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Journal of Clinical Medicine Jan 2024Paediatric and adolescent shoulder instability is caused by a unique combination of traumatic factors, ligamentous laxity, and pattern of muscle contractility. The... (Review)
Review
Paediatric and adolescent shoulder instability is caused by a unique combination of traumatic factors, ligamentous laxity, and pattern of muscle contractility. The multifactorial nature of its aetiology makes interpretation of the literature difficult as nomenclature is also highly variable. The purpose of this review is to summarize the existing literature and shed light on the nuances of paediatric and adolescent shoulder instability. The epidemiology, clinical features, imaging, and management of all forms of paediatric shoulder instability are presented. The main findings of this review are that structural abnormalities following a dislocation are uncommon in pre-pubertal paediatric patients. Young post-pubertal adolescents are at the highest risk of failure of non-operative management in the setting of traumatic instability with structural abnormality, and early stabilisation should be considered for these patients. Remplissage and the Latarjet procedure are safe treatment options for adolescents at high risk of recurrence, but the side-effect profile should be carefully considered. Patients who suffer from instability due to generalized ligamentous laxity benefit from a structured, long-term physiotherapy regimen, with surgery in the form of arthroscopic plication as a viable last resort. Those who suffer from a predominantly muscle patterning pathology do not benefit from surgery and require focus on regaining neuromuscular control.
PubMed: 38337418
DOI: 10.3390/jcm13030724 -
Clinical Pediatric Endocrinology : Case... 2024Chronic inflammatory conditions, such as juvenile idiopathic arthritis, are associated with growth failure. Growth failure appears to be correlated with both the effects... (Review)
Review
Chronic inflammatory conditions, such as juvenile idiopathic arthritis, are associated with growth failure. Growth failure appears to be correlated with both the effects of inflammation and negative effects of glucocorticoids (used as therapeutic option) on the growth hormone axis and locally on the growth plate and bone metabolism. In the last decade, the introduction of biologics has changed the disease course regarding consequences and outcomes. Anyway in some cases, treatment with biologics has failed in restoring normal growth in patients with juvenile idiopathic arthritis; in contrast, several studies have reported improved height velocity and growth rate in patients with juvenile idiopathic arthritis treated with growth hormone. This study aimed to evaluate the impact of growth hormone treatment on the growth and pubertal development in juvenile idiopathic arthritis patients through a narrative review of the literature over the last four decades.
PubMed: 38299178
DOI: 10.1297/cpe.2023-0036 -
Medicine Dec 202317α-Hydroxylase/17, 20-lyase deficiency (17OHD) is a recessively inherited autosomal disease caused by CYP17A1 gene mutations. It is characterized by failure to...
RATIONALE
17α-Hydroxylase/17, 20-lyase deficiency (17OHD) is a recessively inherited autosomal disease caused by CYP17A1 gene mutations. It is characterized by failure to synthesize cortisol, adrenal androgens and gonadal steroids. However, it is rare in clinic combining with type 2 diabetes mellitus (T2DM).
PATIENT CONCERNS
A 21-year-old woman was transferred to an endocrinology clinic because of paroxysmal paralysis. In addition, she presented with hypertension, primary amenorrhea and lack of pubertal development. Blood evaluation revealed hypokalemia, and a low cortisol level with an increased adrenocorticotropic hormone concentration. The renin activity and testosterone and estrogen levels were suppressed, and the gonadotropin levels were high. CT scan showed bilateral adrenal hyperplasia. Besides, this patient had hyperglycemia, hyperinsulinism and negative diabetes type 1 related antibodies. A homozygous mutation c. 985 to 987delinsAA in exon 6 was found in the patient which caused the missense mutation (p.Y329fs).
DIAGNOSES
17α-hydroxylase/17, 20-lyase deficiency combined with T2DM was considered.
INTERVENTIONS
The patient received dexamethasone, estradiol valerate, metformin, amlodipine besylate and D3 calcium carbonate tablets. The doses of dexamethasone was changed according to her blood potassium levels.
OUTCOMES
After treatment, the blood pressure, blood potassium and blood glucose returned to normal range. Besides, she had restored her menstrual cycle.
LESSONS
For patients with hypertension, hypokalemia and lack of pubertal development, the possibility of 17OHD should be considered. The subsequent treatment would be challenging in patients with combined 17OHD and T2DM, considering the potential contribution of glucocorticoids to diabetic balance and osteoporosis.
