Hormone Research in Paediatrics最新文献

{"title":"Fertility in Non-Classic Lipoid CAH: A Case Report and Review of the Literature.","authors":"Emre Murat Altinkilic, Camilla Mains Balle, Clarissa Daniela Voegel, Therina du Toit, Amit V Pandey, Claus H Gravholt, Christa E Flück","doi":"10.1159/000545063","DOIUrl":"10.1159/000545063","url":null,"abstract":"<p><strong>Introduction: </strong>Non-classic lipoid congenital adrenal hyperplasia (LCAH) presents with adrenal insufficiency but typically lacks a gonadal phenotype or features a delayed-onset gonadal presentation. Information on fertility outcomes in affected individuals is limited.</p><p><strong>Case presentation: </strong>We describe an adult male with severe, early onset primary adrenal insufficiency, yet normal fertility, diagnosed in mid-adulthood with compound heterozygous STAR gene variants, including both known and novel mutations. The identified variants, c.814C>T (p.Arg272Cys) and c.743A>C (p.Lys248Thr), underwent structural and functional analysis, revealing partial enzymatic activity. A review of existing reports on the gonadal phenotype and fertility in non-classic LCAH identified only nine adult males. Among these, five exhibited normal gonadal function, but none had documented paternity.</p><p><strong>Conclusion: </strong>STAR variants may be present in adults with unresolved primary adrenal insufficiency and normal gonadal function. Infertility is not an inevitable outcome, as demonstrated by this case.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":" ","pages":"1-8"},"PeriodicalIF":2.6,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596847","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":"Development of Obesity following Treatment for Childhood Malignancies.","authors":"Elpis Athina Vlachopapadopoulou","doi":"10.1159/000545045","DOIUrl":"10.1159/000545045","url":null,"abstract":"<p><strong>Background: </strong>Obesity, long viewed as a reversible outcome of personal choices, is influenced by a complex interplay of genetic, physiological, socioeconomic, and environmental factors. A special group of children and adolescents are the childhood cancer survivors (CCSs), as obesity and its comorbidities have been recognized as long-term effects following treatment for childhood malignancies and craniopharyngioma. The aim of this literature review was to report the epidemiological data, pathophysiology and risk factors regarding obesity development in CCS and the possible mediators. The possible mechanisms contributing to increased body mass index (BMI) include hypothalamic hyperphagia and hypothalamic-pituitary insufficiency, corticosteroid therapy, constitutional factors including genetic predisposition and variable sensitivity to corticosteroids. The risk factors are divided into two categories: those related to the initial diagnosis and the treatment modalities implicated and independent factors such as sex, age at diagnosis, ethnic origin, socioeconomic status and BMI at diagnosis.</p><p><strong>Summary: </strong>Higher risk for developing overweight/obesity face the CCS who had increased BMI at diagnosis, were younger than 6 years of age, received cranial radiation therapy even as low as 6 Gys, had tumors and surgery of the hypothalamic-pituitary region, craniopharyngioma and those who were treated with dexamethasone. They also have high likelihood of developing metabolic syndrome.</p><p><strong>Key messages: </strong>Obesity is one of the most prevalent long-term sequelae of treatment for childhood malignancies. CCSs already face a heightened risk of chronic diseases. Thus, it is crucial to prevent additional avoidable risk factors, such as obesity. All CCS should have height and weight measurements and BMI calculation, as well as being counseled annually on the importance of regular physical activity and heart-healthy diet.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":" ","pages":"1-7"},"PeriodicalIF":2.6,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596846","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 novel variant in an intron splicing enhancer associated with familial growth hormone deficiency.","authors":"Sally Radovick, Mariam Gangat, Bethany Murphy, Jennifer L Miller, Youn Hee Jee","doi":"10.1159/000545037","DOIUrl":"https://doi.org/10.1159/000545037","url":null,"abstract":"<p><strong>Introduction: </strong>Variants in the intron splicing enhancer (ISE) of intron 3 in the GH1 gene are implicated in the etiology of isolated growth hormone deficiency Type 2 (Type II IGHD).</p><p><strong>Methods: </strong>Exome sequencing was performed to screen variants that co-segregated with IGHD in an extended family with Type II IGHD. The causality of the candidate variant was assessed using bioinformatic tools and previous in vitro studies.