Hormone Research in Paediatrics最新文献

{"title":"Ovarian Insufficiency in Adolescent Females with Transfusion Dependent -thalassemia; Pituitary Versus Ovarian Iron Overload.","authors":"Randa M Matter,Laila A Farid,Sherihane S Madkour,Alshimaa H Yassin,Nouran Y Salah","doi":"10.1159/000541171","DOIUrl":"https://doi.org/10.1159/000541171","url":null,"abstract":"INTRODUCTIONFemales with transfusion-dependent -thalassemia (TDT) display menstrual irregularities and subfertility at certain points in their lives, even if well chelated, representing a significant physical and psychological burden. Little is known about the effects of pituitary and ovarian iron contents on ovarian reserve and function. Hence, this study aimed to assess ovarian reserve and pituitary-gonadal axis function in adolescent females with TDT and correlate them with pituitary and ovarian volume, pituitary iron load, and serum ferritin.METHODSFifty adolescent females with TDTs were compared with 50 age-matched healthy females. Age at diagnosis of TDT, transfusion index, type of chelation therapy, age at menarche, and Tanner breast stage were assessed. Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), anti-Müllerian hormone (AMH), and ferritin levels were measured. Magnetic resonance imaging (MRI) was used to measure the pituitary iron content R2* and T2*, and 3-D transabdominal ovarian ultrasound was performed.RESULTSThe mean age of the studied females with TDT was 14.54 ± 2.24 years. Ovarian insufficiency was found in 20 patients (40%). Compared with controls, adolescent females with TDT had a significantly delayed age of menarche, AMH, FSH, LH, antral follicle count (AFC), and ovarian volume. In a comparison of those with and without ovarian insufficiency, adolescents with TDT with ovarian insufficiency had significantly higher serum ferritin and pituitary MRI-R2* values than did those without insufficiency. Multivariate logistic regression revealed that pituitary MRI-R2* was the most significant independent variable associated with ovarian insufficiency among adolescent females with TDT.CONCLUSIONAdolescent females with TDT have decreased ovarian reserves, AFCs and gonadotropins, which are correlated with the serum ferritin level, pituitary iron load and ovarian volume. Hence, regular ovarian reserve assessment should be implemented as a part of the endocrinological follow-up of females with TDT-advising procedures to preserve fertility to those who are likely to have ovarian insufficiency.","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142192901","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":"Use of GLP-1 Receptor Agonists for the Management of Type 1 Diabetes: A Pediatric Perspective.","authors":"Michal Nevo Shenker, Shlomit Shalitin","doi":"10.1159/000541228","DOIUrl":"10.1159/000541228","url":null,"abstract":"<p><strong>Background: </strong>Despite all the technological advances in treatment of patients with type 1 diabetes (T1D), glucose control remains suboptimal in most patients. In addition, a relatively high percentage of patients with T1D, including children, have obesity. Therefore, new interventions are required that focus their effects on weight loss, in order to help with associated insulin resistance and improve glycemic control.</p><p><strong>Summary: </strong>GLP-1 receptor agonists (GLP-1 RAs) have proven to be effective and safe in adults with T1D, showing improvement in glycemic control, body weight and cardiorenal protection. GLP-1 RAs are also approved for children with obesity (above the age of 12 years) or type 2 diabetes (above the age of 10 years). However, currently these medications are not approved for use in children with T1D. Only a few published studies have evaluated their efficacy and safety for this indication.</p><p><strong>Key message: </strong>This review presents the rationale and experience of add-on GLP-1 RA therapy to pediatric and adolescent patients with T1D, otherwise treated, from RCTs and real-world data. Results of studies of GLP-1 RA in children with T1D are still pending, while large multicenter randomized controlled trials (RCTs) in this population are lacking.