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Zhongguo Dang Dai Er Ke Za Zhi =... Mar 2024With an increasing understanding of growth hormone deficiency, there has been a growing emphasis on the management of transition growth hormone deficiency (TGHD) in...
With an increasing understanding of growth hormone deficiency, there has been a growing emphasis on the management of transition growth hormone deficiency (TGHD) in clinical practice. The inadequate diagnosis and treatment of TGHD have been a major clinical concern, leading to the development of relevant guidelines and consensus internationally. This article summarizes the evaluation, diagnosis, treatment, and clinical challenges of TGHD based on these guidelines, consensus, and existing clinical studies, aiming to optimize and further improve the clinical diagnosis, treatment, and management of TGHD.
Topics: Humans; Human Growth Hormone; Dwarfism, Pituitary; Body Height; Consensus
PubMed: 38557372
DOI: 10.7499/j.issn.1008-8830.2309173 -
Journal of Endocrinological... Dec 2023The aim of this study was to produce evidence on quality of life (QoL) among Italian growth hormone deficiency (GHD) children and adolescents treated with growth hormone...
PURPOSE
The aim of this study was to produce evidence on quality of life (QoL) among Italian growth hormone deficiency (GHD) children and adolescents treated with growth hormone (GH) and their parents.
METHODS
A survey was conducted among Italian children and adolescents aged 4-18 with a confirmed diagnosis of GHD and treated with GH therapy and their parents. The European Quality of Life 5 Dimensions 3 Level Version (EQ-5D-3L) and the Quality of Life in Short Stature Youth (QoLISSY) questionnaires were administered between May and October 2021 through the Computer-Assisted Personal Interview (CAPI) method. Results were compared with national and international reference values.
RESULTS
The survey included 142 GHD children/adolescents and their parents. The mean EQ-5D-3L score was 0.95 [standard deviation (SD) 0.09], while the mean visual analogue scale (VAS) score was 86.2 (SD 14.2); the scores are similar to those of a reference Italian population aged 18-24 of healthy subjects. As for the QoLISSY child-version, compared to the international reference values for GHD/ idiopathic short stature (ISS) patients, we found a significantly higher score for the physical domain, and lower scores for coping and treatment; compared to the specific reference values for GHD patients, our mean scores were significantly lower for all domains except the physical one. As for the parents, we found a significantly higher score for the physical domain, and a lower score for treatment; compared to reference values GHD-specific, we found lower score in the social, emotional, treatment, parental effects, and total score domains.
CONCLUSIONS
Our results suggest that the generic health-related quality of life (HRQoL) in treated GHD patients is high, comparable to that of healthy people. The QoL elicited by a disease specific questionnaire is also good, and comparable with that of international reference values of GHD/ISS patients.
Topics: Humans; Adolescent; Quality of Life; Caregivers; Dwarfism, Pituitary; Italy; Human Growth Hormone; Growth Hormone; Surveys and Questionnaires
PubMed: 37209402
DOI: 10.1007/s40618-023-02106-3 -
European Journal of Endocrinology Jul 2023Maternal inactivating GNAS mutations lead to pseudohypoparathyroidism 1A (PHP1A), newly classified as inactivating parathyroid hormone (PTH)/PTHrP-signaling disorder... (Observational Study)
Observational Study
BACKGROUND
Maternal inactivating GNAS mutations lead to pseudohypoparathyroidism 1A (PHP1A), newly classified as inactivating parathyroid hormone (PTH)/PTHrP-signaling disorder type 2 of maternal inheritance (iPPSD2). Patients present with resistance to PTH and other hormones, subcutaneous ossifications, brachydactyly, short stature, and early-onset obesity. They can be born small for gestational age (SGA) and may present with growth hormone (GH) deficiency. The use of recombinant human GH (rhGH) therapy has been sporadically reported, yet we lack data on the long-term efficacy and safety of rhGH, as well as on adult height.
OBJECTIVE
Our multicenter, retrospective, observational study describes growth in patients treated with rhGH in comparison with untreated iPPSD2/PHP1A controls.
METHODS
We included 190 patients, of whom 26 received rhGH. Height, weight, body mass index at various time points, and adult height were documented. We analyzed the effect of rhGH on adult height by using linear mixed models.
RESULTS
Adult height was available for 11/26 rhGH-treated individuals and for 69/164 controls. Patients treated with rhGH showed a gain in height of 0.7 standard deviation scores (SDS) after 1 year (CI +0.5 to +0.8, P < .001) and of 1.5 SDS after 3 years (CI +1.0 to +2.0, P < .001). Additionally, there was a clear beneficial impact of rhGH on adult height when compared with untreated controls, with a difference of 1.9 SDS (CI +1.1 to +2.7, P < .001). Body mass index SDS did not vary significantly upon rhGH therapy.
