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Frontiers in Pediatrics 2020Patients with anorexia nervosa (AN) experience medical complications including impaired bone metabolism, increased fracture rate, kidney stones and chronic renal...
Patients with anorexia nervosa (AN) experience medical complications including impaired bone metabolism, increased fracture rate, kidney stones and chronic renal failure. However, the mechanisms of such complications are not fully understood. Healthy adolescents have been shown to have higher PTH levels when compared with pre-pubertal children and adults. Given the importance of central measures of calcium and vitamin D metabolism in bone and kidney health, 25-hydroxyvitamin D (25OHD) and parathyroid hormone (PTH) have been extensively investigated in patients with AN, however none of the previous studies accounted for age-specific reference ranges for PTH. The aim of this study was to investigate central measures of calcium and vitamin D metabolism in adolescents with newly diagnosed AN using age-specific reference ranges and to determine whether any significant abnormalities required further study. This was a cross-sectional study of 61 adolescents (mean age = aged 15.2 ± 1.56 years) with newly diagnosed AN, referred to a tertiary center over a period of 2 years. Demographic, auxiological, and nutrient (vitamin D and calcium) intake data was obtained. Central measures of calcium and vitamin D metabolism in blood and urine were investigated. PTH results were compared with age-specific reference ranges from the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER). Descriptive statistics and correlation analysis were performed. Low PTH levels were observed in 35% of the cohort. Overall, serum calcium, phosphate and 25OHD were within the reference range. Using loess curves, PTH had a significant negative and non-linear correlation with 25OHD with an inflection point at a 25OHD level of 100 nmol/l, above which the association was no longer present. Correlation analysis did not show a significant association between PTH and total or corrected serum calcium, urine calcium/creatinine (Ca/Cr) ratio, total dietary calcium intake, magnesium or Tanner staging. PTH levels were reduced in approximately a third of adolescents with AN. This observation has not been reported given the universal usage of reference ranges that covers all ages. This finding may unmask a potential role for reduced PTH levels in the pathogenesis of kidney stones and bone phenotype in patients with AN.
PubMed: 32219087
DOI: 10.3389/fped.2020.00099 -
Translational Andrology and Urology Oct 2020The treatment modalities for testicular tumors (surgery, chemotherapy, and radiotherapy), have different associated gonadotoxic risks and the overall survival for most... (Review)
Review
The treatment modalities for testicular tumors (surgery, chemotherapy, and radiotherapy), have different associated gonadotoxic risks and the overall survival for most pediatric patients with testicular tumors is very good. However, necessary treatments may lead to the development of lasting gonadal dysfunction and subsequent negative health and quality of life impact. Research with long-term follow-up for patients who have undergone surgery as the sole treatment modality for testicular tumors in childhood are lacking. It is currently unclear if surgery leads to long-term negative functional outcomes. Alkylating agents (e.g., cyclophosphamide) have long been known to increase risk of infertility; platinum-based therapies used frequently for patients with germ-cell tumors (GCTs) also seem to carry some risk of gonadotoxicity, although they have not been as well studied. Radiotherapy to the gonads is toxic and Leydig cells are particularly sensitive to high doses of radiation (>12 Gy). Long-term fertility and hormonal impact vary based on the patient's age, as well as the type and intensity of the oncological treatment prescribed. Counselling regarding fertility risk and preservation options should ideally take place before initiating potentially gonadotoxic treatments. Hypogonadism in peri-pubertal boys can present as delayed onset or failure to progress through puberty. Sperm cryopreservation should be offered for post-pubertal boys who are able to provide a semen sample. For prepubertal boys or young males who cannot provide a semen sample, only experimental options are currently available. Much of the data reviewed here is extrapolated from research done on adult males whose reproductive and hormonal outcomes may not be comparable to younger patients who do not yet have fully developed reproductive systems. Currently, a lack of good quality evidence in this age range causes this restriction to be unavoidable. Patients and their families want to be informed of the risks and treatment options for preserving testicular function. As research continues in this field, it grows more important for urologists to be aware of the outcomes and options for their patients.
PubMed: 33209712
DOI: 10.21037/tau-19-923 -
Cureus Jan 2022It has been observed that 5% of adolescents are affected by pubertal timing disorders. However, there is limited data about this in Pakistan. This cross-sectional study...
INTRODUCTION
It has been observed that 5% of adolescents are affected by pubertal timing disorders. However, there is limited data about this in Pakistan. This cross-sectional study aimed to observe the patterns and causes of delayed puberty (DP) among patients presenting at the endocrine clinic of a tertiary care hospital in Karachi.
