Childhood-onset Growth Hormone Research Articles

Characterization of patients stopping GH therapy for childhood-onset growth hormone deficiency in belgium - luxemburg

Characterization of patients stopping GH therapy for childhood-onset growth hormone deficiency in belgium - luxemburg

Brain white matter alterations in young adult male patients with childhood-onset growth hormone deficiency: a diffusion tensor imaging study.

This study aimed to detect white matter changes and different effects of thyroid hormone on the white matter integrity in young adult male patients with childhood-onset growth hormone deficiency (CO-GHD), compared with healthy people. Magnetic resonance imaging (structural imaging and diffusion tensor imaging) was performed in 17 young adult male patients with CO-GHD and 17 healthy male controls. The white matter volume, mean diffusivity (MD) values and fractional anisotropy (FA) values were quantified and compared between two groups (CO-GHD group vs. control group). We assessed the interaction effects between thyroid hormone and groups (CO-GHD group vs. control group) on white matter integrity. Patients with CO-GHD exhibited similar white matter volumes compared with controls. However, compared with the controls, patients with CO-GHD showed a significant reduction in FA values in six clusters and a substantial increase in MD values in four clusters, mainly involving the corticospinal tracts, corpus callosum and so on. Moreover, after correcting for insulin-like growth factor-1 levels, the significant interaction effects between groups (CO-GHD group vs. control group) and serum free thyroxine levels on MD values were noted in three clusters, mainly involving in superior longitudinal fasciculus and sagittal stratum. In conclusion, young males with CO-GHD showed white matter changes in multiple brain regions and different effects of thyroid hormone on the white matter integrity.

An audit of the management of childhood-onset growth hormone deficiency (CO-GHD) at completion of linear growth

An audit of the management of childhood-onset growth hormone deficiency (CO-GHD) at completion of linear growth

Management of childhood-onset growth hormone deficiency in patients transitioning from pediatric to adult care: A review of the literature and consensus report from a panel of experts in Saudi Arabia

Despite increased recognition of the importance of optimizing care for patients with childhood-onset growth hormone deficiency (CO-GHD) during the transition period from pediatric to adult services, its implementation in clinical practice in Saudi Arabia remains challenging. By an initiative from the Saudi Society of Endocrinology and Metabolism, a panel comprising 11 experts, including both pediatric and adult endocrinologists with practical experience in the clinical management of patients with CO-GHD, was convened to discuss issues relating to transition care in this patient population. The primary objective of this consensus document was to develop the first clinician-led consensus statement that establishes best practices when transitioning adolescents with persistent CO-GHD to adult care in Saudi Arabia. A modified Delphi method was applied to develop consensus statements. A literature review was performed, and 20 statements were subsequently formulated. After two rounds of Delphi, consensus was achieved for 18 of the 20 statements.

Metabolic Impacts of Discontinuation and Resumption of Recombinant Human Growth Hormone Treatment during the Transition Period in Patients with Childhood-Onset Growth Hormone Deficiency.

Background Discontinuing growth hormone (GH) treatment during the transition to adulthood has been associated with adverse health outcomes in patients with childhood-onset growth hormone deficiency (CO-GHD). This study investigated the metabolic changes associated with interrupting GH treatment in adolescents with CO-GHD during the transition period.Methods This study included 187 patients with CO-GHD who were confirmed to have adult GHD and were treated at six academic centers in Korea. Data on clinical parameters, including anthropometric measurements, metabolic profiles, and bone mineral density (BMD) at the end of childhood GH treatment, were collected at the time of re-evaluation for GHD and 1 year after treatment resumption.Results Most patients (n=182, 97.3%) had organic GHD. The median age at treatment discontinuation and re-evaluation was 15.6 and 18.7 years, respectively. The median duration of treatment interruption was 2.8 years. During treatment discontinuation, body mass index Z-scores and total cholesterol, low-density lipoprotein, and non-high-density lipoprotein (HDL) cholesterol levels increased, whereas fasting glucose levels decreased. One year after GH treatment resumption, fasting glucose levels, HDL cholesterol levels, and femoral neck BMD increased significantly. Longer GH interruption (>2 years, 60.4%) resulted in worse lipid profiles at re-evaluation. The duration of interruption was positively correlated with fasting glucose and non-HDL cholesterol levels after adjusting for covariates.Conclusion GH treatment interruption during the transition period resulted in worse metabolic parameters, and a longer interruption period was correlated with poorer outcomes. GH treatment should be resumed early in patients with CO-GHD during the transition period.

