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Current Medical Research and Opinion Feb 2024Treatment of pediatric growth hormone deficiency (pGHD) with daily injection of recombinant human growth hormone (somatropin) aims to increase height velocity and...
Health-related quality of life in pre-pubertal children with pediatric growth hormone deficiency: 12-month results from a phase 3 clinical trial of once-weekly somatrogon versus once-daily somatropin.
OBJECTIVE
Treatment of pediatric growth hormone deficiency (pGHD) with daily injection of recombinant human growth hormone (somatropin) aims to increase height velocity and improve health-related quality of life (HRQoL). The Quality of Life in Short Stature Youth (QoLISSY) questionnaire was administered in a phase 3 clinical trial that evaluated efficacy and safety of once-weekly somatrogon versus once-daily somatropin in children with pGHD (ClinicalTrials.gov no NCT02968004).
METHODS
Treatment-naïve prepubertal children with pGHD received once-weekly somatrogon or once-daily somatropin for 12 months. The QoLISSY core module (physical/social/emotional subscales) was administered at baseline and 12 months after treatment initiation. QoLISSY-Parent was completed by parents/caregivers of children <7 years old and some parents/caregivers of children ≥7 years old; children ≥7 years old self-completed QoLISSY-Child.
RESULTS
Baseline characteristics were similar between treatment groups ( = 117). Among children <7 years old, QoLISSY-Parent total and subscale scores showed similarly improved HRQoL at 12 months relative to baseline in both treatment groups. Self-reported QoLISSY-Child total and subscale scores in children ≥7 years old indicated HRQoL improvements at 12 months that were numerically better with somatrogon than somatropin (similar results with QoLISSY-Parent in this age group). At both time points, children reported better HRQoL than perceived by their parents/caregivers.
CONCLUSION
Treatment for 12 months with once-weekly somatrogon or once-daily somatropin resulted in comparable improvements in HRQoL among children with pGHD. Lower HRQoL perceived by parents/caregivers possibly reflect children's tendency to emphasize adaptation. These results suggest that evaluation of HRQoL could help support treatment decisions in children with pGHD treated with growth hormone.
Topics: Adolescent; Child; Humans; Human Growth Hormone; Quality of Life; Body Height; Dwarfism, Pituitary
PubMed: 38053515
DOI: 10.1080/03007995.2023.2290623 -
IGF-1 as screening tool for acromegaly and adult-onset growth hormone deficiency in the Netherlands.Clinical Endocrinology Mar 2024Insulin-like growth factor 1 (IGF-1) measurements play a central role in the diagnosis and follow-up of acromegaly and growth hormone deficiency. However, improving...
OBJECTIVE
Insulin-like growth factor 1 (IGF-1) measurements play a central role in the diagnosis and follow-up of acromegaly and growth hormone deficiency. However, improving health care outcomes for these patients involves an intricate process of laboratory diagnostics and skilled health care professionals. The integrated effects of IGF-1 reports on diagnosis and treatment decisions are yet unknown.
DESIGN, PATIENTS AND MEASUREMENTS
Extended quality assessment, distributing the description of five (real) patient cases with accompanying blood samples. Patients suspected or during follow up for acromegaly or adult onset of growth hormone deficiency were included. Laboratory specialists and endocrinologists in the same centre were asked to interpret their centre-specific IGF-1 results by using a laboratory and medical questionnaire. This way, insight could be obtained into the combined effects of different assays, assay harmonisation, reference value sets, and individual physician interpretation in relation to guidelines, thus reviewing the entire diagnostic and management process.
RESULTS
Limited variation (CV 13.8 ± 2.8) was found in IGF-1 concentrations despite different use of the harmonization sample and factor among laboratories. This interlaboratory variation increased upon conversion to SD scores (CV 15.7 ± 40.7) as a consequence of the use of different reference value sets. Furthermore, there was a lack of adherence to international guidelines among endocrinologists.
CONCLUSIONS
Highly variable diagnostic and treatment outcomes in acromegaly and AGHD in the Netherlands can be attributed to increased variability of IGF-1 upon conversion to SD scores and low adherence to clinical guidelines.