METHODS
This observational study was conducted at the endocrine clinic of Jinnah Postgraduate Medical Centre (JPMC) Unit II from 2007 to 2015. A detailed history was obtained from patients presenting with DP. We noted the available demographic data, main complaints, and family history of DP. Physical examinations were performed and the data recorded. Tanner staging was used to assess pubertal development. Relevant laboratory and imaging investigations were performed; data analysis was performed using SPSS 17 (IBM Corp., Armonk, NY).
RESULTS
A total of 2670 patients were registered in the endocrine clinic during the study period, of which 171 presented with DP; 119 were males and 52 were females. There was a wide variation in age at presentation ranging from 10 to 32 years. The majority of patients presented with short stature - 69 (57.98%) males and 19 (36.53%) females. Small testes were present in 28 patients (23.52%); 19 (15.96%) males presented with absent secondary sexual characteristics and infertility was present in three (2.54%) males, primary amenorrhea was observed in 25 (48.07%), both primary amenorrhea and short stature were the presenting symptoms of five (9.61%), and failure of breast development was seen in three (5.76%) females. Constitutional delayed growth and puberty (CDGP) was diagnosed in 42 patients (24.6%). The definitive diagnosis of idiopathic hypogonadotropic hypogonadism (IHH) was made in 18 (10.5%) patients. In another 18 (10.5%) patients, we could not differentiate between CDGP and IHH. Functional hypogonadotropic hypogonadism (FHH) due to non-endocrine illness was present in 16 patients (9.4%). The cause of DP was hypogonadotropic hypogonadism in 33 (19.3%) patients whereas 44 patients presenting with DP could not be classified due to incomplete data.
CONCLUSION
This study showed that CDGP was the most common cause of DP in our patients with the most common presentation being short stature in males and amenorrhea in females. It is essential to differentiate CDGP in children from a small fraction of the pathological and treatable causes of DP.
PubMed: 35228933
DOI: 10.7759/cureus.21574 -
Molecular Psychiatry Mar 2024Tachykinin receptor 3 (TACR3) is a member of the tachykinin receptor family and falls within the rhodopsin subfamily. As a G protein-coupled receptor, it responds to...
Tachykinin receptor 3 (TACR3) is a member of the tachykinin receptor family and falls within the rhodopsin subfamily. As a G protein-coupled receptor, it responds to neurokinin B (NKB), its high-affinity ligand. Dysfunctional TACR3 has been associated with pubertal failure and anxiety, yet the mechanisms underlying this remain unclear. Hence, we have investigated the relationship between TACR3 expression, anxiety, sex hormones, and synaptic plasticity in a rat model, which indicated that severe anxiety is linked to dampened TACR3 expression in the ventral hippocampus. TACR3 expression in female rats fluctuates during the estrous cycle, reflecting sensitivity to sex hormones. Indeed, in males, sexual development is associated with a substantial increase in hippocampal TACR3 expression, coinciding with elevated serum testosterone and a significant reduction in anxiety. TACR3 is predominantly expressed in the cell membrane, including the presynaptic compartment, and its modulation significantly influences synaptic activity. Inhibition of TACR3 activity provokes hyperactivation of CaMKII and enhanced AMPA receptor phosphorylation, associated with an increase in spine density. Using a multielectrode array, stronger cross-correlation of firing was evident among neurons following TACR3 inhibition, indicating enhanced connectivity. Deficient TACR3 activity in rats led to lower serum testosterone levels, as well as increased spine density and impaired long-term potentiation (LTP) in the dentate gyrus. Remarkably, aberrant expression of functional TACR3 in spines results in spine shrinkage and pruning, while expression of defective TACR3 increases spine density, size, and the magnitude of cross-correlation. The firing pattern in response to LTP induction was inadequate in neurons expressing defective TACR3, which could be rectified by treatment with testosterone. In conclusion, our study provides valuable insights into the intricate interplay between TACR3, sex hormones, anxiety, and synaptic plasticity. These findings highlight potential targets for therapeutic interventions to alleviate anxiety in individuals with TACR3 dysfunction and the implications of TACR3 in anxiety-related neural changes provide an avenue for future research in the field.
Topics: Animals; Testosterone; Neuronal Plasticity; Male; Rats; Female; Anxiety; Hippocampus; Receptors, Neurokinin-3; Neurons; Long-Term Potentiation; Receptors, Tachykinin; Rats, Sprague-Dawley
PubMed: 38135756
DOI: 10.1038/s41380-023-02361-z -
Orphanet Journal of Rare Diseases May 2023X-linked adrenal hypoplasia congenita (AHC) is a rare disorder characterized by primary adrenal insufficiency (PAI) and hypogonadotropic hypogonadism (HH), with limited...