Cтан серцево-судинної системи та ліпідний спектр при соматотропній недостатності у молодих дорослих із маніфестацією в дитячому віці (огляд літератури та власні спостереження)

Проведено аналіз наукової літератури стосовно особливостей клінічного перебігу дефіциту гормона росту (ДГР), що маніфестував у дитячому віці, у молодих дорослих. Акцент зроблено на стані ліпідного обміну, а також серцево-судинної системи хворих із ДГР, які не отримували лікування рекомбінантним гормоном росту (рГР). Наведені власні дані, отримані при обстеженні молодих дорослих із ДГР до лікування рГР та на його тлі. Встановлено наявність суттєвих порушень з боку показників ліпідного, вуглеводного обмінів і кардіальних параметрів у хворих, які довготривало не отримували патогенетичного лікування, а також позитивні зміни на тлі призначення препаратів рГР.

Adult growth hormone deficiency: Optimizing transition of care from pediatric to adult services

ObjectiveMost patients with childhood-onset growth hormone deficiency (CO-GHD) receive treatment with exogenous growth hormone (GH) to facilitate the attainment of their full potential adult height. Recent evidence suggests that continuing GH administration during the transition period between the end of linear growth and full adult maturity is necessary for proper body composition and bone and muscle health, and may also have beneficial effects on metabolic parameters, bone mineral density, and quality of life. The timing of this transition period coincides with the transfer of care from a pediatric to an adult endocrinologist, creating the potential for a care gap as a consequence of losing the patient to follow-up. DesignAn advisory board comprising both pediatric and adult endocrinologists was assembled to address current clinical unmet needs and to collaborate on a structured transitional plan for optimal management of patients with CO-GHD. Insights/conclusionThe advisors suggest collaborative, multidisciplinary approaches to ensure continuity of care; ongoing testing and monitoring of GHD status into adulthood; and a clearly structured protocol that includes practical guidance for clinicians to establish best practices for transitioning older adolescents with persistent CO-GHD to adult care.

Body composition and bone mineral density in 107 patients with childhood onset growth hormone deficiency (CO-GHD) at the time of transition from pediatric to adulthood endocrine care

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Effect of long term rhgh treatment on bone mineral density in patients with childhood onset growth hormone deficiency

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

MON-LB56 Metabolic Profile in 107 Patients With Childhood Onset Growth Hormone Deficiency (CO-GHD) at the Time of Transition From Pediatric to Adulthood Endocrine Care

Vulnerability of the transitional period from childhood to adulthood is particularly challenging in treatment of adolescents with CO-GHD. Altered metabolic profile is well described in GHD, but relevant large monocentric studies in transition patients and young adults with CO-GHD are lacking.Patients and Methods: In a monocentric, observational, retrospective cross-sectional study conducted from 2005-2019, 107 CO-GHD patients were analyzed (17-26 years old, 80 males) at the time of transfer from pediatric to adult endocrine care. Median age at transfer was 19.6 ± 2.2 years. Subjects with congenital and idiopathic GHD (CON) were compared with age-, sex- and BMI-matched patients with hypothalamic/pituitary tumor history (TUM). Glycaemia and insulin during OGTT (peak and AUC), HbA1c, serum total cholesterol, HDL, LDL and triglycerides were analyzed in all patients.Results: Congenital and idiopathic causes of CO-GHD were more frequent than hypothalamic/pituitary tumoral causes (74.8% vs. 25.2%). All patients received GH replacement during childhood for average duration of 5.4 ± 1.4yrs. GH replacement was discontinued prior to transfer for 2.7 ± 0.9yrs. Glycaemia peak, glycaemia AUC and insulin peak in OGTT were not significantly different in TUM vs. CON (p>0.05). However, insulin AUC in OGTT was significantly higher in TUM compared to CON (134.38 ± 23.2 vs 114.62 ± 12.4; p<0.05). HbA1c was similar between the two groups (5.2 ± 0.4% TUM vs 5.0 ± 0.3% CON; p>0.05). Total cholesterol (5.2 ±1.1 vs 4.5 ± 0.8 mmol/l; p>0.05), LDL (3.1 ± 0.9 vs 2.7 ± 0.8 mmol/l; p>0.05) and triglycerides (2.1 ± 1.1 vs 1.1 ± 0,7 mmol/l; p<0.05) were increased in TUM compared to CON, while HDL was decreased in TUM group (1.0±0.1 vs 1.4±0,3 mmol/l; p<0.05).Conclusion: Patients with CO-GHD caused by hypothalamic/pituitary tumors are burdened with a worse metabolic profile at the time of childhood to adulthood transition compared to matched transition patients with congenital CO-GHD.