Topics: Female; Humans; Young Adult; Adrenal Hyperplasia, Congenital; Dexamethasone; Diabetes Mellitus, Type 2; Hydrocortisone; Hypertension; Hypokalemia; Lyases; Mixed Function Oxygenases; Mutation; Potassium; Steroid 17-alpha-Hydroxylase
PubMed: 38206738
DOI: 10.1097/MD.0000000000036727 -
Frontiers in Endocrinology 2023Impaired testosterone secretion is a frequent following hematopoietic stem cell transplantation (HSCT) in pediatrics, but long-term longitudinal trendlines of clinical...
INTRODUCTION
Impaired testosterone secretion is a frequent following hematopoietic stem cell transplantation (HSCT) in pediatrics, but long-term longitudinal trendlines of clinical and biochemical findings are still scanty.
METHODS
Monocentric, retrospective analysis. Male patients transplanted <18 years between 1992 and 2021, surviving ≥2 years after HSCT and showing, upon enrollment, clinical and biochemical signs consistent with pubertal onset and progression were included. Clinical and biochemical data collected every 6-12 months were recorded.
RESULTS
Of 130 patients enrolled, 56% were prepubertal, while 44% were peri-/postpubertal upon HSCT. Overall, 44% showed spontaneous progression into puberty and normal gonadal profile, while the remaining experienced pubertal arrest (1%), isolated increase of FSH (19%), compensated (23%) or overt (13%) hypergonadotropic hypogonadism. Post-pubertal testicular volume (TV) was statistically smaller among patients still pre-pubertal upon HSCT ( 0.049), whereas no differences were recorded in adult testosterone levels. LH and testosterone levels showed a specular trend between 20 and 30 years, as a progressive decrease in sexual steroids was associated with a compensatory increase of the luteinizing hormone. A variable degree of gonadal dysfunction was reported in 85%, 51%, 32% and 0% of patients following total body irradiation- (TBI), busulfan-, cyclophosphamide- and treosulfan-based regimens, respectively. TBI and busulfan cohorts were associated with the lowest probability of gonadal event-free course (<0.0001), while it achieved 100% following treosulfan. A statistically greater gonadotoxicity was detected after busulfan than treosulfan ( 0.024). Chemo-only regimens were associated with statistically larger TV (0.001), higher testosterone ( 0.008) and lower gonadotropin levels (0.001) than TBI. Accordingly, the latter was associated with a 2-fold increase in the risk of gonadal failure compared to busulfan (OR 2.34, CI 1.08-8.40), whereas being pre-pubertal upon HSCT was associated with a reduced risk (OR 0.15, CI 0.08-0.30).
CONCLUSIONS
a) patients pre-pubertal upon HSCT showed a reduced risk of testicular endocrine dysfunction, despite smaller adult TV; b) patients showed downwards trend in testosterone levels after full pubertal attainment, despite a compensatory increase in LH; c) treosulfan was associated to a statistically lower occurrence of hypogonadism than busulfan, with a trend towards larger TV, higher testosterone levels and lower gonadotropins.
Topics: Adult; Child; Humans; Male; Busulfan; Leydig Cells; Retrospective Studies; Hypogonadism; Hematopoietic Stem Cell Transplantation; Testosterone
PubMed: 38152128
DOI: 10.3389/fendo.2023.1292683 -
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 -
BioRxiv : the Preprint Server For... Nov 2023Uterine glands are branched, tubular structures whose secretions are essential for pregnancy success. It is known that pre-implantation glandular expression of leukemia...