BACKGROUND
X-linked adrenal hypoplasia congenita (AHC) is a rare disorder characterized by primary adrenal insufficiency (PAI) and hypogonadotropic hypogonadism (HH), with limited clinical and genetic characterization.
METHODS
The clinical, biochemical, genetic, therapeutic, and follow-up data of 42 patients diagnosed with X-linked AHC were retrospectively analysed.
RESULTS
Hyperpigmentation (38/42, 90%), vomiting/diarrhoea (20/42, 48%), failure to thrive (13/42, 31%), and convulsions (7/42, 17%) were the most common symptoms of X-linked AHC at onset. Increased adrenocorticotropic hormone (ACTH) (42/42, 100%) and decreased cortisol (37/42, 88%) were the most common laboratory findings, followed by hyponatremia (32/42, 76%) and hyperkalaemia (29/42, 69%). Thirty-one patients presented with PAI within the first year of life, and 11 presented after three years of age. Three of the thirteen patients over the age of 14 exhibited spontaneous pubertal development, and ten of them experienced delayed puberty due to HH. Six patients receiving human chorionic gonadotropin (hCG) therapy exhibited a slight increase in testicular size and had rising testosterone levels (both P < 0.05). The testicular volumes of the three patients with pulsatile gonadotropin-releasing hormone (GnRH) therapy were larger than those of the six patients undergoing hCG therapy (P < 0.05), and they also exhibited some growth in terms of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone. Of the 42 patients, three had an Xp21 deletion, and 39 had an isolated DAX1 defect. Most patients (9/10) with entire DAX1 deletion accounting for 23.8% (10/42) of the total variants had early onset age of less than one year.
CONCLUSIONS
This study details the clinical features and genetic spectra of X-linked AHC. Patients with X-linked AHC show a bimodal distribution of the age of onset, with approximately 70% presenting within the first year of life. Pulsatile GnRH may be recommended for HH when hCG therapy is not satisfactory, although it is difficult to achieve normal testicular volume. The combination of clinical features and molecular tests provides information for an accurate diagnosis.
Topics: Child; Humans; Male; East Asian People; Gonadotropin-Releasing Hormone; Hypoadrenocorticism, Familial; Hypogonadism; Mutation; Retrospective Studies; Testosterone
PubMed: 37237297
DOI: 10.1186/s13023-023-02737-y -
Animals : An Open Access Journal From... Oct 2019Poor sow retention due to reproductive failure is a common reproductive inefficiency amongst piggeries. This shows that traditional methods of gilt selection are...
Poor sow retention due to reproductive failure is a common reproductive inefficiency amongst piggeries. This shows that traditional methods of gilt selection are inadequate and a marker of reproductive success is needed. The aim of this study was to determine whether circulating levels of AMH and E2 at D80 and D160 are associated with uterine and ovarian traits at D160. Uterine weight, horn length and horn diameter were measured, and ovarian follicle counts were determined histologically. There was a negative relationship between both D80 and D160 AMH levels and D160 ovarian follicle populations. There was also a positive relationship between D80 E2 levels and uterine capacity in gilts that were pubertal at D160. The findings indicate that D80 and D160 AMH could be used to predict ovarian reserve and that D80 E2 levels may be indicative of uterine capacity in precocial gilts.
PubMed: 31619004
DOI: 10.3390/ani9100811 -
Frontiers in Endocrinology 2024We present the evolution of GHD in adolescent males with persistent growth failure, in whom the diagnosis was established after a second GH stimulation test (GST).
INTRODUCTION
We present the evolution of GHD in adolescent males with persistent growth failure, in whom the diagnosis was established after a second GH stimulation test (GST).
METHODS
We performed a retrospective chart review of children who presented for short stature (height less < 2SD for mean/mid-parental height) and/or growth failure (sustained growth velocity < 0 SD) to pediatric endocrinology at Mount Sinai Kravis Children's Hospital, New York and who had 2 GSTs. Data collected from electronic medical records were analyzed using SPSS v28.0.