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142119685","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":"Two Decades of Thyroid Nodule Cytology in Children: Malignancy Risk Assessment at a Tertiary Care Center.","authors":"Consuelo Pino, José Miguel Dominguez, Antonieta Solar, Pablo Zoroquiain, Francisco Cruz, Cristian García, Florencia De Barbieri, Lorena Mosso, Nicole Lustig, Hernán Gonzalez, Augusto León, Ignacio Goñi, Andy Contreras, Francisca Grob","doi":"10.1159/000541134","DOIUrl":"10.1159/000541134","url":null,"abstract":"<p><strong>Introduction: </strong>Pediatric thyroid nodules exhibit higher malignancy rates compared to adults and are associated with increased incidences of metastases and recurrences. The American Thyroid Association recommends surgery for indeterminate thyroid biopsies in children based on these higher malignancy risks, though this approach may lead to overtreatment. However, there remains a lack of comprehensive pediatric data to inform clinical decisions. This study examines the risk of malignancy (ROM) in pediatric thyroid nodules using the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) and assesses the diagnostic accuracy of fine-needle aspiration (FNA) biopsy compared to histological outcomes.</p><p><strong>Methods: </strong>A retrospective cross-sectional analysis was performed on patients under 19 years with thyroid nodules who underwent FNA and thyroidectomy at a tertiary care center. The sensitivity, specificity, positive predictive value, negative predictive value, and ROM of cytological biopsies were evaluated using TBSRTC criteria, with histology serving as the gold standard. Two analyses were conducted to assess diagnostic accuracy: (a) TBSRTC II as negative and TBSRTC VI as positive and (b) TBSRTC II as negative with TBSRTC V and VI as positive. For neoplasia detection, TBSRTC II was deemed negative, while TBSRTC IV, V, and VI were considered positive. TBSRTC categories III and I were excluded from the performance analysis and evaluated separately. Follicular neoplasm or lesions suspicious for follicular neoplasm (FN/SFN) were treated as positive outcomes, correlated with the presence of adenoma or carcinoma in the surgical specimen.</p><p><strong>Results: </strong>Of 75 nodules from 73 patients, 28 (37.3%) were benign and 47 (62.6%) malignant. No significant differences in gender or age were noted between groups. The ROM in each TBSRTC was Bethesda I 0/2, 0%; II 0/13, 0%; III 2/7, 29%: IV 6/14, 43%; V 10/10, 100%, and VI 29/29, 100%. A sensitivity of 78.38% and specificity of 100% for FNA in detecting malignancy was found, with an even higher sensitivity (100%) for detecting neoplasia in TBSRTC IV.</p><p><strong>Conclusions: </strong>This study reveals that indeterminate thyroid nodules in pediatric patients exhibit a higher rate of malignancy compared to adults, yet align with rates previously reported in the pediatric population. These findings highlight the critical need for guidelines tailored specifically to the management of thyroid nodules and thyroid cancer in children.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072584","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":"Defining Success in the Delivery of Fertility-Related Care for Patients with Differences of Sex Development.","authors":"Tara Streich-Tilles, Aimee Morrison, Tara Schafer-Kalkhoff, Melissa Gardner, Kristina I Suorsa-Johnson, Alison Baskin, Erica M Weidler, Kathleen van Leeuwen, David E Sandberg, Meilan M Rutter","doi":"10.1159/000541029","DOIUrl":"10.1159/000541029","url":null,"abstract":"<p><strong>Introduction: </strong>Individuals with differences of sex development (DSD) experience complex, often competing, medical and psychosocial challenges surrounding fertility. The study aimed to characterize how \"success\" in fertility-related care is conceptualized and attained among individuals with a DSD, their parents or caregivers, healthcare providers, and other stakeholders.</p><p><strong>Methods: </strong>As part of a larger study, DSD stakeholders (n = 110) participated in semi-structured interviews covering the clinical care of patients with DSD. Primary questions included \"What is a successful outcome in DSD care?\" and \"How do you achieve it?\" with fertility as either a spontaneous or suggested topic of discussion. Transcripts were analyzed utilizing a phenomenological approach. This analysis focuses on the extracted themes related to fertility.