued GH therapy before age 13. After adjusting for baseline characteristics, all-cause non-GH costs were 5.7times higher (Δ$19,309) for Medicaid patients and 5.5 times higher (Δ$12,305) for commercial patients than matched non-GHD controls. Adjusted all-cause non-GH costs were 0.6 times lower (Δ$14,416) for treated Medicaid patients and 0.7 times lower (Δ$7,650) for treated commercial patients than for untreated patients. Pediatric GHD presents a significant healthcare burden, and many patients remain untreated or undertreated. Untreated GHD was associated with higher non-GH healthcare costs than treated GHD. Strategies to improve adherence may reduce the healthcare burden faced by these patients.
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Hoybye, Charlotte, Peter Jönsson, John P. Monson, Maria Kołtowska-Häggström, Václav Hána, Mitchell Geffner, and Roger Abs. "Impact of the primary aetiology upon the clinical outcome of adults with childhood-onset GH deficiency." European Journal of Endocrinology 157, no. 5 (November 2007): 589–96. http://dx.doi.org/10.1530/eje-07-0364.
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AbstractObjectiveThe impact of the aetiology of childhood-onset GH deficiency (CO-GHD) on the clinical presentation during adulthood and the response to GH replacement has been poorly defined. Our study aims to characterize CO-GHD in adults due to different aetiologies and evaluate the effect of 2 years of GH replacement therapy.Design and methodsData from 353 adults with CO-GHD from Pfizer International Metabolic Database KIMS were retrospectively grouped according to GHD aetiology: non-organic disorder (n=147), organic pituitary disease (n=159), and brain tumour (n=47). Extent of pituitary dysfunction, IGF-I concentration, lipid concentrations and quality-of-life (QoL) were assessed at baseline and after 2 years of GH replacement.ResultsGHD was diagnosed at a later age in the organic pituitary group than in the other groups, resulting in a shorter duration of GH treatment during childhood. However, the final height was greater in the organic pituitary group. Panhypopituitarism was most common in the non-organic disorder and in the organic pituitary groups, while isolated GHD was more prominent in the brain tumour group. Serum IGF-I levels were the lowest in the non-organic group. QoL was the poorest in the brain tumour group. Lipid profile and QoL improved significantly during GH replacement.ConclusionThe adverse consequences of CO-GHD in adulthood vary between aetiologies, but improve similarly with GH treatment. It is, therefore, important to consider retesting all patients with CO-GHD in early adulthood and, if persistent severe GHD is confirmed, recommence GH replacement.
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Garner, Terence, Adam Stevens, Andrew James Whatmore, Peter Ellis Clayton, and Philip G. Murray. "Diagnosis of Childhood and Adolescent Growth Hormone Deficiency Using Transcriptomic Data." Journal of the Endocrine Society 5, Supplement_1 (May 1, 2021): A674—A675. http://dx.doi.org/10.1210/jendso/bvab048.1375.
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Abstract Background: We have shown that gene expression (GE) data have promise as a novel tool to aid in the diagnosis of childhood growth hormone deficiency (GHD)1. Our previous study compared GE data in children with GHD to healthy control children of normal stature. The aim of this study was to assess the utility of GE data in the diagnosis of GHD in childhood and adolescence using non-GHD short stature children as a control group. Methods: GE data were obtained from patients undergoing growth hormone stimulation testing via a sample of blood taken at the start of the test. Arginine and glucagon stimulation tests with a cut-off for peak GH of <7mcg/L (IDS iSYS assay) were used for the diagnosis of GHD. GE was assessed in peripheral blood mononuclear cells via RNA-seq using the Illumina HiSeq 4000 platform. Data were taken for the 271 genes whose expression was utilised in our previous study. The synthetic minority oversampling technique was used to balance the dataset and a random forest algorithm applied to predict GHD status. Boruta was used to assess which of the genes were contributing to the predictive capacity. Results: Twenty-four patients were recruited to the study, with eight subsequently diagnosed with GHD. Of the eight patients diagnosed with GHD, three had two stimulation tests and five had one stimulation test with anterior pituitary hypoplasia (in addition one patient had an arachnoid cyst and another a thin stalk). Median (range) peak GH was 2.5 (0.1 - 5) mcg/L in the GHD group and 11.0 (7.4 - 31) mcg/L in the non-GHD group. There were no significant differences in gender, age, auxology (height SDS, weight SDS, BMI SDS) or biochemistry (IGF-I or IGFBP-3 SDS) between the GHD and non-GHD subjects. 82 of the 271 genes used in our previous study were above the threshold of detection for RNA-seq in this study. A random forest algorithm using these 82 genes gave an AUC of 0.97 (95% CI 0.93 - 1.0) for the diagnosis of GHD. Boruta was able to identify 65/82 genes with predictive capacity greater than permuted data within the dataset. Using a gene ontology approach the top fifty biological processes generated 16 clusters by affinity propagation which included regulation of TORC1 signalling and inositol phosphate metabolism. Conclusion: This study demonstrates highly accurate diagnosis of childhood GHD using a combination of GE data and random forest analysis and validates the findings of our original study. 1Murray etal (2018) JCI Insight 3(7): e93247
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Kołtowska-Häggström, Maria, Mitchell E. Geffner, Peter Jönsson, John P. Monson, Roger Abs, Václav Hána, Charlotte Höybye, and Hartmut A. Wollmann. "Discontinuation of Growth Hormone (GH) Treatment during the Transition Phase Is an Important Factor Determining the Phenotype of Young Adults with Nonidiopathic Childhood-Onset GH Deficiency." Journal of Clinical Endocrinology & Metabolism 95, no. 6 (June 1, 2010): 2646–54. http://dx.doi.org/10.1210/jc.2009-2013.
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Abstract Context: Little is known about the impact of childhood-onset GH deficiency (GHD), in particular the duration of GH cessation during the transition phase, on adult phenotype. Objective: We investigated the association between the manifestations and management of GHD during childhood/adolescence and the clinical features of GHD in adulthood. Design/Setting/Patients/Intervention: Patients with reconfirmed childhood-onset GHD who resumed GH treatment as adults were identified from two sequential databases (n = 313). The cohort was followed up longitudinally from GH start in childhood to reinitiation of treatment in adulthood and 1 yr beyond. Analyses were performed in the total cohort and in subgroups of patients with idiopathic GHD (IGHD) and non-IGHD. The cohorts were stratified based on duration of GH cessation (short, ≤2 yr; long, >2 yr). Main Outcome Measures: Regimen of pediatric GH administration, duration of GH interruption, IGF-I sd score, lipid concentrations, and quality of life were measured. Results: Mean duration of GH interruption was 4.4 yr. IGF-I sd score in adulthood was related to severity of childhood GHD. In non-IGHD patients, a longer duration of GH interruption was associated with a worse lipid profile (P < 0.0001). Non-IGHD patients who gained more height during childhood GH treatment reported better quality of life than those who gained less height (P < 0.05). Conclusions: Pediatricians should tailor GH treatment, not only for its beneficial effect on growth but also for future health in adulthood. In adults with reconfirmed GHD, particularly those with non-IGHD, early recommencement of GH should be considered.
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Ebuchi, Yuki, Toshihide Kubo, Mahoko Furujo, Yousuke Higuchi, Shoko Fujinaga, Hiroki Tsuchiya, Naoko Urata, et al. "Effect of growth hormone therapy on thyroid function in isolated growth hormone deficient and short small for gestational age children: a two-year study, including on assessment of the usefulness of the thyrotropin-releasing hormone (TRH) stimulation test." Journal of Pediatric Endocrinology and Metabolism 33, no. 11 (November 26, 2020): 1417–23. http://dx.doi.org/10.1515/jpem-2020-0151.
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AbstractBackgroundThe relationship between growth hormone (GH)-replacement therapy and the thyroid axis in GH-deficient (GHD) children remains controversial. Furthermore, there have been few reports regarding non-GHD children. We aimed to determine the effect of GH therapy on thyroid function in GHD and non-GHD children and to assess whether thyrotropin-releasing hormone (TRH) stimulation test is helpful for the identification of central hypothyroidism before GH therapy.MethodsWe retrospectively analyzed data from patients that started GH therapy between 2005 and 2015. The free thyroxine (FT4) and thyroid-stimulating hormone (TSH) concentrations were measured before and during 24 months of GH therapy. The participants were 149 children appropriate for gestational age with GHD (IGHD: isolated GHD) (group 1), 29 small for gestational age (SGA) children with GHD (group 2), and 25 short SGA children (group 3).ResultsIn groups 1 and 2, but not in group 3, serum FT4 concentration transiently decreased. Two IGHD participants exhibited central hypothyroidism during GH therapy, and required levothyroxine (LT4) replacement. They showed either delayed and/or prolonged responses to TRH stimulation tests before start of GH therapy.ConclusionsGH therapy had little pharmacological effect on thyroid function, similar changes in serum FT4 concentrations were not observed in participants with SGA but not GHD cases who were administered GH at a pharmacological dose. However, two IGHD participants showed central hypothyroidism and needed LT4 replacement therapy during GH therapy. TRH stimulation test before GH therapy could identify such patients and provoke careful follow-up evaluation of serum FT4 and TSH concentrations.
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Courtillot, Carine, Roselyne Baudoin, Tatiana Du Souich, Lucile Saatdjian, Isabelle Tejedor, Graziella Pinto, Juliane Léger, et al. "Monocentric study of 112 consecutive patients with childhood onset GH deficiency around and after transition." European Journal of Endocrinology 169, no. 5 (November 2013): 587–96. http://dx.doi.org/10.1530/eje-13-0572.
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ObjectivesOur aim was to analyze a large cohort of childhood onset GH deficiency (CO-GHD) adults from a unique adult center, in order to analyze their clinical management and to study the metabolic and bone status in relation to GHD and to the other pituitary deficits, and to evaluate these parameters during the long-term follow-up.Design and methodsObservational retrospective cohort study on 112 consecutive CO-GHD adults transferred to our unit from 1st January 1994 to 1st March 2012. Evaluation of GHD in pediatrics and after transition was conducted following consensus guidelines. Data recorded from pediatric and adult files were GH doses, pituitary magnetic resonance imaging and function, and metabolic and bone status.ResultsMost patients presented with severe CO-GHD (64%) associated with other pituitary deficits (66%). CO-GHD was acquired in 56%, congenital in 33%, and idiopathic in 11% cases. Most patients (83%) stopped GH before transfer, at 16.3 years (median), despite persistence of GHD. Median age at transfer was 19.4 years. After transfer, GHD persisted in 101 patients and four of the 11 resolutive GHD were non idiopathic. IGF1 level was <−2 SDS in 70% of treated patients at transfer and in 34% of them after 3 years of treatment. Follow-up showed improvement in lipid profile and bone mineral density in severely persistent GHD patients under GH therapy. In multivariate analysis, the associated pituitary deficits seemed stronger determinant factors of metabolic and bone status than GHD.ConclusionsThis study raises concern about discontinuation of GH replacement therapy in pediatrics in severely persistent GHD patients and about the often insufficient dose of GH in the treatment of adult patients.
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RUDD, B. T., P. H. W. RAYNER, and P. H. THOMAS. "Observations on the role of GH/IGF-1 and sex hormone binding globulin (SHBG) in the pubertal development of growth hormone deficient (GHD) children." Acta Endocrinologica 113, no. 4_Suppl (December 1986): S164—S169. http://dx.doi.org/10.1530/acta.0.112s164.
