Hormone Research in Paediatrics最新文献

{"title":"Moving from Insulin Substitution to the Treatment of the Underlying Autoimmune Disease in Type 1 Diabetes.","authors":"Jantje Weiskorn, Thomas Danne","doi":"10.1159/000539120","DOIUrl":"10.1159/000539120","url":null,"abstract":"<p><p>Currently, a paradigm change occurs in type 1 diabetes from insulin substitution to the treatment of the underlying autoimmune disease. Teplizumab, a humanized monoclonal anti-CD3 antibody, is the first FDA-approved disease-modifying treatment of preclinical stage 2 diabetes. Research of drugs like golimumab, a monoclonal antibody specific for TNF alpha, baricitinib, a tyrosine kinase inhibitor, or frexalimab, a monoclonal antibody against the CD40 ligand, is still ongoing. Repurposing drugs that have been used in other indications like the calcium channel blocker verapamil, antithymocyte globulin (ATG), an antibody preparation used in solid organ transplantation, glucagon-like peptide-1 agonists utilized in type 2 diabetes and obesity, or the antiviral drugs pleconaril and ribavirin have shown positive effects in preserving beta-cell function. While new therapies to halt autoimmunity and restore beta cells in stages one to three are being developed, replacing beta-cell function via inducible pluripotent stem cells have shown glucose control and insulin independence in long-standing type 1 diabetes, albeit with concomitant immunosuppression. Multicenter multinational initiatives developing a clinical trial network like INNODIA or a research platform with the goal of stopping type 1 diabetes in its early stages like EDENT1FI will be instrumental to study these new strategies.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140863451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unstimulated Luteinizing Hormone for Assessment of Suppression during Treatment of Central Precocious Puberty with 6-Month Subcutaneous Leuprolide Acetate: Correlations with Clinical Response.","authors":"Karen O Klein, Bradley S Miller, Nelly Mauras","doi":"10.1159/000539110","DOIUrl":"10.1159/000539110","url":null,"abstract":"<p><strong>Introduction: </strong>Phase 3 trial of 6-month subcutaneous leuprolide acetate (SC-LA) in children with central precocious puberty (CPP) demonstrated efficacy and safety. The aims of this secondary analysis were to evaluate unstimulated luteinizing hormone (LH) as efficacy measure, assess clinical suppression metrics, and present biochemical and clinical data for subgroups not achieving hormone suppression.</p><p><strong>Methods: </strong>Sixty-two children with treatment-naïve CPP received 2 doses of 45 mg SC-LA at 24-week intervals. Unstimulated and GnRH-stimulated LH, E2, and T concentrations were measured. Clinical measures included bone age (BA) and predicted adult height (PAH).</p><p><strong>Results: </strong>Eighty-four percentage and 86% of children achieved unstimulated LH &lt;1 IU/L at weeks 24 and 48, respectively. Of 8 children not achieving unstimulated LH &lt;1 IU/L at week 24 that completed the study, all showed a lack of pubertal stage progression and stable/decreased BA to chronological age ratio (BA/CA). Received operating characteristic (ROC) analyses suggested unstimulated LH is a good diagnostic predictor of GnRH-stimulated LH &lt;4 IU/L at weeks 24 and 48 (AUC = 0.88). Across all children, mean BA/CA improved from 1.4 (screening) to 1.3 (week 48) and mean PAH increased by 3 cm. Of 7 girls not achieving stimulated LH &lt;4 IU/L at week 24, all achieved E2 &lt;10 pg/mL, showed a lack of pubertal stage progression, and had stable or decreased BA/CA by week 48. Additionally, 6/7 had increased PAH by week 48 and 4 had unstimulated LH &lt;1 IU/L.</p><p><strong>Conclusion: </strong>Unstimulated LH has value as an efficacy measure and concentrations &lt;1 IU/L may be an adequate surrogate of treatment response in children with CPP. All children who completed the study had evidence of pubertal suppression.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140854810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential for Optimization of Growth Hormone Treatment in Children with Growth Hormone Deficiency (GHD), Small for Gestational Age (SGA), and Turner Syndrome (TS) in Germany - Data from the PATRO® Children Study.","authors":"Carl-Joachim Partsch, Christof Land, Roland Pfäffle, Karl Otfried Schwab, Heide Sommer","doi":"10.1159/000539068","DOIUrl":"https://doi.org/10.1159/000539068","url":null,"abstract":"INTRODUCTION\u0000Growth hormone (GH) treatment in children with growth hormone deficiency (GHD), short children born small for gestational age (SGA), and Turner syndrome (TS) is well established. However, a variety of parameters are still under discussion to achieve optimal growth results and efficiency of GH use in real world treatment.