CONCLUSION
Recombinant human growth hormone treatment of iPPSD2/PHP1A patients with short stature improves growth and adult height. More studies are needed to confirm long-term efficacy and safety.
Topics: Humans; Adult; Growth Hormone; Retrospective Studies; Human Growth Hormone; Pseudohypoparathyroidism; Dwarfism, Pituitary; Hypopituitarism; Mutation; Body Height; Recombinant Proteins; Growth Disorders; Chromogranins; GTP-Binding Protein alpha Subunits, Gs
PubMed: 37440712
DOI: 10.1093/ejendo/lvad085 -
Journal of Clinical Research in... Nov 2023Recent reports have indicated the role of the prokineticin receptor 2 gene () in the etiology of pituitary hormone deficiencies, suggesting a potential role for the...
OBJECTIVE
Recent reports have indicated the role of the prokineticin receptor 2 gene () in the etiology of pituitary hormone deficiencies, suggesting a potential role for the PROK2 pathway in pituitary development, in addition to its role in gonadotropin releasing hormone-expressing neuron development. Here, we present the clinical and molecular findings of four patients with mutations.
METHODS
Next-generation targeted sequencing was used to screen 25 genes in 59 unrelated patients with multiple pituitary hormone deficiency (MPHD), isolated growth hormone (GH) deficiency, or idiopathic short stature.
RESULTS
Two different, very rare missense alterations classified as pathogenic (NM_144773.4:c.518T>G; NP_658986.1:p. (Leu173Arg)) and likely pathogenic (NM_144773.4:c.254G>A; NP_658986.1:p.(Arg85His)) were identified in four patients in heterozygous form. Patient 1 and Patient 2 presented with short stature and were diagnosed as GH deficiency. Patient 3 and Patient 4 presented with central hypothyroidism and cryptorchidism and were diagnosed as MPHD. No other pathogenic alterations were detected in the remaining 24 genes related to short stature, MPHD, and hypogonadotropic hypogonadism. Segregation analysis revealed asymptomatic or mildly affected carriers in the families.
CONCLUSION
dominance should be kept in mind as a very rare cause of GH deficiency and MPHD. Expressional variation or lack of penetrance may imply oligogenic inheritance or other environmental modifiers in individuals who are heterozygous carriers.
Topics: Growth Hormone; Pituitary Hormones; Dwarfism, Pituitary; Humans; Pedigree; Male; Female; Infant; Child; Receptors, G-Protein-Coupled; Consanguinity
PubMed: 37338295
DOI: 10.4274/jcrpe.galenos.2023.2023-4-4 -
Frontiers in Endocrinology 2023The standard of care for pediatric growth hormone deficiency (pGHD) is once-daily recombinant human growth hormone (rhGH). Somatrogon, a long-acting rhGH, requires less...
Physician experience with once-weekly somatrogon versus once-daily rhGH regimen in pediatric patients with growth hormone deficiency: a cross-sectional survey of physicians from the global phase 3 study.
INTRODUCTION
The standard of care for pediatric growth hormone deficiency (pGHD) is once-daily recombinant human growth hormone (rhGH). Somatrogon, a long-acting rhGH, requires less frequent, once-weekly, dosing. We describe physicians' preference for, experiences, and satisfaction with once-weekly somatrogon vs once-daily rhGH.
METHODS
English-speaking investigators from somatrogon's global phase III study (NCT02968004) with prior experience using once-daily rhGH were included. Participants answered an online survey containing 14 closed- and open-ended items.
RESULTS
Twenty-four pediatric endocrinologists (41.7% men; 79.2% practiced at public/private hospitals) from 12 countries with 25.8 ± 12.0 years' experience treating pGHD completed the survey. In terms of the time and effort required to explain device instructions, injection regimen, procedure for missed injection, and address patients'/caregivers' concerns, a similar proportion of physicians chose once-weekly somatrogon and once-daily rhGH; 62.5% physicians indicated that once-daily rhGH required greater effort to monitor adherence. Overall, 75% preferred once-weekly somatrogon over once-daily rhGH, 79.2% considered once-weekly somatrogon to be more convenient and less burdensome, and 83.3% were likely to prescribe somatrogon in the future. Overall, 50% felt that once-weekly somatrogon was more beneficial to patients, while 50% chose "No difference". Most physicians (62.5%) felt both regimens were equally likely to support positive long-term growth outcomes and reduce healthcare utilization. More physicians were "very satisfied" with once-weekly somatrogon (62.5%) than with once-daily rhGH (16.7%). Reduced injection frequency, patient and caregiver burden, increased convenience, and improved adherence were reasons for these choices.