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Abstract SHBG concentrations in GHD and non GHD children of both sexes were studied in relation to their weight and androgen status. SHBG was inversely related to age in short and control children, but not for GHD. Correction for body weight restored the inverse relationship in these children and improved the correlation for the other groups. DHAS concentrations were similar in GHD and short children, suggesting GH per se does not influence adrenal androgen synthesis. The mean free testosterone in GHD children 12.7 pmol/L, was similar to that in short children, 14.3 pmol/L, and lower than controls 21.2 pmol/L, but consistent with their pubertal status. The Linear regression of SHBG on IGF-1 was r = -0.605 (P <0.01). It was postulated that IGF-1 and free testosterone may regulate SHBG synthesis. Administration of native and synthetic GH to prepubertal GHD children lowered SHBG without a significant change in TBG, albumin or free testosterone. The fall in SHBG concentration after HGH in GHD children is suggested as a selective mechanism which may lead to improved pubertal development. It is now recognised that many of the biochemical actions of administered human growth hormone (HGH), notably linear growth, protein synthesis and turnover, recorded in the classical studies of Prader et al. (1964), Hubble (1966) and Brown et al. (1967) are mediated by the generation of somatomedin C (IGF-1) (Van Wyk et al., 1974). Less certain is the role that IGF-1 may play in the timing of the growth spurt and subsequent pubertal development. It is documented however, (Laron and Sarel, 1970), that clinical signs of poor genital development in male patients with growth hormone deficiency may be reversed by HGH therapy, but the mechanism is unknown. A specific carbohydrate rich dimeric binding protein, sex hormone binding globulin, with a high Ka for testosterone and oestradiol-17β is present in serum (Anderson, 1974). Levels are raised prepubertally and fall progressively in both sexes as puberty advances (Lee et al., 1985). This fall is a trigger for increased levels of free testosterone and oestradiol-17β which may play a part in the activation of the hypothalamic-pituitary-gonadal axis. Preliminary reports (Rudd et al., 1985), have shown that some GHD children had raised SHBG values for chronological and bone age. These observations suggested that concentrations of non-protein bound sex steroids may be inappropriately low because of a raised In this paper, the weight and the androgen status of GHD SHBG. children is studied in relation to compared to similar data for short addition, the effect of native and Sweden) GH on SHBG and non-protein GHD patients, is examined. their SHBG concentrations and is children and controls. In synthetic (Somatonorm S - Kabi, bound testosterone in the serum of
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Daux, V., I. Garcia de Cortazar-Atauri, P. Yiou, I. Chuine, E. Garnier, E. Le Roy Ladurie, O. Mestre, and J. Tardaguila. "An open-database of Grape Harvest dates for climate research: data description and quality assessment." Climate of the Past Discussions 7, no. 6 (November 15, 2011): 3823–58. http://dx.doi.org/10.5194/cpd-7-3823-2011.
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Abstract. We present a dataset of grape harvest dates (GHD) series that has been compiled from international and non-translated French and Spanish literature and from unpublished documentary sources from public organizations and from wine-growers. As of June 2011, this GHD dataset comprises 378 series mainly from France (93% of the data) as well as series from Switzerland, Italy, Spain and Luxembourg. The series have variable length and contain gaps of variable sizes. The longest and most complete ones are from Burgundy, Switzerland, Southern Rhône valley, Jura and Ile-de-France. The GHD series were grouped into 27 regions according to their location, to geomorphological and geological criteria, and to past and present grape varieties. The GHD regional composite series (GHD-RCS) were calculated and compared pairwise to assess the quality of the series. Significant (p-value < 0.001) and strong correlations exist between most of them. As expected, the correlations tended to be higher when the vineyards are closer, the highest correlation (R = 0.91) being obtained between the High Loire Valley and the Ile-de-France GHD-RCS. The strong dependence of vine cycle on temperature and, therefore, the strong link between GHD and the temperature of the growing season was also used to test the quality of the GHD series. The strongest correlations are obtained between the GHD-RCS and the temperature series of the nearest weather stations. Moreover, the GHD-RCS/temperature correlation maps show spatial patterns similar to temperature correlation maps. The stability of the correlations over time is explored. The most striking feature is their generalized deterioration at the late 19th–early 20th turning point. The possible effects on the GHD of the phylloxera crisis, which took place at this time, are discussed. The median of the standardized GHD-RCS was calculated. The distribution of the extreme years of this general synthetic series is not homogenous. Extremely late years all occur during a two-century long time-window from the early 17th to the early 19th century, while extremely early years are frequent during the 16th and since the mid-19th century. The dataset is made accessible for climate research through the Internet. It should allow a variety of climate studies, including reconstructions of atmospheric circulation over Western Europe.
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Gujral, K., A. Petryk, L. Steffen, K. Baker, J. Perkins, A. S. Kelly, X. Zhou, A. Sinaiko, A. Moran, and J. Steinberger. "Growth hormone deficiency and cardiovascular risk factors in childhood cancer survivors." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): 6614. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.6614.
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6614 Background: Childhood cancer survivors (CCS) have a high frequency of growth hormone deficiency (GHD) and risk of early cardiovascular disease (CVD). This study examined the relations between GHD and risk factors for CVD in CCS. Methods: Anthropometrics, blood pressure, lipids, growth hormone (GH) stimulation test, dual-energy x-ray absorptiometry, abdominal CT, and insulin resistance (IR) (euglycemic, hyperinsulinemic clamp - low M/lbm signifies IR) were obtained in 174 CCS, mean age 15±2 years and 89 healthy sibling controls, mean age 13.5±3 years. Linear regression evaluated the relations between GHD and CVD risk factors, adjusted for sex, age, pubertal stage, and body mass index (BMI) or visceral fat. Results: 62 CCS (36%) had GHD. There were no significant measurement differences between non-GHD CCS and controls. Compared to controls, GHD CCS who never received GH (N = 34) had greater BMI (24.8 vs 20.8 kg/m2, p < 0.0001), percent body fat (36.1% vs 25.8%, p < 0.0001), visceral fat (34.8 vs 19.6 cm2, p < 0.0001), and triglycerides (TG) (120.2 vs 83.8 mg/dL, p = 0.001) and were more IR (M/lbm 11.1 vs 14.2 mg/kg/min, p = 0.0006). Adjustment for BMI and visceral fat did not change the IR or TG results. GHD CCS currently on GH had lower BMI (21.9 kg/m2, p = 0.02), percent body fat (31.2%, p = 0.08), and visceral fat (26.5 cm2, p = 0.03) compared to those not treated. IR and TG were not different between treated and not treated GHD CCS. Conclusions: GHD is a common finding in CCS and is significantly associated with adiposity, IR, and elevated TG.There is a suggestion that GH treatment had a positive impact on adiposity, but not IR and TG levels. These study findings imply that CVD risk factors are present in CCS with GHD independent of body fatness, suggesting that the cancer diagnosis or treatments received may lead to early cardiovascular disease in childhood cancer survivors. No significant financial relationships to disclose.
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Cattoni, Alessandro, Enrico Clarke, and Assunta Albanese. "The Predictive Value of Insulin-Like Growth Factor 1 in Irradiation-Dependent Growth Hormone Deficiency in Childhood Cancer Survivors." Hormone Research in Paediatrics 90, no. 5 (2018): 314–25. http://dx.doi.org/10.1159/000495760.
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Background: The literature contains conflicting reports on the value of low insulin-like growth factor 1 (IGF-1) levels in predicting radiation-induced growth hormone (GH) deficiency (GHD) in childhood cancer survivors (CCS). These reports often involve small samples of patients who have received irradiation or mixed cohorts including non-irradiated subjects. Objective: We undertook an analysis of the predictive value of low IGF-1 in CCS at risk for GHD after cranial radiotherapy involving the hypothalamic-pituitary (HP) area in a large single-centre cohort. Methods: We performed a retrospective analysis on 158 CCS diagnosed with GHD between January 1, 2003 and October 31, 2017 and identified 117 patients who received radiation for tumours not direct ly involving the HP area. Results: In this cohort, IGF-1 levels <–2 standard deviation scores (SDS) had a sensitivity of 31.9% for GHD; however, they were statistically more frequent (p = 0.0023) and had a higher sensitivity (45.6%) among patients with severe GHD. At final height reassessment, IGF-1 <–2 SDS had a sensitivity of 35.0% for GHD, but a positive predictive value of 100%. Finally, pretreatment IGF-1 values showed no correlation with the number of impaired pituitary hormonal axes in patients with multiple pituitary deficiencies. Conclusions: IGF-1 levels <–2 SDS showed a low sensitivity at predicting radiation-induced GHD both in childhood and in adulthood, but a high positive predictive value for GH status at final height reassessment.
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Léger, Juliane, Damir Mohamed, Sophie Dos Santos, Myriam Ben Azoun, Delphine Zénaty, Dominique Simon, Anne Paulsen, et al. "Impact of the underlying etiology of growth hormone deficiency on serum IGF-I SDS levels during GH treatment in children." European Journal of Endocrinology 177, no. 3 (September 2017): 267–76. http://dx.doi.org/10.1530/eje-17-0215.
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ContextRegular monitoring of serum IGF-I levels during growth hormone (GH) therapy has been recommended, for assessing treatment compliance and safety.ObjectiveTo investigate serum IGF-I SDS levels during GH treatment in children with GH deficiency, and to identify potential determinants of these levels.Design, patients and methodsThis observational cohort study included all patients (n = 308) with childhood-onset non-acquired or acquired GH deficiency (GHD) included in the database of a single academic pediatric care center over a period of 10 years for whom at least one serum IGF-I SDS determination during GH treatment was available. These determinations had to have been carried out centrally, with the same immunoradiometric assay. Serum IGF-I SDS levels were determined as a function of sex, age and pubertal stage, according to our published normative data.ResultsOver a median of 4.0 (2–5.8) years of GH treatment per patient, 995 serum IGF-I SDS determinations were recorded. In addition to BMI SDS, height SDS and GH dose (P < 0.01), etiological group (P < 0.01) had a significant effect on serum IGF-I SDS levels, with patients suffering from acquired GHD having higher serum IGF-I SDS levels than those with non-acquired GHD, whereas sex, age, pubertal stage, treatment duration, hormonal status (isolated GHD (IGHD) vs multiple pituitary hormone deficiency (MPHD)) and initial severity of GHD, had no effect.ConclusionsThese original findings have important clinical implications for long-term management and highlight the need for careful and appropriate monitoring of serum IGF-I SDS and GH dose, particularly in patients with acquired GHD, to prevent the unnecessary impact of potential comorbid conditions.
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Ballerini, María Gabriela, Débora Braslavsky, Paula Alejandra Scaglia, Ana Keselman, María Eugenia Rodríguez, Alicia Martínez, Analía Verónica Freire, et al. "Circulating IGF-I, IGFBP-3 and the IGF-I/IGFBP-3 Molar Ratio Concentration and Height Outcome in Prepubertal Short Children on rhGH Treatment over Two Years of Therapy." Hormone Research in Paediatrics 88, no. 5 (2017): 354–63. http://dx.doi.org/10.1159/000479691.
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Objective: To investigate the occurrence of abnormally elevated values of biomarkers of growth hormone (GH) action in short children on recombinant human GH (rhGH) therapy. Methods: Sixty-three prepubertal short children were examined: 31 with GH deficiency (GHD), 25 small for gestational age (SGA), and 9 with Turner syndrome (TS). The main outcomes were the following: standard deviation score (SDS) values of IGF-I, IGFBP-3, and IGF-I/IGFBP-3 molar ratio before, at the 1st and at the 2nd year on rhGH and Δheight (Ht)-SDS to evaluate GH treatment efficacy (adequate 1st-year ΔHt SDS: >0.4 SDS for GHD and >0.3 SDS for non-GHD). Results: Seventy-eight percent of GHD, 78% of SGA and 55% of TS children had adequate 1st-year ΔHt SDS. In GHD, 88% of IGF-I SDS and IGFBP-3 SDS that were ≤–2.0 SDS at baseline normalized on treatment. Abnormal IGF-I values >+2.0 SDS were observed in 52% of SGA and in 55% of TS patients on rhGH. Within each group, the IGF-I/IGFBP-3 molar ratio increased significantly from pretreatment and throughout therapy, remaining within normal range for most patients. ΔIGF-I/IGFBP-3 molar ratio SDS were significantly higher in children with an adequate response (p < 0.01). Conclusion: Non-GHD groups presented markedly elevated concentrations of GH biomarkers on rhGH and normal IGF-I/IGFBP-3 molar ratio in most patients. Since there is a lack of consensus regarding the molar ratio usefulness, we think that interventions towards a more physiological IGF-I serum profile should be implemented.
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Amer, Nadia Mohamad, Marilza J. Modesto, Cláudia Duarte Dos Santos, Oscar Erichsen, Luis P. G. Mascarenhas, Suzana Nesi-França, Rosana Marques-Pereira, and Luiz De Lacerda. "Resistance exercise alone improves muscle strength in growth hormone deficient males in the transition phase." Journal of Pediatric Endocrinology and Metabolism 31, no. 8 (August 28, 2018): 887–94. http://dx.doi.org/10.1515/jpem-2017-0369.
