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Indian Pediatrics Feb 2015Small for gestational age infants have multifold increased risk of growth failure and adulthood disorders. Those who experience rapid catch up growth are at risk of... (Review)
Review
CONTEXT
Small for gestational age infants have multifold increased risk of growth failure and adulthood disorders. Those who experience rapid catch up growth are at risk of developing metabolic syndrome, whereas those without catch up may end up with short stature. These children are also prone to an altered pubertal development.
NEED AND PURPOSE
Scarcity of literature, lack of published guidelines on the follow-up and management plan of children born with small for gestational age.
EVIDENCE ACQUISITION
Literature search in PubMed was conducted with regard to epidemiology, growth and puberty, comorbidities, its pathogenesis and management in small for gestational age, with particular relevance for developing countries. An algorithm for follow-up of these children is outlined, based on available empiric data.
CONCLUSIONS
Being born small for gestational age predisposes to many metabolic and pubertal disorders. Special emphasis is needed for early detection and management through early surveillance in growth clinics, and regular follow-up to prevent associated comorbidities.
Topics: Adolescent; Body Height; Child, Preschool; Fetal Growth Retardation; Humans; India; Infant; Infant, Newborn; Infant, Small for Gestational Age; Puberty
PubMed: 25691182
DOI: 10.1007/s13312-015-0588-z -
Orphanet Journal of Rare Diseases Apr 2006Premature ovarian failure (POF) is a primary ovarian defect characterized by absent menarche (primary amenorrhea) or premature depletion of ovarian follicles before the... (Review)
Review
Premature ovarian failure (POF) is a primary ovarian defect characterized by absent menarche (primary amenorrhea) or premature depletion of ovarian follicles before the age of 40 years (secondary amenorrhea). It is a heterogeneous disorder affecting approximately 1% of women <40 years, 1:10,000 women by age 20 and 1:1,000 women by age 30. The most severe forms present with absent pubertal development and primary amenorrhea (50% of these cases due to ovarian dysgenesis), whereas forms with post-pubertal onset are characterized by disappearance of menstrual cycles (secondary amenorrhea) associated with premature follicular depletion. As in the case of physiological menopause, POF presents by typical manifestations of climacterium: infertility associated with palpitations, heat intolerance, flushes, anxiety, depression, fatigue. POF is biochemically characterized by low levels of gonadal hormones (estrogens and inhibins) and high levels of gonadotropins (LH and FSH) (hypergonadotropic amenorrhea). Beyond infertility, hormone defects may cause severe neurological, metabolic or cardiovascular consequences and lead to the early onset of osteoporosis. Heterogeneity of POF is also reflected by the variety of possible causes, including autoimmunity, toxics, drugs, as well as genetic defects. POF has a strong genetic component. X chromosome abnormalities (e.g. Turner syndrome) represent the major cause of primary amenorrhea associated with ovarian dysgenesis. Despite the description of several candidate genes, the cause of POF remains undetermined in the vast majority of the cases. Management includes substitution of the hormone defect by estrogen/progestin preparations. The only solution presently available for the fertility defect in women with absent follicular reserve is ovum donation.
Topics: Adult; Amenorrhea; Chromosomes, Human, X; Female; Gonadal Hormones; Gonadotropins; Humans; Primary Ovarian Insufficiency; Sex Chromosome Aberrations
PubMed: 16722528
DOI: 10.1186/1750-1172-1-9 -
Indian Pediatrics Jul 2021To assess pubertal development and its determinants in adolescents with transfusion-dependent thalassemia (TDT).
OBJECTIVES
To assess pubertal development and its determinants in adolescents with transfusion-dependent thalassemia (TDT).
METHODS
In this cross-sectional study from a tertiary teaching hospital in Delhi, records of adolescents aged 17-19 years with TDT on regular transfusion at thalassemia day-care centre were reviewed. Pubertal development and its determinants were assessed.