</p><p><strong>Results: </strong>Exome sequencing identified a rare intronic variant (NM_000515.5, c.291+34 G>A) in the second XGGG repeat of ISE in intron 3 of GH1, which occurred de novo in the mother with IGHD and was passed onto her two affected children. The variant was previously shown in vitro to cause exon 3 skipping in 50% of the mRNAs and was predicted to create a new binding site for exonic splicing enhancer binding proteins (SR proteins).</p><p><strong>Conclusion: </strong>Our familial case reiterates the importance of intronic variants in the splicing enhancer region as a cause of IGHD. Consideration should be given to sequencing the splicing enhancer region in intron 3 of GH1 for patients who undergo genetic testing for growth hormone deficiency.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":" ","pages":"1-20"},"PeriodicalIF":2.6,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585538","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":"Children with Growth Hormone Deficiency Treated With Lonapegsomatropin Demonstrated Sustained Height Improvements for up to 6 Years- enliGHten Trial Final Results.","authors":"Aristides K Maniatis, Paul S Thornton, Ulhas M Nadgir, Elpis Vlachopapadopoulou, Oleg Malievskiy, Elena M Aghajanova, Maria Korpal-Szczyrska, Katie A Woods, Meng Mao, Carol Zhao, Sohair G Abdelrahman, Eric A Huang, Allison S Komirenko, Aimee D Shu, Paul Hofman","doi":"10.1159/000545064","DOIUrl":"https://doi.org/10.1159/000545064","url":null,"abstract":"<p><strong>Background: </strong>This international, Phase 3, open-label extension trial evaluated the long-term safety and efficacy of once-weekly lonapegsomatropin in children with growth hormone deficiency (GHD).</p><p><strong>Methods: </strong>Conducted across 63 sites (15 countries), the enliGHten trial enrolled children with GHD who previously participated in a Phase 3 lonapegsomatropin trial (heiGHt or fliGHt). Participants received subcutaneous injections of lonapegsomatropin dosed at 0.24 mg hGH/kg/week. Safety was monitored through adverse events, local tolerability, hormone levels, and metabolic parameters. Efficacy was evaluated through annualized height velocity (AHV), change in height standard deviation score (SDS), and IGF-1 SDS.</p><p><strong>Results: </strong>Lonapegsomatropin demonstrated sustained efficacy with mean height SDS (-0.39 at year 4, n = 298) approaching the mean for average stature children (height SDS=0) over time. Eighty-one participants completed treatment for pediatric GHD during the trial, and 48 (59.3%) of these met or exceeded their average parental height SDS at their last visit. For the full population, mean values of weekly average IGF-1 remained within 0 to 2 SDS throughout the trial. Growth was maintained throughout pubertal development and the dose remained stable throughout the trial. Adverse events were mostly mild or moderate and remained consistent with prior reports of daily somatropin with no evidence of accelerated skeletal maturation or safety signals associated with anti-drug antibodies.</p><p><strong>Conclusion: </strong>Treatment of pediatric GHD with lonapegsomatropin in the enliGHten trial provided robust growth outcomes and maintained a safety profile comparable to daily GH in a population that included a broad range of pubertal status.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":" ","pages":"1-19"},"PeriodicalIF":2.6,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572930","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":"Optimal Low-Dose Synacthen Stimulation Test Sampling Time for Diagnosis of Adrenal Insufficiency Using Monoclonal Antibody Immunoassay.","authors":"Busra Gurpinar Tosun, Serap Turan, Goncagul Haklar, Abdullah Bereket, Tulay Guran","doi":"10.1159/000544945","DOIUrl":"10.1159/000544945","url":null,"abstract":"<p><strong>Introduction: </strong>The low-dose synacthen stimulation test (LDSST) evaluates hypothalamo-pituitary-adrenal axis function. However, studies on the correlation between morning basal and stimulated cortisol concentrations using specific monoclonal antibody (mAb) immunoassays during LDSST are limited. To determine the best time-points and sampling approach for cortisol measurement using mAb immunoassay in children during LDSST.</p><p><strong>Methods: </strong>Morning basal and stimulated serum cortisol measurements in the LDSST were prospectively analyzed in 132 children (61 girls) with clinical suspicion of adrenal insufficiency (AI). Serum cortisol concentrations were assessed at 0, 30, 40, and 60th minutes during LDSST using mAb immunoassay. Simultaneously, morning basal cortisol levels in 119 patients were measured with both mAb immunoassay and liquid chromatography-mass spectrometry. AI was defined by a peak plasma cortisol concentration below 18 μg/dL (500 nmol/L).