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Journal of Clinical Research in... Jun 202417α‑hydroxylase/17,20‑lyase deficiency (17OHD) is a rare form of congenital adrenal hyperplasia that causes decreased cortisol and sex steroid levels and leads to...
17α‑hydroxylase/17,20‑lyase deficiency (17OHD) is a rare form of congenital adrenal hyperplasia that causes decreased cortisol and sex steroid levels and leads to high production of adrenocorticotropic hormone (ACTH). Although affected patients have absolute cortisol deficiency, they do not show clinical signs of cortisol deficiency or hyperpigmentation. These patients most commonly present with delayed puberty and amenorrhea at late pubertal age. Impaired production of sex steroids leads to ambiguous or female external genitalia in affected 46, XY individuals. In this report, we describe a patient with 17OHD who presented with hyperpigmentation and hypergonodotropic hypogonadism while receiving chemotherapy.
PubMed: 38912718
DOI: 10.4274/jcrpe.galenos.2024.2024-3-13 -
The Indian Journal of Radiology &... Jul 2024Macrodystrophia lipomatosa (MDL) is a rare congenital, nonhereditary anomaly characterized by overgrowth of all the mesenchymal elements, predominantly the fibroadipose...
Macrodystrophia lipomatosa (MDL) is a rare congenital, nonhereditary anomaly characterized by overgrowth of all the mesenchymal elements, predominantly the fibroadipose tissue in a sclerotomal distribution commonly involving the median nerve territory in the upper extremity and plantar nerve territory in the lower extremity. It can be either static or progressive, with the former being the more common. MDL is usually present since birth and the affected digit/region increases in length and girth, and growth ceases after puberty. We discuss a rare case of ulnar nerve territory involvement that progressed to grow even after puberty.
PubMed: 38912255
DOI: 10.1055/s-0043-1777745 -
Indian Journal of Endocrinology and... 2024Bone age (BA) assessment is important in evaluating disorders of growth and puberty; the Greulich and Pyle atlas method (GP) is most used. We aimed to determine the...
INTRODUCTION
Bone age (BA) assessment is important in evaluating disorders of growth and puberty; the Greulich and Pyle atlas method (GP) is most used. We aimed to determine the weightage to be attributed by raters to various segments of the hand x-ray, namely, distal end of radius-ulna (RU), carpals, and short bones for rating bone age using the GP atlas method.
METHODS
692 deidentified x-rays from a previous study (PUNE-dataset) and 400 from the Radiological Society of North America (RSNA-dataset) were included in the study. Mean of BA assessed by experienced raters was termed reference rating. Linear regression was used to model reference age as function of age ratings of the three segments. The root-mean-square-error (RMSE) of segmental arithmetic mean and weighted mean with respect to reference rating were computed for both datasets.
RESULTS
Short bones were assigned the highest weightage. Carpals were assigned higher weightage in pre-pubertal PUNE participants as compared to RSNA, vice-versa in RU segment of post-pubertal participants. The RMSE of weighted mean ratings was significantly lower than for the arithmetic mean in the PUNE dataset.
CONCLUSION
We thus determined weightage to be attributed by raters to segments of the hand x-ray for assessment of bone age by the GP method.
PubMed: 38911117
DOI: 10.4103/ijem.ijem_237_23 -
Indian Journal of Endocrinology and... 2024This study aimed to distinguish isolated hypogonadotropic hypogonadism (IHH) from constitutional delay in growth and puberty (CDGP) by various hormonal tests in both...
Role of Inhibin B, AMH, GnRHa Test and HCG Stimulation Test to Distinguish Isolated Hypogonadotropic Hypogonadism (IHH) from Constitutional Delay in Growth and Puberty (CDGP).
INTRODUCTION
This study aimed to distinguish isolated hypogonadotropic hypogonadism (IHH) from constitutional delay in growth and puberty (CDGP) by various hormonal tests in both sexes.
METHODS
Boys with testicular volume (TV) <4 ml (14-18 years) and girls with breast B stage (13-18 years) were enrolled in this study. A detailed history, clinical examination and hormonal analysis including basal luteinising hormone (LH), follicle-stimulating hormone (FSH), inhibin B, anti-Mullerian hormone (AMH), testosterone (boys), oestradiol (girls), triptorelin stimulation test and 3-day human chorionic gonadotropin (HCG) stimulation test (boys) were performed. All patients were followed for 1.5 years or till 18 years of age. Receiver operating characteristic (ROC) curve analysis was performed to determine the optimal cut-offs with sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for various hormones to distinguish IHH from CDGP.