\u0000\u0000\u0000METHODS\u0000German GH-treatment naïve patients of the PATRO Children database were grouped according to their start of treatment into groups of 3 years from 2007 to 2018. Time trends in age, gender, GH dose, height standard deviation score (SDS), first year growth response, and Index of Responsiveness (IoR) were investigated in children with GHD, short children born SGA, and TS starting GH treatment in the German patient population of the PATRO Children database from 2007 - 2018 to determine specific parameters for GH treatment optimization.\u0000\u0000\u0000RESULTS\u0000All patient groups started GH treatment at a relatively high chronological age (2007 - 2009: GHD 8.33 ± 3.19, SGA 7.32 ± 2.52, TS 8.65 ± 4.39) with a slight but not significant trend towards younger therapy start up to 2016 to 2018 (GHD 8.04 ± 3.36, SGA 6.67 ± 2.65, TS 7.85 ± 3.38). In the GHD and SGA groups female patients were underrepresented compared to male patients (GHD 32.3 %, SGA 43.6 %) with no significant change over the 4 time periods. Patients with GHD started GH treatment at a low dose (0.026 mg/kg/day). In SGA and TS patients GH therapy was started below the registered dose recommendation (0.030 mg/kg/day and 0.0337 mg/kg/day, respectively). In the first year of treatment the mean GH dose was increased moderately (GHD: 0.0307, SGA: 0.0357, TS: 0.0408 mg/kg/day). There was no significant change of GH dosing over time from 2007 - 2018. The IoR was comparable between time-groups for all three diagnoses.\u0000\u0000\u0000DISCUSSION\u0000This study shows potential for improvement of GH treatment results in GHD, SGA, and TS patients in terms of early dose adjustment and younger age at start of treatment. This is in accordance with important parameters used in prediction models.","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140654827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pediatric Endocrine Society Statement on Considerations for Use of Teplizumab (Tzield™) in Clinical Practice.","authors":"Shilpa Mehta, Anna Ryabets-Lienhard, Neha Patel, Emily Breidbart, Ingrid Libman, Michael J. Haller, Kimber M Simmons, Emily K Sims, Linda A. DiMeglio, S. Gitelman, Kurt J. Griffin, Ksenia N Tonyushkina","doi":"10.1159/000538775","DOIUrl":"https://doi.org/10.1159/000538775","url":null,"abstract":"Teplizumab (TzieldTM, Provention Bio), a monoclonal antibody directed at t-cell marker CD3, is the first medication approved by the FDA to delay progression from Stage 2 to Stage 3 type 1 diabetes (T1D). To date, the overwhelming majority of pediatric endocrinologists do not have experience using immunotherapeutics and seek guidance the use of teplizumab in clinical practice. To address this need, the Pediatric Endocrine Society (PES) Diabetes Special Interest Group (Diabetes SIG) and Drug and Therapeutics Committee assembled a task force to review clinical trial data and solicit expert recommendations on the approach to teplizumab infusions. We present considerations on all aspects of teplizumab administration, utilizing evidence where possible and providing a spectrum of expert opinions on unknown aspects. We discuss patient selection and prescreening, highlighting the safety and considerations for monitoring and treatment of side effects. We propose a schedule of events, a protocol for administration and discuss practice management aspects. We advocate for the need for further long-term systematic surveillance studies to continue evaluating the efficacy and safety of teplizumab.","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140658647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-Acting Gonadotropin-Releasing Hormone Analogues for Central Precocious Puberty, Including 45-mg 6-month Subcutaneous Leuprolide Acetate: Use for Treatment and Treatment Monitoring.","authors":"Lawrence A. Silverman, Mitchell E. Geffner, Matthew Benson","doi":"10.1159/000539020","DOIUrl":"https://doi.org/10.1159/000539020","url":null,"abstract":"INTRODUCTION\u0000Studies of gonadotropin-releasing hormone analogues [intramuscular (IM) leuprolide acetate (LA) and triptorelin] for treatment monitoring of central precocious puberty (CPP) demonstrate this approach is effective for confirming pubertal hormone suppression. Herein, we provide new data using subcutaneous LA (SC LA) suggesting similar efficacy for treatment monitoring.