RESULTS
Records of 58 (33 male) adolescents with TDT were reviewed. Among them, 42 (72.4%) had normal/delayed onset with spontaneous progression of puberty, while 16 (27.6%) had pubertal arrest/failure and received hormonal replacement therapy (HRT). Short stature was observed in all adolescents on HRT. Amongst other endocrinopathies, only hypoparathyroidism was found to be significantly higher in the HRT group. On multivariate analysis, serum ferritin (OR-1.005, 95% CI 1.002, 1.009) was observed to be the only significant determinant of pubertal arrest/failure.
CONCLUSIONS
A significant proportion of adolescents with TDT continue to have pubertal arrest/failure. High systemic iron load is the key determinant for this.
Topics: Adolescent; Blood Transfusion; Cross-Sectional Studies; Endocrine System Diseases; Humans; Male; Puberty; Thalassemia; beta-Thalassemia
PubMed: 33772533
DOI: No ID Found -
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 -
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 -
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 -
Transplantation and Cellular Therapy Aug 2022Male gonadal dysfunction is a frequent late effect after pediatric hematopoietic stem cell transplantation (HSCT) that can lead to disturbances in pubertal development,...
Male gonadal dysfunction is a frequent late effect after pediatric hematopoietic stem cell transplantation (HSCT) that can lead to disturbances in pubertal development, sexual dysfunction, and infertility. However, no systematic review exists regarding prevalence and risk factors in relation to different treatment regimens. We aimed to systematically evaluate the current evidence regarding the prevalence of male gonadal dysfunction after pediatric HSCT, related risk factors, and the diagnostic value of surrogate markers of spermatogenesis in this patient group. We searched PubMed and Embase using a combination of text words and subject terms. The eligibility screening was conducted using predefined criteria. Data were extracted corresponding to the Leydig cell compartment involved in testosterone production and the germ cell compartment involved in spermatogenesis, respectively. Subsequently, data synthesis was performed. Of 2369 identified records, 25 studies were eligible. The studies were heterogeneous in terms of included diagnoses, gonadotoxic therapy, follow-up time, and definitions of gonadal dysfunction. The data synthesis revealed a preserved Leydig cell function in patients treated with non-total body irradiation (TBI) regimens, whereas the evidence regarding the impact of TBI conditioning on Leydig cell function was conflicting. Based on surrogate markers of spermatogenesis and only limited data on semen quality, the germ cell compartment was affected in half of the patients treated with non-TBI regimens and in nearly all patients treated with TBI conditioning. Testicular irradiation as part of front-line therapy before referral to HSCT led to complete Leydig cell failure and germ cell failure. Evidence regarding the impact of diagnosis, pubertal stage at HSCT, and chronic graft-versus-host disease is limited, as is the evidence of the diagnostic value of surrogate markers of spermatogenesis. Testicular irradiation as part of front-line therapy and TBI conditioning are the main risk factors associated with male gonadal dysfunction after pediatric HSCT; however, impaired spermatogenesis is also observed in half of the patients treated with non-TBI regimens. Methodological shortcomings limit existing evidence, and future studies should include semen quality analyses, follow-up into late adulthood, and evaluation of the cumulative exposure to gonadotoxic therapy.
Topics: Adult; Child; Gonadal Disorders; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Male; Semen Analysis; Transplantation Conditioning; Whole-Body Irradiation
PubMed: 35644480
DOI: 10.1016/j.jtct.2022.05.036 -
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 -
Andes Pediatrica : Revista Chilena de... Feb 2022The increased survival of children and adolescents after Stem Cell Transplantation (SCT) has allowed us to gain a better understanding of the late effects that this...
INTRODUCTION
The increased survival of children and adolescents after Stem Cell Transplantation (SCT) has allowed us to gain a better understanding of the late effects that this procedure might have.
OBJECTIVE
to measure ovarian function and reserve after SCT.