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Abstract Background During the transition phase (TP), patients with growth hormone deficiency (GHD) exhibit decreased muscle strength. Studies assessing the effects of resistance exercise alone on muscle strength in these individuals are scarce. The objective of this study was to evaluate the effects of a program of resistance exercise (PRE) on parameters of muscle strength in subjects in the TP and with childhood-onset GHD treated with recombinant GH (rGH). Methods Sixteen male patients were enrolled and divided into two groups: GHD (n=9) and GH sufficiency (GHS, n=7). Patients with GHD underwent a 12-week PRE followed by another 12-week PRE plus rGH, while GHS patients underwent a 12-week PRE alone. Dynamic knee muscle strength was evaluated using an isokinetic dynamometer. Results Before PRE, there were significant differences between the groups regarding the results of flexor peak torque (FPT) normalized to body weight (BW-FPT) in the dominant (DO, p=0.008) and non-dominant (ND, p=0.01) limbs, and in the agonist/antagonist (A/A) ratio in the DO (p=0.02) and ND (p=0.006) limbs. After PRE in the GHD group, values of FPT and BW-FPT in both limbs increased significantly (p<0.001) and independently of rGH, while the A/A ratio value improved significantly (p<0.001) in the ND limb. Conclusions A short period of PRE alone was sufficient to improve parameters of muscle strength in young male adults with childhood-onset GHD.
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Oks, Eugene. "Application of the Generalized Hamiltonian Dynamics to Spherical Harmonic Oscillators." Symmetry 12, no. 7 (July 7, 2020): 1130. http://dx.doi.org/10.3390/sym12071130.
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Dirac’s Generalized Hamiltonian Dynamics (GHD) is a purely classical formalism for systems having constraints: it incorporates the constraints into the Hamiltonian. Dirac designed the GHD specifically for applications to quantum field theory. In one of our previous papers, we redesigned Dirac’s GHD for its applications to atomic and molecular physics by choosing integrals of the motion as the constraints. In that paper, after a general description of our formalism, we considered hydrogenic atoms as an example. We showed that this formalism leads to the existence of classical non-radiating (stationary) states and that there is an infinite number of such states—just as in the corresponding quantum solution. In the present paper, we extend the applications of the GHD to a charged Spherical Harmonic Oscillator (SHO). We demonstrate that, by using the higher-than-geometrical symmetry (i.e., the algebraic symmetry) of the SHO and the corresponding additional conserved quantities, it is possible to obtain the classical non-radiating (stationary) states of the SHO and that, generally speaking, there is an infinite number of such states of the SHO. Both the existence of the classical stationary states of the SHO and the infinite number of such states are consistent with the corresponding quantum results. We obtain these new results from first principles. Physically, the existence of the classical stationary states is the manifestation of a non-Einsteinian time dilation. Time dilates more and more as the energy of the system becomes closer and closer to the energy of the classical non-radiating state. We emphasize that the SHO and hydrogenic atoms are not the only microscopic systems that can be successfully treated by the GHD. All classical systems of N degrees of freedom have the algebraic symmetries ON+1 and SUN, and this does not depend on the functional form of the Hamiltonian. In particular, all classical spherically symmetric potentials have algebraic symmetries, namely O4 and SU3; they possess an additional vector integral of the motion, while the quantal counterpart-operator does not exist. This offers possibilities that are absent in quantum mechanics.
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Ishikawa, Mayumi, Susumu Yokoya, Katsuhiko Tachibana, Yukihiro Hasegawa, Toshiaki Yasuda, Etsurou Tokuhiro, Yoshihide Hashimoto, and Toshiaki Tanaka. "Serum Levels of 20-Kilodalton Human Growth Hormone (GH) Are Parallel Those of 22-Kilodalton Human GH in Normal and Short Children." Journal of Clinical Endocrinology & Metabolism 84, no. 1 (January 1, 1999): 98–104. http://dx.doi.org/10.1210/jcem.84.1.5402.
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Twenty-kilodalton human GH (20K), which is one of the human GH (hGH) variants, is thought to be produced by alternative premessenger ribonucleic acid splicing. However, its physiological role is still unclear due to the lack of a specific assay. We have measured serum 20K and 22-kDa hGH (22K) by specific ELISAs to investigate the physiological role of 20K in children. The subjects were 162 normal children, aged 1 month to 20 yr; 12 patients with GH deficiency (GHD), aged 11 months to 13 yr; 57 children with non-GHD short stature, aged 2–17 yr; and 13 girls with Turner’s syndrome, aged 5 months to 15 yr. Samples were collected at random from normal children and were collected after hGH provocative tests and 3-h nocturnal sleep from GHD, non-GHD short stature, and Turner’s syndrome children. The mean basal serum concentrations of 22K and 20K were 2.4 ± 2.8 ng/mL and 152.3 ± 184.0 pg/mL in normal boys and 2.5 ± 3.1 ng/mL and 130.6 ± 171.5 pg/mL in normal girls, respectively. The percentages of 20K (%20K) were 5.8 ± 2.1% and 6.0 ± 3.2% in 83 normal boys and 79 normal girls, respectively. There was no significant difference in %20K either among ages or between the prepubertal stage and the pubertal stage in normal boys and girls. The mean %20K values in basal samples of provocative tests in 12 patients with GHD, non-GHD short stature, and Turner’s syndrome were 6.5 ± 2.4%, 6.5 ± 3.8%, and 5.9 ± 3.2%, respectively. There was no significant difference in %20K among normal children and these growth disorders, and there was no significant difference in %20K throughout the hGH provocative tests and 3-h nocturnal sleep in these growth disorders. There was also no significant correlation between the percentage of 20K and the height sd score or body mass index in either normal children or subjects with these growth disorders. In conclusion, the %20K is constant, regardless of age, sex, puberty, height sd score, body mass index, and GH secretion status. The regulation of serum 20K levels remains to be established.
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Egger, A., T. Buehler, C. Boesch, P. Diem, C. Stettler, and E. R. Christ. "The effect of GH replacement therapy on different fat compartments: a whole-body magnetic resonance imaging study." European Journal of Endocrinology 164, no. 1 (January 2011): 23–29. http://dx.doi.org/10.1530/eje-10-0702.
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ObjectivePatients with GH deficiency (GHD) are insulin resistant with an increase in visceral fat mass (FM). Whether this holds true when sedentary control subjects (CS) are matched for waist has not been documented.GH replacement therapy (GHRT) results in a decrease in FM. Whether the decrease in FM is mainly related to a reduction in visceral FM remains to be proven. The aim was to separately assess visceral and subcutaneous FM in relation to insulin resistance (IR) in GHD patients before and after GHRT and in sedentary CS.MethodsTen patients with GHD were investigated before and 6 months after GHRT. Sedentary CS matched for age, gender, body mass index, and waist were assessed. Exercise capacity was measured as VO2maxusing an incremental work load on a treadmill. Visceral and subcutaneous FM were measured using whole-body magnetic resonance imaging and IR by the homeostasis model assessment of IR (HOMA-IR) index.ResultsGHD patients had a non-significantly lower VO2maxbut did not have increased subcutaneous and visceral FM compared with CS. GHRT resulted in a similar relative decrease in subcutaneous and visceral FM. Compared with CS, GHD patients showed a lower HOMA-IR. GHRT tended to increase HOMA-IR.ConclusionMatching for waist and separate assessment of visceral and subcutaneous FM may be critical in the evaluation of body composition and IR in GHD patients before and after GHRT.
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Maghnie, Mohamad, Anders Lindberg, Maria Koltowska-Häggström, and Michael B. Ranke. "Magnetic resonance imaging of CNS in 15 043 children with GH deficiency in KIGS (Pfizer International Growth Database)." European Journal of Endocrinology 168, no. 2 (February 2013): 211–17. http://dx.doi.org/10.1530/eje-12-0801.
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ObjectivesNeuroimaging has become an essential part of the diagnostic process in children with GH deficiency (GHD). The aim of the study was to document the frequency of neuroanatomical abnormalities in a very large cohort of children with GHD and to relate these findings to patient clinical characteristics.Design and methodsResults of magnetic resonance imaging (MRI) were reported in 15 043 of 43 725 children with non-acquired GHD (idiopathic, neurosecretory dysfunction (NSD) and known congenital cause) who were enrolled in KIGS (Pfizer International Growth Database) between 1987 and 2011. Clinical characteristics of patients before GH treatment with normal MRI (idiopathic GHD (IGHD) and NSD) were compared with those of patients with abnormal pituitaries (hypoplasia, empty sella (ES), HME (hypoplastic anterior pituitary, missing pituitary stalk and ectopic posterior pituitary)).ResultsAbnormal MRIs were found in 4032 (26.8%) children, within which ES (n=1178 (7.8%)) and HME (n=1019 (6.8%)) were the most frequent findings. In 2361 children diagnosed as IGHD or NSD before MRI examination, anatomical abnormalities ((pituitary hypoplasia: n=974); (HME: n=459)) were documented. Patients with anatomical abnormalities had more severe characteristics of GHD: normal MRI < pituitary hypoplasia < ES < HME.ConclusionsGHD is associated with a great variety of neuroanatomical abnormalities as identified by MRI. The investigation and evaluation of MRI need to be conducted in a structured mode. There is an association between anatomical and functional abnormalities of the pituitary.
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Blijdorp, K., L. Khajeh, G. M. Ribbers, E. M. Sneekes, M. H. Heijenbrok-Kal, H. J. G. van den Berg-Emons, A. J. van der Lely, F. van Kooten, and S. J. C. M. M. Neggers. "Diagnostic value of a ghrelin test for the diagnosis of GH deficiency after subarachnoid hemorrhage." European Journal of Endocrinology 169, no. 4 (October 2013): 497–502. http://dx.doi.org/10.1530/eje-13-0436.
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ObjectiveTo determine the diagnostic value of a ghrelin test in the diagnosis of GH deficiency (GHD) shortly after aneurysmal subarachnoid hemorrhage (SAH).DesignProspective single-center observational cohort study.MethodsA ghrelin test was assessed after the acute phase of SAH and a GH-releasing hormone (GHRH)–arginine test 6 months post SAH. Primary outcome was the diagnostic value of a ghrelin test compared with the GHRH–arginine test in the diagnosis of GHD. The secondary outcome was to assess the safety of the ghrelin test, including patients' comfort, adverse events, and idiosyncratic reactions.ResultsForty-three survivors of SAH were included (15 males, 35%, mean age 56.6±11.7). Six out of 43 (14%) SAH survivors were diagnosed with GHD by GHRH–arginine test. In GHD subjects, median GH peak during ghrelin test was significantly lower than that of non-GHD subjects (5.4 vs 16.6,P=0.002). Receiver operating characteristics analysis showed an area under the curve of 0.869. A cutoff limit of a GH peak of 15 μg/l corresponded with a sensitivity of 100% and a false-positive rate of 40%. No adverse events or idiosyncratic reactions were observed in subjects undergoing a ghrelin test, except for one subject who reported flushing shortly after ghrelin infusion.ConclusionOwing to its convenience, validity, and safety, the ghrelin test might be a valuable GH provocative test, especially in the early phase of SAH.
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Oliveira, Francielle T., Roberto Salvatori, José Marcondes, Larissa B. Macena, Alecia A. Oliveira-Santos, Augusto C. N. Faro, Viviane C. Campos, Carla R. P. Oliveira, Ursula M. M. Costa, and Manuel H. Aguiar-Oliveira. "Altered sleep patterns in patients with non-functional GHRH receptor." European Journal of Endocrinology 177, no. 1 (July 2017): 51–57. http://dx.doi.org/10.1530/eje-17-0145.
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ObjectivesGH-releasing hormone (GHRH) exerts hypnotic actions increasing the non-rapid eye movement (NREM) sleep. Conversely, GH stimulates the REM sleep. GH deficiency (GHD) often leads to sleep problems, daytime fatigue and reduced quality of life (QoL). GHD may be due to lack of hypothalamic GHRH or destruction of somatotroph cells. We have described a cohort with isolated GHD (IGHD) due to GHRH resistance caused by a homozygousnullmutation (c.57 + 1G > A) in the GHRH receptor gene. They have normal QoL and no obvious complaints of chronic tiredness. The aim of this study was to determine the sleep quality in these subjects.MethodsA cross-sectional study was carried out in 21 adult IGHD subjects, and 21 age- and gender-matched controls. Objective sleep assessment included polygraphic records of the awake, stages NREM [N1 (drowsiness), N2 and N3 (already sleeping)] and REM (R). Subjective evaluation included the Pittsburgh Sleep Quality Index, the Insomnia Severity Index and the Epworth Sleepiness Scale.ResultsIGHD subjects showed a reduction in sleep efficiency (P = 0.007), total sleep time (P = 0.028), duration of N2 and R in minutes (P = 0.026 andP = 0.046 respectively), but had increased duration and percentage of N1 stage (P = 0.029 andP = 0.022 respectively), wake (P = 0.007) and wake-time after sleep onset (P = 0.017). There was no difference in N3 or in sleep quality questionnaire scores.ConclusionPatients with IGHD due to GHRH resistance exhibit objective reduction in the sleep quality, with changes in NREM and REM sleep, with no detectable subjective consequences. GHRH resistance seems to have a preponderant role over GHD in the sleep quality of these subjects.
