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Euroasian Journal of... 2023Autoimmune hepatitis (AIH) accounts for cases of chronic liver disease with greater incidence in females than males. It has a bimodal distribution in the age group...
UNLABELLED
Autoimmune hepatitis (AIH) accounts for cases of chronic liver disease with greater incidence in females than males. It has a bimodal distribution in the age group peaking around pubertal periods and later in the fourth to sixth decade of life. It is characterized by continual hepatocellular inflammation and necrosis which bears the potential to progress to fibrosis and cirrhosis. Approximately a third of the patients manifest with features of acute hepatitis while some patients may progress to chronic liver disease with acute liver failure manifesting in the form of jaundice and coagulopathy. Management has long involved administration of corticosteroids alone or in association with other immunosuppressants like azathioprine to achieve long-term remission. Response to therapy is significantly variable as few patients achieve remission while some may relapse, thereby becoming candidates requiring lifelong therapy. It can either present as insidious onset or acute with manifestations ranging broadly from fatigue malaise, lethargy right upper quadrant pain weight loss anorexia, and jaundice, where up to one-third of patients may have progressed to frank cirrhosis at the time of diagnosis. A 62-year female presented with complaints of facial puffiness more around the eyes, associated with profoundly reduced appetite, yellowish discoloration of the skin, conjunctiva since 1 month, and sudden onset generalized itching not associated with fever, joint pains, weight loss, vomiting, loose stools, rash, or bleeding manifestations. She was admitted for further evaluation and workup. Liver function test revealed predominant unconjugated hyperbilirubinemia with direct bilirubin of 0.7 mg/dL and indirect bilirubin of 1.6 mg/day and transaminitis. Further investigations showed significantly elevated immunoglobulin G (IgG) and 1:80 titer of antinuclear antibodies (ANAs). In view of the high suspicion of autoimmune etiologies, the patient was subjected to a liver biopsy that confirmed cirrhosis with moderate interface hepatitis in the background of negative viral serologies and substance abuse history. She was started on a steroid course on a monthly follow-up basis to ensure biochemical remission.
HOW TO CITE THIS ARTICLE
Fatima R, Mohammed V, Fatima A, . Case of Autoimmune Hepatitis. Euroasian J Hepatogastroenterol 2023;13(2):166-168.
PubMed: 38222952
DOI: 10.5005/jp-journals-10018-1413 -
American Journal of Men's Health 2020During adolescence, androgens are responsible for the development of secondary sexual characteristics, pubertal growth, and the anabolic effects on bone and muscle mass.... (Review)
Review
During adolescence, androgens are responsible for the development of secondary sexual characteristics, pubertal growth, and the anabolic effects on bone and muscle mass. Testosterone is the most abundant testicular androgen, but some effects are mediated by its conversion to the more potent androgen dihydrotestosterone (DHT) or to estradiol. Androgen deficiency, requiring replacement therapy, may occur due to a primary testicular failure or secondary to a hypothalamic-pituitary disorder. A very frequent condition characterized by a late activation of the gonadal axis that may also need androgen treatment is constitutional delay of puberty. Of the several testosterone or DHT formulations commercially available, very few are employed, and none is marketed for its use in adolescents. The most frequently used androgen therapy is based on the intramuscular administration of testosterone enanthate or cypionate every 3 to 4 weeks, with initially low doses. These are progressively increased during several months or years, in order to mimic the physiology of puberty, until adult doses are attained. Scarce experience exists with oral or transdermal formulations. Preparations containing DHT, which are not widely available, are preferred in specific conditions. Oxandrolone, a non-aromatizable drug with higher anabolic than androgenic effects, has been used in adolescents with preserved testosterone production, like Klinefelter syndrome, with positive effects on cardiometabolic health and visual, motor, and psychosocial functions. The usual protocols applied for androgen therapy in boys and adolescents are discussed.
