-
Annals of Medicine and Surgery (2012) Feb 2022Isolated Hypogonadotropic Hypogonadism (IHH) is a clinical syndrome that results from gonadal failure due to abnormal pituitary gonadotropin levels, in the presence of...
BACKGROUND
Isolated Hypogonadotropic Hypogonadism (IHH) is a clinical syndrome that results from gonadal failure due to abnormal pituitary gonadotropin levels, in the presence of normal baseline and reserve testing of the remaining pituitary hormones.
CASE PRESENTATION
An 18 years old female came with primary amenorrhea, accompanied by poor breast and pubic development, with low levels of estradiol and gonadotropins but normal levels of other anterior pituitary hormones. Imaging of the hypothalamic-pituitary region revealed hypophyseal hypoplasia due to ischemia. Sex steroids therapy was given to induce pubertal development. IHH represents a rare condition but with a good prognosis.
DISCUSSION
Early diagnosis and treatment can prevent negative physical and psychological sequelae, and restore fertility in affected patients. Constant surveillance is required due to the possibility of gonadal axis reversal and/or relapse of gonadal axis failure and to identify any adverse effects related to therapy.
CONCLUSION
Early identification of IHH can help in treatment efficiency.
PubMed: 35145667
DOI: 10.1016/j.amsu.2022.103289 -
Trials Jan 2022Of the 2 million children living with HIV globally, 90% live in sub-Saharan Africa. Despite antiretroviral therapy, longstanding HIV infection is associated with several...
Vitamin D and calcium carbonate supplementation for adolescents with HIV to reduce musculoskeletal morbidity and immunopathology (VITALITY trial): study protocol for a randomised placebo-controlled trial.
BACKGROUND
Of the 2 million children living with HIV globally, 90% live in sub-Saharan Africa. Despite antiretroviral therapy, longstanding HIV infection is associated with several chronic complications in children including growth failure, particularly stunting and delayed puberty. Vitamin D deficiency, which is highly prevalent among children living with HIV in sub-Saharan Africa, has a further adverse impact on bone health. This trial aims to establish whether supplementation with vitamin D and calcium carbonate improves musculoskeletal health among peripubertal children living with HIV.
METHODS/DESIGN
We will conduct an individually randomised, double-blinded, placebo-controlled trial of weekly high-dose vitamin D (20,000 IU) plus daily calcium carbonate (500mg) supplementation for 48 weeks. Eight hundred and forty children living with HIV aged 11-19 years taking ART for ≥6 months will be enrolled and followed up for 96 weeks. The primary outcome is total body less-head bone mineral content for lean mass adjusted for height (TBLH-BMC) Z-score at 48 weeks, measured by dual-energy X-ray absorptiometry (DEXA). Secondary outcomes are DEXA-measured lumbar spine bone mineral apparent density Z-score, number of respiratory infections, lean muscle mass and grip strength at 48 and 96 weeks and TBLH-BMC Z-scores at 96 weeks. Sub-studies will investigate the effect of the intervention on vitamin D pathway metabolites and markers of bone turnover, intestinal microbiota, and innate and acquired immune function.
DISCUSSION
This is the largest trial to date of vitamin D supplementation in children living with HIV. Intervening to address deficits in bone accrual in childhood is critical for optimising adolescent and early adult bone health and prevention of later adult osteoporotic fractures. Trial results will draw attention to the need to screen for and treat long-term comorbidities in children living with HIV in resource-limited settings.
TRIAL REGISTRATION
Pan African Clinical Trials Registry PACTR20200989766029 . Registered on 3 September 2020.
Topics: Adolescent; Bone Density; Calcium Carbonate; Child; Cholecalciferol; Dietary Supplements; Double-Blind Method; HIV Infections; Humans; Morbidity; Randomized Controlled Trials as Topic; Vitamin D; Young Adult
PubMed: 35081986
DOI: 10.1186/s13063-021-05985-0 -
Case Reports in Pediatrics 2021. Griscelli syndrome (GS) is a rare disorder characterized by partial albinism and silver hair with alteration in genes necessary for melanin transport. Type 2 GS is...