CONCLUSION
Physicians had a positive experience with, and perception of, treating pGHD with once-weekly somatrogon.
Topics: Male; Humans; Child; Female; Human Growth Hormone; Cross-Sectional Studies; Dwarfism, Pituitary; Physicians; Recombinant Proteins
PubMed: 37955005
DOI: 10.3389/fendo.2023.1254424 -
Biomedicines Oct 2023Cyclin-dependent kinases (CDKs) play a crucial role in regulation of the mammalian cell cycle. CDK4 and CDK6 control the G1/S restriction checkpoint through their...
Cyclin-dependent kinases (CDKs) play a crucial role in regulation of the mammalian cell cycle. CDK4 and CDK6 control the G1/S restriction checkpoint through their ability to associate with cyclin D proteins in response to growth factor signals. CDK4 deficiency in mice gives rise to a range of endocrine-specific phenotypes including diabetes, infertility, dwarfism, and atrophy of the anterior pituitary. Although CDK6 deficiency can cause thymic atrophy due to a block in the double-negative (DN) to double-positive (DP) stage of T cell development, there are no overt defects in immune cell development reported for CDK4-deficient mice. Here, we examined the impact of a novel -ethyl--nitrosourea-induced point mutation in the gene encoding CDK4 on immune cell development. Mutant mice () showed normal development and differentiation of major immune cell subsets in the thymus and spleen. Moreover, T cells from mice exhibited normal cytokine production in response to in vitro stimulation. However, analysis of the mixed bone marrow chimeras revealed that -derived T cell subsets and NK cells are at a competitive disadvantage compared to -derived cells in the thymus and periphery of recipients. These results suggest a possible role for the CDK4 mutation in the development of some immune cells, which only becomes apparent when the mutant cells are in direct competition with wild-type immune cells in the mixed bone marrow chimera.
PubMed: 37893220
DOI: 10.3390/biomedicines11102847 -
The Journal of Clinical Endocrinology... Sep 2023Despite having normal growth hormone (GH) secretion, individuals with Turner syndrome (TS) have short stature. Treatment with recombinant human GH is recommended for TS...
CONTEXT
Despite having normal growth hormone (GH) secretion, individuals with Turner syndrome (TS) have short stature. Treatment with recombinant human GH is recommended for TS girls with short stature.
OBJECTIVE
This work aimed to evaluate the effectiveness and safety of Norditropin (somatropin, Novo Nordisk) with up to 10 years of follow-up in children with TS.
METHODS
Secondary analysis was conducted of Norditropin data from 2 non-interventional studies: NordiNet® IOS (NCT00960128) and the ANSWER program (NCT01009905).
RESULTS
A total of 2377 girls with TS were included in the safety analysis set (SAS), with 1513 in the treatment-naive effectiveness analysis set (EAS). At the start of treatment, 1273 (84%) participants were prepubertal (EAS); mean (SD) age was 8.8 (3.9) years. Mean (SD) dose received at the start of GH treatment was 0.045 (0.011) mg/kg/day (EAS). Mean (SD) baseline insulin-like growth factor-1 (IGF-I) SD score (SDS) was -0.86 (1.52), and mean (SD) duration of GH treatment (SAS) was 3.8 (2.8) years.Height SDS (HSDS) increased throughout follow-up, with near-adult HSDS reached by 264 (17%) participants (mean [SD] -1.99 [0.94]; change from baseline +0.90 [0.85]). During the study, 695 (46%) participants (EAS) entered puberty at a mean (SD) age of 12.7 (1.9) years (whether puberty was spontaneous or induced was unknown). Within the SAS, mean IGF-I SDS (SD) at year 10 was 0.91 (1.69); change from baseline +1.48 (1.70). Serious adverse reactions were reported in 10 participants (epiphysiolysis [n = 3]).
CONCLUSION
GH-treated participants with TS responded well, without new safety concerns. Our real-world data are in agreement with previous studies.
Topics: Adult; Child; Female; Humans; Body Height; Dwarfism, Pituitary; Growth Disorders; Human Growth Hormone; Insulin-Like Growth Factor I; Turner Syndrome; Child, Preschool
PubMed: 36947589
DOI: 10.1210/clinem/dgad159 -
Growth Hormone & IGF Research :... Aug 2023Late night spontaneous growth hormone (GH) pulses may influence the pituitary GH response to provocation tests. We evaluated GH response during...
OBJECTIVE
Late night spontaneous growth hormone (GH) pulses may influence the pituitary GH response to provocation tests. We evaluated GH response during arginine-insulin-tolerance test (AITT) after a GH peak during a short spontaneous nocturnal profile (SSNP) in children with short stature or low growth velocity.
