Establishing a molecular genetic diagnosis in children with Differences of Sex Development – a clinical approach
Background Despite distinct underlying aetiologies, the clinical phenotypes and hormonal profiles of children with various differences of sex development (DSD) are often similar, which presents challenges to ascertaining an accurate diagnosis on clinical grounds alone. Associated features and important clinical outcomes can, however, vary significantly in different DSD, thus establishing an accurate molecular diagnosis may have important implications for decision-making and management planning in a given individual. Summary The wider availability of next generation sequencing techniques in recent years has led to recomm...
Source: Hormone Research in Paediatrics - November 15, 2021 Category: Endocrinology Source Type: research

Up-to-Date Clinical and Biochemical Workup of the Child and the Adolescent with a Suspected Disorder of Sex Development
Background: The suspicion of a disorder of sex development (DSD) often arises at birth, when the newborn presents with ambiguous genitalia, or even during prenatal ultrasound assessments. Less frequently, the aspect of the external genitalia is typically female or male, and the diagnosis of DSD may be delayed until a karyotype is performed for another health issue, or until pubertal age when a girl presents with absence of thelarche and/or menarche or a boy consults for gynaecomastia and/or small testes.Summary: In this review, we provide a practical, updated approach to clinical and hormonal laboratory workup of the newbo...
Source: Hormone Research in Paediatrics - November 15, 2021 Category: Endocrinology Source Type: research

Evolution and future of growth plate therapeutics
Abstract Background: Longitudinal bone growth is regulated by multiple endocrine signals (e.g. growth hormone, insulin-like growth factor I, estrogen, androgen) and local factors (e.g. fibroblast growth factors and their receptors and the C-natriuretic peptide/NPR-2 pathway). Summary: Abnormalities in both endocrine and local regulation of growth plate physiology cause many disorders of human skeletal growth. Knowledge of these pathways creates therapeutic potential for sustaining or even augmenting linear growth. Key message: During the past four decades, advances in understanding growth plate physiology have been acco...
Source: Hormone Research in Paediatrics - November 10, 2021 Category: Endocrinology Source Type: research

Early nutrition and later excess adiposity during childhood. A narrative review
BACKGROUND: Studies on childhood obesity mainly focus on the genetic component and on the lifestyle that may be associated with the development of obesity. However, the study of perinatal factors in their programming effect towards future obesity in children or adults is somewhat more recent and there are still mechanisms to be disentangled. SUMMARY: In this narrative review, a comprehensive route based on the influence of some early factors in life in the contribution to later obesity development is presented. Maternal pre-pregnancy BMI and gestational weight gain has been pointed out as independent determinants of infan...
Source: Hormone Research in Paediatrics - November 10, 2021 Category: Endocrinology Source Type: research

Bariatric surgery in adolescents with obesity - long term perspectives and potential alternatives
Background: Severe obesity among adolescent shows a worrisome trend in regard of its increasing prevalence and poses a great challenge for treatment. Conservative measures have modest effects on weight loss, usually fail in achieving a sustainable weight loss and resolution of comorbidities. This has led to greater utilization of bariatric surgery (BS) that offers a fast reduction in body mass index (BMI) with little perioperative complications. Despite the increasing utilization of BS, data is still insufficient, regarding their long-term outcome in adolescents. We review short and long-term effects of bariatric surgery a...
Source: Hormone Research in Paediatrics - November 10, 2021 Category: Endocrinology Source Type: research

Primary ovarian failure in addition to classical clinical features of Coats Plus Syndrome in a female carrying two truncating variants of CTC1
Coats plus syndrome is an autosomal recessive multisystemic and pleiotropic disorder affecting the eyes, brain, bone, and gastrointestinal tract, usually caused by compound heterozygous variants of the Conserved Telomere maintenance Component 1 gene (CTC1), involved in telomere homeostasis and replication. So far, most reported patients are compound heterozygous for a truncating mutation and a missense variant. The phenotype is believed to result from telomere dysfunction, with accumulation of DNA damage, cellular senescence, and stem cell depletion. Here, we report a 23-year-old female with prenatal and postnatal growth r...
Source: Hormone Research in Paediatrics - October 27, 2021 Category: Endocrinology Source Type: research

DLG2 mutations in the etiology of pubertal delay and Idiopathic Hypogonadotropic Hypogonadism
Introduction: Idiopathic Hypogonadotropic hypogonadism (IHH) is caused by dysfunction of the hypothalamic-pituitary-gonadal axis. DLG2 was recently implicated as a gene associated with delayed puberty and which may also contribute to IHH. The confirmation of the candidate puberty genes in independent IHH cohorts has become crucial due to the lack proper genotype phenotype segregations in reported pedigrees. Therefore, we aimed to screen DLG2 in patients variants in a large cohort of IHH patients. Methods: The present study included a total of 336 IHH patients from 290 independent families. The coding and flanking regions...
Source: Hormone Research in Paediatrics - October 25, 2021 Category: Endocrinology Source Type: research