\u0000\u0000\u0000METHODS\u0000PubMed, Embase, and CINAHL were searched for studies of GnRHa use to monitor treatment of CPP. The titles and the abstracts were reviewed; five studies were selected. Additionally, new unpublished data for SC LA from the original phase 3 trial (primary data published by Klein et al.) were evaluated. Serum LH and leuprolide levels at screening, 1, 4, and 6 hours after the first dose SC LA were analyzed and plotted.\u0000\u0000\u0000RESULTS\u0000Data from 162 children (155 girls) were evaluated. SC and IM LA produced overlapping median LH concentration curves and peak LH concentrations after the first dose. For IM LA, subsequent doses yielded suppressed peak LH levels (2.7 IU/L [mean]). For SC LA, subsequent doses also resulted in significant suppressed peak LH levels (0.2±0.02 IU/L) and achieved sex-steroid hormone suppression in >98%.\u0000\u0000\u0000CONCLUSIONS\u0000Compared to IM LA and triptorelin, long-acting SC LA shows similar burst kinetics and rapid LH rise after the first dose, followed by similar suppression of LH and sex steroids after subsequent doses. Since IM LA and triptorelin have demonstrated usefulness that is comparable to that of traditional GnRH stimulation testing for monitoring CPP, we presume that SC LA may be similarly employed.","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140666077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Congenital Hypothyroidism with thyroid in situ: a case report with NKX2-1 and DUOX2 hypomorphic variants.","authors":"Erika Uehara, Naoaki Hori, Kanako Tanase-Nakao, K. Akiba, Hidefumi Sueoka, Keiko Matsubara, Satoshi Narumi","doi":"10.1159/000538895","DOIUrl":"https://doi.org/10.1159/000538895","url":null,"abstract":"INTRODUCTION\u0000NK2 homeobox 1 (NKX2-1) encodes a transcription factor NKX2-1 that is expressed in the thyroid gland, lung and brain. Dual oxidase 2 (DUOX2) encodes an enzyme which generates hydrogen peroxide and is involved in the thyroid hormone synthesis. Cases of congenital hypothyroidism (CH) with dyshormonogenesis showing two or more genetic variants are increasingly reported. We describe the first case of transient dyshormonogenesis who had experimentally-verified a loss of function NKX2-1 variant and DUOX2 variants.\u0000\u0000\u0000CASE PRESENTATION\u0000The proband was a 15-year-old female patient with CH who was diagnosed in the frame of newborn screening for CH. She had a mildly elevated serum TSH level (14.56 mU/L), a low free thyroxine level (0.87 ng/dL), and a high thyroglobulin (Tg) level (>800 ng/mL). Ultrasonography revealed goiter. She was followed clinically without levothyroxine treatment, and showed normal growth and development. She had slightly high Tg levels throughout the clinical course. Next-generation sequencing-based genetic analysis revealed that the patient was heterozygous for an NKX2-1 variant (p.Ile228Ser), a nonsense DUOX2 variant (p.[Lys530*;His678Arg]), and a functional DUOX2 polymorphism (p.His678Arg). NKX2-1 p.Ile228Ser showed about 50% reduced residual activity on the Tg-promoter.\u0000\u0000\u0000CONCLUSION\u0000A partial loss-of-function NKX2-1 variant with a monoallelic nonsense DUOX2 variant and a DUOX2 functional polymorphism can cause transient CH with high serum Tg levels.","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140688534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Growth hormone therapy: Comparison of short- and long-term outcomes between children with Growth Hormone Deficiency and Small for Gestational Age.","authors":"Andreas Gleiss, A. Raimann, Florentina Haufler, D. Ertl, S. Sagmeister, Gabriele Hartmann","doi":"10.1159/000538798","DOIUrl":"https://doi.org/10.1159/000538798","url":null,"abstract":"Introduction Direct comparisons of both short-term and long-term auxological outcome of growth hormone therapy (GHT) between growth hormone deficiency (GHD) and small for gestational age (SGA) are scarce. Methods 103 patients with GHD and 53 patients with SGA treated at our tertiary center were investigated. Short-term and long-term outcomes were compared between these groups using multi-variable linear regression models with adjustment for age, sex and height at therapy start, also allowing for sex-specific group comparisons. Results Mean delta height standard deviation scores (SDS) after 1 year of treatment was significantly higher in GHD (0.90, CI 0.82 to 0.99) compared to SGA (0.67, C I 0.54 to 0.79)(p= 0.003) with no sex difference. As expected, the mean increase in height SDS at final height (FH) was significantly higher in GHD (2.21, CI 2.00 to 2.42) compared to SGA (1.05, CI 0.75 to 1.35)(p<0.001), leading to a target height corrected FH of -0.39 SDS (CI -0.62 to -0.15) in GHD and -1.22 SDS (CI-1.57 to -0.87) in SGA ( p<0.001). Girls with GHD had a better