RESULTS
Of 34 children (male: 22 and female: 12), CDGP and IHH were diagnosed in 21 and 13 children, respectively. 4 hours post-triptorelin LH had the highest sensitivity (100%) and specificity (100%) for identifying IHH in both sexes. Basal inhibin B had good sensitivity (male: 85.7% and female: 83.8%) and specificity (male: 93.3% and female: 100%) for diagnosing IHH. 24 hours post-triptorelin testosterone (<34.5 ng/dl), day 4 post-HCG testosterone (<99.7 ng/dl) and 24 hours post-triptorelin oestradiol (<31.63 pg/ml) had reasonable sensitivity and specificity for identifying IHH. Basal LH, FSH and AMH were poor discriminators for IHH in both sexes.
CONCLUSION
The best indicator was post-triptorelin 4-hour LH followed by inhibin B, which had a reasonable diagnostic utility to distinguish IHH from CDGP in both boys and girls.
PubMed: 38911112
DOI: 10.4103/ijem.ijem_146_23 -
Progress in Orthodontics Jun 2024Determining the right time for orthodontic treatment is one of the most important factors affecting the treatment plan and its outcome. The aim of this study is to...
INTRODUCTION
Determining the right time for orthodontic treatment is one of the most important factors affecting the treatment plan and its outcome. The aim of this study is to estimate the mandibular growth stage based on cervical vertebral maturation (CVM) in lateral cephalometric radiographs using artificial intelligence. Unlike previous studies, which use conventional CVM stage naming, our proposed method directly correlates cervical vertebrae with mandibular growth slope.
METHODS AND MATERIALS
To conduct this study, first, information of people achieved in American Association of Orthodontics Foundation (AAOF) growth centers was assessed and after considering the entry and exit criteria, a total of 200 people, 108 women and 92 men, were included in the study. Then, the length of the mandible in the lateral cephalometric radiographs that were taken serially from the patients was calculated. The corresponding graphs were labeled based on the growth rate of the mandible in 3 stages; before the growth peak of puberty (pre-pubertal), during the growth peak of puberty (pubertal) and after the growth peak of puberty (post-pubertal). A total of 663 images were selected for evaluation using artificial intelligence. These images were evaluated with different deep learning-based artificial intelligence models considering the diagnostic measures of sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV). We also employed weighted kappa statistics.
RESULTS
In the diagnosis of pre-pubertal stage, the convolutional neural network (CNN) designed for this study has the higher sensitivity and NPV (0.84, 0.91 respectively) compared to ResNet-18 model. The ResNet-18 model had better performance in other diagnostic measures of the pre-pubertal stage and all measures in the pubertal and post-pubertal stages. The highest overall diagnostic accuracy was also obtained using ResNet-18 model with the amount of 87.5% compared to 81% in designed CNN.
CONCLUSION
The artificial intelligence model trained in this study can receive images of cervical vertebrae and predict mandibular growth status by classifying it into one of three groups; before the growth spurt (pre-pubertal), during the growth spurt (pubertal), and after the growth spurt (post-pubertal). The highest accuracy is in post-pubertal stage with the designed networks.
Topics: Humans; Cephalometry; Mandible; Male; Female; Cervical Vertebrae; Artificial Intelligence; Child; Adolescent; Puberty; Deep Learning
PubMed: 38910180
DOI: 10.1186/s40510-024-00527-1 -
Clinical Epigenetics Jun 2024Genetic and environmental factors are implicated in many developmental processes. Recent evidence, however, has suggested that epigenetic changes may also influence the...
BACKGROUND
Genetic and environmental factors are implicated in many developmental processes. Recent evidence, however, has suggested that epigenetic changes may also influence the onset of puberty or the susceptibility to a wide range of diseases later in life. The present study aims to investigate changes in genomic DNA methylation profiles associated with pubertal onset analyzing human peripheral blood leukocytes from three different groups of subjects: 19 girls with central precocious puberty (CPP), 14 healthy prepubertal girls matched by age and 13 healthy pubertal girls matched by pubertal stage. For this purpose, the comparisons were performed between pre- and pubertal controls to identify changes in normal pubertal transition and CPP versus pre- and pubertal controls.