. Griscelli syndrome (GS) is a rare disorder characterized by partial albinism and silver hair with alteration in genes necessary for melanin transport. Type 2 GS is fatal due to severe immunodeficiency without curative stem cell transplant (SCT). Late endocrinopathies are quite common in other disorders after SCT. These complications have not been reported in GS. . A 7-year-old female presented for growth failure with a history of GS status post curative SCT and consequently developed graft-versus-host disease (GvHD). She also had a history of eosinophilic enterocolitis, for which she was taking supraphysiologic glucocorticoids for the past year. She presented with severe short stature along with mild hyperthyroxinemia with subsequent diagnosis of Graves' disease, which was treated with methimazole. GH therapy was commenced due to persistent growth failure, with a robust increase in growth parameters. She started spontaneous puberty; however, initial biochemical evaluation revealed hypergonadotropic hypogonadism with undetectable anti-Mullerian hormone (AMH) consistent with low ovarian reserve and premature ovarian failure. . Growth failure was multifactorial due to her inflammatory condition and poor weight gain from multiple underlying illnesses, including hyperthyroidism, as well as chronic supraphysiologic glucocorticoid use. Although hypothyroidism is more commonly seen after SCT, rare cases of hyperthyroidism have been reported. In addition to SCTs, GvHD and GS have been associated with autoimmune conditions. It is important to monitor pubertal progression as the majority of those treated with alkylating agents prior to SCT have pubertal and ovarian failure and remain at risk for premature menopause.
PubMed: 34987878
DOI: 10.1155/2021/9981306 -
Journal of Animal Science Jan 2022Age at first estrus is the earliest phenotypic indicator of future reproductive success of gilts. Prebreeding anestrus is a major reason for reproductive failure leading...
Age at first estrus is the earliest phenotypic indicator of future reproductive success of gilts. Prebreeding anestrus is a major reason for reproductive failure leading to culling of replacement gilts. The two types of prebreeding anestrus are delay in attaining puberty (prepubertal anestrus, PPA) and silent ovulation (behavioral anestrus, BA). Neural tissues such as amygdala and hippocampus play a major role in regulating sexual behavior, social interactions, and receptivity to males. Differences in gene expression in the amygdala and hippocampus of gilts were analyzed in three comparisons: 1) PPA cases and cyclic controls at follicular phase of estrous cycle, 2) BA cases and cyclic controls at luteal phase of estrous cycle, and 3) gilts at different stages of the ovarian cycle (cyclic gilts at follicular phase and luteal phase of estrous cycle) to gain functional understanding of how these rarely studied tissues may differ between pubertal phenotypes and different stages of the estrous cycle of gilts. Differentially expressed genes (DEG) between PPA and BA cases and their respective cyclic controls were involved in neurological and behavioral disorders as well as nervous system functions that could directly or indirectly involved in development of behaviors related to estrus. The comparison between cyclic follicular and luteal phase control gilts identified the greatest number of DEG in the hippocampus and amygdala. These DEG were involved in adult neurogenesis and neural synapse (e.g., GABAergic, dopamine, cholinergic), suggesting that these tissues undergo structural changes and synaptic plasticity in gilts. This is the first report to demonstrate that the stage of estrous cycle is associated with dynamic changes in gene expression within porcine hippocampus and amygdala and indicates a role of gonadal steroids in regulating their biology.
Topics: Amygdala; Animals; Estrus; Female; Gene Expression; Hippocampus; Male; Progesterone; Sus scrofa; Swine
PubMed: 34984470
DOI: 10.1093/jas/skab372 -
Antimicrobial Agents and Chemotherapy Feb 2022This phase 2 study investigated long-term safety and efficacy of rilpivirine (RPV) plus two investigator-selected nucleos(t)ide reverse transcriptase inhibitors (NRTIs)...