</p><p><strong>Results: </strong>Fertility was discussed by 19/24 individuals with DSD, 12/19 parents or caregivers, 35/37 healthcare providers, and 19/30 other stakeholders. Components of successful fertility-related care included (1) specific discussions surrounding the relationship between DSD and fertility potential, options for fertility preservation, and options for non-biologic parenthood; (2) early and repeated introduction of these topics; and (3) consideration of age, developmental maturity, and cultural context on decisions around fertility. Challenges included the lack of fertility outcome data in this population and the irreversibility of gonadectomy. Trade-offs identified included anatomic typicality versus function, fertility preservation versus cancer risk reduction, and balancing the different priorities of stakeholders.</p><p><strong>Discussion/conclusions: </strong>A wide range of DSD stakeholders highlighted the importance of addressing fertility concerns in achieving favorable outcomes for individuals with DSD. These stakeholder perspectives should inform fertility-related education, shared decision-making processes, and clinical care.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072638","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":"Pubertal, Auxological, and Adult Height Outcomes in Children Treated for Adrenocortical Tumors: Half a Century Experience.","authors":"Fernanda Bora Moletta, Maria Cláudia Schmitt Lobe, Suzana Nesi França, Luiz de Lacerda, Rosana Marques Pereira","doi":"10.1159/000540706","DOIUrl":"10.1159/000540706","url":null,"abstract":"<p><strong>Introduction: </strong>Most children with adrenocortical tumors (ACTs) present with accelerated growth and skeletal maturation at diagnosis, which potentially compromises their adult heights (AHs). Knowledge about growth and pubertal patterns after ACT resection is scarce. This study presents the pubertal and auxological development of patients treated for ACT and followed up at a single pediatric endocrinology service in Brazil.</p><p><strong>Methods: </strong>Retrospective cohort study including 63 patients (47 girls) followed up between 1966 and 2021. Pubertal and auxological data from ACT diagnosis to AH were analyzed.</p><p><strong>Results: </strong>At diagnosis, the patients had median values of bone age (BA) more advanced than chronological age (CA), height standard deviation score greater than target height (TH-SDS), and predicted adult height (PAH-SDS) lower than TH-SDS. The difference between BA and CA decreased gradually during follow-up and the PAH-SDS moved closer to the TH-SDS 7 years after tumor resection. Puberty started at a median CA of 9.3 (8.3-11.3) years in girls and 9.9 (9.2-13.6) years in boys. Nine patients (6 girls) developed central precocious puberty (CPP), which was influenced by a CA &gt;4 years at diagnosis. The difference between AH-SDS and TH-SDS was not significant (p = 0.3). The factors independently associated with AH below TH were CA &gt;4 years at diagnosis, time between clinical manifestation and diagnosis &gt;1 year, and development of CPP.</p><p><strong>Conclusion: </strong>Most patients treated for ACT during childhood attained AH within the TH despite presenting with advanced skeletal maturation at diagnosis. Development of CPP was not infrequent.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035678","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":"Characterization of Digestive Manifestations in Patients with Impaired PTH/PTHrP Signaling Disorder/Pseudohypoparathyroidism.","authors":"Bérénice Goy, Jugurtha Berkenou, Anya Rothenbuhler, Christelle Audrain, Agnès Linglart, Béatrice Dubern","doi":"10.1159/000539995","DOIUrl":"10.1159/000539995","url":null,"abstract":"<p><strong>Introduction: </strong>Pseudohypoparathyroidism, newly classified as inactivating PTH/PTHrP signaling disorder (iPPSD) type 2 or type 3, is a rare disease caused by defects in the GNAS imprinted gene that encodes Gsα. The most common phenotype comprises resistance to hormones binding to G protein-coupled receptors such as PTH, PTHrP, or TSH, subcutaneous ossifications, short stature, brachydactyly, and early onset obesity. Uncommon features have been described including sleep apnea, asthma, and resistance to calcitonin. At the national French reference center for rare calcium and phosphate metabolism diseases, a large cohort of patients with iPPSD type 2 and type 3 is followed. Interestingly, digestive manifestations and in particular intractable constipation were regularly reported by families of children with iPPSD type 2 or type 3.