Topics: Adult; Humans; Acromegaly; Insulin-Like Growth Factor I; Human Growth Hormone; Netherlands; Dwarfism, Pituitary; Growth Hormone
PubMed: 38044875
DOI: 10.1111/cen.15000 -
Journal of Endocrinological... Jul 2024Growth hormone deficiency (GHD) is a rare condition with a worldwide prevalence of 1 patient in 4000 to 10,000 live births, placing a significant economic burden on...
PURPOSE
Growth hormone deficiency (GHD) is a rare condition with a worldwide prevalence of 1 patient in 4000 to 10,000 live births, placing a significant economic burden on healthcare systems. The aim of this study is to generate evidence on the economic burden of children and adolescents with GHD treated with rhGH and their parents in Italy.
METHODS
A cost of illness analysis, adopting the prevalence approach, has been developed, producing evidence on the total annual cost sustained by the Italian National Health System (NHS) and by the society. The study is based on original data collected from a survey conducted among Italian children and adolescents with GHD and their parents.
RESULTS
143 children/adolescents with GHD and their parents participated to the survey, conducted from May to October 2021. Patients had a mean age of 12.2 years (SD: 3.1) and were mostly males (68.5%). The average direct healthcare cost sustained by the NHS was € 8,497.2 per patient/year; adding the out-of-pocket expenses (co-payments and expenses for private healthcare service), the total expense was € 8,568.6. The indirect costs, assessed with the human capital approach, were € 847.9 per patient/year. The total of direct and indirect cost is € 9,345.1 from the NHS perspective, and € 9,416.5 from a social perspective. The total cost incurred by the Italian NHS for children with GHD (range: 5,708-8,354) was estimated in € 48.5-71.0 million, corresponding to 0.04-0.06% of the total Italian public health expense in the year 2020.
CONCLUSIONS
The total annual cost for GHD children is close to € 10,000, and is mainly due to the cost of rhGH treatment. This cost is almost entirely sustained by the NHS, with negligible out-of-pocket expenses. The economic burden on the Italian NHS for the health care of established GHD children is fourfold higher than the prevalence of the disease in the overall Italian population.
Topics: Humans; Male; Italy; Cost of Illness; Child; Female; Adolescent; Human Growth Hormone; Health Care Costs; Health Expenditures; Dwarfism, Pituitary; Growth Disorders; Prevalence; Parents
PubMed: 38198073
DOI: 10.1007/s40618-023-02277-z -
Journal of Pediatric Endocrinology &... Sep 2023The aim of our study was the longitudinal assessment of bone health index (BHI) in short-statured children during growth hormone (GH) treatment to estimate changes in...
OBJECTIVES
The aim of our study was the longitudinal assessment of bone health index (BHI) in short-statured children during growth hormone (GH) treatment to estimate changes in their bone health.
METHODS
256 short-statured children (isolated GH deficiency (IGHD) n=121, multiple pituitary hormone deficiency (MPHD) n=49, intrauterine growth retardation (small for gestational age (SGA)) n=52, SHOX (short stature homeobox gene) deficiency n=9, Ullrich Turner syndrome (UTS) n=25) who started with GH between 2010 and 2018 were included. Annual bone ages (Greulich and Pyle, GP) and BHI were, retrospectively, analysed in consecutive radiographs of the left hand (BoneXpert software) from GH therapy start (T0) up to 10 years (T10) thereafter, with T max indicating the individual time point of the last available radiograph. The results are presented as the median (25 %/75 % interquartile ranges, IQR) and statistical analyses were performed using non-parametric tests as appropriate.
RESULTS
The BHI standard deviation scores (SDS) were reduced (-0.97, -1.8/-0.3) as bone ages were retarded (-1.6 years, -2.31/-0.97) in all patients before start of GH and were significantly lower in patients with growth hormone deficiency (GHD) (-1.04, -1.85/-0.56; n=170) compared to non-GHD patients (-0.79, -1.56/-0.01; n=86; p=0.022). BHI SDS increased to -0.17 (-1/0.58) after 1 year of GH (T1, 0.5-1.49, p<0.001) and to -0.20 (-1/-0.50, p<0.001) after 5.3 years (T max, 3.45/7.25).