Growth hormone deficiency with late-onset hypothalamic hypoadrenocorticism associated with respiratory and renal dysfunction: a case report

BackgroundThe prevalence of childhood-onset growth hormone (GH) deficiency (GHD) is estimated to be approximately 1 in 5000 or more, with the cause unknown in most cases (idiopathic isolated GHD). However, additional disorders of secretion of other pituitary hormones reportedly develop over time, with a frequency of 2–94% (median, 16%). Furthermore, median times to development of other anterior pituitary hormone deficiencies have been reported to be 6.4–9.4 years. On the other hand, adult patients affected by childhood-onset GHD reportedly develop impaired ventilation function due to reduced lung volumes and respiratory pressures, probably due to reductions in respiratory muscle strength. In addition, GH is known to play a role in stimulating the glomerular filtration rate (GFR), and the estimated GFR (eGFR) is decreased in patients with GHD.Case presentationThis case involved a 65-year-old woman. Her short stature had been identified at around 3 years of age, but no effective treatments had been provided. The patient was mostly amenorrheic, and hair loss became apparent in her late 30s. She developed hyperuricemia, dyslipidemia, and hypertension at 45 years of age. In addition, the patient was diagnosed with hypothyroidism at 50 years of age. At 58 years of age, endocrinological examination showed impaired secretion of thyroid-stimulating hormone, luteinizing hormone/follicle-stimulating hormone, and growth hormone, and magnetic resonance imaging showed an empty sella turcica. However, secretion ability of adrenocorticotropic hormone was retained. At 63 years of age, respiratory function tests confirmed a markedly restricted ventilation disorder (vital capacity, 0.54 L; percentage predicted vital capacity, 26.9%). Renal function had also decreased (eGFR, 25.0 mL/min/1.73 m2). Furthermore, she was diagnosed with hypothalamic secondary hypoadrenocorticism. The patient developed CO2 narcosis at 65 years of age, and noninvasive positive pressure ventilation was started.ConclusionsThe rare case of a 65-year-old woman with childhood-onset GHD with panhypopituitarism, including late-onset secondary hypoadrenocorticism in her 60s, associated with severely impaired respiratory function and renal dysfunction, was reported. In GHD patients with risk factors for progression from isolated GHD to combined pituitary hormone deficiency, such as empty sella turcica, lifelong endocrinological monitoring may be important.

Effects of 24 Weeks of Growth Hormone Treatment on Bone Microstructure and Volumetric Bone Density in Patients with Childhood-Onset Adult GH Deficiency.