Topics: Adolescent; Androgens; Child; Clinical Protocols; Disorders of Sex Development; Hormone Replacement Therapy; Humans; Klinefelter Syndrome; Male; Outcome Assessment, Health Care; Puberty
PubMed: 32448030
DOI: 10.1177/1557988320922443 -
Frontiers of Hormone Research 2021Modern advances in oncological treatments determined a significant improvement in survival rates for several malignancies. Nevertheless, survivorship and quality of life... (Review)
Review
Modern advances in oncological treatments determined a significant improvement in survival rates for several malignancies. Nevertheless, survivorship and quality of life of cancer survivors may be negatively impaired by metabolic and endocrine side effects related to anticancer treatments, including alterations of pituitary-gonadal axis function. In fact, both medical (chemo- and radiotherapy) and surgical approaches may negatively impact on gonadal function, leading to transient or permanent hypogonadism and infertility. In view of these considerations, fertility preservation (FP) should be a primary concern in all oncological patients who may potentially achieve parenthood, irrespectively from their sex and pubertal status at treatment, and adequate counselling should be provided before undergoing gonadotoxic therapy or gonadectomy. Cryopreservation of gametes, when feasible, represents the mainstay for FP in postpubertal age, while procedures involving storage of tissue specimens or stem cells should still be considered as experimental. Given the complexity of both hormonal and psychological implications in this clinical setting, a multidisciplinary approach is advisable for optimal FP and for early diagnosis and treatment of hypogonadism.
Topics: Cancer Survivors; Cryopreservation; Fertility Preservation; Humans; Infertility; Neoplasms; Quality of Life
PubMed: 33957624
DOI: 10.1159/000515460 -
Frontiers in Endocrinology 2023Idiopathic hypogonadotropic hypogonadism (IHH) is characterized by the absence of pubertal development and subsequent impaired fertility often due to...
Idiopathic hypogonadotropic hypogonadism (IHH) is characterized by the absence of pubertal development and subsequent impaired fertility often due to gonadotropin-releasing hormone (GnRH) deficits. Exome sequencing of two independent cohorts of IHH patients identified 12 rare missense variants in in 15 patients. encodes two distinct isoforms. In the adult mouse, expression of both isoform1 and isoform2 was detected in the brain, pituitary, and gonads. However, only isoform1 was detected in mouse primary GnRH cells and three immortalized GnRH cell lines, two mouse and one human. To date, the function of isoform2 has been verified as a transcription factor, while the function of isoform1 has been unknown. In the present report, bioinformatics and cell assays on a human-derived GnRH cell line reveal a novel function for isoform1, demonstrating it can act as a transcriptional regulator, decreasing expression. In addition, the impact of the two most prevalent variants, identified in five IHH patients, that were located at/or close to the DNA-binding domain was examined. Notably, one of these mutations prevented the repression of GnRH transcripts by isoform1. Normally, GnRH transcription increases as GnRH cells mature as they near migrate into the brain. Augmentation earlier during development can disrupt normal GnRH cell migration, consistent with some POU6F2 variants contributing to the IHH pathogenesis.
Topics: Animals; Humans; Mice; Brain; Gonadotropin-Releasing Hormone; Mutation, Missense; POU Domain Factors; Hypogonadism
PubMed: 37600690
DOI: 10.3389/fendo.2023.1203542 -
Journal of Pediatric Urology Jun 2021Klinefelter syndrome (KS) is an uncommon chromosomal disorder in males that has a variable clinical appearance. Classic KS involves an extra X chromosome, (47, XXY),... (Review)
Review
Klinefelter syndrome (KS) is an uncommon chromosomal disorder in males that has a variable clinical appearance. Classic KS involves an extra X chromosome, (47, XXY), although other variations may exist, including a milder mosaic form as well as multiple extra sex chromosomes with more dramatic phenotypes. KS is underdiagnosed, especially pre-pubertally, owing to a paucity of concrete clinical signs; however, diagnostic rates increase during and after puberty, as the consequences of hypergonadotropic hypogonadism begin to manifest. Testicular failure causing decreased circulating testosterone (T) and germ cell depletion, a hallmark feature in KS, commonly begins shortly after the onset of puberty and leads to the most commonly recognized KS traits: small testes, azoospermia, gynecomastia, decreased facial and pubic hair. While many KS men maintain adequate T levels leading up to young adulthood, some may have lower T levels at an earlier age leading to varied levels of androgenization and clinical KS features. At certain critical time points, absent or decreased T may alter the development of normal male reproductive organs, external genitalia, development of secondary sexual characteristics and spermatogenesis. Testicular failure in utero may lead to ambiguous genitalia, cryptorchidism and/or hypospadias, all of which depend on fetal T production. In the neonatal period and childhood, decreased T levels during the mini-puberty of infancy may negatively impact germ cell differentiation and male neuropsychological development. Finally, decreased T during pubertal and young adulthood can lead to decreased virilization during puberty, eunuchoid skeleton and decreased spermatogenesis. Depending on the timing of the testicular failure, a reproductive window of sperm production may exist to achieve paternity for KS men. The presence or absence of clinical characteristics reflecting decreased androgenization provides an insight to the relative testicular function during these developmental time points for those with KS and contributes to variability within the syndrome.
