Stimulating Hormone Research Articles

Enhanced glucose production in norepinephrine and palmitate stimulated hepatocytes following endurance training

Enhanced hepatic gluconeogenesis plays an important role in exercise glucose homeostasis when hepatic glycogen stores are depleted. Livers from trained animals demonstrate greater rates of gluconeogenesis in the presence of elevated substrate with and without hormonal stimulation. Training has been reported to have a particularly profound impact on norepinephrine-stimulated gluconeogenesis, but this was only demonstrated in the presence of other gluconeogenic hormones. Here we reexamine the impact of endurance training on norepinephrine-stimulated gluconeogenesis in the absence of any other hormones. Isolated hepatocytes from trained and untrained rats were incubated in 6 mM lactate with various concentrations of norepinephrine (0 nM–20 nM). Absent norepinephrine, gluconeogenic rates were significantly greater from trained hepatocytes compared to controls (97.2 ± 6.7 vs 57.6 ± 8.7 nmol/mg protein; p < 0.01). In the presence of NE (0.5–20 nM), gluconeogenesis from trained liver cells was significantly greater at all NE concentrations compared to controls. The NE-stimulated increase in gluconeogenesis above basal (0 nM NE) was also greater for trained vs control (36% vs 19%, respectively). Concomitant with the max NE-stimulated increase in gluconeogenesis, lactate uptake was significantly elevated for trained vs. control hepatocytes (307.22 ± 44.5 vs 124.5 ± 23.9 nmol/mg protein; p < 0.01), with lactate uptake quantitatively accounting for the entire increase in gluconeogenesis for trained hepatocytes. Endurance training was also observed to significantly elevate glucose production in presence of 0.6 mM palmitate, both in the absence and presence of NE. These findings confirm that hepatocytes from endurance-trained animals demonstrate enhanced rates of NE-stimulated gluconeogenesis, as well as palmitate-stimulated glucose production.

EVIDENCE FOR ADRENAL DYSFUNCTION CONTRIBUTING TO PERACUTE MORTALITY SYNDROME IN RED PANDA (AILURUS FULGENS).

Red pandas (Ailurus fulgens) are endangered with extinction due to deforestation and habitat fragmentation. Reported causes of unexpected death in managed red pandas include kidney, liver, gastrointestinal, and cardiac disease. A previously undetailed syndrome, red panda peracute mortality syndrome, may be emerging, as red pandas have died unexpectedly, with no clear cause of death identified at necropsy. This case series describes the clinical and postmortem findings of five red pandas at Brookfield Zoo with abnormal adrenal size and associated histologic lesions as possible contributing factors to acute death. Antemortem clinical signs consisted of thin body condition, vomiting, intermittent diarrhea, neck ventroflexion, ataxia, and electrolyte abnormalities. Mortality may have been due to abnormal adrenal function, resulting in fatal electrolyte disturbances. Antemortem adrenocorticotropic hormone (ACTH) stimulation tests indicated an inappropriate response to ACTH with persistently low cortisol and aldosterone levels after cosyntropin administration. Clinical improvement was seen when red pandas were provided steroids, but all cases were eventually fatal. Further study is needed to understand red panda peracute mortality syndrome and associated adrenal dysfunction.

A Child with Non-Growth Hormone-Deficient Short Stature with Chromosome 2 Deletion of 2q35-36.1: A Case Report and Literature Review of Haploinsufficiency of Epha4 Gene

AbstractNon-growth hormone-deficient short stature is a group of growth developmental disorders with complex pathophysiological mechanisms involving multiple pathways, including abnormalities in the growth hormone/insulin-like growth factor 1 signal pathway. We report a 4-year-old girl with severe growth and developmental delay: her height was 91 cm (<–3 standard deviation [SD]), and her growth rate was 3 to 4 cm/year (<–2 SD). Growth hormone stimulation tests indicated a normal peak growth hormone level (11.1 μg/L), while insulin-like growth factor-1 levels were reduced (7.98 nmol/L, <–1SD). Whole exome sequencing and copy number variation analysis revealed a 3.19 Mb deletion at 2q35-q36.1 on chromosome 2, encompassing all coding regions of the Epha4 gene. This study suggests an association between Epha4 gene deletion and non-growth hormone-deficient short stature, highlighting the importance of further research on this gene and its related signaling pathways to understand the molecular mechanisms of the disease and potential therapeutic approaches.