Objective Adults with childhood-onset growth hormone deficiency (CO AGHD) have prominently impaired volumetric bone density (vBMD) and bone microarchitecture. Effects of recombinant human growth hormone (rhGH) on bone microarchitecture in CO AGHD were insufficiently evaluated. The objective of this study is to assess the effects of rhGH on bone microarchitecture and vBMD in CO AGHD patients. Design In this single-center prospective study, nine CO AGHD patients received rhGH treatment for 24 weeks. High-resolution peripheral quantitative computerized tomography (HR-pQCT) of distal tibia and radius was performed at baseline and at the end of treatment. Main outcomes were vBMD and morphometric parameters from HR-pQCT. Results After 24-week treatment, IGF-1 SDS gradually increased from −3.31 ± 1.56 to −1.92 ± 1.65 (p=0.113). Serum phosphate (1.17 ± 0.17 vs. 1.35 ± 0.18 mmol/L, p=0.030), alkaline phosphatase (83.6 ± 38.6 vs. 120.5 ± 63.7, p=0.045), and β-CTX (0.67 ± 0.32 vs. 1.09 ± 0.58, p=0.022) were significantly elevated. In distal tibia, total vBMD (200.2 ± 41.7 vs 210.3 ± 40.9 mg HA/cm3, p=0.017), cortical area (89.9 ± 17.7 vs 95.5 ± 19.9 mm2, p=0.032), and cortical thickness (0.891 ± 0.197 vs 0.944 ± 0.239 mm, p=0.028) were significantly improved. Trabecular area decreased from 795.3 ± 280.9 to 789.6 ± 211.4 mm2 (p=0.029). Trabecular bone volume fraction increased from 0.193 ± 0.038 to 0.198 ± 0.036 (p=0.027). In radius, cortical perimeter (74.1 ± 10.0 vs 75.0 ± 10.9 mm, p=0.034), trabecular thickness (0.208 ± 0.013 vs 0.212 ± 0.013 mm, p=0.008), trabecular separation (0.743 ± 0.175 vs 0.796 ± 0.199 mm, p=0.019), and inhomogeneity of network (Tb.1/N.SD) (0.292 ± 0.087 vs 0.317 ± 0.096 mm, p=0.026) were significantly improved, while trabecular number (1.363 ± 0.294 vs 1.291 ± 0.325 1/mm, p=0.025) decreased significantly. Conclusions Our results provide evidence for improvement of vBMD and bone microarchitecture in AGHD patients at a relatively early stage of rhGH treatment.

Alterations in Cortical Thickness in Young Male Patients With Childhood-Onset Adult Growth Hormone Deficiency: A Morphometric MRI Study.

BackgroundThe growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis plays an important role in brain structure and maintenance of brain function. There is a close correlation between serum GH and IGF1 levels and age-related cognitive function. The effects of childhood-onset growth hormone deficiency (GHD)on brain morphology are underestimated so far.MethodsIn this cross-sectional study, T1-weighted magnetic resonance imaging was assessed in 17 adult males with childhood-onset GHD and 17 age and gender-matched healthy controls. The cortical thickness was analyzed and compared between the two groups of subjects. Effects of disease status and hormone levels on cortical thickness were also evaluated.ResultsAlthough there was no difference in whole brain volume or gray matter volume between the two groups, there was decreased cortical thickness in the parahippocampal gyrus, posterior cingulate gyrus and occipital visual syncortex in the adult growth hormone deficiency (AGHD) group, and increased cortical thickness in a partial area of the frontal lobe, parietal lobe and occipital visual syncortex in AGHD group. Cortical thickness of the posterior cingulum gyrus was prominently associated with FT3 serum levels only in control group after adjusting of IGF-1 levels.ConclusionThese results suggest that young adult male patients with childhood-onset GHD have alterations in cortical thickness in different brain lobes/regions.

Childhood-onset growth hormone deficiency: evaluation after reaching final adult height

Childhood-onset growth hormone deficiency: evaluation after reaching final adult height

Bone microarchitecture and volumetric bone density impairment in young male adults with childhood-onset growth hormone deficiency.