RESULTS
Analysis of methylation changes associated with normal pubertal transition identified 1006 differentially methylated CpG sites, 86% of them were found to be hypermethylated in prepubertal controls. Some of these CpG sites reside in genes associated with the age of menarche or transcription factors involved in the process of pubertal development. Analysis of methylome profiles in CPP patients showed 65% and 55% hypomethylated CpG sites compared with prepubertal and pubertal controls, respectively. In addition, interestingly, our results revealed the presence of 43 differentially methylated genes coding for zinc finger (ZNF) proteins. Gene ontology and IPA analysis performed in the three groups studied revealed significant enrichment of them in some pathways related to neuronal communication (semaphorin and gustation pathways), estrogens action, some cancers (particularly breast and ovarian) or metabolism (particularly sirtuin).
CONCLUSIONS
The different methylation profiles of girls with normal and precocious puberty indicate that regulation of the pubertal process in humans is associated with specific epigenetic changes. Differentially methylated genes include ZNF genes that may play a role in developmental control. In addition, our data highlight changes in the methylation status of genes involved in signaling pathways that determine the migration and function of GnRH neurons and the onset of metabolic and neoplastic diseases that may be associated with CPP in later life.
Topics: Humans; Puberty, Precocious; Female; DNA Methylation; Child; CpG Islands; Epigenesis, Genetic; Epigenome; Case-Control Studies
PubMed: 38909248
DOI: 10.1186/s13148-024-01683-1 -
Trends in Immunology Jun 2024Over the past decade our research has implemented a multimodal approach to human lymphopoiesis, combining clonal-scale mapping of lymphoid developmental architecture... (Review)
Review
Over the past decade our research has implemented a multimodal approach to human lymphopoiesis, combining clonal-scale mapping of lymphoid developmental architecture with the monitoring of dynamic changes in the pattern of lymphocyte generation across ontogeny. We propose that lymphopoiesis stems from founder populations of CD127/interleukin (IL)7R or CD127/IL7R early lymphoid progenitors (ELPs) polarized respectively toward the T-natural killer (NK)/innate lymphoid cell (ILC) or B lineages, arising from newly characterized CD117 multi-lymphoid progenitors (MLPs). Recent data on the lifelong lymphocyte dynamics of healthy donors suggest that, after birth, lymphopoiesis may become increasingly oriented toward the production of B lymphocytes. Stemming from this, we posit that there are three major developmental transitions, the first occurring during the neonatal period, the next at puberty, and the last during aging.
PubMed: 38908962
DOI: 10.1016/j.it.2024.05.007 -
Journal of Pediatric and Adolescent... Jun 2024We aimed to identify critical factors for uterine development by comparing uterine volume (UV) among patients with Turner syndrome (TS) who underwent pubertal induction...
STUDY OBJECTIVE
We aimed to identify critical factors for uterine development by comparing uterine volume (UV) among patients with Turner syndrome (TS) who underwent pubertal induction (PI), patients with TS who had natural menarche (NM), and patients in a non-TS control group.
METHODS
This retrospective case-control study included patients with TS who had undergone PI with oral estrogen in a PI group(n=31) and a NM group(n=7). The control group included patients without TS with spontaneous puberty who underwent pelvic ultrasound at 16 years of age. For TS patients, both the UV from the first ultrasound performed at age 16 or older (1st-UV) and the UV from the most recent final ultrasound (final-UV) were obtained.
RESULTS
The 1st-UV was larger for patients in the NM group than those in the PI group (p<0.001), but did not differ significantly between the NM and control groups (p=0.375). The final-UV of the PI group was larger than their 1st-UV (p<0.001), but still smaller than the NM group (p=0.021). HRT duration and 1st-UV of PI group were positively correlated (p=0.048). There were no variables that were significantly correlated with final-UV of PI group.
CONCLUSION
Patients with TS who experienced NM showed normal uterine development, but TS patients who underwent PI showed significantly smaller, undeveloped UV. While HRT duration and UV are positively correlated at the beginning of HRT, it is unclear what determines the final UV; however, late PI initiation and use of oral estrogen probably contributed to the lack of UV development.