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Lone, Diana, Karim Thomas Sadak, Bradley S. Miller, Michelle Roesler, and Jenny N. Poynter. "Prevalence of childhood growth hormone deficiency in survivors of pediatric intracranial germ cell tumors." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): e22526-e22526. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.e22526.
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e22526 Background: Survival rates for childhood cancer continue to rise, and there are now greater than 420,000 survivors in the United States. However, high cure rates come at the cost of short and long-term treatment-related toxicities. Endocrine disorders are among the most common late effects and are associated with poor health outcomes and lower quality of life. Survivors of pediatric intracranial germ cell tumors (iGCTs) are at high risk for endocrine disorders, particularly for growth hormone deficiency (GHD), due to their exposures to cranial radiation, chemotherapy, and brain surgery. To date, no long-term follow-up studies have explored the late effects experienced by survivors of iGCTs. Methods: Study participants were enrolled in the Germ Cell Tumor Epidemiology Study, which is a case-parent triad study conducted using the resources of the Children’s Oncology Group’s Childhood Cancer Research Network. Eligibility criteria included diagnosis with a germ cell tumor in any location at age 0-19 years in the years 2008-2015. The study population included 233 cases with a diagnosis of iGCT. We are currently following the cohort to evaluate outcomes and late effects of treatment, including medical record review to extract data on treatment characteristics and hormone deficiencies. This interim analysis includes chart review for 57 iGCT cases. Results: Of the 57 cases reviewed, there was a male predominance (73.7%) with the highest prevalence in non-Hispanic whites (80.4%). Cases of iGCTs can be subdivided into two main histologic subtypes, germinomas (36 cases) and non-germinomatous GCTs (NGGCT, 21 cases). The median age at diagnosis was 14.6 years for the germinomas and 10.5 years for NGGCTs. Data on growth hormone deficiency (GHD) was available for 42 of the 57 cases with a median follow-up of 7.4 years. Twenty-eight of the 42 cases (66.7%) had GHD; 19 in the germinoma group and 9 in the NGGCT group (p = 0.47). 17 of those with GHD were males (p = 0.10). There was no significant difference in prevalence of GHD by age of tumor diagnosis (p = 0.20). Conclusions: Survivors of iGCTs are at high risk for growth hormone deficiency. Identifying specific risk factors for developing GHD amongst these survivors can enhance the current guidelines for screening and management.
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van der Klaauw, A. A., A. M. Pereira, S. W. van Thiel, J. W. A. Smit, E. P. M. Corssmit, N. R. Biermasz, M. Frolich, et al. "GH deficiency in patients irradiated for acromegaly: significance of GH stimulatory tests in relation to the 24 h GH secretion." European Journal of Endocrinology 154, no. 6 (June 2006): 851–58. http://dx.doi.org/10.1530/eje.1.02163.
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Background: Radiotherapy for pituitary adenomas frequently leads to GH deficiency (GHD). The characteristics of GH secretion in GHD induced by postoperative radiotherapy for acromegaly are not known. Hypothesis: In the long term, stimulated and spontaneous GH release is not different between patients with GHD treated by postoperative radiotherapy for acromegaly or for other pituitary adenomas. Design/subjects: We compared the characteristics of basal and stimulated GH secretion in patients with GHD, who had previously received adjunct radiotherapy after surgery for GH-producing adenomas (n=10) vs for other pituitary adenomas (n=10). All patients had a maximal GH concentration by insulin tolerance test (ITT) of 3 μg/l or less, compatible with severe GHD. Mean time after radiation was 17 and 18.7 years, respectively. Stimulated GH release was also evaluated by infusion of growth hormone-releasing hormone (GHRH), GHRH–arginine and arginine, and spontaneous GH by 10 min blood sampling for 24 h. Pulse analyses were performed by Cluster and approximate entropy. Outcomes: There were no differences between both patient groups in stimulated GH concentrations in any test. Spontaneous GH secretion was not different between both patient groups, including basal GH release, pulsatility and regularity. Pulsatile secretion was lost in two acromegalic and three non-acromegalic patients. Insulin-like growth factor-I (IGF-I) was below −2 s.d. score in nine patients in each group. Conclusion: Acromegalic patients treated by surgery and postoperative radiotherapy with an impaired response to the ITT do not differ, in the long term, in GH secretory characteristics from patients treated similarly for other pituitary tumors with an impaired response to the ITT. The ITT (or the GHRH–arginine test) is therefore reliable in establishing the diagnosis of GHD in patients treated for acromegaly by surgery and radiotherapy.
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Ogawa, E., BH Breier, I. Fujiwara, and K. Iinuma. "Gonadal suppression by a GnRH analogue does not alter somatic growth in rats with complete GH deficiency." Journal of Endocrinology 166, no. 2 (August 1, 2000): 355–61. http://dx.doi.org/10.1677/joe.0.1660355.
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Sexual dimorphism of somatic growth in rats appears to reflect differing actions of sex steroids. However, mechanisms of gonadal steroid effects on the somatotropic axis are incompletely understood. To evaluate whether GH is involved in the effects of long-term gonadal suppression on somatic growth in rats, a GnRH agonistic analogue (GnRHa) was administered to normal Sprague-Dawley rats (controls) and to a strain of rats with complete growth hormone deficiency (GHD; n=4-6 in each group). Subcutaneous injection of GnRHa (2 mg/kg) or saline were given within 48 h after birth and repeated every 3 weeks. GnRHa treatment significantly reduced serum gonadal steroid levels in rats of both sexes with small testes in males and impaired development of internal genitalia in females. GnRHa-treated control females became significantly heavier (P<0.01 ANOVA for repeated measures) than saline-treated rats beginning at 8 weeks. However, female GHD rats with GnRHa treatment did not differ in body weight from rats receiving saline. In male rats, GnRHa treatment did not change body weight in either control or GHD rats. Serum IGF-I concentrations did not differ between treatment groups in GHD and control rats of either sex. Hepatic GH binding was reduced significantly by GnRHa treatment in female control rats (P<0.01), but not in female GHD rats. These data suggest that sexual dimorphism in body size and its modulation by estrogens are independent of circulating IGF-I levels suggesting non-endocrine IGF-I-mediated mechanisms, and that GH-induced somatic growth is modulated by estrogens, but not androgens, in rats.
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Backeljauw, Philippe, Bradley S. Miller, Richard Levy, Kenneth McCormick, Hichem Zouater, Markus Zabransky, and Kim Campbell. "PATRO children, a multi-center, non-interventional study of the safety and effectiveness of Omnitrope® (somatropin) treatment in children: update on the United States cohort." Journal of Pediatric Endocrinology and Metabolism 34, no. 4 (February 26, 2021): 431–40. http://dx.doi.org/10.1515/jpem-2020-0360.
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Abstract Objectives Omnitrope® (somatropin, Sandoz Inc.) is one of several recombinant human growth hormones (rhGH) approved in the United States (US) for use in pediatric indications, including growth hormone deficiency (GHD) and idiopathic short stature (ISS). We report data on the effectiveness and safety of Omnitrope® in the US cohort of the PATRO Children (international, longitudinal, non-interventional) study. Methods All visits and assessments are carried out according to routine clinical practice, and doses of Omnitrope® are given according to country-specific prescribing information. Results By September 2018, 294 US patients were recruited; the two largest groups were GHD (n=193) and ISS (n=62). Across all indications, HSDS improvement (ΔHSDS) from baseline at three years was +1.0 (rhGH-naïve, +1.2; pre-treated, +0.7). In pre-pubertal patients, ΔHSDS from baseline at three years was +0.94 (rhGH-naïve, +1.3; pre-treated, +0.7). Following three years of treatment, ΔHSDS from baseline was +1.3 in rhGH-naïve GHD patients and +1.1 in rhGH-naïve ISS patients. In pre-pubertal rhGH-naïve patients, ΔHSDS from baseline was +1.3 and +1.2 in GHD and ISS patients, respectively. Overall, 194 patients (66.0%) experienced adverse events (AEs; n=886 events); most were of mild-moderate intensity. Five patients (1.7%) had AEs that were suspected to be treatment-related (n=5 events). All reported neoplasms were benign, non-serious, and considered unrelated to rhGH therapy. No AEs of diabetes mellitus or hyperglycemia were reported. Conclusions Omnitrope® appears to be well tolerated and effective in the majority of patients, without evidence of an increased risk of developing unexpected AEs, diabetes mellitus, or new malignancies during treatment.
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Cruz, Juliana B., Vania S. Nunes, Sueli A. Clara, Denise Perone, Peter Kopp, and Célia R. Nogueira. "Molecular analysis of the PROP1 and HESX1 genes in patients with septo-optic dysplasia and/or pituitary hormone deficiency." Arquivos Brasileiros de Endocrinologia & Metabologia 54, no. 5 (2010): 482–87. http://dx.doi.org/10.1590/s0004-27302010000500009.
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OBJECTIVE: The present study aimed at evaluating the PROP1 and HESX1 genes in a group of patients with septo-optic dysplasia (SOD) and pituitary hormone deficiency (combined - CPHD; isolated GH deficiency - GHD). Eleven patients with a clinical and biochemical presentation consistent with CPHD, GHD or SOD were evaluated. SUBJECTS AND METHODS: In all patients, the HESX1 gene was analyzed by direct sequence analysis and in cases of CPHD the PROP1 gene was also sequenced. RESULTS: A polymorphism (1772 A > G; N125S) was identified in a patient with SOD. We found three patients carrying the allelic variants 27 T > C; A9A and 59 A > G; N20S in exon 1 of the PROP1 gene. Mutations in the PROP1 and HESX1 genes were not identified in these patients with sporadic GHD, CPHD and SOD. CONCLUSION: Genetic alterations in one or several other genes, or non-genetic mechanisms, must be implicated in the pathogenic process.
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Degerblad, Marie, Bengt-Åke Bengtsson, Margareta Bramnert, Olof Johnell, Per Manhem, Thord Rosén, and Marja Thorén. "Reduced bone mineral density in adults with growth hormone (GH) deficiency: increased bone turnover during 12 months of GH substitution therapy." European Journal of Endocrinology 133, no. 2 (August 1995): 180–88. http://dx.doi.org/10.1530/eje.0.1330180.
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Degerblad M, Bengtsson B-Å, Bramnert M, Johnell O, Manhem P, Rosén T, Thorén M. Reduced bone mineral density in adults with growth hormone (GH) deficiency: increased bone turnover during 12 months of GH substitution therapy. Eur J Endocrinol 1995;133:180–8. ISSN 0804–4643 To evaluate the consequences of growth hormone (GH) deficiency on bone mineral density and to evaluate the effects of GH substitution therapy, 68 adults (25 females and 43 males) aged 22–61 (mean 44.2 ± 1.2) years with GH deficiency (GHD) were studied. Fifty-eight patients had panhypopituitarism, three had isolated GHD and in seven patients at least one additional pituitary function was affected. Twenty-one patients had childhood onset GHD. The patients were randomized to receive either GH in daily injections (0.125 IU · kg−1 · week−1 for the first 4 weeks and subsequently 0.25 IU · kg−1 · week−1) or placebo for 6 months. The trial continued as an open study with GH treatment for 6 or 12 months, with data presented as compiled data of 12 months of GH treatment in 64 patients. Bone mineral density (BMD) was measured by dual energy x-ray absorptiometry and bone turnover was assessed by serum markers of bone metabolism (osteocalcin, procollagen I peptide, crosslinked telopeptide of type I collagen and alkaline phosphatase activity). In women with adult onset GHD (N = 19) and in men with childhood onset GHD (N = 15), total body, spine and hip BMD was significantly reduced at baseline compared to Swedish age- and sex-matched control material. In men with adult onset of GHD (N = 28), BMD did not differ from male controls. During the placebocontrolled period, GH induced decreased total body and spine BMD, probably due to an expansion of the remodelling space, whereas all serum markers of bone turnover increased. Compiled GH data showed similar results after 6 months of treatment. After 12 months of GH treatment, BMD did not differ from basal values except for total body BMD, which was lower, whereas the serum markers of bone metabolism were still increased as compared to basal values. Two-thirds of the patients experienced fluid retention with peripheral oedema and arthralgias on the higher GH dosage. One obese patient developed non-insulin-dependent diabetes mellitus and was withdrawn from the study. These results demonstrate that GHD has negative effects on BMD and that GH substitution induces increased bone turnover. Continued long-term observations will reveal if there is a positive effect of GH substitution on bone mass in the adult GHD patient. Marie Degerblad, Department of Endocrinology and Diabetology, Karolinska Hospital, S-17176 Stockholm, Sweden
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Spector-Cohen, Inna, Ariel Koren, Waheeb Sakran, Yardena Tenenbaum-Rakover, and Rephael Halevy. "Growth hormone deficiency in children with antenatal Bartter syndrome." Journal of Pediatric Endocrinology and Metabolism 32, no. 3 (March 26, 2019): 225–31. http://dx.doi.org/10.1515/jpem-2018-0188.