Uterine glands are branched, tubular structures whose secretions are essential for pregnancy success. It is known that pre-implantation glandular expression of leukemia inhibitory factor (LIF) is crucial for embryo implantation, however contribution of uterine gland structure to gland secretions such as LIF is not known. Here we use mice deficient in estrogen receptor 1 (ESR1) signaling to uncover the role of ESR1 signaling in gland branching and the role of a branched structure in LIF secretion and embryo implantation. We observed that deletion of ESR1 in neonatal uterine epithelium, stroma and muscle using the progesterone receptor causes a block in uterine gland development at the gland bud stage. Embryonic epithelial deletion of ESR1 using a mullerian duct Cre line - , displays gland bud elongation but a failure in gland branching. Surprisingly, adult uterine epithelial deletion of ESR1 using the lactoferrin-Cre () displays normally branched uterine glands. Intriguingly, unbranched glands from uteri fail to express glandular pre-implantation , preventing implantation chamber formation and embryo alignment along the uterine mesometrial-antimesometrial axis. In contrast, branched glands from uteri display reduced expression of glandular resulting in delayed implantation chamber formation and embryo-uterine axes alignment but deliver a normal number of pups. Finally, pre-pubertal unbranched glands in control mice express in the luminal epithelium but fail to express in the glandular epithelium even in the presence of estrogen. These data strongly suggest that branched glands are necessary for pre-implantation glandular expression for implantation success. Our study is the first to identify a relationship between the branched structure and secretory function of uterine glands and provides a framework for understanding how uterine gland structure-function contributes to pregnancy success.
PubMed: 37961508
DOI: 10.1101/2023.11.01.565233 -
Osteoporosis International : a Journal... Feb 2024Glucocorticoid use in Duchenne and Becker muscular dystrophy prolongs ambulation but cause significant skeletal toxicity. Our analysis has immediate clinical...
UNLABELLED
Glucocorticoid use in Duchenne and Becker muscular dystrophy prolongs ambulation but cause significant skeletal toxicity. Our analysis has immediate clinical implications, suggesting that growth hormone and testosterone have a stronger effect prior to first and subsequent vertebral fracture, respectively, relative to bisphosphonates alone in children with dystrophinopathies on chronic glucocorticoids.
PURPOSE
Glucocorticoids prolong ambulation in boys with Duchenne muscular dystrophy; however, they have significant endocrine side effects. We assessed the impact of growth hormone (GH), testosterone, and/or zoledronic acid (ZA) on vertebral fracture (VF) incidence in patients with dystrophinopathies on chronic glucocorticoids.
METHODS
We conducted a longitudinal retrospective review of 27 males with muscular dystrophy. Accelerated failure time (AFT) models were used to estimate the relative time to VF while on GH, testosterone, and/or ZA compared to ZA alone. Results are reported as failure time ratio, where >1 indicates prolonged time versus <1 indicates shorter time to next VF.
RESULTS
The prevalence of growth impairment was 96% (52% utilized GH), pubertal delay was 86% (72% utilized testosterone), and low trauma fractures were 87% (72% utilized ZA). Multivariable analysis of the AFT models showed that participants on either GH or testosterone treatment relative to ZA alone experienced prolonged time to next VF (1.253, P<0.001), with GH being the significant contributor when analyzed independently from testosterone (1.229, P<0.001). Use of ZA with GH or testosterone relative to ZA alone resulted in prolonged time to next VF (1.171, P<0.001), with testosterone being a significant contributor (1.130, P=0.033).
CONCLUSION
GH and testosterone each decreased VF risk in patients independent of or in combination with ZA, respectively.
Topics: Male; Child; Humans; Spinal Fractures; Glucocorticoids; Testosterone; Growth Hormone; Muscular Dystrophy, Duchenne; Zoledronic Acid
PubMed: 37872346
DOI: 10.1007/s00198-023-06951-z -
Endocrine Connections Nov 2023Hypogonadism is a clinical syndrome resulting from failure to produce physiological concentrations of sex steroid hormones with accompanying symptoms, such as slowed... (Review)
Review
Hypogonadism is a clinical syndrome resulting from failure to produce physiological concentrations of sex steroid hormones with accompanying symptoms, such as slowed growth and delayed pubertal maturation. Hypogonadism may arise from gonadal disease (primary hypogonadism), dysfunction of the hypothalamic-pituitary axis (secondary hypogonadism) or functional hypogonadism. Disrupted puberty (delayed or absent) leading to hypogonadism can have a significant impact on both the physical and psychosocial well-being of adolescents with lasting effects. The diagnosis of hypogonadism in teenagers can be challenging as the most common cause of delayed puberty in both sexes is self-limited, also known as constitutional delay of growth and puberty (CDGP). Although an underlying congenital cause should always be considered in a teenager with hypogonadism, acquired conditions such as obesity, diabetes mellitus, other chronic diseases and medications have all been associated with low sex steroid hormone levels. In this review, we highlight some forms of functional hypogonadism in adolescents and the clinical challenges to differentiate normal variants from pathological states.
PubMed: 37615381
DOI: 10.1530/EC-23-0190