CONCLUSIONS
BHI SDS are reduced in treatment-naive short-statured children regardless of their GH status, increase initially with GH treatment while plateauing thereafter, suggesting sustained improved bone health.
Topics: Humans; Child; Growth Hormone; Human Growth Hormone; Retrospective Studies; Bone Density; Hypopituitarism; Dwarfism, Pituitary; Body Height; Growth Disorders; Short Stature Homeobox Protein
PubMed: 37531076
DOI: 10.1515/jpem-2023-0084 -
Journal of Clinical Research in... May 2024The aim of this study was to evaluate executive function (EF), such as inhibition and working memory, in children with isolated growth hormone deficiency (IGHD) using...
OBJECTIVE
The aim of this study was to evaluate executive function (EF), such as inhibition and working memory, in children with isolated growth hormone deficiency (IGHD) using performance-based tests and parent-report scales.
METHODS
A total of seventy children between the ages of 7 and 12 years were included in the study. Half (n=35) had children with IGHD and half were healthy controls. To evaluate the EF performances of the participants, the Visual Aural Digit Span Test-B Form (VADS-B) and Stroop task were applied. EF was also evaluated using the Behavior Rating Inventory of Executive Function (BRIEF).
RESULTS
Children with IGHD scored lower on the VADS-B form for short-term memory (p<0.05) compared to healthy controls. In addition, the completion time for the Stroop-color/word test was significantly longer in children with IGHD (p<0.05). For children with IGHD, their parents reported higher scores on all sub-scales of the BRIEF scale, with statistically significant differences for all sub-scales with the exception of “organization of materials” (p<0.05).
CONCLUSION
In this study, children with IGHD had poorer EF skills compared to unaffected peers. EF skills may influence academic success by affecting children’s language skills, mathematical comprehension, cognitive flexibility, and hypothetical thinking. We believe that psychiatric evaluation of children with IGHD before and during treatment may positively contribute to both their academic performance and social relationships.
Topics: Humans; Child; Female; Executive Function; Male; Cross-Sectional Studies; Human Growth Hormone; Neuropsychological Tests; Dwarfism, Pituitary; Memory, Short-Term; Case-Control Studies
PubMed: 38275147
DOI: 10.4274/jcrpe.galenos.2024.2023-10-6 -
Growth Hormone & IGF Research :... Feb 2024Children with growth hormone deficiency (GHD) face multiple challenges that can negatively impact the transition from pediatric to adult endocrinology care. For children...
OBJECTIVE
Children with growth hormone deficiency (GHD) face multiple challenges that can negatively impact the transition from pediatric to adult endocrinology care. For children with GHD resulting from brain cancer or its treatment, the involvement of oncology care providers and possible disease-related comorbidities add further complexity to this transition.
DESIGN
An advisory board of pediatric and adult endocrinologists was convened to help better understand the unique challenges faced by childhood cancer survivors with GHD, and discuss recommendations to optimize continuity of care as these patients proceed to adulthood. Topics included the benefits and risks of growth hormone (GH) therapy in cancer survivors, the importance of initiating GH replacement therapy early in the patient's journey and continuing into adulthood, and the obstacles that can limit an effective transition to adult care for these patients.
RESULTS/CONCLUSIONS
Some identified obstacles included the need to prioritize cancer treatment over treatment for GHD, a lack of patient and oncologist knowledge about the full range of benefits provided by long-term GH administration, concerns about tumor recurrence risk in cancer survivors receiving GH treatment, and suboptimal communication and coordination (e.g., referrals) between care providers, all of which could potentially result in treatment gaps or even complete loss of follow-up during the care transition. Advisors provided recommendations for increasing education for patients and care providers and improving coordination between treatment team members, both of which are intended to help improve continuity of care to maximize the health benefits of GH administration during the critical period when childhood cancer survivors transition into adulthood.
Topics: Adult; Child; Humans; Brain; Brain Neoplasms; Cancer Survivors; Dwarfism, Pituitary; Growth Hormone; Human Growth Hormone; Hypopituitarism; Patient Transfer
PubMed: 38368660
DOI: 10.1016/j.ghir.2024.101573 -
Gene May 2024Isolated growth hormone deficiency (IGHD) is a rare genetically heterogeneous disorder caused primarily by mutations in GH1 and GH releasing hormone receptor (GHRHR)....