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Abstract Background Bartter syndrome is a group of rare autosomal-recessive renal disorders characterized by hypokalemic hypochloremic metabolic alkalosis associated with severe growth failure; the exact causes for growth retardation are unclear. GH deficiency (GHD) has been reported in a few cases of Bartter syndrome. The aim of our study was to determine the prevalence of GHD in children with antenatal Bartter syndrome and to assess their response to GH therapy. Methods Ten patients aged 1.5–14.5 years and diagnosed with antenatal Bartter syndrome were enrolled. Seven children with short stature underwent GH stimulation tests. Results Common presenting symptoms were failure to thrive and polyuria. The mean patient height at study entry was −2.7 standard deviation (SD) (range 0.89 to −5.95) and mean weight (SD) was −1.7 (range 1.89 to −4.11). A decline in height and weight (SD) was observed over the years. GHD was diagnosed in four children and GH therapy was started in all of them. Two patients responded very well and gained >1 SD in height, one patient stopped therapy due to non-adherence and one had a poor response. Conclusions In addition to other important causes for poor growth in antenatal Bartter syndrome, our findings suggest that GHD should also be considered as a cause of growth retardation and therefore, clinical assessment of the GH axis is recommended. GH therapy has a role in the treatment of growth failure in some individuals with Bartter syndrome.
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Fleseriu, Maria, Jens Otto Jorgensen, Kevin C. J. Yuen, Charlotte Hoybye, Meng Mao, Jennifer Kang, Wenjie Song, Allison Komirenko, Aimee D. Shu, and Michael Beckert. "Design of the ForesiGHt Trial: A Multicenter, Randomized, Placebo- and Active-Controlled Trial to Compare Once-Weekly TransCon hGH (lonapegsomatropin) to Placebo and Daily Somatropin in Adults With Growth Hormone Deficiency (GHD)." Journal of the Endocrine Society 5, Supplement_1 (May 1, 2021): A519—A520. http://dx.doi.org/10.1210/jendso/bvab048.1060.
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Abstract BackgroundAdult GHD results from insufficient growth hormone (GH) secretion from the anterior pituitary gland and may represent either a continuation of childhood-onset GHD or GHD acquired during adulthood. Clinically, adult GHD is associated with central adiposity, decreased lean muscle mass, increased fat mass, decreased bone mineral density, and reduced quality of life. Current standard of care consists of GH replacement via daily injections. Lonapegsomatropin is a long-acting prodrug of somatropin (hGH), designed to deliver unmodified hGH with a weekly exposure profile. Lonapegsomatropin consists of somatropin that is transiently bound to a carrier via a proprietary TransCon Linker. The carrier extends the duration of somatropin in the circulation through a shielding effect that minimizes renal excretion and receptor-mediated clearance of the prodrug. At physiologic conditions, lonapegsomatropin releases fully active, unmodified somatropin via autocleavage of the linker in a controlled manner. The safety and efficacy of lonapegsomatropin have previously been evaluated in two phase 3 trials and one long-term extension trial in pediatric GHD. Changes in body composition are an objective and sensitive endpoint that reflects biologic activity of GH and clinical efficacy of GH replacement. Methods: The primary objective of the foresiGHt trial is to evaluate the efficacy of once-weekly lonapegsomatropin compared to placebo at 38 weeks in adults with GHD. The trial will be conducted at approximately 120 sites in North America, Europe, Asia, and Oceania. Approximately 240 subjects will be randomized 1:1:1 to once-weekly lonapegsomatropin, once-weekly placebo, or daily somatropin (Norditropin®). Subjects will be treatment-naïve or without GH therapy for at least 12 months. Subjects with well-controlled non-insulin dependent diabetes mellitus (HbA1c ≤ 7.5%) will be eligible. Following screening, the 38-week treatment period will consist of a 12-week gradual dose titration period and 26 weeks of fixed dose maintenance. Fixed dosing will be used to ensure maximal comparability across the treatment arms in the trial. Three dosing groups per arm will be established to allow for differences in age and oral estrogen intake in women. The primary endpoint is change from baseline in trunk percent fat at week 38, as measured by dual energy X-ray absorptiometry (DXA). Secondary efficacy endpoints are change from baseline in trunk fat mass and change in total body lean mass at week 38. Exploratory efficacy endpoints include total body fat mass, trunk lean mass, visceral adipose tissue, and patient-reported outcomes. Conclusion: The ongoing global phase 3 foresiGHt trial is designed to assess the efficacy, safety, and tolerability of lonapegsomatropin by weekly administration, compared to weekly placebo and daily hGH replacement therapy in adults with GHD.
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Appelman-Dijkstra, Natasha M., Kim M. J. A. Claessen, Ferdinand Roelfsema, Alberto M. Pereira, and Nienke R. Biermasz. "Therapy of Endocrine disease: Long-term effects of recombinant human GH replacement in adults with GH deficiency: a systematic review." European Journal of Endocrinology 169, no. 1 (July 2013): R1—R14. http://dx.doi.org/10.1530/eje-12-1088.
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BackgroundThe beneficial effects of recombinant human GH (rhGH) therapy in GH deficient (GHD) adults are well-established in the short term. However, data documenting the effects during prolonged follow-up are relatively scarce.ObjectiveTo evaluate the reported effects of rhGH replacement (≥5 years) in GHD adults on biochemical and anthropometric parameters, quality of life (QoL), bone metabolism, muscle strength, serious adverse events and mortality.MethodsWe conducted a systematic literature search. Quality assessment of retrieved papers was performed using a quality assessment based on the modified STROBE statement.ResultsWe included 23 prospective studies with a rhGH treatment duration ranging from 5 to 15 years. Overall, beneficial effects were reported on QoL, body composition, lipid profile, carotid intima media thickness and bone mineral density. In contrast, the prevalence of the metabolic syndrome, glucose levels, BMI and muscle strength were not, or negatively, influenced. Most of the studies were uncontrolled, lacked the presence of a control group (of non-treated GHD patients), and reported no data on lipid-lowering and anti-diabetic medication. Overall mortality was not increased.ConclusionrhGH treatment in adult GHD patients is well-tolerated and positively affects QoL in the long term. However, the metabolic and cardiovascular effects during long-term treatment are variable. The low numbers of long-term studies and studied patients and lack of control data hamper definite statements on the efficacy of prolonged treatment. Therefore continuous monitoring of the effects of rhGH replacement to enable an adequate risk-benefit analysis that may justify prolonged, potentially life-long, treatment is advisable.
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Gardner, Chris J., Anders F. Mattsson, Christina Daousi, Márta Korbonits, Maria Koltowska-Haggstrom, and Daniel J. Cuthbertson. "GH deficiency after traumatic brain injury: improvement in quality of life with GH therapy: analysis of the KIMS database." European Journal of Endocrinology 172, no. 4 (April 2015): 371–81. http://dx.doi.org/10.1530/eje-14-0654.
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ObjectivePrevalence of GH deficiency (GHD) caused by traumatic brain injury (TBI) is highly variable. Short-term studies show improvement in quality of life (QoL) during GH replacement (GHR), but long-term data are lacking. The aim of this study was to analyse the clinical characteristics of post-traumatic hypopituitarism and the QoL effects of long-term GHR.Design/methodsPfizer International Metabolic Database patients with GHD caused by TBI and by non-functioning pituitary adenoma (NFPA) were compared regarding: clinical characteristics at baseline and 1-year of GHR, and QoL response up to 8-years of GHR (QoL-AGHDA total scores and dimensions) in relationship with country-specific norms.ResultsTBI patients compared with NFPA patients were younger, diagnosed with GHD 2.4 years later after primary disease onset (P<0.0001), had a higher incidence of isolated GHD, higher GH peak, a more favourable metabolic profile and worse QoL, were shorter by 0.9 cm (1.8 cm when corrected for age and gender; P=0.004) and received higher GH dose (mean difference: 0.04 mg/day P=0.006). In TBI patients, 1-year improvement in QoL was greater than in NFPA (change in QoL-AGHDA score 5.0 vs 3.5, respectively, P=0.04) and was sustained over 8 years. In TBI patients, socialisation normalised after 1 year of GHR, self-confidence and tenseness after 6 years and no normalisation of tiredness and memory was observed.ConclusionCompared with NFPA, TBI patients presented biochemically with less severe hypopituitarism and worse QoL scores. GHR achieved clinically relevant, long-term benefit in QoL.
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Stojanovic, Marko, Zida Wu, Craig E. Stiles, Dragana Miljic, Ivan Soldatovic, Sandra Pekic, Mirjana Doknic, et al. "Circulating aryl hydrocarbon receptor-interacting protein (AIP) is independent of GH secretion." Endocrine Connections 8, no. 4 (April 2019): 326–37. http://dx.doi.org/10.1530/ec-19-0082.
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Background Aryl hydrocarbon receptor-interacting protein (AIP) is evolutionarily conserved and expressed widely throughout the organism. Loss-of-function AIP mutations predispose to young-onset pituitary adenomas. AIP co-localizes with growth hormone in normal and tumorous somatotroph secretory vesicles. AIP protein is detectable in circulation. We aimed to investigate possible AIP and GH co-secretion, by studying serum AIP and GH levels at baseline and after GH stimulation or suppression, in GH deficiency (GHD) and in acromegaly patients. Subjects and methods Insulin tolerance test (ITT) was performed in GHD patients (n = 13) and age-BMI-matched normal GH axis control patients (n = 31). Oral glucose tolerance test (OGTT) was performed in active acromegaly patients (n = 26) and age-BMI-matched normal GH axis control patients (n = 18). In-house immunometric assay was developed for measuring circulating AIP. Results Serum AIP levels were in the 0.1 ng/mL range independently of gender, age or BMI. Baseline AIP did not differ between GHD and non-GHD or between acromegaly and patients with no acromegaly. There was no change in peak, trough or area under the curve during OGTT or ITT. Serum AIP did not correlate with GH during ITT or OGTT. Conclusions Human circulating serum AIP in vivo was assessed by a novel immunometric assay. AIP levels were independent of age, sex or BMI and unaffected by hypoglycaemia or hyperglycaemia. Despite co-localization in secretory vesicles, AIP and GH did not correlate at baseline or during GH stimulation or suppression tests. A platform of reliable serum AIP measurement is established for further research of its circulatory source, role and impact.
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Polak, Michel, Jo Blair, Primoz Kotnik, Effie Pournara, Birgitte Tønnes Pedersen, and Tilman R. Rohrer. "Early growth hormone treatment start in childhood growth hormone deficiency improves near adult height: analysis from NordiNet® International Outcome Study." European Journal of Endocrinology 177, no. 5 (November 2017): 421–29. http://dx.doi.org/10.1530/eje-16-1024.
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Objective To investigate the effect of age at growth hormone (GH) treatment start on near adult height (NAH) in children with isolated GH deficiency (GHD). Design NordiNet® International Outcome Study (IOS) (Nbib960128), a non-interventional, multicentre study, evaluates the long-term effectiveness and safety of Norditropin® (somatropin) (Novo Nordisk A/S) in the real-life clinical setting. Methods Patients (n = 172) treated to NAH (height at ≥18 years, or height velocity <2 cm/year at ≥16 (boys) or ≥15 (girls) years) were grouped by age (years) at treatment start (early (girls, <8; boys, <9), intermediate (girls, 8–10; boys, 9–11) or late (girls, >10; boys, >11)) and GHD severity (<3 ng/mL or 3 to ≤10 ng/mL). Multiple regression analysis was used to evaluate the effect of age at treatment start (as a categorical and continuous variable) on NAH standard deviation score (SDS). Results Age at treatment start had a marked effect on NAH SDS; NAH SDS achieved by patients starting treatment early (n = 40 (boys, 70.0%); least squares mean (standard error) −0.76 (0.14)) exceeded that achieved by those starting later (intermediate, n = 42 (boys, 57.1%); −1.14 (0.15); late, n = 90 (boys, 68.9%); −1.21 (0.10)). Multiple regression analysis showed a significant association between NAH SDS and age at treatment start (P < 0.0242), baseline height SDS (HSDS) (P < 0.0001), target HSDS (P < 0.0001), and GHD severity (P = 0.0012). Most (78.5%) patients achieved a normal NAH irrespective of age at treatment start. Conclusions Early initiation of GH treatment in children with isolated GHD improves their chance of achieving their genetic height potential.