DESIGN
Using SSNP and subsequent AITT, we examined 257 children 4-18 years old (138 (53.7%) males) recruited from three hospitals. Medical records were reviewed retrospectively. Refractory children were defined as a GH peak ≥7 μg/L during SSNP but no GH peak ≥7 μg/L during AITT.
RESULTS
In total, 201/257 children had a GH peak ≥7 μg/L at SSNP and/or AITT. Of these, 21.9% were refractory. The proportion of males (p = 0.033) and body mass index (BMI) standard deviation score (SDS) (p = 0.037) were higher in the refractory group than in children with a GH peak ≥7 μg/L during AITT. The median period between last GH peak ≥7 μg/L during SSNP and GH at AITT was 210 (30-390) minutes. The GH at AITT occurred 30 min earlier for children without a peak ≥7 μg/L during the SSNP (p = 0.004). The number of refractoriness differed somewhat between the hospitals (p = 0.025).
CONCLUSIONS
Many children with short stature were refractory at testing; among them we found few clinical characteristics. Refractoriness might be influenced by some differences in procedure, but needs to be considered when evaluating GH response in children.
Topics: Male; Humans; Child; Child, Preschool; Adolescent; Female; Retrospective Studies; Prevalence; Insulin-Like Growth Factor I; Growth Hormone; Human Growth Hormone; Insulin; Dwarfism; Arginine; Growth Disorders
PubMed: 37562165
DOI: 10.1016/j.ghir.2023.101549 -
Hormone Research in Paediatrics 2024Recombinant human growth hormone (rhGH) therapy effectively increases height in various disorders of childhood growth. However, whether rhGH affects pubertal timing is... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Recombinant human growth hormone (rhGH) therapy effectively increases height in various disorders of childhood growth. However, whether rhGH affects pubertal timing is unclear. We aimed to review systematically published evidence on the effect of rhGH on pubertal timing.
METHODS
Embase, MEDLINE, and Cochrane Library databases were searched until December 2021 on randomized and non-randomized controlled studies of rhGH in children.
RESULTS
Twenty-five articles (n = 1,433 children) were identified, describing 12 randomized and 13 non-randomized controlled studies in children with idiopathic short stature (ISS; 15 studies), small for gestational age (n = 6 studies), chronic renal failure (n = 3), Noonan syndrome (n = 1), and growth hormone deficiency (n = 1). Significant differences in the effects of rhGH on pubertal timing were found by clinical indication. Only among children with ISS, rhGH promoted earlier age at pubertal timing (mean difference = -0.46 years; 95% CI, -0.90 to -0.03; 9 studies; n total = 397) or higher relative risk for pubertal onset during study follow-up (1.26; 95% CI, 1.03 to 1.54; 6 studies; n total = 284).
CONCLUSIONS
Treatment with rhGH appears to promote earlier pubertal timing among children with ISS. Evidence was lacking in children with growth hormone deficiency due to the absence of studies with untreated controls.
Topics: Child; Humans; Human Growth Hormone; Growth Hormone; Body Height; Growth Disorders; Dwarfism, Pituitary; Recombinant Proteins
PubMed: 37075730
DOI: 10.1159/000530578 -
Indian Pediatrics Feb 2024To analyse the clinical and radiological characteristics of pituitary stalk interruption syndrome (PSIS).
OBJECTIVE
To analyse the clinical and radiological characteristics of pituitary stalk interruption syndrome (PSIS).
METHODS
A retrospective analysis of confirmed cases of PSIS was performed. The development of new pituitary hormonal deficiencies and response to recombinant human growth hormone (rhGH) therapy were assessed during follow-up.
RESULTS
This study included 14 children (10 boys) of PSIS with median (range) age of 12.15 years (2 months - 18 years). Short stature was the most common presentation (n = 13), and micropenis (n = 4), cleft lip (n = 1) and single central incisor (n = 1) were other midline defects. Growth hormone (GH) deficiency was present in 14 children and 7 of them also had multiple pituitary hormone deficiencies at baseline. Central hypothyroidism (n = 5), secondary adrenal deficiency (n = 4) and gonadotropin deficiencies (n = 2) were also seen. All children received rhGH. The mean height gain on follow-up was 12.78 cm in first year (n = 14), 6.5 cm in second year (n = 8) and 4.07 cm in third year (n = 7) of rhGH therapy. Four children developed additional pituitary hormone deficiency on follow-up.
CONCLUSION
Short stature with isolated GH deficiency was the most common presentation of PSIS that showed good response to rhGH therapy.
Topics: Child; Humans; Male; Dwarfism, Pituitary; Growth Hormone; Human Growth Hormone; Hypopituitarism; Pituitary Gland; Retrospective Studies; Female; Infant; Child, Preschool; Adolescent
PubMed: 38321728
DOI: No ID Found