</p><p><strong>Results: </strong>AI was excluded in 80.3% (n = 106) of patients. The 40th minute showed the highest specificity (89.1%) for predicting LDSST outcomes with a single cortisol measurement. For two time-point measurements, the 40th and 60th minutes were significantly more sensitive than other possibilities (p < 0.001). A morning basal cortisol level below 6.5 μg/dL was identified as predictive of a failed LDSST result.</p><p><strong>Conclusions: </strong>In LDSST, measurement of plasma cortisol at 40th and 60th minutes reduces the risk of false positivity. Single sampling at 40th minute yielded fewer false negatives than sampling at 30th or 60th minute.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":" ","pages":"1-8"},"PeriodicalIF":2.6,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143541476","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":"Erratum.","authors":"","doi":"10.1159/000543580","DOIUrl":"https://doi.org/10.1159/000543580","url":null,"abstract":"","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":" ","pages":"1"},"PeriodicalIF":2.6,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536954","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":"Prolonged Pubertal Suppression due to Retained Histrelin Implant in Three Children with Central Precocious Puberty.","authors":"Ian Marpuri, Mitchell E Geffner, Lily C Chao","doi":"10.1159/000544181","DOIUrl":"10.1159/000544181","url":null,"abstract":"<p><strong>Introduction: </strong>Histrelin acetate implant (HI) is an approved treatment option for children with central precocious puberty. Implant duration has been reported to surpass the recommended replacement interval of 1-2 years. Implant breakage is a known potential adverse effect during the extraction procedure. However, the bioactivity of the retained fragment has not been reported previously.</p><p><strong>Case presentation: </strong>We present 3 cases of females with central precocious puberty, who received HI for pubertal suppression and experienced implant breakage during extraction. In 2 cases, the retained fragment suppressed pubertal hormone for 5 years. In the third case, the HI was left in place due to loss of follow-up, and the patient was amenorrheic for the next 6 years. In all 3 cases, menstruation occurred after the HI fragments were surgically removed.</p><p><strong>Conclusion: </strong>Our case series demonstrates that retained HI fragment can be bioactive for up to 5 years. If HI breakage occurs during removal, ultrasound localization and surgical extraction of the fragment should be performed.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":" ","pages":"1-5"},"PeriodicalIF":2.6,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523320","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":"Unveiling the Link: Obesity, Diet, Hypothalamic Inflammation, and Central Precocious Puberty - Recent Insights and Implications.","authors":"Galateia Stathori, Anastasia-Maria Tzounakou, Nikolaos F Vlahos, Evangelia Charmandari, Georgios Valsamakis","doi":"10.1159/000544837","DOIUrl":"10.1159/000544837","url":null,"abstract":"<p><strong>Background: </strong>Childhood obesity is on the rise globally, raising concerns among the medical community. The phenomenon is closely linked to high-fat diets. Concurrently, the prevalence of central precocious puberty (CPP) is increasing. Recent evidence demonstrates that obesity and high-fat diets induce inflammation in the mediobasal hypothalamus in humans, a region housing both the primary appetite-regulating centers and the GnRH neurons. Early activation of GnRH neurons is implicated in CPP. The proximity of these hypothalamic sites, exposed to obesity-/diet-induced neuroinflammation, coupled with the positive association between CPP, obesity, and high-fat diets, prompts exploration into the potential involvement of hypothalamic inflammation (HI) in CPP occurrence.</p><p><strong>Summary: </strong>This article delves into the molecular mechanisms through which HI may contribute to CPP in obese and lean girls, based on existing literature. We present evidence suggesting that HI could activate the gonadotropic axis by influencing cytokines and prostaglandins production, BDNF, and potentially phoenixin.</p><p><strong>Key messages: </strong>HI emerges as a potential pathophysiological mechanism linking obesity, high-fat diets, and CPP. Further research is imperative to elucidate the relationship between HI and CPP, providing insights into the origins of CPP, often termed as idiopathic.