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Ragnarsson, Oskar, Charlotte Höybye, Peter J. Jönsson, Ulla Feldt-Rasmussen, Gudmundur Johannsson, Beverly M. K. Biller, and Maria Kołtowska-Häggström. "Comorbidity and cardiovascular risk factors in adult GH deficiency following treatment for Cushing's disease or non-functioning pituitary adenomas during childhood." European Journal of Endocrinology 166, no. 4 (April 2012): 593–600. http://dx.doi.org/10.1530/eje-11-0942.
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ObjectiveCushing's disease (CD) and non-functioning pituitary adenoma (NFPA) are rare in paediatric patients. The aim of this study was to describe long-term consequences in adults with GH deficiency (GHD) treated for CD or NFPA during childhood.Design, patients and methodsThis was a retrospective analysis of data from KIMS (Pfizer International Metabolic Database). Background characteristics, anthropometry and comorbidity were studied in 47 patients diagnosed with childhood-onset (CO)-CD and 62 patients with CO-NFPA. Data from 100 ACTH-sufficient patients with CO-idiopathic hypopituitarism (CO-Idio) were used for comparison. Cardiovascular risk profile was analysed at baseline and at 1 year on GH treatment in a subgroup of patients (17 CO-CD, 24 CO-NFPA and 55 CO-Idio) not receiving GH treatment at study entry.ResultsThe median age at diagnosis of pituitary tumour was 14.0 years (range 10–17) in patients with CO-CD and 13.7 years (range 8–17) in CO-NFPA. In addition to GHD, 41% of patients with CO-CD had three or four other pituitary hormone deficiencies compared with 78% of patients with CO-NFPA (P<0.001). Eighty-nine per cent of patients with CO-CD had height SDS lower than 0 compared with 61% of patients with CO-NFPA (P=0.002). Hypertension was more common in CO-CD compared with CO-Idio (23 vs 9%,P=0.018). At 1 year on GH treatment, total- and low-density lipoprotein-cholesterol decreased significantly in CO-CD but not in CO-NFPA.ConclusionAdult patients with GHD following treatment for paediatric CD and NFPA have long-term adverse consequences. Despite more severe hypopituitarism in CO-NFPA, patients with CO-CD have more frequently compromised final stature.
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Graham, Selina, John Weinman, and Vivian Auyeung. "Identifying Potentially Modifiable Factors Associated with Treatment Non-Adherence in Paediatric Growth Hormone Deficiency: A Systematic Review." Hormone Research in Paediatrics 90, no. 4 (2018): 221–27. http://dx.doi.org/10.1159/000493211.
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Background: Despite the developments of recombinant growth hormone (rhGH) treatment and the benefits in long-term clinical health outcomes, evidence has shown that many children with growth hormone deficiency (GHD) still fail to achieve their target adult height. Suboptimal outcomes have been largely attributed to treatment non-adherence. Methods: A search of 11 electronic databases was undertaken to identify relevant articles, published in English, between 1985 and 2018. Additional search strategies included hand-searching topic review articles to identify eligible studies. Articles were screened against the inclusion eligibility criteria and data on sample characteristics, study design, outcomes, and key findings was extracted. The results were narratively synthesised and categorised using the COM-B theoretical framework. Results: Twenty-one full-text articles were assessed for eligibility, of which 6 articles met the inclusion criteria. The prevalence of non-adherence in the included studies varied from 7 to 71%. Potentially modifiable factors associated with rhGH non-adherence were categorised within the COM-B framework; key factors included: a lack of knowledge and understanding of the condition and treatment, discomfort and pain associated with injections, and the quality of the healthcare professional-patient relationship. Conclusion: This review highlights the scope of the adherence problem evident amongst the paediatric GHD population and in addition presents the wide range of potentially modifiable factors that explain this health-related behaviour.
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Chattu, Vijay Kumar, and Georgina Chami. "Global Health Diplomacy Amid the COVID-19 Pandemic: A Strategic Opportunity for Improving Health, Peace, and Well-Being in the CARICOM Region—A Systematic Review." Social Sciences 9, no. 5 (May 25, 2020): 88. http://dx.doi.org/10.3390/socsci9050088.
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Increased globalization has ushered in changes in diplomatic purposes and practices. As such, global health diplomacy (GHD) has become a growing field connecting the urgencies of global health and foreign affairs. More academics and policy-makers are thinking about how to structure and utilize diplomacy in pursuit of global health goals. This article aims to explore how the health, peace, and well-being of people in the region can be achieved through global health diplomacy. A systematic review of the literature was conducted on various terms such as “Global Health Diplomacy OR Foreign Policy”; “Disasters”, “Infectious disease epidemics” OR “Non-Communicable diseases” AND “Caribbean” by searching PubMed, Scopus, Embase, Web of Science databases, and Google Scholar search engines. A total of 33 articles that met the inclusion criteria were analyzed, and the critical role of GHD was highlighted. There is an increasing need to understand the complex global health challenges, coupled with the need to design appropriate solutions. Many regional initiatives addressing infectious and chronic diseases have been successful in multiple ways by strengthening unity and also by showing directions for other nations at a global level, e.g., the Port of Spain Summit declaration. GHD has a great scope to enhance preparedness, mitigation, peace, and development in the region. Amid the COVID-19 pandemic, the region needs to strengthen its efforts on equity issues, health promotion, and sustainable development to promote peace and well-being.
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Miller, Bradley S., Eric Velazquez, and Kevin C. J. Yuen. "Long-Acting Growth Hormone Preparations – Current Status and Future Considerations." Journal of Clinical Endocrinology & Metabolism 105, no. 6 (November 2, 2019): e2121-e2133. http://dx.doi.org/10.1210/clinem/dgz149.
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Abstract Context Long-acting GH (LAGH) preparations are currently being developed in an attempt to improve adherence. The profile of GH action following administration of LAGH raises practical questions about clinical monitoring and long-term safety and efficacy of these new therapeutic agents. Methods Recent literature and meeting proceedings regarding LAGH preparations are reviewed. Results Multiple LAGH preparations are currently at various stages of development, allowing for decreased GH injection frequency from daily to weekly, biweekly, or monthly. Following administration of LAGH, the serum peak and trough GH and IGF-I levels vary depending upon the mechanism used to prolong GH action. Randomized, controlled clinical trials of some LAGH preparations have reported non-inferiority compared with daily recombinant human GH (rhGH) for improved growth velocity and body composition in children and adults with GH deficiency (GHD), respectively. No significant LAGH-related adverse events have been reported during short-term therapy. Conclusion Multiple LAGH preparations are proceeding through clinical development with some showing promising evidence of short-term clinical efficacy and safety in children and adults with GHD. The relationship of transient elevations of GH and IGF-I following administration of LAGH to efficacy and safety remain to be elucidated. For LAGH to replace daily rhGH in the treatment of individuals with GHD, a number of practical questions need to be addressed including methods of dose adjustment, timing of monitoring of IGF-I, safety, efficacy, and cost-effectiveness. Long-term surveillance of efficacy and safety of LAGH preparations will be needed to answer these clinically relevant questions.
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Bollerslev, Jens, Jens Møller, Sian Thomas, Ole Djøseland, and Jens S. Christiansen. "Dose-dependent effects of recombinant human growth hormone on biochemical markers of bone and collagen metabolism in adult growth hormone deficiency." European Journal of Endocrinology 135, no. 6 (December 1996): 666–71. http://dx.doi.org/10.1530/eje.0.1350666.
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Bollerslev J, Møller J, Thomas S, Djøseland O, Christiansen JS. Dose-dependent effects of recombinant human growth hormone on biochemical markers of bone and collagen metabolism in adult growth hormone deficiency. Eur J Endocrinol 1996:135:666–71. ISSN 0804–4643 Administration of growth hormone (GH) to patients with growth hormone deficiency (GHD) has beneficial effects, but so far has been employed only empirically. We have, therefore, investigated the dose-dependent effect of GH on target tissue by studying biochemical markers of bone and collagen turnover in GHD. Then patients with GHD (nine males and one female aged 21–43 years, mean age 28 years) participated in the study. Growth hormone deficiency was defined as a peak serum GH response of less than 15 mU/l in two provocation tests. After a 4-week run-in period, the study population received increasing doses of GH at 4-week intervals (1,2 and 4U/m2). Blood samples were collected in the fasting state at 7.00 h on the last day of each period and assayed for serum levels of osteocalcin (S-BGP), bone alkaline phosphatase (B-ALP), C-terminal propeptide of type I collagen (S-PICP), carboxy-terminal pyridinoline cross-linked telopeptide of type I collagen (S-ICTP) and N-terminal propeptide of type III collagen (S-PIIINP). Following replacement therapy, serum insulin-like growth factor I and insulin-like growth factor binding protein 3 increased sequentially with time (p<0.001 and p<0.001, MANOVA) and the values were elevated significantly over baseline levels after treatment with 1 U/m2. Serum BGP values were below normal at the start of the study and increased gradually following GH treatment to levels in the low–normal range. Baseline values for serum bone alkaline phosphatase (B-ALP), PICP and PIIINP were within the normal range. The collagen parameters increased with GH replacement (p<0.001, MANOVA) to levels above normal, whereas B-ALP stayed within normal limits. Serum ICTP values were elevated above the normal range at baseline, indicating increased bone resorption in GHD. A linear increase in values was observed with GH treatment (p< 0.001, MANOVA). Serum ICTP did not correlate significantly with the bone formative parameters but was correlated positively to PIIINP. The sensitivity of S-ICTP as a bone resorptive marker is thus questioned. In conclusion, a dose-dependent increase in markers of growth hormone metabolism and in biochemical markers of both bone and non-bone collagen synthesis was seen following incremental doses of GH in GHD. Jens Bollerslev, Department of Medical Endocrinology, National University Hospital, N-0027 Oslo, Norway
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Rochmah, Nur, and Muhammad Faizi. "Impact of growth hormone treatment on children’s height." Paediatrica Indonesiana 54, no. 6 (December 30, 2014): 318. http://dx.doi.org/10.14238/pi54.6.2014.318-23.
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Background The use of growth hormone (GH) is a routinetreatment for growth hormone deficiency (GHD), small forgestational age (SGA), and Turner syndrome (TS). During thetreatment, height measurement at regular intervals is a vital stepto assess success. To date, there have been no previous studieson GH treatment in Dr. Soetomo Hospital, Surabaya, the referralhospital in East Indonesia.Objective To compare body height between pre- and post-growthhormone treatment in pediatric patients.Method This study was a non-randomized, pre-post clinical trialperformed at Dr. Soetomo Hospital, Surabaya. The prospectivecohort was accessed during January 2008-June 2013. Theinclusion criteria was GH treatment for more than 3 months.Clinical data on GH treatment, including diagnosis, age, heightpre-and post-treatment, height gain, duration of treatment, andparental satisfaction were collected. Two-tailed, paired T-test andPearson’s test were used for statistical analyses.Result Nineteen patients underwent GH treatment during thestudy period, but only twelve patients had complete data and wereincluded in the study. Eight subjects were female. Subjects’ meanage was 11 (range 8-15) years. Nine patients had GHD, 2 hadTS, and 1 had SGA. Mean pre-treatment height was 121.05 cm,while mean post-treatment height was 130.5 cm. Mean durationof treatment was 10.5 (range 3-30) months. Mean height gainwas 0.8 cm/month in GHD and SGA cases, and 0.78 cm/monthfor the TS cases. Eleven parents reported satisfaction with theresults of GH treatment in their children. There is significantdiffrent between pre- and post-treatment (P=0.001). Pearson’scorrelation test (r=0.90) revealed a strong correlation betweengrowth hormone treatment and height gain.Conclusion Growth hormone treatment has impact on heights inGH defficiency, Turner syndrome, and small for gestational age.
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Blijdorp, Karin, Marry M. van den Heuvel, Rob Pieters, Annemieke Boot, Aartjan van der Lely, and Sebastian J. C. M. M. Neggers. "The Limited Screening Value of Insulin-Like Growth Factor-I in 610 Very Long Term Adult Survivors of Leukemia and Other Types of Childhood Cancer." Blood 118, no. 21 (November 18, 2011): 506. http://dx.doi.org/10.1182/blood.v118.21.506.506.