A Rare Cause of Precocious Puberty - Testotoxicosis

Background: Testotoxicosis, also known as familial male-limited precocious puberty (FMPP), is a rare cause of gonadotropin-independent precocious puberty in boys due to an activating mutation in the luteinizing hormone (LH))/choriogonadotropin receptor (LHCGR) gene. Case report: A 3-year 2-month-old boy presented with acne, pubic hair, phallic growth, height accelerations, and aggressiveness. At physical examination, his height was 106cm (+2.36 SDS) and weight was 16kg (+0.77 SDS). He had Tanner stage 2 pubic hair, stretched penile length was 6 cm (>2 SDS), and both testicular volumes were 5mls. Bone age was advanced at 7 years old. Testosterone level was high at 17nmol/L and the gonadotropin-releasing hormone (GnRH) stimulation test was suggestive of peripheral precocious puberty. Whole exome sequencing identified a heterozygous pathogenic variant c.1691A>G (p.Asp564Gly) in the LHCGR gene which supports the diagnosis of testotoxicosis. The child was started on both aromatase inhibitor, anastrozole, and anti-androgen, spironolactone. At 6 months of treatment, there was a halt in pubertal progression with reduced height velocity from 9cm/year to 6cm/year. Conclusion: Without intervention, the patient will have rapid progressive skeletal maturation and virilization which will result in compromised final adult height and psychosocial distress.

Mitochondria remodeling during endometrial stromal cell decidualization.

Upon hormonal stimulation, uterine endometrial stromal cells undergo a dramatic morpho-functional metamorphosis that allows them to secrete large amounts of matrix proteins, cytokines, and growth factors. This step, known as decidualization, is crucial for embryo implantation. We previously demonstrated how the secretory pathway is remodelled during this process. Here we show that hormonal stimulation rapidly induces the expression of many mitochondrial genes, encoded in both the mitochondrial and the nuclear genomes. Altogether, the mitochondrial network quadruples its size and establishes more contacts with the ER. This new organization results in the increased respiratory capacity of decidualized cells. These findings reveal how achieving an efficient secretory phenotype requires a radical metabolic rewiring.

DJ-1-mediated repression of the RNA-binding protein FMRP is predicted to impact known Alzheimer's disease-related protein networks.

RNA-binding proteins (RBPs) modulate the synaptic proteome and are instrumental in maintaining synaptic homeostasis. Moreover, aberrant expression of an RBP in a disease state would have deleterious downstream effects on synaptic function. While many underlying mechanisms of synaptic dysfunction in Alzheimer's disease (AD) have been proposed, the contribution of RBPs has been relatively unexplored. To investigate alterations in RBP-messenger RNA (mRNA) interactions in AD, and its overall impact on the disease-related proteome. We first utilized RNA-immunoprecipitation to investigate interactions between RBP, DJ-1 (Parkinson's Disease protein 7) and target mRNAs in controls and AD. Surface Sensing of Translation - Proximity Ligation Assay (SUnSET-PLA) and western blotting additionally quantified alterations in mRNA translation and protein expression of DJ-1 targets. Finally, we utilized an unbiased bioinformatic approach that connects AD-related pathways to two RBPs, DJ-1 and FMRP (Fragile X messenger ribonucleoprotein 1). We find that oligomeric DJ-1 in AD donor synapses were less dynamic in their ability to bind and unbind mRNA compared to synapses from cognitively unimpaired, neuropathologically-verified controls. Furthermore, we find that DJ-1 associates with the mRNA coding for FMRP, Fmr1, leading to its reduced synaptic expression in AD. Through the construction of protein-protein interaction networks, aberrant expression of DJ-1 and FMRP are predicted to lead to the upregulation of key AD-related pathways, such as thyroid hormone stimulating pathway, autophagy, and ubiquitin mediated proteolysis. DJ-1 and FMRP are novel targets that may restore established neurobiological mechanisms underlying AD.