PubMed: 38906216
DOI: 10.1016/j.jpag.2024.06.006 -
European Child & Adolescent Psychiatry Jun 2024Klinefelter syndrome (KS), also referred to as XXY syndrome, is a significant but inadequately studied risk factor for neuropsychiatric disability. Whether alterations...
BACKGROUND
Klinefelter syndrome (KS), also referred to as XXY syndrome, is a significant but inadequately studied risk factor for neuropsychiatric disability. Whether alterations in functional brain connectivity or pubertal delays are associated with aberrant cognitive-behavioral outcomes in individuals with KS is largely unknown. In this observational study, we investigated KS-related alterations in the resting-state brain network, testosterone level, and cognitive-behavioral impairment in adolescents with Klinefelter syndrome.
METHODS
We recruited 46 boys with KS, ages 8 to 17 years, and 51 age-matched typically developing (TD) boys. All participants underwent resting-state functional magnetic resonance imaging scans, pubertal, and cognitive-behavioral assessments. Resting-state functional connectivity and regional brain activity of the participants were assessed.
RESULTS
We found widespread alterations in global functional connectivity among the inferior frontal gyrus, temporal-parietal area, and hippocampus in boys with KS. Aberrant regional activities, including enhanced fALFF in the motor area and reduced ReHo in the caudate, were also found in the KS group compared to the TD children. Further, using machine learning methods, brain network alterations in these regions accurately differentiated boys with KS from TD controls. Finally, we showed that the alterations of brain network properties not only effectively predict cognitive-behavioral impairment in boys with KS, but also appear to mediate the association between total testosterone level and language ability, a cognitive domain at particular risk for dysfunction in this condition.
CONCLUSION
Our results offer an informatic neurobiological foundation for understanding cognitive-behavioral impairments in individuals with KS and contribute to our understanding of the interplay between pubertal status, brain function, and cognitive-behavioral outcome in this population.
PubMed: 38904702
DOI: 10.1007/s00787-024-02501-y -
Molecular Medicine Reports Aug 2024Estrogens are involved in a number of physiological functions, including in the development of the brain, growth, reproduction and metabolism. The biological actions of... (Review)
Review
Estrogens are involved in a number of physiological functions, including in the development of the brain, growth, reproduction and metabolism. The biological actions of estrogens are achieved by binding to estrogen receptors (ERs) in numerous types of tissues. ERα and ERβ belong to the nuclear receptor superfamily and the G‑protein coupled ER1 (GPER1) is a membrane receptor. The primary biologically active estrogen, 17β‑estradiol demonstrates a high affinity for ERs. Mechanistically, estrogens bind to the ERs in the nucleus, and the complex then dimerize and bind to estrogen response elements (EREs) located in the promoter regions of the target genes. This is referred to as the genomic mechanism of ERs' function. Furthermore, ERs can also act through kinases and other molecular interactions leading to specific gene expression and functions, referred to as the non‑genomic mechanism. While ERα and ERβ exert their functions via both genomic and non‑genomic pathways, GPER1 exerts its function primarily via the non‑genomic pathways. Any aberrations in ER signaling can lead to one of a number of diseases such as disorders of growth and puberty, fertility and reproduction abnormalities, cancer, metabolic diseases or osteoporosis. In the present review, a focus is placed on three target tissues of estrogens, namely the bones, the breasts and the brain, as paradigms of the multiple facets of the ERs. The increasing prevalence of breast cancer, particularly hormone receptor‑positive breast cancer, is a challenge for the development of novel antihormonal therapies other than tamoxifen and aromatase inhibitors, to minimize toxicity from the long treatment regimens in patients with breast cancer. A complete understanding of the mechanism of action of ERs in bones may highlight options for novel targeted treatments for osteoporosis. Likewise, the aging of the brain and related diseases, such as dementia and depression, are associated with a lack of estrogen, particularly in women following menopause. Furthermore, gender dysphoria, a discordance between experienced gender and biological sex, is commonly hypothesized to emerge due to discrepancies in cerebral and genital sexual differentiation. The exact role of ERs in gender dysphoria requires further research.
Topics: Humans; Receptors, Estrogen; Signal Transduction; Brain; Bone and Bones; Breast; Animals; Female; Estrogens; Receptors, G-Protein-Coupled
PubMed: 38904201
DOI: 10.3892/mmr.2024.13268