This phase 2 study investigated long-term safety and efficacy of rilpivirine (RPV) plus two investigator-selected nucleos(t)ide reverse transcriptase inhibitors (NRTIs) in HIV-1-infected antiviral therapy-naive adolescents. Participants (≥12 to <18 years of age) were treated with RPV at 25 mg once daily (q.d.) plus 2 NRTIs and entered the treatment extension period for up to 240 weeks, with visits every 3 months. Long-term safety (analysis of adverse events [AEs] and laboratory results), efficacy (virologic response and outcome for patients with viral loads of <50 and <400 by time to loss of virologic response [TLOVR] and FDA Snapshot methods, as well as CD4 cell count), and adherence (by pill count) for up to 240 weeks are presented. Twenty-four of 36 participants entered the treatment extension period, and 21 completed week 240. At week 240, a viral load of <50 copies/mL was achieved by 14/32 (43.8%) participants; virologic response by TLOVR was higher in participants with a baseline viral load of ≤100,000 copies/mL (48.0%) versus a viral load of >100,000 copies/mL (28.6%). By FDA Snapshot, a viral load of <50 copies/mL at week 240 was found in 53.1% (17/32) of participants with a baseline viral load of ≤100,000 copies/mL. Higher response was observed in participants with adherence of >95% and a baseline viral load of ≤100,000 copies/mL. Through week 240, 16/32 participants (50.0%) experienced virologic failure, including seven who developed treatment-emergent RPV resistance-associated mutations (RAMs [frequently E138K]): all 7 had ≥1 treatment-emergent NRTI RAM. No serious AEs after week 48, no discontinuations due to AEs between week 48 and week 240, and no new safety signals were observed. RPV did not affect pubertal development or adolescent growth. At the 5-year follow-up, efficacy was low in adolescents, particularly those with poor adherence and/or a high baseline viral load of >100,000 copies/mL. To limit the risk of virologic failure, RPV is restricted to patients with a baseline VL of ≤100,000 copies/mL in most countries. In addition, adequate treatment adherence to RPV treatment is imperative for long-term viral suppression and should be emphasized in the management of adolescents living with HIV. RPV exhibited a favorable long-term safety profile for adolescents living with HIV-1 with adequate adherence. (This study has been registered at ClinicalTrials.gov under identifier NCT00799864.).
Topics: Adolescent; Anti-HIV Agents; Anti-Retroviral Agents; HIV Infections; HIV-1; Humans; Rilpivirine; Treatment Outcome; Viral Load
PubMed: 34871089
DOI: 10.1128/AAC.00916-21 -
Endocrine Reviews Sep 2022Delayed puberty (DP) defines a retardation of onset/progression of sexual maturation beyond the expected age from either a lack/delay of the... (Review)
Review
Delayed puberty (DP) defines a retardation of onset/progression of sexual maturation beyond the expected age from either a lack/delay of the hypothalamo-pituitary-gonadal axis activation or a gonadal failure. DP usually gives rise to concern and uncertainty in patients and their families, potentially affecting their immediate psychosocial well-being and also creating longer term psychosexual sequelae. The most frequent form of DP in younger teenagers is self-limiting and may not need any intervention. Conversely, DP from hypogonadism requires prompt and specific treatment that we summarize in this review. Hormone therapy primarily targets genital maturation, development of secondary sexual characteristics, and the achievement of target height in line with genetic potential, but other key standards of care include body composition and bone mass. Finally, pubertal induction should promote psychosexual development and mitigate both short- and long-term impairments comprising low self-esteem, social withdrawal, depression, and psychosexual difficulties. Different therapeutic options for pubertal induction have been described for both males and females, but we lack the necessary larger randomized trials to define the best approaches for both sexes. We provide an in-depth and updated literature review regarding therapeutic options for inducing puberty in males and females, particularly focusing on recent therapeutic refinements that better encompass the heterogeneity of this population, and underlining key differences in therapeutic timing and goals. We also highlight persistent shortcomings in clinical practice, wherein strategies directed at "the child with delayed puberty of uncertain etiology" risk being misapplied to older adolescents likely to have permanent hypogonadism.