</p><p><strong>Objective: </strong>The aim of our study was therefore to specify the frequency and characteristics of digestive manifestations in children followed up for iPPSD2 or iPPSD3 in our reference center.</p><p><strong>Material and methods: </strong>Thirty-six patients aged between 2 and 18 years (32 followed up for iPPSD2 and 4 for iPPSD3) were included. Parents completed a specific questionnaire to assess any digestive disorders in their child. The diagnosis of constipation was established using the Bristol visual scale in the event of a score of less than 2 according to stool appearance.</p><p><strong>Results: </strong>Parents reported constipation through the questionnaires in 22/36 (over 60%) of the children. It was the most frequently reported digestive disorder. Among these 22 children, 19 (87%) had a Bristol score for stool shape and texture between 1 and 2 on a scale of 7, confirming constipation. Dedicated treatment had been initiated for 10 (55%) of them, yet only 3 families (16%) considered this treatment effective. Neonatal vomiting and eating disorders, such as lack of satiety or food selectivity, were also noted in 18 (50%) of patients, as was gastroesophageal reflux present in the neonatal period in 14 (40%) of children. There were no significant differences according to the type of iPPSD or patient age.</p><p><strong>Conclusion: </strong>Our work shows for the first time that digestive manifestations, including constipation, occur frequently in children followed for iPPSD, suggesting a potential role of Gsα and G protein receptors in the digestive tract. It is well known that constipation and digestive symptoms alter quality of life. Early management is therefore essential to improve the quality of life of children followed for iPPSD. Our data need to be confirmed on a larger cohort.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999778","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":"Nocturnal Salivary Cortisol Is an Accurate Non-Invasive Test to Assess Endogenous Hypercortisolism in Children with Obesity and a Clinical Phenotype Suspicious for Cushing's Syndrome.","authors":"María Gabriela Ballerini, Analía Verónica Freire, María Eugenia Rodríguez, Luciana Brenzoni, Luciana Daga, Laura Castro, Ana Carolina Arias Cau, Graciela Testa, Melina Gil, Débora Braslavsky, Ana Vieites, Ana Keselman, Ignacio Bergadá, Andrea Josefina Arcari, María Gabriela Ropelato","doi":"10.1159/000540785","DOIUrl":"10.1159/000540785","url":null,"abstract":"<p><strong>Introduction: </strong>Cushing's syndrome (CS) constitutes one of the most challenging diagnostic assessments for paediatric endocrinologists. The clinical presentation of some children with exogenous obesity overlaps with those observed in hypercortisolism states. Accurate, non-invasive first-line tests are necessary to avoid false-positive results in the obese. We aimed to evaluate the diagnostic accuracy of salivary cortisol to assess endogenous hypercortisolism in children with obesity and clinical overlapping signs of CS.</p><p><strong>Methods: </strong>Case-control study that included children aged 2-18 years, BMI-SDS ≥2.0 and a follow-up &gt;2 years. Patients were assigned to three categories: group A, features strongly indicative of paediatric CS (growth failure combined with increasing weight); group B, features suggestive of CS (e.g., moon face and striae); and group C, less specific features overlapping with CS (e.g., hypertension, hirsutism, insulin resistance). Children in categories A and B formed the control group. Ten patients with confirmed CS were the case group. All children collected saliva samples on the same day in the morning between 7 and 8:00 a.m. (morning salivary cortisol: mSC) and at 11 p.m. (nocturnal salivary cortisol: nSC). The mSC and nSC results were used to calculate the percentage decrease of cortisol at night (%D). Main outcomes by receiver operating characteristic for nSC and the %D were sensitivity, specificity, positive (P) and negative (N) predictive values (PV) and their corresponding 95% CI. Salivary cortisol was measured by electrochemiluminescence assay (lower limit of quantification: 2.0 nmol/L).