Topics: Adult; Azoospermia; Child; Cryptorchidism; Female; Humans; Infant; Infant, Newborn; Klinefelter Syndrome; Male; Spermatogenesis; Testis; Virilism; Young Adult
PubMed: 33726973
DOI: 10.1016/j.jpurol.2021.02.021 -
Pediatric Rheumatology Online Journal Mar 2021Juvenile Idiopathic Arthritis is one of the most prevalent chronic diseases in children, with an annual incidence of 2-20 cases per 100,000 and a prevalence of 16-150... (Review)
Review
Juvenile Idiopathic Arthritis is one of the most prevalent chronic diseases in children, with an annual incidence of 2-20 cases per 100,000 and a prevalence of 16-150 per 100,000. It is associated with several complications that can cause short-term or long-term disability and reduce the quality of life. Among these, growth and pubertal disorders play an important role. Chronic inflammatory conditions are often associated with growth failure ranging from slight decrease in height velocity to severe forms of short stature. The prevalence of short stature in JIA varies from 10.4% in children with polyarticular disease to 41% of patients with the systemic form, while oligoarthritis is mostly associated with localized excessive bone growth of the affected limb, leading to limb dissymmetry. The pathogenesis of growth disorders is multifactorial and includes the role of chronic inflammation, long-term use of corticosteroids, undernutrition, altered body composition, delay of pubertal onset or slow pubertal progression. These factors can exert a systemic effect on the GH/IGF-1 axis and on the GnRH-gonadotropin-gonadic axis, or a local influence on the growth plate homeostasis and function. Although new therapeutic options are available to control inflammation, there are still 10-20% of patients with severe forms of the disease who show continuous growth impairment, ending in a short final stature. Moreover, delayed puberty is associated with a reduction in the peak bone mass with the possibility of concomitant or future bone fragility. Monitoring of puberty and bone health is essential for a complete health assessment of adolescents with JIA. In these patients, an assessment of the pubertal stage every 6 months from the age of 9 years is recommended. Also, linear growth should be always evaluated considering the patient's bone age. The impact of rhGH therapy in children with JIA is still unclear, but it has been shown that if rhGH is added at high dose in a low-inflammatory condition, post steroids and on biologic therapy, it is able to favor a prepubertal growth acceleration, comparable with the catch-up growth response in GH-deficient patients. Here we provide a comprehensive review of the pathogenesis of puberty and growth disorders in children with JIA, which can help the pediatrician to properly and timely assess the presence of growth and pubertal disorders in JIA patients.
Topics: Adolescent; Arthritis, Juvenile; Child; Growth Disorders; Humans; Puberty
PubMed: 33712046
DOI: 10.1186/s12969-021-00521-5 -
Surgical Oncology Clinics of North... Apr 2021Survivors of pediatric cancer are at increased risk for infertility and premature hormonal failure. Surgeons caring for children with cancer have an important role to... (Review)
Review
Survivors of pediatric cancer are at increased risk for infertility and premature hormonal failure. Surgeons caring for children with cancer have an important role to play in understanding this risk, as well as advocating for and performing appropriate fertility preservation procedures. Fertility preservation options in males and females vary by pubertal status and include nonexperimental (oocyte harvest, ovarian tissue cryopreservation, sperm cryopreservation) and experimental (testicular tissue cryopreservation) options. This review summarizes the basics of risk assessment and fertility preservation options and explores unique considerations in pediatric fertility preservation.
Topics: Adolescent; Child; Cryopreservation; Female; Fertility Preservation; Humans; Male; Neoplasms; Risk Assessment; Survivors
PubMed: 33706908
DOI: 10.1016/j.soc.2020.11.009 -
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