Topics: Adolescent; Child; Female; Gonadotropins; Humans; Hypogonadism; Male; Puberty; Puberty, Delayed; Testosterone
PubMed: 34864951
DOI: 10.1210/endrev/bnab043 -
International Journal of Molecular... Nov 2021Although the cancer survival rate has increased, cancer treatments, including chemotherapy and radiotherapy, can cause ovarian failure and infertility in women of... (Review)
Review
Although the cancer survival rate has increased, cancer treatments, including chemotherapy and radiotherapy, can cause ovarian failure and infertility in women of reproductive age. Preserving fertility throughout cancer treatment is critical for maintaining quality of life. Fertility experts should propose individualized fertility preservation methods based on the patient's marital status, pubertal status, partner status, and the urgency of treatment. Widely practiced fertility preservation methods, including ovarian transposition and embryo and oocyte cryopreservation, are inappropriate for prepubertal girls or those needing urgent initiation of cancer treatment. Ovarian tissue cryopreservation and transplantation, an emerging new technology, may be a solution for these cancer patients. The use of stem cells in ovarian tissue cryopreservation and transplantation increases oxygenation, angiogenesis, and follicle survival rates. This review discusses the recent advances in ovarian tissue cryopreservation and transplantation with special focus on the use of stem cells to improve fertilization techniques.
Topics: Cryopreservation; Female; Fertility Preservation; Humans; Oocytes; Ovarian Follicle; Primary Ovarian Insufficiency; Stem Cell Transplantation; Stem Cells
PubMed: 34830363
DOI: 10.3390/ijms222212482 -
Theranostics 2021Sertoli cells are essential regulators of testicular fate in the differentiating gonad; however, its role and underlying molecular mechanism of regulating testicular...
Sertoli cells are essential regulators of testicular fate in the differentiating gonad; however, its role and underlying molecular mechanism of regulating testicular development in prepubertal testes are poorly understood. Although several critical regulatory factors of Sertoli cell development and function have been identified, identifying extrinsic factors that regulate gonocyte proliferation and migration processes during neonatal testis development remains largely unknown. We used the Sertoli cell-specific conditional knockout strategy (Cre/Loxp) in mice and molecular biological analyses (Luciferase assay, ChIP-qPCR, RNA-Seq, etc.) in vitro and in vivo to study the physiological roles of hnRNPU in Sertoli cells on regulating testicular development in prepubertal testes. We identified a co-transcription factor, hnRNPU, which is highly expressed in mouse and human Sertoli cells and required for neonatal Sertoli cell and pre-pubertal testicular development. Conditional knockout of hnRNPU in murine Sertoli cells leads to severe testicular atrophy and male sterility, characterized by rapid depletion of both Sertoli cells and germ cells and failure of spermatogonia proliferation and migration during pre-pubertal testicular development. At molecular levels, we found that hnRNPU interacts with two Sertoli cell markers WT1 and SOX9, and enhances the expression of two transcriptional factors, and in Sertoli cells by directly binding to their promoter regions. Further RNA-Seq and bioinformatics analyses revealed the transcriptome-wide of key genes essential for Sertoli cell and germ cell fate control, such as biological adhesion, proliferation and migration, were deregulated in Sertoli cell-specific hnRNPU mutant testes. Our findings demonstrate an essential role of hnRNPU in Sertoli cells for prepubertal testicular development and testis microenvironment maintenance and define a new insight for our understanding of male infertility therapy.
Topics: Animals; Cell Differentiation; Gene Expression; Gene Expression Regulation; Heterogeneous-Nuclear Ribonucleoprotein U; Humans; Male; Mice; Mice, Inbred C57BL; SOX9 Transcription Factor; SOXE Transcription Factors; Sertoli Cells; Testis; Transcription Factors; Transcriptome; WT1 Proteins
PubMed: 34815802
DOI: 10.7150/thno.66819 -
Orphanet Journal of Rare Diseases Nov 2021For chronic congenital endocrine conditions, age at diagnosis is a key issue with implications for optimal management and psychological concerns. These conditions are... (Observational Study)
Observational Study
BACKGROUND
For chronic congenital endocrine conditions, age at diagnosis is a key issue with implications for optimal management and psychological concerns. These conditions are associated with an increase in the risk of comorbid conditions, particularly as it concerns growth, pubertal development and fertility potential. Clinical presentation and severity depend on the disorder and the patient's age, but diagnosis is often late.
