Topical Collection "Novel Treatments, Approaches, Prevention Strategies and Insights in Pediatric, Adolescent, and Gynecological Endocrinology"

Editors

Dr. Dimitrios T. Papadimitriou
E-Mail Website
Guest Editor
1. Department of Pediatric-Adolescent Endocrinology & Diabetes, Athens Medical Center, 15125 Athens, Greece
2. Division of Endocrinology, Aretaieion Hospital, National and Kapodistrian University of Athens, 157 72 Athens, Greece
Interests: vitamin D; type 1 diabetes prevention; aromatase inhibitors; hypogonadism
Prof. Dr. Nicoletta Iacovidou
E-Mail Website
Guest Editor
National and Kapodistrian University of Athens, 157 72 Athens, Greece
Interests: pediatrics; neonatology; neonatal resuscitation; medical education; ethics
Prof. Dr. Nikos F. Vlahos
E-Mail Website
Guest Editor
2nd Department of Obstetrics and Gynecology, Aretaieion Hospital, National and Kapodistrian University of Athens, Athens, Greece
Interests: reproductive endocrinology; infertility; endometriosis; assisted reproduction; endoscopic surgery
Special Issues and Collections in MDPI journals
Prof. Dr. George Mastorakos
E-Mail Website
Guest Editor
Division of Endocrinology, Aretaieion Hospital, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece
Interests: stress; women’s endocrinology; pregnancy-related endocrine disorders; endocrine disruptors; Diabesity; metabolic syndrome
Special Issues and Collections in MDPI journals

Topical Collection Information

Dear Colleagues,

Pediatric, adolescent, and gynecological endocrinology are entering a new era. Novel treatments are being developed for previously devastating diseases, such as enzyme replacement therapy using bone-targeting recombinant alkaline phosphatase for the treatment of hypophosphatasia, or the development of c-natriuretic peptide analogues for the treatment of achondroplasia. Old drugs are being repurposed with ongoing clinical trials in order to assess safety, tolerability, and efficacy, such as dantrolene sodium for Wolfram syndrome. The conventional approaches to hormone deficiencies are rapidly changing, such as the use of rPTH in hypoparathyroidism and the use of rLH/rFSH combinations in hypogonadotropic hypogonadism, whereas the weekly administration of growth hormones for children and adolescents is on the way. New formulations that have been long awaited in order to attain physiological replacement therapy are arriving, such as modified release hydrocortisone preparations for congenital adrenal hyperplasia and Addison’s disease. Technology is rapidly advancing, offering non-invasive prenatal diagnosis of congenital adrenal hyperplasia, using cell-free foetal DNA from early as 6 weeks of gestation. New developments in the field of adolescent reproductive health are arising. A whole exome sequencing approach with targeted gene panels has become widely available, leading to the elucidation of genetic diagnosis in endocrine and gynaecological diseases, as well as for prenatal screening. Aromatase inhibitors are widely used to manipulate growth and resolve the issue of compromised growth potential in both sexes, alone or in combination with pubertal inhibition and growth hormone; yet their use in resolving fertility issues is emerging. Genetics and gene therapy are advancing, and the treatment of inherited neurometabolic detrimental diseases, as well as neuroendocrine tumours, is envisioned and anticipated. Prevention strategies with immunization protocols for gynaecological cancers have been established. Prevention strategies for autoimmune diseases such as type 1 diabetes are progressing, with ongoing clinical trials generating hope, even with immune modulating interventions in established disease. The pleiotropic effects of vitamin D are being recognized and the potent immunomodulating effects of calcitriol analogues are being tested. A deeper understanding of mechanisms involved in sexuality, sex identity, hypothalamic amenorrhea, endometriosis, and polycystic ovarian syndrome requires age-appropriate management, with timely intervention strategies during the transition through puberty being developed.

In this Special Issue, we invite you to share your expertise as well as the results of your research through articles (original research manuscripts), reviews, and case reports addressing the above challenges.