BACKGROUND
Isolated growth hormone deficiency (IGHD) is a rare genetically heterogeneous disorder caused primarily by mutations in GH1 and GH releasing hormone receptor (GHRHR). The aim of this study was to identify the molecular etiology of a Chinese boy with IGHD.
METHODS
Whole-exome sequencing, sanger sequencing and bioinformatic analysis were performed to screen for candidate mutations. The impacts of candidate mutation on gene expression, intracellular localization and protein function were further evaluated by in vitro assays.
RESULTS
A novel heterozygous frameshift mutation in the GHRH gene (c.91dupC, p.R31Pfs*98) was identified in a Chinese boy clinically diagnosed as having IGHD. The mutation was absent in multiple public databases, and considered as deleterious using in silico prediction, conservative analysis and three-dimensional homology modeling. Furthermore, mRNA and protein expression levels of mutant GHRH were significantly increased than wild-type GHRH (p < 0.05). Moreover, mutant GHRH showed an aberrant accumulation within the cytoplasm, and obviously reduced ability to stimulate GH secretion and cAMP accumulation in human GHRHR-expressing pituitary GH3 cells compared to wild-type GHRH (p < 0.05).
CONCLUSION
Our study discovered the first loss-of function mutation of GHRH in a Chinese boy with IGHD and provided new insights on IGHD pathogenesis caused by GHRH haploinsufficiency.
Topics: Humans; Male; China; Dwarfism, Pituitary; Frameshift Mutation; Growth Hormone; Human Growth Hormone; Mutation; Receptors, Neuropeptide; Receptors, Pituitary Hormone-Regulating Hormone; Growth Hormone-Releasing Hormone; East Asian People
PubMed: 38354915
DOI: 10.1016/j.gene.2024.148283 -
Journal of Clinical Research in... Nov 2023Neurofibromatosis-Noonan syndrome (NFNS), a rare autosomal-dominant hereditary disease, is characterized by clinical manifestations of both neurofibromatosis type 1 ()...
Neurofibromatosis-Noonan syndrome (NFNS), a rare autosomal-dominant hereditary disease, is characterized by clinical manifestations of both neurofibromatosis type 1 () and NS. We present a case of NFNS with short stature caused by a heterozygous nonsense variant of the gene. A 12-year-old boy was admitted because of short stature, numerous café-au-lait spots, low-set and posteriorly rotated ears, sparse eyebrows, broad forehead, and inverted triangular face. Cranial and spinal magnetic resonance imaging showed abnormal nodular lesions. Molecular analysis revealed a novel heterozygous c.6189 C > G (p.(Tyr2063*)) variant in the gene. The patient was not prescribed recombinant growth hormone (GH) therapy because exogenous GH may have enlarged the abnormal skeletal lesions. During follow-up, Lisch nodules were found in the ophthalmologic examination. NFNS, a variant form of , is caused by heterozygous mutations in the gene. The mechanism of GH deficiency caused by is still unclear. Whether NFNS patients should be treated with exogenous GH remains controversial.
Topics: Male; Humans; Child; Neurofibromatosis 1; Neurofibromatoses; Dwarfism, Pituitary; Growth Hormone
PubMed: 35633639
DOI: 10.4274/jcrpe.galenos.2022.2021-12-24 -
The Journal of Clinical Endocrinology... Jul 2023
Randomized Controlled Trial
Response to Letter to the Editor From Chatelain et al: "Weekly Somapacitan Is Effective and Well Tolerated in Children With GH Deficiency: The Randomized Phase 3 REAL4 Trial".
Topics: Humans; Child; Human Growth Hormone; Dwarfism, Pituitary
PubMed: 36869702
DOI: 10.1210/clinem/dgad095 -
The Journal of Clinical Endocrinology... Jul 2023
Randomized Controlled Trial
Topics: Humans; Child; Human Growth Hormone; Dwarfism, Pituitary
PubMed: 36869710
DOI: 10.1210/clinem/dgad096