Genetic obesity in children: overview of possible diagnoses with a focus on SH2B1 deletion
Conclusion: Chromosomal microdeletions in 16 p11.2, including the SH2B1 gene, in children are associated with severe, early-onset obesity and comorbidities associated with insulin resistance. Early genetic testing in suspicious patients and early screening for comorbidities is recommended. (Source: Hormone Research in Paediatrics)
Source: Hormone Research in Paediatrics - October 22, 2021 Category: Endocrinology Source Type: research

Gender Dysphoria In Young People: A Model Of Chronic Stress
We describe the evidence for GD as a chronic stressor, drawing parallels to other established models of stress, activating both innate psychological and biological stress responses. As well as being an inherently distressing experience, a person who experiences GD may also experience minority stress. Minority stress has been demonstrated in young people who experience GD with higher rates of social rejection and internalised stigma and shame. The biological stress response in young people with GD is illustrated through the activation of the Hypothalamic-Pituitary-Adrenal axis, autonomic nervous system, and pro-inflammatory...
Source: Hormone Research in Paediatrics - October 21, 2021 Category: Endocrinology Source Type: research

Lethal encephalopathy in an infant with hypophosphatasia despite enzyme-replacement therapy
Hypophosphatasia (HPP) is an inborn error of metabolism caused by loss ‑of‑function mutations in the biomineralization associated alkaline phosphatase (ALPL) gene, encoding tissue-nonspecific alkaline phosphatase (TNSALP). Symptoms include skeletal hypomineralization and extra-skeletal manifestations such as pyridoxine (B6) responsive seizures due to impaired cereb ral B6 passage. Since the introduction of enzyme-replacement therapy (ERT) skeletal manifestations and B6-responsive seizures were reported to improve significantly. Nevertheless, there is increasing evidence of B6-independent neurological manifestation of H...
Source: Hormone Research in Paediatrics - October 21, 2021 Category: Endocrinology Source Type: research

Variable Clinical Presentation of Children with Hereditary Hypophosphatemic Rickets with Hypercalciuria: A Case Series and Review of the Literature
Conclusion: These three cases highlight the variability of presenting signs and symptoms among individuals with HHRH. An accurate diagnosis is critical, as treatment differs from other disorders of phosphate wasting, urinary stones, and mineralization defects. (Source: Hormone Research in Paediatrics)
Source: Hormone Research in Paediatrics - October 19, 2021 Category: Endocrinology Source Type: research

Growth hormone stimulation testing patterns contribute to sex differences in pediatric growth hormone treatment
This study investigates whether sex differences in GH stimulation testing and subsequent GH prescription further contribute to male predominance in GH treatment. Methods: Retrospective chart review was conducted of all individuals, age 2-16 years, evaluated for short stature or poor growth at a single large tertiary referral center between 2012-2019. Multiple logistic regression models were constructed to analyze sex differences. Results: Of 10,125 children referred for evaluation, a smaller proportion were female (35%). More males (13.1%) than females (10.6%) underwent GH stimulation testing (p (Source: Hormone Research in Paediatrics)
Source: Hormone Research in Paediatrics - October 18, 2021 Category: Endocrinology Source Type: research

Increased prevalence of β-cell dysfunction despite normal HbA1c in youth and young adults with Turner Syndrome
This study aimed to determine the prevalence of β-cell dysfunction in youth with TS and the impact of traditional therapies on insulin sensitivity and insulin sec retion. Methods: Cross-sectional, observational study recruited 60 girls with TS and 60 healthy controls (HC) matched on pubertal status. Each subject had a history, physical exam and oral glucose tolerance test (OGTT). Oral glucose and c-peptide minimal modeling was used to determine β-cell functi on. Results: Twenty-one TS girls (35%) met criteria for pre-diabetes. Impaired fasting glucose (IFG) was present in 18% of girls with TS and 2% HC (p-value = 0.0003...
Source: Hormone Research in Paediatrics - October 15, 2021 Category: Endocrinology Source Type: research

Growth Hormone and Insulin-Like Growth Factor Dysregulation in Pediatric Chronic Kidney Disease
The benefit/risk ratio of GH use presented by Brown and Bauer (1) in their review encompass more than three decades. The information for GH us is solid but there is no data for recommending IGF-I use in CKD. Its main reference (2) is from the founder and chief technical officer the company that commercialized IGF-I, lacking any human data to support the use of IGF-I in this population questioning the validity of this endorsement. In 2005 IGF-I was approved in the US for the long-term treatment of growth failure in children with severe primary IGF-1 deficiency or with GH gene deletion who have developed neutralizing antibo...
Source: Hormone Research in Paediatrics - October 13, 2021 Category: Endocrinology Source Type: research

The 2021 European Training Requirements in Paediatric Endocrinology and Diabetes
(Source: Hormone Research in Paediatrics)
Source: Hormone Research in Paediatrics - October 12, 2021 Category: Endocrinology Source Type: research