Dr. Dimitris T. Papadimitriou
Prof. Dr. Nicoletta Iacovidou
Prof. Dr. Nikos F. Vlahos
Prof. Dr. George Mastorakos
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the collection website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Children is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Pediatric endocrinology
  • Adolescent endocrinology
  • Gynecological endocrinology
  • Adolescent gynecology
  • Pediatric gynecology
  • Novel treatments
  • Hormonal replacement therapy
  • Innovative diagnostics
  • Immune modulation
  • Bone diseases
  • Growth disorders
  • Neurometabolic disorders
  • Transition to adulthood

Published Papers (6 papers)

2021

Article
The Assessment of Brain Volume Differences in Idiopathic Central Precocious Puberty Girls; Comparison of Age-Matched Girls and Normal Puberty Girls
Children 2021, 8(9), 797; https://doi.org/10.3390/children8090797 - 11 Sep 2021
Viewed by 272
Abstract
Objective: Although there have been several studies on the neuroanatomical changes in idiopathic central precocious puberty (ICPP), the association between each brain region and ICPP has not yet been clearly elucidated. This study aimed to evaluate the difference in brain structure in ICPP [...] Read more.
Objective: Although there have been several studies on the neuroanatomical changes in idiopathic central precocious puberty (ICPP), the association between each brain region and ICPP has not yet been clearly elucidated. This study aimed to evaluate the difference in brain structure in ICPP compared with age-matched healthy controls and normal puberty controls, and additionally the correlation between brain volume difference and the luteinizing hormone (LH). Materials and Methods: The study enrolled fifteen girls with ICPP, as well as 15 age-matched healthy girls and 15 normal puberty girls as controls. The subjects underwent a 1.5 Tesla Avanto MR Scanner. Anatomical T1-weighted images were acquired with a T1 spin-echo sequence. The volumes of total and regional brain were compared with each of the two control groups and analyzed through the paired T-test, and the brain region related to the peak LH level was also analyzed through a simple correlation test. Results: The mean age of the ICPP group, age-matched group, and puberty group were 8.0 ± 0.9 years, 7.8 ± 0.9 years, and 11.9 ± 0.9 years, respectively. In our findings, the regional cerebral volumes in ICPP were different from age-matched controls. Compared with controls, ICPP showed a significant increase in gray matter (GM) volumes (the medial prefrontal cortex, superior parietal gyrus, supramarginal gyrus, angular gyrus, postcentral gyrus, superior occipital gyrus, cuneus, hippocampus, parahippocampal gyrus, posterior cingulate gyrus (PCgG), cerebellar cortex (Cb)) and in white matter (WM) volumes (the insular, caudate, splenium of corpus callosum (p < 0.001)). Especially, the GM volumes of the PCgG (r = 0.57, p = 0.03) and Cb (r = 0.53, p = 0.04) were correlated positively with LH concentrations stimulated by the gonadotropin-releasing hormone agonist. Compared to the normal puberty control, no significant difference in GM volume was found. Conclusions: This study showed the overall brain volumetric differences between ICPP girls and age-matched controls using voxel-based morphometric analysis, and further showed the correlation between brain volume and the sex hormone in ICPP. Through a comparison between the two groups, the cerebral development pattern of ICPP is similar to that of normal puberty, and these local differences in cerebral volume may affect social and congenital changes. These findings will be useful for understanding the neuroanatomical mechanisms on the specific morphological variations associated with ICPP. Full article
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Case Report
Fetal Fractures in an Infant with Maternal Ehlers-Danlos Syndrome, CCDC134 Pathogenic Mutation and a Negative Genetic Test for Osteogenesis Imperfecta
Children 2021, 8(6), 512; https://doi.org/10.3390/children8060512 - 17 Jun 2021
Viewed by 1579
Abstract
Intrauterine fractures are a rare clinical finding caused by abnormal early-life osteogenesis. In this case report, we reported a male infant with twenty-three intrauterine/fetal fractures resembling osteogenesis imperfecta and tested negative for COL1A1 and COL1A2 mutations. The infant’s mother had Ehlers–Danlos syndrome, hypermobility [...] Read more.