One Stage Modified KOYANAGI-HAYASHI Technique with Tunica Vaginalis Intermediate Layer for Severe Hypospadias Surgery

Introduction: In recent years, the modified Koyanagi-Hayashi technique has attracted considerable interest due to its satisfactory results and low risk of major postoperative complications for the patient during surgery for severe hypospadias. The aim of this work is to evaluate this technique and compare our results with those of other research series. Materials and methods: A single-center prospective study of an inhomogeneous series of 32 children with proximal hypospadias and a mean age of 44 months was operated on by the same surgeon using the Koyanagi-Hayashi technique. Preoperative hormonal stimulation with testosterone was indicated in 17 children. The tunica vaginalis was used as the urethroplasty covering plane for all patients. Functional results were assessed, and a questionnaire was completed to evaluate the functional and aesthetic satisfaction of the parents and the surgeon. Results: Complete curvature of the penis was obtained in all patients except 2, who retained a minimal curvature, not requiring surgical correction at this time. There were 6 cases of urethral fistula, 2 cases of total urethroplasty release, 2 cases of partial release, 9 cases of glanduloplasty release, one urethrocele, and 2 meatus strictures. Overall, the success rate after the first procedure was 31.20%, rising to 74.95% after the first repeat procedure and 84.32% after the second. The result was very satisfactory for the parents at 84.37% and satisfactory at 15.62%. Conclusion: The Koyanagi technique modified by Hayashi is a good alternative for severe forms of hypospadias. Correction of the curvature of the penis is generally achieved without further procedures, and the aesthetic result is generally satisfactory. Using the tunica vaginalis as an intermediate plane to cover the urethroplasty has greatly reduced the rate of serious complications. The complication rate is high, and parents need to be aware of the risk of repeat surgeries. But these complications are always easy to manage

Clinical and Analytical Presentation of Central Precocious Puberty: A 20-Year Cross-Sectional Study

Objectives − This study aims to compare the clinical and analytical presentation of Central precocious puberty (CPP), considering age.Methods − An observational, cross-sectional study was conducted on children diagnosed with CPP at a level III hospital, between January 2002 and April 2022. Clinical, auxological, sociodemographic, laboratory, and imaging parameters were analyzed.Results − Out of the 52 children studied, the majority were girls (N=44). The median age of puberty onset in girls was 6.79 years and the mean age at first consultation of 8.13 years, with a significantly lower age at hospital referral (7.65 years; P=0.045) compared to boys. Idiopathic etiology was predominant in both. In girls, breast development appeared at older mean ages (P=0.009), while pubic hair growth and accelerated growth were associated with younger ages at puberty onset (P=0.021; P=0.018, respectively). Basal and peak levels of gonadotropin hormones were higher in girls, although not statistically significant. In girls, age at puberty onset correlated negatively with standard deviation of body mass index (P=0.023), while age at first consultation correlated positively with bone age (P<0.001), and was associated with younger ages at Gonadotropin-Releasing Hormone stimulation test (P=0.020).Conclusion − This study provides innovative and relevant findings that enhance understanding of CPP presentation according to age, thereby improving clinical management of this condition.

Analysis of The Incidence of Uterine Leiomyoma Based on Body Mass Index and Neutrophil-Lymphocyte Ratio

Leiomyoma is the most common benign uterine tumor in the female with an incidence rate of 70-80%. The cause of these tumors is still unknown, but one of the known causes is that they grow in response to hormonal stimulation. Lymphocytic infiltration in this disease has been identified as an unusual finding. This suggests a potential role for lymphocytes in the development of such tumors. A bibliometric analysis of various sources found minimal research on the Neutrophil-Lymphocyte Ratio (NLR) in uterine leiomyoma, especially in Indonesia. This study analyzed the incidence of uterine leiomyoma based on Body Mass Index (BMI) and Neutrophil-Lymphocyte Ratio (NLR). This study used an observational analytic method with a case-control design. The sampling technique used was consecutive sampling and 129 samples were obtained in the form of 65 uterine leiomyoma case groups and 64 adenomyosis control groups. BMI variable parameters were obesity (>25kg/m2) and not obese (≤25kg/m2), while NLR was at risk (>3.53) and not at risk (≤3.53). Data analysis consisted of univariate, bivariate with a Chi-Square test, and continued with multivariate using logistic regression analysis. There was a significant relationship between BMI and uterine leiomyoma incidence (p = 0.028). There was also a significant relationship between NLR and uterine leiomyoma (p = 0.017). NLR had a 3,688-fold more association with the incidence of uterine leiomyoma than BMI. In conclusion, a relationship exists between BMI and NLR in the incidence of uterine leiomyoma. NLR can be a predictor of uterine leiomyoma, especially in women of reproductive age.