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":" ","pages":"1-9"},"PeriodicalIF":2.6,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523322","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":"Familial Non-Autoimmune Hyperthyroidism Caused by an Extracellular Domain Variant (p.Leu267Phe) of the TSH Receptor.","authors":"Kazuhiro Shimura, Yosuke Ichihashi, Kiyomi Abe, Tomohiro Ishii, Tomonobu Hasegawa, Satoshi Narumi","doi":"10.1159/000544836","DOIUrl":"10.1159/000544836","url":null,"abstract":"<p><strong>Introduction: </strong>Non-autoimmune hyperthyroidism (NAH) is a rare genetic disorder caused by germline-activating variants in the TSH receptor (TSHR) gene. While most NAH-related TSHR variants are located in the seven-transmembrane domain (7TMD), three variants (p.Leu267Phe, p.Ser281Asn, and p.Asn406Ser) have been identified in the extracellular domain (ECD), with p.Leu267Phe previously not showing constitutively active in vitro.</p><p><strong>Methods: </strong>We searched for TSHR variants in a Japanese family with NAH using PCR-based direct sequencing. We created three ECD variants (p.Leu267Phe, p.Ser281Asn, and p.Asn406Ser) and a series of variants in which Leu267 was mutated to 18 amino acids other than Leu and Phe. Based on the cryo-electron microscopic structures, we evaluated the structure-function relationship of TSHR. We compared their cAMP-producing capacities to WT-TSHR in the luciferase activity assay using HEK293 cells. Western blot and fluorescence immunostaining were performed using HA-tagged TSHR vectors to compare Leu267Phe-TSHR with WT-TSHR.</p><p><strong>Results: </strong>A heterozygous TSHR variant (p.Leu267Phe) was identified. Comparison of the cryo-electron microscopy structures of the activated and inactivated TSHRs revealed a significant change in the ECD structure around Leu267. The ligand-independent cAMP-producing capacities compared to WT-TSHR were 238 ± 20% (mean ± SEM) for Leu267Phe. Of all 19 possible variants created through systematic mutagenesis, only Leu267Phe-TSHR and Leu267Tyr-TSHR exhibited significantly higher ligand-independent cAMP-producing capacities. Immunoblotting and fluorescence immunostaining showed that the Leu267Phe variant did not affect protein expression levels and intracellular localization of TSHR.</p><p><strong>Discussion/conclusion: </strong>Leu267Phe-TSHR causes NAH. Substituting Leu267 to aromatic amino acids may shift the equilibrium of the TSHR state toward activation.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":" ","pages":"1-9"},"PeriodicalIF":2.6,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483107","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":"Hypothyroidism in Infants after Enteral Administration of Iodinated Contrast Media: A Rare but Serious Complication.","authors":"Adinda G H Pijpers, Nitash Zwaveling-Soonawala, Joost van Schuppen, Wes Onland, A S Paul van Trotsenburg, L W Ernest van Heurn, Joep P M Derikx, Christiaan F Mooij","doi":"10.1159/000544706","DOIUrl":"10.1159/000544706","url":null,"abstract":"<p><strong>Introduction: </strong>Excessive exposure to iodine early in life can cause primary hypothyroidism by failure to escape the Wolff-Chaikoff effect. Although reported for intravenous iodinated contrast medium (ICM) and topical iodine, prospective studies on thyroid function after enterally administered ICM are lacking. This study aimed to determine the occurrence of hypothyroidism after enteral ICM administration in young infants.</p><p><strong>Methods: </strong>Prospective cohort study was conducted between November 1st, 2022, and July 1st, 2024, in infants <6 months of age, who underwent radiological examination (mostly abdominal X-ray, AXR) with enteral ICM administration. Stasis of contrast was evaluated by AXR on day two after ICM administration. Serum thyroid-stimulating hormone (TSH) and free thyroxine (fT4) levels were measured around days 5 and 10 after ICM administration and, if abnormal, repeated on day 15.</p><p><strong>Results: </strong>Thirty-three patients were included. Seventeen patients (51.5%) were born preterm. Stasis of ICM after 2 days was present in 12 of 28 patients (42.9%). In 5 male patients (15.2%), abnormal TSH or fT4 levels were observed during follow-up. One of these 5 patients developed ICM-induced hypothyroidism requiring treatment. In 2 cases, physiological escape of the Wolff-Chaikoff effect was seen. In 2 cases, non-thyroidal illness/hypothyroxinemia of prematurity was observed. Four of the 5 patients with abnormal TSH or fT4 levels were born preterm.</p><p><strong>Conclusion: </strong>In this study, 1 patient developed primary hypothyroidism requiring levothyroxine treatment after enteral ICM administration. We recommend monitoring of thyroid function in infants younger than 6 months after enteral ICM administration, especially in preterm born infants.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":" ","pages":"1-6"},"PeriodicalIF":2.6,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414095","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}