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Abstract Abstract 506FN2 Introduction Over the last decades childhood cancer survival rates have improved significantly. Currently, 70–80% of patients become long term cancer survivors. It has been estimated that 1 out of 640 young adults in the U.S. is a survivor of childhood cancer. Consequently, the incidence of late, treatment-related complications is increasing. Endocrine sequelae, such as the metabolic syndrome, osteopenia, sub fertility, thyroid dysfunction and growth hormone deficiency represent an important category of such late effects. Growth hormone deficiency (GHD) in childhood cancer survivors, mainly caused by cranial radiotherapy, is reflected by low levels of insulin like growth factor 1 (IGF-I). Whereas the value of IGF-I measurement for the diagnosis of GHD is controversial, low IGF-I levels are associated with high body mass index and high visceral fat percentage. However the clinical relevance of low IGF-I levels in long term childhood cancer survivors is not extensively studied. In this study we evaluated whether IGF-I is useful as a marker for altered body composition and growth hormone deficiency in this group. Methods We retrospectively analyzed data of 610 adult childhood cancer survivors, retrieved from the Rotterdam late effects clinic, which starts 5 years after cessation of therapy. Median age at diagnosis was 6 years (interquartile range (IQR) 3–11) and follow up time was 18 years (13–24). We assessed IGF-I Z-scores, anthropometrical measures, growth hormone stimulation tests in patients with clinical suspicion of GHD and measures of body composition (assessed by dual X-ray absorptiometry, Lunar Prodigy). Results Cranial irradiated acute leukaemia survivors (25 Gy (24–25)) and locally irradiated brain tumour survivors (42 Gy (35–54)) had significantly lower IGF-I Z-scores (p<0.001), lower height SDS (p<0.001), higher body mass index (p=0.01), higher waist-hip ratio (p=0.001), higher visceral fat percentage (p<0.001), higher total fat percentage (p<0.001) and lower lean body mass (p<0.001), compared to non cranial irradiated survivors. IGF-I did not show a strong correlation with BMI (r=-0.12, p=0.04), waist hip ratio (r=-0.15, p=0.01), total fat percentage (r=-0.14, p=0.02) and lean body mass (r=0.15, p=0.01). In the patients with low IGF-I levels who had growth hormone stimulation, IGF-I Z-scores did not significantly differ between the patients with and without severe GHD (p = 0.39). Conclusion This study shows that there is a limited value of IGF-I as marker for alterations in body composition, and confirms the fact that low IGF-I levels are not predictive for GHD, in a large cohort of childhood cancer survivors. Therefore the use of IGF-I should not be encouraged in adult childhood cancer survivors. Disclosures: No relevant conflicts of interest to declare.
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Maiter, D., R. Abs, G. Johannsson, M. Scanlon, P. J. Jönsson, P. Wilton, and M. Koltowska-Häggström. "Baseline characteristics and response to GH replacement of hypopituitary patients previously irradiated for pituitary adenoma or craniopharyngioma: data from the Pfizer International Metabolic Database." European Journal of Endocrinology 155, no. 2 (August 2006): 253–60. http://dx.doi.org/10.1530/eje.1.02209.
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Objective: To test the hypothesis whether the effects of GH replacement therapy in adults could be affected by prior pituitary irradiation, the baseline characteristics and response to GH were evaluated in adults with severe GH deficiency (GHD), who had received or not irradiation for the treatment of pituitary adenoma or craniopharyngioma. Design: Data from 447 patients, who had received radiotherapy (427 in addition to surgery), and 630 patients, who were operated on but not irradiated for their tumour, were retrieved from Pfizer International Metabolic Database (KIMS) and compared at baseline and 1 and 2 years following the onset of GH replacement. Results: Irradiated and non-irradiated patients exhibited the expected phenotype of GHD at baseline. However, irradiated patients had a greater impairment in the quality of life (QoL), a higher fat mass, lower high-density lipoprotein cholesterol levels and a lower bone mineral content (BMC) than non-irradiated patients. Treatment with GH induced similar changes in both groups. After 1 year of GH replacement, there was an increase in serum IGF-I and fat-free mass, a reduction in fat mass and an improvement in QoL, all changes being equivalent in irradiated and non-irradiated patients. The lipid profile also improved with the irradiated patients showing a better response. These beneficial effects were maintained and the BMC also increased in both groups by the second year of treatment. Conclusions: This analysis shows that prior irradiation for pituitary adenoma or craniopharyngioma does not compromise the beneficial effects of GH replacement therapy.
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Luo, Xiaoping, Ling Hou, Li Liang, Guanping Dong, Shuixian Shen, Zhuhui Zhao, Chun Xiu Gong, et al. "Long-acting PEGylated recombinant human growth hormone (Jintrolong) for children with growth hormone deficiency: phase II and phase III multicenter, randomized studies." European Journal of Endocrinology 177, no. 2 (August 2017): 195–205. http://dx.doi.org/10.1530/eje-16-0905.
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Objective We assessed the efficacy and safety of a weekly pegylated human growth hormone (PEG-rhGH) (Jintrolong) vs daily rhGH for children with growth hormone deficiency (GHD). Design Phase II and III, multicenter, open-label, randomized controlled trials. Methods 108 and 343 children with treatment-naive GHD from 6 hospitals in China were enrolled in the phase II and III studies respectively. Patients in the phase II study were randomized 1:1:1 to weekly Jintrolong (0.1 mg/kg/week PEG-rhGH complex), weekly Jintrolong (0.2 mg/kg/week PEG-rhGH complex) or daily rhGH (0.25 mg/kg/week) for 25 weeks. Patients in the phase III study were randomized in a 2:1 ratio to weekly Jintrolong (0.2 mg/kg/week) or daily rhGH (0.25 mg/kg/week) for 25 weeks. The primary endpoint for both studies was height velocity (HV) increase at the end of treatment. Other growth-related parameters, safety and compliance were also monitored. Results The phase II study established the preliminary efficacy, safety and recommended dose of Jintrolong PEG-rhGH. In the phase III study, we demonstrated significantly greater HV increases in patients receiving Jintrolong treatment (from 2.26 ± 0.87 cm/year to 13.41 ± 3.72 cm/year) vs daily rhGH (from 2.25 ± 0.82 cm/year to 12.55 ± 2.99 cm/year) at the end of treatment (P < 0.05). Additionally, significantly greater improvement in the height standard deviation scores was associated with Jintrolong throughout the treatment (P < 0.05). Adverse event rates and treatment compliance were comparable between the two groups. Conclusion Jintrolong PEG-rhGH at a dose of 0.2 mg/kg/week for 25 weeks is effective and safe for GHD treatment and is non-inferior to daily rhGH.
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Inoue-Lima, Thais H., Gabriela A. Vasques, Renata C. Scalco, Marilena Nakaguma, Berenice B. Mendonca, Ivo J. P. Arnhold, and Alexander A. L. Jorge. "IGF-1 assessed by pubertal status has the best positive predictive power for GH deficiency diagnosis in peripubertal children." Journal of Pediatric Endocrinology and Metabolism 32, no. 2 (February 25, 2019): 173–79. http://dx.doi.org/10.1515/jpem-2018-0435.
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Abstract Background When evaluating peripubertal short stature patients, the interpretation of insulin-like growth factor 1 (IGF-1) levels based on chronological age (CA) can be inaccurate due to the influence of sex steroids and, presently, there is no evidence to support the assessment of IGF-1 values according to bone age (BA) and pubertal status (PS). Our objective was to assess the discriminatory performance of IGF-1 levels based on CA, BA and PS in the diagnosis of growth hormone (GH) deficiency. Methods We evaluated IGF-1 levels from 154 peripubertal short stature patients classified as GH deficient (GHD, n=23) or non-GHD (n=131). IGF-1 was assayed by a chemiluminescent immunometric assay and transformed into standard deviation scores (SDS) according to CA (IGF-1-SDS-CA), BA (IGF-1-SDS-BA) and PS (IGF-1-SDS-PS). Results The performances of IGF-1-SDS-CA, IGF-1-SDS-BA and IGF-1-SDS-PS in the receiver operator characteristics (ROC) curves were similar. There were greater accuracy and specificity of IGF-1-SDS-PS (98.4% and 93.3%, respectively) and IGF-1-SDS-BA (92.7% and 90.1%, respectively) when compared to IGF-1-SDS-CA (65.6% and 69.5%, respectively). The post-test probability of the IGF-1-SDS was also improved when compared to PS and BA – 44.8% (IGF-1-SDS-PS), 16.8% (IGF-1-SDS-BA) and 5.1% (IGF-1-SDS-CA), with similar negative predictive values. Conclusions The evaluation of IGF-1 levels based on CA has a higher sensitivity than those based on BA or PS, which justify its use as a screening tool. Additionally, IGF-1 assessed by PS has the best positive predictive power for GHD diagnosis in peripubertal age and could reduce the necessity of a second GH stimulation test.
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Rohrer, Tilman R., Sabine Ceplis-Kastner, Norbert Jorch, Hermann L. Müller, Roland Pfäffle, Thomas Reinehr, Annette Richter-Unruh, Claudia Weißenbacher, Paul-Martin Holterhus, and Dr Sabine Clips-Kastner Ferring Arzneimittel GmbH. "Needle-Free and Needle-Based Growth Hormone Therapy in Children: A Pooled Analysis of Three Long-Term Observational Studies." Hormone Research in Paediatrics 90, no. 6 (2018): 393–406. http://dx.doi.org/10.1159/000496614.
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Background: Treatment with growth hormone (GH) is standard clinical practice in children with GH deficiency (GHD) or Turner syndrome (TS). Hitherto, no long-term data on auxological outcome and safety of Zomacton® have been published. Data comparing needle-free administration (NF) and needle injection (NI) of GH are very sparse. Aims: To analyse longitudinal auxological outcome and safety data of GH treatment-naïve patients diagnosed with GHD or TS and to compare NF and NI in a real-life setting. Methods: Pooled auxological data and safety information from three consecutive prospective observational Zomacton® studies covering 22 years of treatment were analysed and NF was compared to NI. Results: The safety cohort comprised 1,595 patients who received at least one GH dose. The auxological outcome cohort comprised 856 treatment-naïve patients with follow-up data ≥12 months. Height-SDS and height velocity improved significantly during the first 3 years of treatment. Documented choice of device was available for 658 patients (NF 69.1%, NI 30.9%). NF administration was non-inferior to NI. No previously unknown safety signals occurred. Conclusion: Real-life data show that treatment with Zomacton® improves auxological outcome parameters without new safety concerns. NF administration of GH represents a useful alternative to NI in children with growth disorders.
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Keleştimur, Fahrettin, Peter Jonsson, Senay Molvalilar, Jose Manuel Gomez, Christoph J. Auernhammer, Ramiz Colak, Maria Koltowska-Häggström, and Miklos I. Goth. "Sheehan’s syndrome: baseline characteristics and effect of 2 years of growth hormone replacement therapy in 91 patients in KIMS – Pfizer International Metabolic Database." European Journal of Endocrinology 152, no. 4 (April 2005): 581–87. http://dx.doi.org/10.1530/eje.1.01881.
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Objective: Sheehan’s syndrome occurs as a result of ischaemic pituitary necrosis due to severe postpartum haemorrhage. It is one of the most important causes of hypopituitarism, and hence growth hormone deficiency (GHD), in developing countries. However, little is known about the effects of growth hormone (GH) replacement therapy in patients with Sheehan’s syndrome. Design: The demographic background characteristics of 91 GH-deficient patients with Sheehan’s syndrome (mean age ± s.d., 46.3 ± 9.4 years) were compared with those of a group of 156 GH-deficient women (mean age ± s.d., 51.5 ± 13.1 years) with a non-functional pituitary adenoma (NFPA). The baseline characteristics and the effects of 2 years of GH replacement therapy were also studied in the 91 patients with Sheehan’s syndrome and an age-matched group of 100 women with NFPA (mean age ± s.d. 44.5 ± 10.2 years). Results: All patients were enrolled in KIMS (Pfizer International Metabolic Database). Patients with Sheehan’s syndrome were significantly younger at pituitary disorder onset, diagnosis of GHD and at entry into KIMS than patients with NFPA (P < 0.01), and had significantly lower insulin-like growth factor I levels (P < 0.001). At baseline, quality of life (QoL) was significantly (P < 0.05) reduced in patients with Sheehan’s syndrome compared with those with NFPA (P < 0.001). With regard to treatment effects, lean body mass increased significantly (P < 0.05), QoL improved significantly (P < 0.05) and total and low-density lipoprotein-cholesterol decreased significantly (P < 0.05) in patients with Sheehan’s syndrome after 1 year of GH replacement therapy. Similar significant changes in QoL and lipid profiles occurred in patients with NFPA after 2 years of GH replacement. Blood pressure remained unchanged in patients with Sheehan’s syndrome, but decreased significantly (P < 0.01) in the group with NFPA after 1 year, before returning to pretreatment levels at 2 years. Conclusions: In conclusion, patients with Sheehan’s syndrome have more severe GHD compared with individuals with NFPA. GH replacement therapy in patients with Sheehan’s syndrome may have beneficial effects on QoL, body composition and lipid profile.