OBJECTIVE
To evaluate age at diagnosis for the most frequent congenital endocrine diseases affecting growth and/or development.
PATIENTS AND METHODS
This observational cohort study included all patients (n = 4379) with well-defined chronic congenital endocrine diseases-non-acquired isolated growth hormone deficiency (IGHD), isolated congenital hypogonadotropic hypogonadism (ICHH), ectopic neurohypophysis (NH), Turner syndrome (TS), McCune-Albright syndrome (MAS), complete androgen insensitivity syndrome (CAIS) and gonadal dysgenesis (GD)-included in the database of a single multisite reference center for rare endocrine growth and developmental disorders, over a period of 14 years. Patients with congenital hypothyroidism and adrenal hyperplasia were excluded as they are generally identified during neonatal screening.
RESULTS
Median age at diagnosis depended on the disease: first year of life for GD, before the age of five years for ectopic NH and MAS, 8-10 years for IGHD, TS (11% diagnosed antenatally) and CAIS and 17.4 years for ICHH. One third of the patients were diagnosed before the age of five years. Diagnosis occurred in adulthood in 22% of cases for CAIS, 11.6% for TS, 8.8% for GD, 0.8% for ectopic NH, and 0.4% for IGHD. A male predominance (2/3) was observed for IGHD, ectopic NH, ICHH and GD.
CONCLUSION
The early recognition of growth/developmental failure during childhood is essential, to reduce time-to-diagnosis and improve outcomes.
Topics: Adult; Androgen-Insensitivity Syndrome; Child, Preschool; Cohort Studies; Endocrine System Diseases; Gonadal Dysgenesis; Humans; Infant, Newborn; Male; Rare Diseases
PubMed: 34736502
DOI: 10.1186/s13023-021-02099-3 -
Journal of Eating Disorders Aug 2021Childhood-onset Anorexia Nervosa (AN) is recognised to be atypical in presentation, both in terms of extent and nature of eating pathology, exercise and compensatory...
BACKGROUND
Childhood-onset Anorexia Nervosa (AN) is recognised to be atypical in presentation, both in terms of extent and nature of eating pathology, exercise and compensatory behaviours with many falling short of full diagnostic criteria. Failure to consider an eating disorder diagnosis in youth who present with extreme weight loss may have serious immediate and long term implications. However, failure to consider other non-organic causes of weight loss may be equally detrimental to the child's health.
CASE PRESENTATION
This case reports on the acute presentation of a 12-year old boy, who presented to hospital in a severely malnourished state eight weeks into lockdown. To compensate for Covid-19 induced restrictions on sporting activity, this boy had followed a self-imposed daily schedule of arduous exercise, without increasing his nutritional intake. This report examines the clinical features suggestive of AN and other differential diagnosis. A discussion on the specific diagnostic differential of exercise addiction and challenges faced by youth during Covid-19 restrictions are presented.
CONCLUSION
Accepting that AN may present atypically in pre-pubertal youth, it is important that clinicians maintain an open mind in youth presenting without goal directed weight loss. Although weight loss was significant in this case, it was due to an excessive exercise regime. This may have commenced as a coping strategy in response to Covid-19 restrictions but subsequently became excessive and impairing in nature. The collateral damage of Covid-19 mandated restrictions, aimed at containing the spread of the virus, are evident in this case. Clinicians need to be alert to potentially maladaptive coping strategies and unusual or altered pathways of presentation, especially in younger children during these challenging times.
PubMed: 34372925
DOI: 10.1186/s40337-021-00450-4