ContextAdult growth hormone deficiency (AGHD) is characterized by low bone density and increased risk of fracture. Bone microarchitecture is insufficiently evaluated in patients with childhood-onset AGHD (CO AGHD).ObjectiveTo assess volumetric bone density (vBMD) and bone microarchitecture in CO AGHD in early adulthood after cessation of recombinant growth hormone (rhGH) treatment.Design and subjectsCase–control study in a major academic medical center in Beijing, including 20 young male adults with CO AGHD and 30 age- and weight-matched non-athletic healthy men. High-resolution peripheral quantitative computerized tomography (HR-pQCT) of distal radius and tibia was performed.OutcomesThe main outcomes were vBMD and morphometry parameters from HR-pQCT.ResultsCompared with healthy controls, CO AGHD group had significantly decreased insulin-like growth factor 1 (IGF-1) level and IGF-1 SDS (P < 0.001). β-CTX and alkaline phosphatase levels in CO AGHD group were significantly increased (P < 0.001). CO AGHD group had significantly decreased total vBMD, cortical vBMD, trabecular vBMD, cortical area, cortical thickness as well as trabecular thickness and trabecular bone volume fraction of both tibia and radius (P < 0.001). CO AGHD patients had an 8.4 kg decrease in grip strength and a significant decrease in creatinine levels (P = 0.001). At both tibia and radius, by finite element analysis, bone stiffness and failure load of the CO AGHD patients were significantly decreased (P < 0.001). After adjusting for age, BMI and serum levels of testosterone and free thyroxin, serum IGF-1 level was a positive predictor for total vBMD, cortical vBMD, cortical area, trabecular vBMD, bone stiffness and failure load of both tibia and distal radius in all subjects.ConclusionsYoung adult male patients with childhood-onset adult growth hormone deficiency who are no longer receiving growth hormone replacement have prominently impaired volumetric bone density and bone microarchitecture and lower estimated bone strength.

Childhood-onset growth hormone deficiency and the transition to adulthood: current perspective.

Childhood-onset growth hormone deficiency (CO-GHD) is an endocrine condition associated with a broad range of health issues from childhood through to adulthood, which requires particular attention during the transition period from adolescence to young adulthood. There is uncertainty in the clinical practice of the management of CO-GHD during transition regarding the clinical assessment and management of individual patients during and after transition to obtain optimal follow-up and improved health outcomes. Despite the availability of clinical guidelines providing the framework for transition of young adults with CO-GHD, there remains substantial variation in approaching transitional care among pediatric and adult services. A well-structured and coordinated transitional plan with clear communication and direct collaboration between pediatric and adult health care to ensure optimal management of adolescents with CO-GHD during transition is needed.

Correlation Between the Responses to Growth Hormone (GH) Treatment During Childhood and Adulthood in a Monocentric Cohort of GH-Deficient Patients.

Our aim was to analyze a cohort of patients with childhood-onset growth hormone deficiency (GHD) to evaluate if there is some correlation between the response to GH treatment during childhood and adulthood, respectively. This was an observational retrospective monocentric cohort study of 47 patients treated with GH during childhood and adulthood. Changes in growth parameters during childhood were compared with the increase of IGF-I z-score and other indexes of GH response (body composition, lipid profile) after 1 year of treatment in adulthood. The only significant positive correlation was observed between final growth velocity during the last year of childhood GH treatment and increase in IGF-I z-score in GH-treated adults (r=0.592, p=< 0.01). No correlation was observed between growth-promoting effects of GH as child and metabolic changes induced by GH as adult. We also observed a negative correlation between weight at the end of childhood GH treatment and the IGF-I response during first year of treatment in adults (r=- 0.335, p <0.05). No significant positive correlation could be observed between the main parameters that evaluate response to GH treatment in children and adults. However, the final growth velocity, which may be considered as one of the main criteria of end of GH treatment in children, was identified as parameter that could predict future response to GH treatment in adulthood.