Intrauterine fractures are a rare clinical finding caused by abnormal early-life osteogenesis. In this case report, we reported a male infant with twenty-three intrauterine/fetal fractures resembling osteogenesis imperfecta and tested negative for COL1A1 and COL1A2 mutations. The infant’s mother had Ehlers–Danlos syndrome, hypermobility type. Whole-genome sequencing revealed that there were no pathologic mutations previously documented to be associated with intrauterine fracture. Genetic mutations reported to be associated with fragility fractures were identified. These include the pathogenic homozygous mutation in the CCDC134 gene. Other genetic variants that might be responsible for variable expressivity of the skeletal manifestation include the homozygous variants of the genes CCDC134, COL15A1 and ZFPM1, and the heterozygous variants of the genes MYH3, BCHE, AUTS2. This is the first reported case of in utero fractures, that was confirmed by X-ray after birth, in an infant who had no genetic evidence for osteogenesis imperfecta, had a homozygous pathogenic mutation of an osteogenesis gene and whose mother had Ehlers-Danlos syndrome hypermobility type. Therefore, we have identified a new genetic cause for in utero fractures. If after birth, this infant were found to have these fractures in various stages of healing with a negative genetic test for osteogenesis imperfecta he would have been misdiagnosed as due to nonaccidental trauma. Full article
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Review
Endocrine-Disrupting Chemicals and Early Puberty in Girls
Children 2021, 8(6), 492; https://doi.org/10.3390/children8060492 - 10 Jun 2021
Viewed by 832
Abstract
In recent decades, pubertal onset in girls has been considered to occur at an earlier age than previously. Exposure to endocrine-disrupting chemicals (EDCs) has been associated with alterations in pubertal timing, with several reports suggesting that EDCs may have a role in the [...] Read more.
In recent decades, pubertal onset in girls has been considered to occur at an earlier age than previously. Exposure to endocrine-disrupting chemicals (EDCs) has been associated with alterations in pubertal timing, with several reports suggesting that EDCs may have a role in the secular trend in pubertal maturation, at least in girls. However, relevant studies give inconsistent results. On the other hand, the majority of girls with idiopathic precocious or early puberty present the growth pattern of constitutional advancement of growth (CAG), i.e., growth acceleration soon after birth. Herein, we show that the growth pattern of CAG is unrelated to exposure to endocrine-disrupting chemicals and is the major determinant of precocious or early puberty. Presented data suggest that EDCs, at most, have a minor effect on the timing of pubertal onset in girls. Full article
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Review
The Effect of Thyrotropin-Releasing Hormone and Antithyroid Drugs on Fetal Thyroid Function
Children 2021, 8(6), 454; https://doi.org/10.3390/children8060454 - 28 May 2021
Viewed by 776
Abstract
A euthyroid pregnant woman will normally have a fetus that displays normal fetal development. However, studies have long demonstrated the role of T3 (Triiodothyronine), T4 (Thyroxine), and TSH (Thyroid Stimulating Hormone) and their degree of penetrability into the fetal circulation. Maternal thyrotropin-releasing hormone [...] Read more.
A euthyroid pregnant woman will normally have a fetus that displays normal fetal development. However, studies have long demonstrated the role of T3 (Triiodothyronine), T4 (Thyroxine), and TSH (Thyroid Stimulating Hormone) and their degree of penetrability into the fetal circulation. Maternal thyrotropin-releasing hormone (TRH) crosses the placental site and, from mid-gestation onward, is able to promote fetal TSH secretion. Its origin is not only hypothalamic, as was believed until recently. The maternal pancreas, and other extraneural and extrahypothalamic organs, can produce TRH variants, which are transported through the placenta affecting, to a degree, fetal thyroid function. Antithyroid drugs (ATDs) also cross the placenta and, because of their therapeutic actions, can affect fetal thyroid development, leading in some cases to adverse outcomes. Furthermore, there are a number of TRH analogues that share the same properties as the endogenous hormone. Thus, in this narrative review, we highlight the interaction of all the above with fetal growth in uncomplicated pregnancies. Full article
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Graphical abstract

