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Trends in Endocrinology and Metabolism:... Dec 2019The classical definition of hypogonadism, used in adult medicine, as gonadal failure resulting in deficient steroid and gamete production, and its classification into... (Review)
Review
The classical definition of hypogonadism, used in adult medicine, as gonadal failure resulting in deficient steroid and gamete production, and its classification into hypergonadotropic and hypogonadotropic refer to primary gonadal and hypothalamic-pituitary disorders respectively and may lead to under- or misdiagnosis in pediatrics. Indeed, in children with primary gonadal failure, gonadotropin levels may be within the reference range for age. Conversely, since gonadotropins and steroids are normally low during childhood, it may prove impossible to show the existence of a hypogonadotropic state before pubertal age. Anti-Müllerian hormone (AMH) and inhibin B arise as more adequate biomarkers to assess gonadal function and increase the possibility of making an earlier diagnosis of hypogonadism in children, which may positively impact on timely management.
Topics: Androgens; Anti-Mullerian Hormone; Female; Genitalia; Gonadotropins; Humans; Hypogonadism; Male; Pediatrics; Pregnancy; Primary Ovarian Insufficiency; Testosterone
PubMed: 31471249
DOI: 10.1016/j.tem.2019.08.002 -
The Journal of Clinical Endocrinology... Dec 2023Executive dysfunction is a well-recognized component of the cognitive phenotype of Klinefelter syndrome (KS), yet the neural basis of KS-associated cognitive weaknesses,...
CONTEXT
Executive dysfunction is a well-recognized component of the cognitive phenotype of Klinefelter syndrome (KS), yet the neural basis of KS-associated cognitive weaknesses, and their association with testicular failure is unknown.
OBJECTIVE
We investigated executive function, brain activation, and pubertal development in adolescents with and without KS.
METHODS
Forty-three adolescents with KS (mean age 12.3 ± 2.3 years) and 41 typically developing boys (mean age 11.9 ± 1.8 years) underwent pubertal evaluation, behavioral assessment, and completed functional magnetic resonance imaging (fMRI) as they performed an executive function task, the go/no-go task. Group differences in activation were examined. Associations among activation, executive function, and pubertal development measures were tested in secondary analyses.
RESULTS
Boys with KS exhibited reduced executive function, as well as lower activation in brain regions subserving executive function, including the inferior frontal gyrus, anterior insula, dorsal anterior cingulate cortex, and caudate nucleus. Secondary analyses indicated that the magnitude of activation differences in boys with KS was associated with severity of pubertal developmental delay, as indexed by lower testosterone (t(36) = 2.285; P = .028) and lower testes volume (t(36) = 2.238; P = .031). Greater parent-reported attention difficulties were additionally associated with lower testicular volume (t(36) = -2.028; P = .050).
CONCLUSION
These findings indicate a neural basis for executive dysfunction in KS and suggest alterations in pubertal development may contribute to increased severity of this cognitive weakness. Future studies that examine whether these patterns change with testosterone replacement therapy are warranted.
Topics: Male; Adolescent; Humans; Child; Klinefelter Syndrome; Brain; Testosterone; Executive Function; Cognitive Dysfunction
PubMed: 37595261
DOI: 10.1210/clinem/dgad487 -
Frontiers in Endocrinology 2019Congenital hypogonadotrophic hypogonadism (CHH) is a rare but important etiology of pubertal failure and infertility, resulting from impaired gonadotrophin-releasing... (Review)
Review
Congenital hypogonadotrophic hypogonadism (CHH) is a rare but important etiology of pubertal failure and infertility, resulting from impaired gonadotrophin-releasing hormone secretion or action. Despite the availability of effective hormonal therapies, the majority of men with CHH experience unsatisfactory outcomes, including chronic psychosocial and reproductive sequelae. Early detection and timely interventions are crucial to address the gaps in medical care and improve the outlook for these patients. In this paper, we review the clinical implications of missing minipuberty in CHH and therapeutic strategies that can modify the course of disease, as well as explore a targeted approach to identifying affected male infants by integrating clinical and biochemical data in the early postnatal months.