</p><p><strong>Results: </strong>75/112 children met the inclusion criteria, whereas 22/75 children were eligible for the control group. Only controls decreased nSC (median and interquartile range: 2.0 [2.0-2.5] nmol/L) compared to mSC (6.9 [4.8-10.4] nmol/L), p &lt; 0.0001. A cut-off for nSC ≥8 nmol/L confirmed CS within a sensitivity: 1.0 (0.69-1.0), specificity: 1.0 (0.85-1.0), PPV: 1.0 (0.69-0.99), and NPV: 1.0(0.85-0.99), achieving a diagnostic efficiency of 100%. The cut-off obtained for %D was 50%. No child with CS had a %D ≥50%, but 6/22 children in the control group had a %D below the cut-off, resulting in a lower overall diagnostic accuracy of 81% compared to nSC.</p><p><strong>Conclusion: </strong>Salivary cortisol at 11 p.m. is an accurate, feasible, and non-invasive first-line test to assess endogenous hypercortisolism in children with obesity and clinical suspicion of CS. The nSC was also useful in showing that the circadian rhythm of cortisol was preserved in children with exogenous obesity. In patients with nSC ≥8.0 nmol/L, other biochemical assessments and imaging studies are needed to further confirm the aetiology.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916595","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":"Adrenal Cushing Syndrome: Diagnosis and Management in a 10-Year-Old Boy with Carney Complex.","authors":"Domenico Corica, Cecilia Lugarà, Jerome Bertherat, Eric Pasmant, Mariella Valenzise, Giorgia Pepe, Francesco Ferraù, Salvatore Cannavò, Tommaso Aversa, Malgorzata Gabriela Wasniewska","doi":"10.1159/000540691","DOIUrl":"10.1159/000540691","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Adrenocorticotropic hormone (ACTH)-independent Cushing syndrome (CS) is very rare condition in children. Primary pigmented nodular adrenocortical disease (PPNAD) is a rare cause of CS, which in most cases occurs in the context of Carney complex (CNC). CNC is a rare autosomal-dominantly inherited genetic syndrome, usually due to pathogenic variants of the PRKAR1A (regulatory subunit R1A of the protein kinase A) gene located at 17q22-24. The clinical picture is characterized by spotty skin pigmentation, cardiac, cutaneous, and mammary myxomas, melanocytic schwannomas, endocrinopathies, and tumours of the endocrine glands (mostly adrenal, pituitary, and thyroid).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Case presentation: &lt;/strong&gt;A 10-year-old boy first came to our outpatient clinic due to severe obesity. During the first 3 months of follow-up, the height growth rate was normal, but the response to dietary-behavioural indications was poor in terms of weight loss. Later, 10 months after the last evaluation, there was evidence of significant worsening of obesity, growth failure (growth velocity 0.7 cm/year), arterial hypertension, and the occurrence of violaceous striae at the trunk and root of the limbs. Endocrinological causes of obesity associated with growth failure were investigated. The circadian rhythm of cortisol, ACTH, and cortisoluria were suggestive of ACTH-independent hypercortisolaemia. Iatrogenic causes were ruled out. Adrenal ultrasound and computer tomography scan were performed, which initially indicated the presence of a nodule or hyperplasia of the medial arm of the left adrenal gland. Conversely, magnetic resonance imaging showed a significant increase in the global dimensions of the adrenals with a bilateral micronodular appearance. In light of the association between ACTH-independent hypercortisolism and bilateral micronodular adrenal hyperplasia, a genetic investigation was performed, which found a pathogenic variant of the PRKAR1A gene. The patient was begun on treatment with metyrapone which was well tolerated over a 2-year period. The clinical picture has slightly improved, cortisoluria returned and remains within normal limits, but ACTH suppression persists.