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Mukherjee, Annice, Judith E. Adams, Linda Smethurst, and Stephen M. Shalet. "Interdependence of lean body mass and total body water, but not quality of life measures, during low dose GH replacement in GH-deficient adults." European Journal of Endocrinology 153, no. 5 (November 2005): 661–68. http://dx.doi.org/10.1530/eje.1.02017.
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Lean body mass (LBM) and total body water (TBW) are reduced in GH-deficient (GHD) adults and alter with GH replacement. Whether these parameters are interdependent and whether alterations in their homeostasis contribute to the perceived quality of life (QOL) deficit in GHD remains unclear. In this study, IGF-I, body composition by whole-body dual-energy X-ray absorptiometry, TBW by deuterium dilution (D2O) and two validated QOL instruments - psychological general well-being schedule (PGWB, generic, 6 domains; lower score worse QOL) and assessment of GH deficiency in adults (AGHDA, disease orientated; higher score worse QOL) were studied at baseline and after 3 and 6 months of GH replacement in thirty GHD adults. Patients with diabetes insipidus, and cardiac and renal failure were excluded. Median age-adjusted IGF-I standard deviation score increased from −3.40 (−6.40 to −1.60) to −0.2 (−1.88 to 0.78) (P < 0.0001) at a median daily GH dose of 0.4 mg. During treatment, LBM increased from 47.4 ± 10.7 kg at baseline to 49.5 ± 10.8 kg at 6 months (P = 0.0008), and fat mass decreased from 28.0 ± 12.1 kg at baseline to 27.2 ± 12.6 kg at 6 months (P = 0.0004). A non-significant trend towards an increase in TBW was observed (mean 1.7 kg, P = 0.08). The PGWB score increased from 62.9 ± 20.6 to 73.7 ± 21.7 (P = 0.0006). The AGHDA score decreased from 13.7 ± 7.3 to 8.75 ± 7.75 (P = 0.0002). At each time point, a linear correlation between LBM and TBW was demonstrated, defined by TBW = (0.972 × LBM)–10.6. However, only a weakly positive correlation existed between the percentage changes in these variables (R = 0.40, P = 0.04). No correlations were demonstrated between QOL measures and body composition. The change in LBM with physiological GH replacement correlates weakly with change in TBW, therefore factors other than TBW may also contribute to the LBM changes. Improved QOL with GH replacement is not explained by favourable changes in body composition.
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Quigley, Charmian A., Christopher J. Child, Alan G. Zimmermann, Ron G. Rosenfeld, Leslie L. Robison, and Werner F. Blum. "Mortality in Children Receiving Growth Hormone Treatment of Growth Disorders: Data From the Genetics and Neuroendocrinology of Short Stature International Study." Journal of Clinical Endocrinology & Metabolism 102, no. 9 (May 26, 2017): 3195–205. http://dx.doi.org/10.1210/jc.2017-00214.
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Abstract Context Although pediatric growth hormone (GH) treatment is generally considered safe for approved indications, concerns have been raised regarding potential for increased risk of mortality in adults treated with GH during childhood. Objective To assess mortality in children receiving GH. Design Prospective, multinational, observational study. Setting Eight hundred twenty-seven study sites in 30 countries. Patients Children with growth disorders. Interventions GH treatment during childhood. Main Outcome Measure Standardized mortality ratios (SMRs) and 95% confidence intervals (CIs) using age- and sex-specific rates from the general population. Results Among 9504 GH-treated patients followed for ≥4 years (67,163 person-years of follow-up), 42 deaths were reported (SMR, 0.77; 95% CI, 0.56 to 1.05). SMR was significantly elevated in patients with history of malignant neoplasia (6.97; 95% CI, 3.81 to 11.69) and borderline elevated for those with other serious non–GH-deficient conditions (2.47; 95% CI, 0.99-5.09). SMRs were not elevated for children with history of benign neoplasia (1.44; 95% CI, 0.17 to 5.20), idiopathic GHD (0.11; 95% CI, 0.02 to 0.33), idiopathic short stature (0.20; 95% CI, 0.01 to 1.10), short stature associated with small for gestational age (SGA) birth (0.66; 95% CI, 0.08 to 2.37), Turner syndrome (0.51; 95% CI, 0.06 to 1.83), or short stature homeobox-containing (SHOX) gene deficiency (0.83; 95% CI, 0.02 to 4.65). Conclusions No significant increases in mortality were observed for GH-treated children with idiopathic GHD, idiopathic short stature, born SGA, Turner syndrome, SHOX deficiency, or history of benign neoplasia. Mortality was elevated for children with prior malignancy and those with underlying serious non–GH-deficient medical conditions.
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Child, Christopher J., Alan G. Zimmermann, Whitney W. Woodmansee, Daniel M. Green, Jian J. Li, Heike Jung, Eva Marie Erfurth, and Leslie L. Robison. "Assessment of primary cancers in GH-treated adult hypopituitary patients: an analysis from the Hypopituitary Control and Complications Study." European Journal of Endocrinology 165, no. 2 (August 2011): 217–23. http://dx.doi.org/10.1530/eje-11-0286.
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ObjectiveGH and IGFs have mitogenic properties, causing speculation that GH treatment could increase risk of malignancy. While studies in GH-treated childhood cancer survivors have suggested a slight increase in second neoplasms, studies in GH-treated adults have been equivocal.DesignIncidence of de novo and second cancers was evaluated in 6840 GH-treated and 940 non GH-treated adult patients in the Hypopituitary Control and Complications Study pharmacoepidemiological database.MethodsEvident cancer cases were evaluated in the main analysis, with sensitivity analyses including probable and possible cancers. Standardized incidence ratios (SIRs) for cancers were calculated using Surveillance, Epidemiology and End Results for the USA and GLOBOCAN for all other countries.ResultsDuring the mean follow-up of 3.7 years/GH-treated patient, 142 evident cancer cases were identified, giving an overall SIR of 0.88 (95% confidence interval (CI) 0.74–1.04); 95% CIs included the value of 1.0 for each country examined. The SIR for GH-treated patients from the USA (71 cases) was 0.94 (95% CI 0.73–1.18), and for non GH-treated patients from the USA (27 cases) was 1.16 (95% CI 0.76–1.69). For GH-treated patients from the USA aged <35 years, the SIR (six cases) was 3.79 (1.39–8.26), with SIR not elevated for all other age categories; SIR for patients from the USA with childhood onset (CO) GH deficiency (GHD) was 2.74 (95% CI 1.18–5.41). The SIR for colorectal cancer in GH-treated patients (11 cases) was 0.60 (95% CI 0.30–1.08).ConclusionsWith relatively short follow-up, the overall primary cancer risk in 6840 patients receiving GH as adults was not increased. Elevated SIRs were found for subgroups in the USA cohort defined by age <35 years or CO GHD.
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Elmi, S., REZAErfani Sayyar, and SAM Elmi. "PO-0155 Evaluation Of Growth Hormone Deficiency (ghd) In Children With Acute Lymphoblastic Leukemia (all) And Non-hodgkin’s Lymphoma (nhl)." Archives of Disease in Childhood 99, Suppl 2 (October 2014): A298.1—A298. http://dx.doi.org/10.1136/archdischild-2014-307384.817.
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Naparst, Monica, Liam McGuirk, Matthew Krasnow, Charanpreet Sasan, Alice Alexandrov, Nicholas Andrew Krasnow, Zeyad El-Naghy, et al. "Pituitary Volume Is a Better Predictor of Growth During Growth Hormone Therapy Than the Growth Hormone Stimulation Test." Journal of the Endocrine Society 5, Supplement_1 (May 1, 2021): A684. http://dx.doi.org/10.1210/jendso/bvab048.1394.
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Abstract Background: Patients with diminished GH secretion are candidates for GH therapy (GHT). The GH stimulation test (GHST) is considered the gold standard for the diagnosis of GH deficiency (GHD), yet the cutoff of 10 ng/mL has not been well validated statistically. Another proposed method to define GHD has been to measure patients’ pituitary volumes (PV), as the size of the gland may correlate with the amount of GH produced. Objective: This study seeks to ascertain whether the GHST or PV is a better predictor of response to GHT, and determine which method can better define true GHD. Patients and Methods: A database at a Pediatric Endocrinology center was queried for patients aged 6-18 yrs who underwent a GHST, MRI, and GHT between 1/2018 - 6/2019. Patients with relevant comorbidities, those with GHST peak ≥ 10.0 ng/mL, and patients that were non-adherent to their GHT were excluded. Clonidine and L-dopa were stimulants for the GHST. MRIs were acquired on a Philips 1.5 or 3.0 T scanner (1mm slices) and PV was calculated using the ellipsoid formula (LxWxH/2). 87 patients met these criteria for analysis. PV was converted to standard deviation scores (SDS) based on age and sex using the largest data set of pituitary volumes available in the literature. To account for sex-related growth rate differences by age, heights at the initial and subsequent time points were also converted to SDS based on age and sex using parameters provided by the National Center of Health Statistics. Response to treatment was defined as change in height SDS over the assessed time interval. The initial height was included as a covariate. R statistical software was utilized to analyze the correlation between response to GHT and GHST peak value, as well as response to GHT and PV. The relationship between GHST peak value and PV SDS was analyzed with a Spearman correlation. Results: The GHST peak was not a significant predictor of growth response to treatment in both the first or second intervals (r= -0.01, p= 0.207 and r= 0.00, p= 0.815 respectively). GHST peak and PV SDS were not correlated (r=0.08, 95% CI: -0.14, 0.28). Lower SDS of PV significantly predicted growth response to therapy in the first 1 to 8.7 months of treatment (n= 87, model r2=0.231, b=-0.05, SE=0.02, P=0.012). This association in the second interval between 7.8 and 17.4 months of treatment was neither as strong as the first interval nor was it statistically significant (n=62, model r2=0.145, b=-0.05, SE=0.03, P=0.127). Within-person growth velocity was greater in the first interval (mean = 0.37, SD = 0.17) than in the second interval (mean = 0.20, SD = 0.16). Conclusion: Our data indicates that PV can be a valuable tool in defining GHD and should be considered a criterion for determining eligibility for GHT. To our knowledge this is the first study to determine that PV is a better predictor of growth response to GHT than the GHST.
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Saja S. Falih, Falah S. Al-Fartusie, and Noor T. Tahir. "Association between lipid profile and other biochemical parameters with growth hormone in children and adolescents with short stature." International Journal of Research in Pharmaceutical Sciences 11, no. 3 (July 27, 2020): 4295–302. http://dx.doi.org/10.26452/ijrps.v11i3.2642.
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Short stature is a general term that usually accompanies a lack of growth hormone among people, and is more common among children. In this study, some kidney functions and lipid profile tests were evaluated in children and adolescents with short stature to find any relationship between the disturbance in these parameters and the etiology of short stature. A total of 60 short stature patients with a growth hormone deficiency, age range between 4-18 years, along with 60 age-matched healthy volunteers, were included in this study. Serum levels of GH, IGF-1, urea, and creatinine, as well as lipid profile, were determined, and then statistical analysis was performed on the collected data. The obtained results indicated a significant decrease in serum levels of GH and IGF-1 (p <0.01) in patients compared to control values. The results also indicated a substantial increase in serum levels of triglycerides and VLDL, mainly seen in children, and reported non-significant differences in HDL, LDL, and urea levels for GHD patients compared to control values. Additionally, the results showed a significant increase in the creatinine level of adolescent patients only. This study concluded that there is a clear relationship between disturbances in creatinine levels and the promotion of GHD in short stature patients. Current work has demonstrated that anomalies in the lipid profile, especially triglycerides and VLDL, are closely related to the causes of short stature. Finally, and most importantly, we can suggest that triglycerides and VLDL may help identify patients at an early age who are at risk of short stature, especially children.