PubMed: 30846970
DOI: 10.3389/fendo.2019.00097 -
Ginekologia Polska 2018Current treatment schemes of childhood cancer are usually effective enough to enable successful management of the disease. With the high rates of survival, another... (Review)
Review
Current treatment schemes of childhood cancer are usually effective enough to enable successful management of the disease. With the high rates of survival, another problem arises because patients often suffer much later from side effects of the toxic therapy. A common complication caused by cancer treatment is impairment of the female reproductive system including dysfunction of the hypothalamus and hypophysis, the killing of gonadal cells, and uterine injury. This may lead to altered pubertal timing, gonadotropin insufficiency or deficiency, acute ovarian failure, premature ovarian insufficiency, sexual dysfunction, and complicated pregnancy. The severity of these side effects depends a lot on the patient's age at treatment and the particularities of their chemo- and/or radiotherapy regimens. While some types of cancer require aggressive treatment, and therefore negative side effects cannot be avoided, strategies which preserve the patient's reproductive potential are essential. Such strategies are more established in the treatment of adult women, however there are also promising opportunities in the treatment of pediatric oncology patients. Ovar-ian transposition is already widely applied before pelvic radiotherapy. Cryopreservation of ovarian tissue, cryopreservation and in vitro maturation of immature oocytes, or cryopreservation of mature oocytes when the patient's age is appropriate, have also shown to have promising results in pediatric patients. Concurrent combinations of several techniques can also be successful. Counselling of pediatric patients and their families is challenging, and the urgent commencement of anticancer therapies often discourages attempts to preserve the girl's reproductive system. Given that successful methods of fertility preserva-tion are already accessible, it is crucial not to leave this topic aside at the time of diagnosis.
Topics: Cancer Survivors; Child; Cryopreservation; Female; Fertility Preservation; Humans; Infertility, Female; Neoplasms; Primary Ovarian Insufficiency; Reproductive Health; Reproductive Techniques, Assisted
PubMed: 30084481
DOI: 10.5603/GP.a2018.0048 -
Current Drug Metabolism 2016Valproic acid (VPA) is a broad spectrum antiepileptic drug (AED) that is generally regarded as a first-choice agent for most forms of idiopathic and symptomatic... (Review)
Review
BACKGROUND
Valproic acid (VPA) is a broad spectrum antiepileptic drug (AED) that is generally regarded as a first-choice agent for most forms of idiopathic and symptomatic generalised epilepsies. Available data suggest that menstrual disorders and certain endocrine manifestations of reproductive system disorders may be more common in women treated with VPA than in those treated with other AEDs.
METHODS
A PubMed search for MEDLINE was undertaken to look for studies using the terms "VPA metabolism", "VPA and sexual functions in men", "VPA and sexual functions in women" and "VPA metabolism and endocrine disorders" as key words. The period covered was approximately 20 years.
RESULTS
In women, VPA medication is associated with hyperandrogenism, polycystic ovary/polycystic ovarian syndrome, menstrual disorders and ovulatory failure. Men on VPA therapy show abnormalities in androgens blood levels, sperm motility and erectile dysfunctions. VPA negatively affects the release of luteinizing hormone, follicle stimulating hormone and prolactin but also the drug interferes in peripheral endocrine hormones. Its broad inhibitory action on cytochrome and glucuronidation systems can lead to high serum concentration of testosterone, androstenedione and dehydroepiandrosterone sulfate. VPA-dependent obesity and hyperinsulinemia can further contribute to an increase in sexual dysfunctions.
CONCLUSIONS
VPA interferes with the endocrine system at multiples levels causing several reproductive and sexual dysfunctions in women and men with epilepsy, especially when administered in pubertal age. Since VPA is a first line AED both in children and adult with epilepsy and long-term medication with this drug is sometimes necessary, it is very important for physicians to implement strict monitoring of patients taking VPA in order to identify these kinds of side effects at an early stage.
Topics: Animals; Anticonvulsants; Biotransformation; Endocrine System; Endocrine System Diseases; Female; Humans; Male; Reproduction; Risk Factors; Sexual Behavior; Sexual Dysfunction, Physiological; Valproic Acid
PubMed: 27000076
DOI: 10.2174/1389200217666160322143504 -
Jornal de Pediatria 2019To review the pathophysiology and evaluation methods of linear growth and bone mineral density in children and adolescents diagnosed with inflammatory bowel disease. (Review)
Review
OBJECTIVE
To review the pathophysiology and evaluation methods of linear growth and bone mineral density in children and adolescents diagnosed with inflammatory bowel disease.
SOURCE OF DATA
Narrative review carried out in the PubMed and Scopus databases through an active search of the terms: inflammatory bowel disease, growth, failure to thrive, bone health, bone mineral density, and children and adolescents, related to the last ten years, searching in the title, abstract, or keyword fields.
