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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 -
Cureus Jul 2023Crohn's disease (CD) is a chronic inflammatory bowel disease involving entire gastrointestinal tract, most commonly affecting terminal ileum and colon. It usually...
Crohn's disease (CD) is a chronic inflammatory bowel disease involving entire gastrointestinal tract, most commonly affecting terminal ileum and colon. It usually presents with gastrointestinal symptoms like bloody diarrhea, fever and loss of weight. The clinical course of CD includes gastrointestinal complications like fistulas, abscesses and perianal disease. Inflammatory bowel diseases (IBD) are usually diagnosed during childhood and adolescence, majority during puberty and pubertal growth spurt. Various extraintestinal manifestations may be a presentation of CD that poses a diagnostic challenge. Growth failure is an important complication of IBD rather than a manifestation. Herein we present a case of a 16-year-old Sri Lankan girl presenting with growth failure and primary amenorrhea. She had minimal gastrointestinal symptoms. She also had microcytic anemia with marginally elevated inflammatory markers and hormonal profile. She underwent colonoscopy and was diagnosed to have Crohn's disease confirmed by ileal biopsy. On initiation of treatment with immunosuppressants, she attained menarche, although no improvement in height was observed.
PubMed: 37593289
DOI: 10.7759/cureus.42020 -
Indian Journal of Pediatrics Oct 2023Enlargement of breasts among boys is termed gynecomastia. This could be due to an alteration in the androgen-estrogen ratio along with the effects of other hormones... (Review)
Review
Enlargement of breasts among boys is termed gynecomastia. This could be due to an alteration in the androgen-estrogen ratio along with the effects of other hormones including growth hormone, insulin like growth factor 1, prolactin, and other factors affecting aromatase enzyme. The common causes of gynecomastia are pubertal gynecomastia, obesity, drugs and hypogonadism. Several other diseases including liver or renal failure, thyrotoxicosis, Klinefelter syndrome, tumors and environmental pollutants can cause gynecomastia. History and clinical examination will help formulate targeted investigations and management. The factors to be evaluated in these include examination of breasts and testes, in addition to other parts of systemic examination. Treatment of underlying disorders can improve gynecomastia, such as use of testosterone in hypogonadism. Some boys may not need any intervention as gynecomastia may resolve on its own. Medical management is useful in simple gynecomastia. Tamoxifen has been tried successfully in adolescents with gynecomastia. Other drugs including clomiphene, danazol, letrozole and anastrozole have not been consistently useful in this age group. In severe chronic gynecomastia, surgery is the treatment of choice.
Topics: Adolescent; Male; Humans; Gynecomastia; Hypertrophy; Tamoxifen; Growth Hormone; Hypogonadism
PubMed: 37592101
DOI: 10.1007/s12098-023-04810-7 -
Endocrine Reviews Jan 2024Kisspeptin (KP) and neurokinin B (NKB) are neuropeptides that govern the reproductive endocrine axis through regulating hypothalamic gonadotropin-releasing hormone... (Review)
Review
Kisspeptin (KP) and neurokinin B (NKB) are neuropeptides that govern the reproductive endocrine axis through regulating hypothalamic gonadotropin-releasing hormone (GnRH) neuronal activity and pulsatile GnRH secretion. Their critical role in reproductive health was first identified after inactivating variants in genes encoding for KP or NKB signaling were shown to result in congenital hypogonadotropic hypogonadism and a failure of pubertal development. Over the past 2 decades since their discovery, a wealth of evidence from both basic and translational research has laid the foundation for potential therapeutic applications. Beyond KP's function in the hypothalamus, it is also expressed in the placenta, liver, pancreas, adipose tissue, bone, and limbic regions, giving rise to several avenues of research for use in the diagnosis and treatment of pregnancy, metabolic, liver, bone, and behavioral disorders. The role played by NKB in stimulating the hypothalamic thermoregulatory center to mediate menopausal hot flashes has led to the development of medications that antagonize its action as a novel nonsteroidal therapeutic agent for this indication. Furthermore, the ability of NKB antagonism to partially suppress (but not abolish) the reproductive endocrine axis has supported its potential use for the treatment of various reproductive disorders including polycystic ovary syndrome, uterine fibroids, and endometriosis. This review will provide a comprehensive up-to-date overview of the preclinical and clinical data that have paved the way for the development of diagnostic and therapeutic applications of KP and NKB.
Topics: Pregnancy; Female; Humans; Neurokinin B; Kisspeptins; Gonadotropin-Releasing Hormone; Reproduction; Hypothalamus
PubMed: 37467734
DOI: 10.1210/endrev/bnad023 -
Hormone Research in Paediatrics 2024Recombinant human growth hormone (rhGH) therapy effectively increases height in various disorders of childhood growth. However, whether rhGH affects pubertal timing is... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Recombinant human growth hormone (rhGH) therapy effectively increases height in various disorders of childhood growth. However, whether rhGH affects pubertal timing is unclear. We aimed to review systematically published evidence on the effect of rhGH on pubertal timing.