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;This is the first report on the clinical and biochemical effects of 2-year medical treatment with metyrapone of PPNAD-related hypercortisolaemia in a paediatric patient with CNC. Currently, there are no established protocols for the management of hypercortisolism in PPNAD and data are scarce, especially in the paediatric field. Medical therapies may play a role in reducing the need, at least initially, for patients to undergo bilateral adrenalectomy. However, further studies on larger case series are needed to clarify this aspect. In cases of CS due to PPNAD in which medical therapy was the initial approach, in the absence of clear clinical, auxological, and biochemical improvements, metyrapone may have to be discontinued in fav","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893320","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":"Challenges in Hypophosphatasia: Suspicion, Diagnosis, Genetics, Management, and Follow-Up.","authors":"Rodrigo Montero-Lopez, Mariam R Farman, Florian Högler, Vrinda Saraff, Wolfgang Högler","doi":"10.1159/000540692","DOIUrl":"10.1159/000540692","url":null,"abstract":"<p><strong>Background: </strong>Hypophosphatasia (HPP) is a rare genetic disorder caused by loss-of-function variants in the ALPL gene, leading to deficient tissue-nonspecific alkaline phosphatase (ALP) activity. This results in a distinctive biochemical profile marked by low serum ALP levels and elevated pyridoxal-5-phosphate (PLP). The clinical spectrum of HPP ranges from perinatal lethality to asymptomatic cases, presenting significant diagnostic and therapeutic challenges.</p><p><strong>Summary: </strong>Diagnosis of HPP relies on identifying the characteristic biochemical signature (low ALP, high PLP), concomitant with skeletal (osteomalacia, rickets, pseudofracture) or extraskeletal (muscle weakness, musculoskeletal pain, dental) manifestations. Current diagnostic frameworks lack uniformity, highlighting the imperative for a standardized diagnostic approach. Molecular genetic testing plays a pivotal role in making the diagnosis of HPP, but difficulties persist in diagnosing milder cases and correlating genotypes with phenotypes. Comprehensive multidisciplinary care is indispensable, with enzyme replacement therapy (ERT) proving efficacious in severe cases and more nuanced management approaches for milder presentations. Overcoming challenges in ERT initiation, treatment response assessment, dose titrations, and long-term surveillance necessitates further refinement of management guidelines.</p><p><strong>Key message: </strong>Mild forms of HPP and asymptomatic carriers of pathogenic ALPL variants pose substantial diagnosis and management challenges. Developing consensus-driven guidelines is crucial to enhance clinical outcomes and patient care.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893345","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":"Accelerated Linear Growth during Erdafitinib Treatment: An FGFR-Related, but Growth Factor and Sex Steroid-Independent Mechanism?","authors":"Adalbert Raimann, Natalia Stepien, Amedeo A Azizi, Gabriele Hartmann, Johannes Gojo","doi":"10.1159/000540485","DOIUrl":"10.1159/000540485","url":null,"abstract":"<p><strong>Introduction: </strong>Growth acceleration during postnatal growth only occurs during puberty as a physiological event and during catch-up growth mediated by growth-promoting therapies in growth disorders. Here we report on novel observations of skeletal symptoms during treatment with erdafitinib, a tyrosine kinase inhibitor (TKI) prescribed on the basis of a compassionate-use program.</p><p><strong>Methods: </strong>Analysis of anthropometric, biochemical, clinical, and radiographic data of patients with CNS tumors who revealed an unanticipated growth spurt with initiation of therapy with erdafitinib was performed retrospectively.</p><p><strong>Results: </strong>Linear growth acceleration was independent of sex steroids and IGF1 levels, which is especially remarkable in the context of heavily pretreated pediatric neuro-oncology patients with severe growth impairment before initiation of therapy. Growth acceleration was accompanied by a distinct widening of the growth plate and enhanced metaphyseal mineralization shortly after the start of TKI therapy.</p><p><strong>Conclusions: </strong>While targeted therapies including TKIs have become an essential part of adult cancer treatment, applications in children are still limited. Off-target effects specific to the pediatric population have been observed in various organ systems; however, knowledge about the effect of TKIs on the growing skeleton is scarce. Treatment with erdafitinib inhibits FGFR3-mediated effects and thus represents a very logical hypothetical framework of growth factor and sex steroid-independent growth acceleration.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141859572","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}