Metabolic status, body composition and bone mineral density in 85 patients with childhood onset growth hormone deficiency (COGHD) in transition period

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Identification of candidate serum biomarkers of childhood-onset growth hormone deficiency using SWATH-MS and feature selection

A typical clinical manifestation of growth hormone deficiency (GHD) is a short stature resulting from delayed growth, but GHD affects bone health, cardiovascular function and metabolic profile and therefore quality of life. Although early GH treatment during childhood has been shown to improve outcomes, no single biochemical parameter is currently available for the accurate diagnosis of GHD in children. There is hence a need for non-invasive biomarkers. In this study, the relative abundance of serum proteins from GHD children and healthy controls was measured by next-generation proteomics SWATH-MS technology. The data generated was analysed by machine-learning feature-selection algorithms in order to discover the minimum number of protein biomarkers that best discriminate between both groups. The analysis of serum proteins by a SWATH-MS approach yielded a useful method for discovering potential biomarkers of GHD in children. A total of 263 proteins were confidently detected and quantified in each sample. Pathway analysis indicated an effect on tissue/organ structure and morphogenesis. The top ten serum protein biomarker candidates were identified after applying feature-selection data analysis. The combination of three proteins – apolipoprotein A-IV, complement factor H-related protein 4 and platelet basic protein – demonstrated the best classification performance for our data. In addition, the apolipoprotein group resulted in strong over-representation, thus highlighting these proteins as an additional promising biomarker panel. SignificanceCurrently there is no single biochemical parameter available for the accurate diagnosis of growth hormone (GH) deficiency (GHD) in children. Simple GH measurements are not an option: because GH is released in a pulsatile action, its blood levels fluctuate throughout the day and remain nearly undetectable for most of that time. This makes measurements of GH in a single blood sample useless for assessing GH deficiency. Actually, the diagnosis of GHD includes a combination of direct and indirect non-accurate measurements, such as taking several body measurements, testing GH levels in multiple blood samples after provocative tests (GH peak <7.3ng/mL, using radioimmunoassay), and conducting magnetic resonance imaging (MRI), among others. Therefore, there is a need for simple, non-invasive, accurate and cost-effective biomarkers. Here we report a case-control study, where relative abundance of serum proteins were measured by next-generation proteomics SWATH-MS technology in 15 GHD children and 15healthy controls matched by age, sex, and not receiving any treatment. Data generated was analysed by machine learning feature selection algorithms. 263 proteins could be confidently detected and quantified on each sample. The top 10 serum protein biomarker candidates could be identified after applying a feature selection data analysis. The combination of three proteins, apolipoprotein A-IV, complement factor H-related protein 4 and platelet basic protein, showed the best classification performance for our data. In addition, the fact that the pathway and GO analysis we performed pointed to the apolipoproteins as over-represented highlights this protein group as an additional promising biomarker panel for the diagnosis of GHD and for treatment evaluation.

An audit of the management of childhood-onset growth hormone deficiency during young adulthood in Scotland.

BackgroundAdolescents with childhood onset growth hormone deficiency (CO-GHD) require re-evaluation of their growth hormone (GH) axis on attainment of final height to determine eligibility for adult GH therapy (rhGH).AimRetrospective multicentre review of management of young adults with CO-GHD in four paediatric centres in Scotland during transition.PatientsMedical records of 130 eligible CO-GHD adolescents (78 males), who attained final height between 2005 and 2013 were reviewed. Median (range) age at initial diagnosis of CO-GHD was 10.7 years (0.1–16.4) with a stimulated GH peak of 2.3 μg/l (0.1–6.5). Median age at initiation of rhGH was 10.8 years (0.4–17.0).ResultsOf the 130 CO-GHD adolescents, 74/130(57 %) had GH axis re-evaluation by stimulation tests /IGF-1 measurements. Of those, 61/74 (82 %) remained GHD with 51/74 (69 %) restarting adult rhGH. Predictors of persistent GHD included an organic hypothalamic-pituitary disorder and multiple pituitary hormone deficiencies (MPHD). Of the remaining 56/130 (43 %) patients who were not re-tested, 34/56 (61 %) were transferred to adult services on rhGH without biochemical retesting and 32/34 of these had MPHD. The proportion of adults who were offered rhGH without biochemical re-testing in the four centres ranged between 10 and 50 % of their total cohort.ConclusionsA substantial proportion of adults with CO-GHD remain GHD, particularly those with MPHD and most opt for treatment with rhGH. Despite clinical guidelines, there is significant variation in the management of CO-GHD in young adulthood across Scotland.