Article
Thyroid Microcarcinoma in Pediatric Population in Romania
Children 2021, 8(5), 422; https://doi.org/10.3390/children8050422 - 20 May 2021
Viewed by 461
Abstract
Thyroid microcarcinoma in pediatric population in Romania Non-medullary thyroid cancer (TC) is the most common endocrine malignancy, with an increasing incidence in the recent years, due to the increase of the thyroid microcarcinoma. Thyroid microcarcinoma (mTC) is defined, according to WHO criteria, as [...] Read more.
Thyroid microcarcinoma in pediatric population in Romania Non-medullary thyroid cancer (TC) is the most common endocrine malignancy, with an increasing incidence in the recent years, due to the increase of the thyroid microcarcinoma. Thyroid microcarcinoma (mTC) is defined, according to WHO criteria, as ≤1 cm dimension thyroid carcinoma, being a rare disease in children population. In adults, the current guidelines recommend a limited surgical approach. In children, however, there are no specific guidelines for mTC. Due to the scarcity of these tumors, mTC in children have largely been understudied, to our knowledge with only one previous publication reporting on the outcomes of a large historic series of patients with mTC from the USA. In Romania, the incidence of TC is rising, one of the reason may be the effect of Chernobyl nuclear accident in the past and the iodine deficiency. The purpose of this study was to describe the characteristics and outcome of children diagnosed with mTC in Romania diagnosed from 1 January 2000 to 31 December 2018. During the study period we identified 77 cases of differentiated TC (papillary and follicular) and of these 20 cases (19.4%) were mTC. The mTC represented roughly one fifth of our nationwide pediatric population diagnosed in the last 20 years, the majority of cases being recorded in adolescents aged between 15–18 years. Although patients with apparently more unfavorable local phenotype were identified, this was not reflected in the outcome of the patients in terms of remission of the disease and survival. Our study illustrates the heterogeneity of the real-life practice with respect to the pediatric mTC, and underscores the need for carefully designed multicenter international studies, including larger cohorts of patients in order to provide the data required for establishing evidence based uniform protocols. The European Reference Networks (ERN), such as the ERN for Rare Endocrine Diseases (Endo-ERN) provides an ideal platform to initiate such collaborative studies. Full article
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Review
Perinatal Inflammation: Could Partial Blocking of Cell Adhesion Molecule Function Be a Solution?
Children 2021, 8(5), 380; https://doi.org/10.3390/children8050380 - 12 May 2021
Viewed by 440
Abstract
In spite of the great advances made in recent years in prenatal and perinatal medicine, inflammation can still frequently result in injury to vital organs and often constitutes a major cause of morbidity. It is today well established that in neonates—though vulnerability to [...] Read more.
In spite of the great advances made in recent years in prenatal and perinatal medicine, inflammation can still frequently result in injury to vital organs and often constitutes a major cause of morbidity. It is today well established that in neonates—though vulnerability to infection among neonates is triggered by functional impairments in leukocyte adhesion—the decreased expression of cell adhesion molecules also decreases the inflammatory response. It is also clear that the cell adhesion molecules, namely, the integrins, selectins, and the immunoglobulin (Ig) gene super family, all play a crucial role in the inflammatory cascade. Thus, by consolidating our knowledge concerning the actions of these vital cell adhesion molecules during the prenatal period as well as regarding the genetic deficiencies of these molecules, notably leukocyte adhesion deficiency (LAD) I, II, and III, which can provoke severe clinical symptoms throughout the first year of life, it is anticipated that intervention involving blocking the function of cell adhesion molecules in neonatal leukocytes has the potential to constitute an effective therapeutic approach for inflammation. A promising perspective is the potential use of antibody therapy in preterm and term infants with perinatal inflammation and infection focusing on cases in which LAD is involved, while a further important scientific advance related to this issue could be the combination of small peptides aimed at the inhibition of cellular adhesion. Full article
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