RESULTS
Of 53 patients included, 42 were males. Average GH peak on initial GST was 15.48 ± 4.92 ng/ml, at 10.07 ± 2.65 years, mean height -1.68 ± 0.56SD(28% had <2SD), IGF-1 -1.00 ± 0.88SD. After 2.23 ± 1.22 years, at 12.04 ± 2.41years, height SDs decreased to -1.82 ± 0.63SD and IGF-1 was -1.08 ± 0.84SD. At repeat GST, average GH peak was 7.59 ± 2.12 ng/dL, with 36% ≤7 ng/dl and 32% in puberty. 12 males reached adult height of 0.08 ± 0.69 SD with a mean height gain of 1.83 ± 0.56SD(p<0.005), IGF-1 of -1.15 ± 0.81SD after 4.64 ± 1.4 years of GH.
CONCLUSION
We offer evidence for Evolving Growth Hormone Deficiency (EGHD) through repeat GST in children with persistent growth slowdown, even with pubertal progression; emphasizing the need for careful longitudinal follow-up to make accurate diagnosis.
Topics: Humans; Male; Human Growth Hormone; Adolescent; Retrospective Studies; Child; Growth Disorders; Female; Body Height; Insulin-Like Growth Factor I; Proof of Concept Study; Dwarfism, Pituitary
PubMed: 38752175
DOI: 10.3389/fendo.2024.1398171 -
Frontiers in Endocrinology 2022Despite decades of experience, the diagnosis of growth hormone deficiency (GHD) remains challenging, especially in peripubertal children. Failure to respond to GH... (Review)
Review
Despite decades of experience, the diagnosis of growth hormone deficiency (GHD) remains challenging, especially in peripubertal children. Failure to respond to GH stimulation tests (GHSTs) is needed to confirm GHD, but long-standing controversies regarding the number of tests needed and the interpretation of GH peaks are still a matter of debate worldwide. Diagnostic workup is even more problematic in short children with slow growth and delayed sexual development: they often exhibit low GH peaks under GHST, which often normalize as puberty progresses. Consequently, this transient suboptimal response to GHST may result in GH overtreatment, carrying both health and economic concerns. Considering the complex and bound link between GH axis and sex steroids, the use of sex steroid priming prior to GHST might be helpful in peripubertal setting. However, its use is still controversial. There is no consensus regarding patient selection, timing, dose, and preparation of sex steroids. In this review, we aim to overview the use of sex steroid priming in clinical practice, highlighting the need to develop appropriate guidelines in order to overcome diagnostic pitfalls in peripubertal age.
Topics: Humans; Child; Human Growth Hormone; Dwarfism, Pituitary; Gonadal Steroid Hormones; Puberty; Hypopituitarism; Steroids
PubMed: 36523598
DOI: 10.3389/fendo.2022.1072271 -
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 -
The Journal of Veterinary Medical... May 2023Cryptorchid bulls have low economic value owing to the effects of masculinization. Moreover, surgical removal of an ectopic testis is difficult in certain clinical...
Cryptorchid bulls have low economic value owing to the effects of masculinization. Moreover, surgical removal of an ectopic testis is difficult in certain clinical cases. Recently, immunocastration has garnered popularity as a nonsurgical castration method in pig farming; however, the effects of immunocastration on cryptorchid bulls are yet to be yet. Herein, we investigated endocrine changes due to immunocastration in cryptorchid bulls and studied its effectiveness. This study included 13 Holstein bulls diagnosed with cryptorchidism and classified into two groups based on pubertal period: <8 months of age (pregroup) and ≥8 months of age (postgroup). Antigonadotropin-releasing hormone (GnRH) vaccine was used for immunocastration, and two vaccine doses were administered. Blood testosterone and anti-Müllerian hormone (AMH) levels were measured and analyzed for endocrine evaluation. The testosterone levels significantly decreased following the start of immunocastration in both groups, thereby confirming the efficacy of antiGnRH vaccination in cryptorchid bulls. The AMH levels significantly increased in the pregroup with two antiGnRH vaccination, suggesting a compensatory response via the neutralization of GnRH antibodies. The AMH levels did not significantly change in the postgroup, indicating the partial suppression of AMH secretion in Sertoli cells during sexual maturation and failure of Sertoli cell maturation. Thus, we successfully restrained the serum testosterone levels in cryptorchid bulls using antiGnRH vaccine. The testosterone levels are a useful indicator of the immunocastration effect on cryptorchid bulls. Hereafter, a vaccine program that can sustain the castration effect on cryptorchid bulls is necessary.
Topics: Male; Animals; Cattle; Swine; Gonadotropin-Releasing Hormone; Cryptorchidism; Testis; Testosterone; Vaccines; Cattle Diseases; Swine Diseases
PubMed: 36927961
DOI: 10.1292/jvms.22-0571