long-term outcome, as did boys with SGA when compared to the respective opposite sex. The cut-off of delta height of 0.5 SDS during the first year had a low sensitivity to detect long-term non-responders. We found a relation between short-term and long-term outcome in GHD, but not in SGA (adjusted R2 = 0.66 vs. 0.01). Conclusion In contrast to GHD, we observed practically no relationship between 1st-year and long-term outcome in SGA patients treated with GH.","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140687251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic Conundrum of a Sertoli Cell Tumor in a 2-Year-Old Girl with Peripheral Precocious Puberty and a Café-Au-Lait Macule: A Case Report.","authors":"Lauren A Ray, Deborah F. Billmire, Michael J Ferguson, Erica A Eugster","doi":"10.1159/000538945","DOIUrl":"https://doi.org/10.1159/000538945","url":null,"abstract":"INTRODUCTION\u0000Ovarian Sertoli cell tumors represent a subset of sex cord-stromal tumors and are exceedingly rare in prepubertal children. Here we report a girl with vaginal bleeding due to a Sertoli cell tumor who was originally thought to have McCune-Albright syndrome (MAS).\u0000\u0000\u0000CASE PRESENTATION\u0000A previously healthy girl presented at age two years six months with breast development and vaginal bleeding. On exam, she had Tanner 4 breasts, Tanner 1 pubic hair, estrogenized vaginal mucosa, and a café-au-lait macule. Laboratory studies revealed an elevated estradiol with suppressed gonadotropins and negative tumor markers. Her bone age was advanced by more than three years. Pelvic ultrasound (US) revealed an enlarged uterus and a slightly larger left compared to right ovary. She was started on tamoxifen for presumed MAS. A repeat pelvic US one month later showed a heterogenous mass in the left ovary which was subsequently resected. Pathology revealed a Sertoli cell tumor, lipid-rich variant. Germline sequencing revealed a pathogenic STK11 variant, diagnostic for Peutz-Jeghers syndrome (PJS).\u0000\u0000\u0000CONCLUSION\u0000The findings in our patient were strikingly similar to those encountered in MAS. To our knowledge, our patient is the youngest ever reported to present with precocious puberty due to a Sertoli cell tumor in the setting of PJS.","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140698353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The digital-human interface: an essential combination for clinical progress.","authors":"Martin O Savage","doi":"10.1159/000538896","DOIUrl":"https://doi.org/10.1159/000538896","url":null,"abstract":"","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140708280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A new variant in the GATA6 gene associated with tracheoesophageal fistula, pulmonary vein stenosis and neonatal diabetes.","authors":"Flaminia Pugnaloni, L. Martini, D. D. De Rose, F. Landolfo, P. Giliberti, Rosario Ruta, Antonio Novelli, N. Rapini, Fabrizio Barbetti, Alessandra Toscano, A. Conforti, Pietro Bagolan, I. Capolupo, A. Dotta","doi":"10.1159/000536621","DOIUrl":"https://doi.org/10.1159/000536621","url":null,"abstract":"INTRODUCTION\u0000GATA6 is a gene that encodes a transcription factor with a key role in the development of several organ systems, including the development of the pancreas. It is associated with neonatal diabetes but also with other extra-pancreatic anomalies.\u0000\u0000\u0000CASE PRESENTATION\u0000This report describes the association of tracheoesophageal fistula (TEF), pulmonary vein stenosis (PVS), and neonatal diabetes caused by a novel mutation of the GATA6 gene in a small-for-gestational-age male neonate born at 32 weeks of gestation. Next-Generation Sequencing revealed the novel heterozygous variant c.1502C>G in the GATA6 gene, which determines the introduction of the premature stop codon p.Ser501Ter at the protein level. This de novo nonsense variant was not detected in the analyzed parental DNA samples and has not been previously described in the literature. At about two months of life, a PVS was suspected. The PVS progressively increased with the development of an intramural component, resulting in severe postcapillary pulmonary hypertension. The child died at about 4 months of life.\u0000\u0000\u0000CONCLUSION\u0000TEF can be associated with GATA6 variants. In the case of neonatal diabetes and TEF, neonatologists should be aware of this association and should also investigate the child for complex congenital heart disorders, such as in our case, with a cardiac computed tomography.","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140744907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}