METHODS
Embase, MEDLINE, and Cochrane Library databases were searched until December 2021 on randomized and non-randomized controlled studies of rhGH in children.
RESULTS
Twenty-five articles (n = 1,433 children) were identified, describing 12 randomized and 13 non-randomized controlled studies in children with idiopathic short stature (ISS; 15 studies), small for gestational age (n = 6 studies), chronic renal failure (n = 3), Noonan syndrome (n = 1), and growth hormone deficiency (n = 1). Significant differences in the effects of rhGH on pubertal timing were found by clinical indication. Only among children with ISS, rhGH promoted earlier age at pubertal timing (mean difference = -0.46 years; 95% CI, -0.90 to -0.03; 9 studies; n total = 397) or higher relative risk for pubertal onset during study follow-up (1.26; 95% CI, 1.03 to 1.54; 6 studies; n total = 284).
CONCLUSIONS
Treatment with rhGH appears to promote earlier pubertal timing among children with ISS. Evidence was lacking in children with growth hormone deficiency due to the absence of studies with untreated controls.
Topics: Child; Humans; Human Growth Hormone; Growth Hormone; Body Height; Growth Disorders; Dwarfism, Pituitary; Recombinant Proteins
PubMed: 37075730
DOI: 10.1159/000530578 -
Journal of Pediatric Urology Aug 2023Anatomical studies of hypospadias show failure of zipping-up of histologically normal urethral plate and corpus spongiosum. With the commonly utilized substitution...
Post-pubertal functional outcomes of one-stage anatomical reconstruction of the corpus spongiosum, bulbo-spongiosus muscle and dartos in 46 children with proximalhypospadias.
INTRODUCTION
Anatomical studies of hypospadias show failure of zipping-up of histologically normal urethral plate and corpus spongiosum. With the commonly utilized substitution urethroplasties for proximal hypospadias, a reconstructed urethra of just an "epithelial-lined tube" with no spongiosal support, is apt to long-term urinary and ejaculatory dysfunctions. We completed a one-stage anatomical reconstruction in children with proximal hypospadias whenever the ventral curvature could be reduced to <30° and evaluated the post-pubertal outcomes.
METHOD
This is a retrospective analysis of prospectively maintained data on one-stage anatomical repair of proximal hypospadias between 2003 and 2021. In children with proximal hypospadias, the corpus spongiosum, bulbo-spongiosus muscle (BSM), Bucks', and Dartos' layers of the shaft were anatomically re-aligned prior to assessing the ventral curvature visually. When the curvature was >30°, the urethral plate was divided at the glans for a 2-stage procedure, and those patients were excluded from the study. Otherwise, the anatomical repair was continued (this series). The Hypospadias Objective Scoring Evaluation (HOSE) and the Paediatric Penile Perception Score (PPPS) were used for post-pubertal assessment.
RESULTS
Prospective records provided details of 105 patients with proximal hypospadias who had complete primary anatomical repair. The median age at surgery was 1.6 years, and 15.9 years at the post-pubertal assessment. Forty-one (39%) had complications that necessitated re-operations. Thirty-five (33.3%) patients had complications involving the urethra. For fistula and diverticula, eighteen cases required only one corrective procedure, while one required two. Other 16 patients required an average of 1.78 corrective operations for severe chordee and/or breakdown, with 7 requiring Bracka's 2-stage procedure.
RESULTS OF PUBERTAL REVIEW
Fifty patients (47.6%) were over 14 years old; 46 (92.0%) had pubertal reviews and scoring, while four were lost to follow-up. The mean HOSE score was 14.8/16, and the mean PPPS score was 17.8/18. Five patients had residual curvature of >10°. 17 and 10 patients, respectively, were unable to comment on glans firmness and ejaculation quality. During erections, 26/29 (89.7%) patients reported a firm glans, and 36/36 (100%) reported normal ejaculations.
CONCLUSION
This study proves the need for reconstruction of normal anatomy for normal post-pubertal function. In all proximal hypospadias, we strongly recommend anatomical reconstruction (zipping up) of the corpus spongiosum and BSM. When the curvature can be reduced to <30°, a complete one-stage reconstruction is possible; otherwise, anatomical reconstruction of the bulbar and proximal penile urethra is recommended, reducing the length of the epithelial-lined substitution tube for the distal shaft and glans.
Topics: Male; Child; Humans; Infant; Adolescent; Hypospadias; Retrospective Studies; Prospective Studies; Urologic Surgical Procedures, Male; Urethra; Muscles; Treatment Outcome
PubMed: 37012103
DOI: 10.1016/j.jpurol.2023.03.024 -
Biotechnic & Histochemistry : Official... Nov 2023Diabetes mellitus (DM) is a chronic disease at all ages including childhood and puberty. Failure to treat DM can cause retinopathy, nephropathy and neuropathy. Endocrine...