PATIENTS AND METHOD
A descriptive, observatio nal, and cross-sectional study of girls and adolescents with SCT between 1999 and 2011. External gynecologic examination, hormone tests, and abdominal gynecologic ultrasound were performed, observing pubertal development pre-SCT. The following data from the clinical record were recorded: baseline pathology, type of conditioning, use of radiotherapy in conditioning, age at the time of SCT, and history of acute or chronic graft-versus-host disease (GVHD). Hormonal tests included follicle- stimulating hormone (FSH), luteinizing hormone (LH), estradiol, prolactin (PRL), thyroid-stimula ting hormone (TSH), free thyroxine, total testosterone, sex hormone-binding globulin (SHBG), and anti-Müllerian hormone (AMH). Statistical analysis included the chi-square or Fisher's Exact test with a p-value < 0.05.
RESULTS
41 patients were evaluated. The median age at the time of SCT was 6.8 years (1.5-14.1) and the median age at evaluation was 14.8 years (range: 4-25.4 years). 93% of the transplants were in patients with oncological disease and with myeloablative conditioning regimens. All patients presented decreased ovarian reserve, and 72% showed Premature Ovarian Failure (POF).
CONCLUSIONS
All patients had decreased ovarian reserve and most of them had a high prevalence of POF. Before SCT, a gynecological evaluation and subsequent follow-up for hormone monitoring and initiation of hormone replacement are essential.
Topics: Adolescent; Anti-Mullerian Hormone; Child; Cross-Sectional Studies; Female; Follicle Stimulating Hormone; Hematopoietic Stem Cell Transplantation; Humans; Menopause, Premature; Ovarian Reserve; Primary Ovarian Insufficiency
PubMed: 35506772
DOI: 10.32641/andespediatr.v93i1.3693 -
American Journal of Medical Genetics.... Dec 2017Mutations in the gene CHD7 cause CHARGE syndrome, a rare multi-organ syndromic disorder. Gonadal defects are common in individuals with CHARGE syndrome (seen in... (Review)
Review
Mutations in the gene CHD7 cause CHARGE syndrome, a rare multi-organ syndromic disorder. Gonadal defects are common in individuals with CHARGE syndrome (seen in ∼60-80% of cases) and represent the letter "G" in the CHARGE syndrome acronym. The gonadal defect in CHARGE syndrome results from congenital deficiency of the hypothalamic hormone Gonadotropin-releasing hormone (GnRH), which manifests clinically as pubertal failure and infertility, and biochemically as hypogonadotropic hypogonadism (low sex steroid hormone levels with inappropriately normal or low gonadotropin levels). In addition to the gonadal endocrine abnormalities, in a small minority of individuals with CHARGE, additional endocrine defects including growth hormone deficiency, multiple pituitary hormone deficits and primary hypothyroidism may also be seen. CHD7 mutations disrupt the targeting of olfactory axons and the migration of GnRH-synthesizing neurons during embryonic development, resulting in congenital idiopathic hypogonadotropic hypogonadism (IHH) and anosmia (or hyposmia), two features that define human Kallmann syndrome. Since Kallmann syndrome is one of the constituent phenotypes within CHARGE, recent studies have investigated the role of CHD7 mutations in individuals with IHH and established that deleterious missense mutations in CHD7 are associated with Kallmann syndrome as well as normosmic form of IHH. These missense mutations affect the ATPase and nucleosome remodeling activities of the CHD7 protein. These observations suggest that CHD7 protein function is critical for the ontogeny of GnRH neurons and neuroendocrine regulation of GnRH secretion.
Topics: Abnormalities, Multiple; Animals; CHARGE Syndrome; DNA Helicases; DNA-Binding Proteins; Disease Models, Animal; Endocrine System Diseases; Genetic Association Studies; Genitalia; Humans; Mice; Mutation; Phenotype
PubMed: 29152903
DOI: 10.1002/ajmg.c.31585