Endocrine management of transgender and gender diverse adolescents: expert opinion of the ESPE Working Group on Gender Incongruence and the Endo-ERN main thematic group on Sexual Development and Maturation.

Increasing numbers of transgender and gender diverse adolescents seek endocrine treatment to align their body to their gender identity. In this relatively young field of medicine, there is a limited body of evidence, and the available evidence generally is of low quality. However, in the absence of randomised trials, much can be learned from prospective observational studies.

Estrogen receptor signaling and targets: Bones, breasts and brain (Review).

Estrogens are involved in a number of physiological functions, including in the development of the brain, growth, reproduction and metabolism. The biological actions of estrogens are achieved by binding to estrogen receptors (ERs) in numerous types of tissues. ERα and ERβ belong to the nuclear receptor superfamily and the G‑protein coupled ER1 (GPER1) is a membrane receptor.

Obesogens in Adolescence: Challenging Aspects and Prevention Strategies.

Childhood obesity has become a global epidemic, with significant increases in prevalence over recent decades. While excessive calorie consumption and physical inactivity are known factors, emerging research highlights the role of endocrine-disrupting chemicals (EDCs), particularly obesogens, in obesity's pathogenesis. This review explores the historical context of the environmental obesogens hypothesis, their sources, mechanism of action, impact on prenatal and postnatal development, and epigenetics.

Inherited metabolic disorders in Cyprus.

Selective screening for inherited metabolic disorders (IMD) began in Cyprus in 1990. Over the last thirty-three years 7388 patients were investigated for IMD and 200 diagnoses were made (diagnostic yield 2.7%).

Gonadotropin-Releasing Hormone Receptor (GnRHR) and Hypogonadotropic Hypogonadism.

Human sexual and reproductive development is regulated by the hypothalamic-pituitary-gonadal (HPG) axis, which is primarily controlled by the gonadotropin-releasing hormone (GnRH) acting on its receptor (GnRHR). Dysregulation of the axis leads to conditions such as congenital hypogonadotropic hypogonadism (CHH) and delayed puberty. The pathophysiology of GnRHR makes it a potential target for treatments in several reproductive diseases and in congenital adrenal hyperplasia.

RET Proto-Oncogene Variants in Patients with Medullary Thyroid Carcinoma from the Mediterranean Basin: A Brief Report.

Multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominant (AD) condition with very high penetrance and expressivity. It is characterized into three clinical entities recognized as MEN2A, MEN2B, and familial medullary thyroid carcinoma (FMTC). In both MEN2A and MEN2B, there is a manifestation of multicentric tumor formation in the major organs such as the thyroid, parathyroid, and adrenal glands where the proto-oncogene is expressed.

The pathogenic p.Gln319Ter variant is not causing congenital adrenal hyperplasia when inherited in one of the duplicated CYP21A2 genes.

Objective: The study aimed to identify the pathogenic status of p.Gln319Ter (NM_000500.7: c.

Seminoma in 46, XY Gonadal Dysgenesis: Rare Presentation and Review of the Literature.

Swyer syndrome is a rare congenital condition that serves as a risk factor for developing germ cell tumors. The condition belongs to the group of 46, XY disorders of sexual development, is characterized by complete gonadal dysgenesis (CGD) and is mostly manifested as delayed puberty and primary amenorrhea during adolescence. Individuals with Swyer syndrome are known to be phenotypically female with normal internal and external female genitalia at birth.

Methylation status of hypothalamic promoter across puberty.

Makorin RING finger protein 3 (MKRN3) is an important factor located on chromosome 15 in the imprinting region associated with Prader-Willi syndrome. Imprinted is expressed in hypothalamic regions essential for the onset of puberty and mutations in the gene have been found in patients with central precocious puberty. The pubertal process is largely controlled by epigenetic mechanisms that include, among other things, DNA methylation at CpG dinucleotides of puberty-related genes.

Salt-wasting congenital adrenal hyperplasia phenotype as a result of the TNXA/TNXB chimera 1 (CAH-X CH-1) and the pathogenic IVS2-13A/C > G in CYP21A2 gene.