Diabetes mellitus (DM) is a chronic disease at all ages including childhood and puberty. Failure to treat DM can cause retinopathy, nephropathy and neuropathy. Endocrine and metabolic changes during the pubertal period complicate management of DM. Noopept is a cognitive enhancer that exhibits antidiabetic properties. We investigated the effect of noopept on the histopathology of the cornea, retina, kidney and pancreas in pubertal diabetic rats. We allocated 60 prepubertal male rats randomly into six groups of 10: untreated control (C), DM control (DC), noopept control (NC), DM + noopept (D + N), DM + insulin (D + I) and DM + insulin + noopept (D + I + N). DM was induced by streptozotocin in the DC, D + N, D + I and D + I + N groups. Noopept was administered to the NC, D + N and D + I + N groups; insulin was administered to the D + I and D + I + N groups for 14 days. On day 18 of the experiment, animals were sacrificed and eyes, kidneys and pancreata were excised for histological investigation. Renal tubule diameter and corneal and retinal thickness were increased significantly in DC groups compared to the control group. The D + I, D + N and D + I + N groups exhibited fewer DM induced pathological changes than the DC group. The D + I + N group exhibited no significant differences in renal tubule diameter and corneal and retinal thickness compared to the DC group. Our findings suggest that noopept is protective against DM end organ complications in streptozotocin induced diabetic pubertal rats.
Topics: Rats; Male; Animals; Diabetes Mellitus, Experimental; Streptozocin; Sexual Maturation; Kidney; Insulin; Pancreas
PubMed: 36946173
DOI: 10.1080/10520295.2023.2187460 -
Biomedical Papers of the Medical... Mar 2024We report four pediatric subjects with Cushing's disease (CD) diagnosed in the Czech Republic. We focus on initial symptoms of Cushing's syndrome (CS) which can lead to...
BACKGROUND
We report four pediatric subjects with Cushing's disease (CD) diagnosed in the Czech Republic. We focus on initial symptoms of Cushing's syndrome (CS) which can lead to early diagnosis, on typical symptoms of CS in children, their age and sex distribution, the mean length of symptoms prior to diagnosis, indication for examination, post-cure growth, sexual development and pituitary function in our four CD patients after transsphenoidal pituitary surgery (TSS). We describe the diagnostic process leading to confirmation of CD and we emphasize the biochemical and radiological diagnostic difficulties.
CONCLUSIONS
Pediatric CD has a number of features distinct from adult CD. Our retrospective analysis confirmed the presence of growth retardation and change in facial appearance with development of moon face as the first symptoms of CS. According to our observation, growth retardation is prior to development of moon face. The other typical symptoms frequently seen in pediatric patients are pseudo-precocious puberty in both sexes, hirsutism in pubertal girls due to excessive adrenal androgen secretion and pubertal delay. A corticotropin-releasing hormone (CRH) test and especially bilateral inferior petrosal sinus sampling for ACTH (BIPSS) contribute to confirming the diagnosis of CD and excluding ectopic ACTH syndrome in children with unvisible adenoma on pituitary magnetic resonance imaging (MRI).
Topics: Adult; Female; Male; Humans; Child; Pituitary ACTH Hypersecretion; Retrospective Studies; Czech Republic; Growth Disorders; Pituitary Neoplasms; Diagnosis, Differential
PubMed: 36504094
DOI: 10.5507/bp.2022.049 -
Wellcome Open Research 2022Endstage kidney failure rates are higher in South Asians than in White Europeans. Low birth weight is associated with adult chronic kidney disease and is more common in...
Endstage kidney failure rates are higher in South Asians than in White Europeans. Low birth weight is associated with adult chronic kidney disease and is more common in South Asians. Foetal kidney size was smaller in South Asians in the Born in Bradford (BiB) birth cohort. As part of BiB follow up, we aimed to investigate if there were ethnic differences in kidney function and blood pressure in early childhood and whether this was different by foetal kidney size. Serum creatinine, cystatin C, urea, and urinary albumin to creatinine ratio (ACR), protein to creatinine ratio (PCR) and retinol binding protein (RBP) were analysed in blood and urine samples from those who participated in the BiB follow-up at 7-11 years. Ethnicity was categorised by parental self-report as White European and South Asian. Estimated glomerular filtration rate (eGFR) was calculated using Schwartz, and cystatin C Zappitelli and Filler equations. Linear regression was used to examine the association between ethnicity and eGFR, PCR and blood pressure. 1591 children provided blood (n=1403) or urine (n=625) samples. Mean eGFR was 92 ml/min/1.73m (standard deviation (SD) 9) using Schwartz (n=1156) and 94 (SD 11) using Zappitelli (n=1257). CKD prevalence was rare (1 with eGFR <60 ml/min/1.73m , 14 (2.4%) had raised ACR (>2.5 mg/mmol in boys/3.5 mg/mmol in girls). Diastolic blood pressure was higher in South Asian children (difference 2.04 mmHg, 95% CI 0.99 to 3.10) but was not significant in adjusted analysis. There was no evidence of association in adjusted models between ethnicity and any eGFR or urinary measure at this age. There was no evidence of significant ethnic differences in kidney function at pre-pubertal age despite differences in kidney volume at birth. Longitudinal follow-up is required to track ethnic patterns in kidney function and blood pressure as children develop through puberty.
PubMed: 37274450
DOI: 10.12688/wellcomeopenres.17796.1