SYNTHESIS OF FINDINGS
Inflammatory bowel diseases of childhood onset may present as part of the clinical picture of delayed linear growth in addition to low bone mineral density. The presence of a chronic inflammatory process with elevated serum levels of inflammatory cytokines negatively interferes with the growth rate and bone metabolism regulation, in addition to increasing energy expenditure, compromising nutrient absorption, and favoring intestinal protein losses. Another important factor is the chronic use of glucocorticoids, which decreases the secretion of growth hormone and the gonadotrophin pulses, causing pubertal and growth spurt delay. In addition to these effects, they inhibit the replication of osteoblastic lineage cells and stimulate osteoclastogenesis.
CONCLUSION
Insufficient growth and low bone mineral density in pediatric patients with inflammatory bowel disease are complex problems that result from multiple factors including chronic inflammation, malnutrition, decreased physical activity, late puberty, genetic susceptibility, and immunosuppressive therapies, such as glucocorticoids.
Topics: Bone Density; Child; Growth Disorders; Humans; Inflammatory Bowel Diseases
PubMed: 30562479
DOI: 10.1016/j.jped.2018.11.002 -
Frontiers in Endocrinology 2022Hemoglobinopathies are autosomal recessive disorders that occur when genetic mutations negatively impact the function of hemoglobin. Common hemoglobinopathies that are... (Review)
Review
Hemoglobinopathies are autosomal recessive disorders that occur when genetic mutations negatively impact the function of hemoglobin. Common hemoglobinopathies that are clinically significant include sickle cell disease, alpha thalassemia, and beta thalassemia. Advancements in disease-modifying and curative treatments for the common hemoglobinopathies over the past thirty years have led to improvements in patient quality of life and longevity for those who are affected. However, the diseases, their treatments and cures pose infertility risks, making fertility preservation counseling and treatment an important part of the contemporary comprehensive patient care. Sickle cell disease negatively impacts both male and female infertility, primarily by testicular failure and decreased ovarian reserve, respectively. Fertility in both males and females with beta thalassemia major are negatively impacted by iron deposition due to chronic blood transfusions. Hematopoietic stem cell transplant (HSCT) is currently the only curative treatment for SCD and transfusion dependent beta thalassemia. Many of the conditioning regimens for HSCT contain chemotherapeutic agents with known gonadotoxicity and whole-body radiation. Although most clinical studies on toxicity and impact of HSCT on long-term health do not evaluate fertility, gonadal failure is common. Male fertility preservation modalities that exist prior to gonadotoxic treatment include sperm banking for pubertal males and testicular cryopreservation for pre-pubertal boys. For female patients, fertility preservation options include oocyte cryopreservation and ovarian tissue cryopreservation. Oocyte cryopreservation requires controlled ovarian hyperstimulation (COH) with ten to fourteen days of intensive monitoring and medication administration. This is feasible once the patient has undergone menarche. Follicular growth is monitored transvaginal or transabdominal ultrasound, and hormone levels are monitored through frequent blood work. Oocytes are then harvested a minimally invasive approach under anesthesia. Complications of COH are more common in patients with hemoglobinopathies. Ovarian hyperstimulation syndrome creates a greater risk to patients with underlying vascular, pulmonary, and renal injury, as they may be less able to tolerate fluids shifts. Thus, it is critical to monitor patients undergoing COH closely with close collaboration between the hematology team and the reproductive endocrinology team. Counseling patients and families about future fertility must take into consideration the patient's disease, treatment history, and planned treatment, acknowledging current knowledge gaps.
Topics: Humans; Male; Female; Fertility Preservation; beta-Thalassemia; Quality of Life; Semen; Counseling; Anemia, Sickle Cell; Ovarian Hyperstimulation Syndrome
PubMed: 36353243
DOI: 10.3389/fendo.2022.985525 -
Chemosphere Aug 2020Perfluoroalkyl substances (PFASs) are a group of man-made organic substances. Some of PFASs have been classified as persistent organic pollutants and endocrine... (Review)
Review
Perfluoroalkyl substances (PFASs) are a group of man-made organic substances. Some of PFASs have been classified as persistent organic pollutants and endocrine disruptors. They might interfere with the male sex endocrine system, causing the abnormal development of the male reproductive tract and failure of pubertal onset and infertility. The present review discusses the development and function of two generations of Leydig cells in rodents and the effects of PFASs on Leydig cell development after their exposure in gestational and postnatal periods. We also discuss human epidemiological data for the effects of PFASs on male sex hormone levels. The structure-activity relationship of PFASs on Leydig cell steroidogenesis and enzyme activities are also discussed.
Topics: Endocrine Disruptors; Environmental Pollutants; Fluorocarbons; Humans; Leydig Cells; Male
PubMed: 32464778
DOI: 10.1016/j.chemosphere.2020.126764