Background: Genetic diversity of mutations in the CYP21A2 gene is the main cause of the monogenic congenital adrenal hyperplasia (CAH) disorder. On chromosome 6p21.3, the CYP21A2 gene is partially overlapped by the TNXB gene, the two residing in tandem with their highly homologous corresponding pseudogenes (CYP21A1P and TNXA), which leads to recurrent homologous recombination.

Molecular modelling of novel ADCY3 variant predicts a molecular target for tackling obesity.

Severe early‑onset obesity is mainly attributed to single gene variations of the hypothalamic leptin‑melanocortin system, which is critical for controlling the balance between appetite and energy expenditure. Adenylate cyclase 3 (ADCY3), a transmembrane enzyme localized in primary neuronal cilia, is a key genetic candidate, which appears to have an essential role in regulating body weight. The present study aimed to identify ADCY3 genetic variants in severely obese young patients of Greek‑Cypriot origin by genomic sequencing.

Stress and Growth in Children and Adolescents.

The infantile, childhood, and adolescent periods of growth and development also represent times of increased vulnerability to stressors. Growth velocity in each period is dependent on the interplay of genetic, environmental, dietary, socioeconomic, developmental, behavioral, nutritional, metabolic, biochemical, and hormonal factors. A stressor may impact growth directly through modulation of the growth hormone axis or indirectly through other factors.

Pathogenic and Low-Frequency Variants in Children With Central Precocious Puberty.

Background: Central precocious puberty (CPP) due to premature activation of GnRH secretion results in early epiphyseal fusion and to a significant compromise in the achieved final adult height. Currently, few genetic determinants of children with CPP have been described. In this translational study, rare sequence variants in , , , and genes were investigated in patients with CPP.

GnRH Deficient Patients With Congenital Hypogonadotropic Hypogonadism: Novel Genetic Findings in , and Genes in a Case Series and Review of the Literature.

Congenital hypogonadotropic hypogonadism (CHH) is a rare genetic disease caused by Gonadotropin-Releasing Hormone (GnRH) deficiency. So far a limited number of variants in several genes have been associated with the pathogenesis of the disease. In this original research and review manuscript the retrospective analysis of known variants in (, and genes is described, along with novel variants identified in patients with CHH by the present study.

Polycystic ovarian syndrome in adolescents: From diagnostic criteria to therapeutic management.

Polycystic ovarian syndrome is a common endocrinologic condition diagnosed in women of childbearing age. It is primarily associated with androgen excess and ovarian dysfunction, which contribute to menstrual irregularity, oligo-anovulation, infertility, hirsutism and acne. It is associated with several systemic conditions, including type 2 diabetes mellitus, cardiovascular disease, obesity and neuropsychological disorders.

Gender dysphoria in children and adolescents: an overview.

Over the last decade, we have witnessed considerable progress in gender dysphoria (GD) terminology in an attempt to better describe the condition based on certain criteria. The ever-increasing social acceptance and destigmatization of children and adolescents with GD have resulted in an increased number of transgender individuals seeking endocrine care. In addition to terminology and diagnostic criteria, the tremendous progress of genetics and neuroimaging has enabled us to have a deeper understanding of the complex pathogenesis of GD.

Central Precocious Puberty Caused by Novel Mutations in the Promoter and 5'-UTR Region of the Imprinted Gene.

Central Precocious Puberty (CPP) is clinically defined by the development of secondary sexual characteristics before the age of 8 years in girls and 9 years in boys. To date, mutations in the coding region of , and genes have been reported as causative for CPP. This study investigated the presence of causative mutations in both the promoter and the 5'-UTR regions of the gene.

The Spectrum of Genetic Defects in Congenital Adrenal Hyperplasia in the Population of Cyprus: A Retrospective Analysis.

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) is caused by mutations in the gene. The study refers to CAH patients of Greek-Cypriot ancestry between years 2007 and 2018. One hundred and twenty patients with various degrees of CAH were categorized and genotyped.