TMOD-06. ESTABLISHMENT OF PITUITARY NEUROENDOCRINE TUMOR (PITNET) ORGANOID MODELS

Abstract Pituitary neuroendocrine tumors (PitNETs) are tumors that originate from the anterior pituitary gland. While they are mostly benign, they can cause various clinical symptoms due to hormonal secretion abnormalities. PitNET can be broadly categorized into three lineages, each of which has its differentiation controlled by specific transcription factors. Treatment options for PitNET include surgical resection and pharmacotherapy, but available drugs are limited, and their efficacy markers remain unclear. To develop novel drugs for PitNET and identify their efficacy markers, it is necessary to develop new research models. In recent years, organoid models have garnered attention as novel research models for various cancer types. In this study, we established novel organoid models derived from PitNET patients and analyzed their histological and endocrinological characteristics. Surgical specimens from 4 cases of somatotroph adenoma, 1 case of double adenoma, 1 case of gonadotroph adenoma, and 1 case of corticotroph adenoma were minced in dissection medium and embedded in Matrigel basement membrane matrix respectively. The organoids were cultured under 5% CO2 at 37°C using media supplemented with various growth factors. After 28 days of culture, formalin-fixed paraffin-embedded sections were prepared to examine histological homology with patient tumors. Hematoxylin and eosin staining results showed that all organoids maintained cell morphology and tissue structure similar to the original tumors. Immunohistochemical staining for markers specific to each PitNET revealed similar staining patterns between the organoids and the original tumors. Furthermore, analysis of hormone levels in the culture medium showed that hormone production capabilities, such as growth hormone and follicle stimulating hormone, were maintained even after long-term culture. In this study, we successfully established PitNET organoid models that retain histological and endocrinological characteristics. These models are expected to serve as useful research tools for elucidating the molecular mechanisms of PitNET and developing novel therapies targeting critical molecular abnormalities.

MORPHOFUNCTIONAL CHARACTERISTICS OF THE TESTES IN YOUNG SEXUALLY MATURE RATS FOLLOWING PRENATAL EXPOSURE TO LOW-LEVEL ELECTROMAGNETIC RADIATION

The aim of this study is to investigate the functional and morphological characteristics of the testes in young sexually mature rats exposed to low-intensity centimeter-range electromagnetic radiation during the intrauterine period (within the “mother-fetus” system). Materials and methods. Intrauterine exposure to electromagnetic radiation was simulated using a high-frequency generator G4-190-3/1, equipped with a P-6-23A radiating antenna. To evaluate the reproductive system, a morphological examination of the testes and measurement of blood testosterone levels were performed. Morphometric methods were employed to quantify histological findings. The area of Leydig cell nuclei was measured, and the optical density of stromal connective tissue was assessed using the PAS reaction. The proliferative activity of spermatogenic epithelium cells was determined through an immunohistochemical reaction to the Ki-67 antigen. Results. In this experiment, the consequences of intrauterine damage to the testicles of male offspring were observed. We can presume that there is not only intrauterine damage, which may undergo regeneration later in life, but also the formation of epigenetic changes of regulatory factors that affect the expression of genes determining the morphofunctional state of the spermatogenic epithelium. Epigenetic changes developed during intrauterine period can manifest throughout the offspring’s lifetime after birth. Conclusions. Functional and morphological changes were found in the testes of sexually mature young males, offspring of mothers exposed to low-intensity centimeter-level electromagnetic fields during pregnancy. Hypoplastic changes in the testicles, a decrease in the proliferative potential of the spermatogenic epithelium were revealed. Hormonal stimulation of spermatogenesis (hypertestosteronemia and an increase in the number of Leydig cells and the size of their nuclei) obviously have a compensatory nature. The obtained results provide the basis for large epidemiological studies with the involvement of a wide range of specialists in both medical and technical specialties.

Identification and Characterization of EIN3/EIL Transcription Factor Family Members in Pinus massoniana Lamb.

Transcription factors refer to types of proteins that perform significant functions in the process of gene expression regulation. The ethylene insensitive 3/ethylene insensitive 3-like (EIN3/EIL) family, functioning as significant transcription factors regulating ethylene, plays a critical role in the growth and development of plants and participates in the plant's response to diverse environmental stresses. Pinus massoniana is an excellent native tree with high economic and ecological value. However, the study of EIN3/EIL genes in gymnosperms, for instance, P. massoniana, is still relatively limited. In this research, four putative EIN3/EIL genes were identified in the transcriptome of P. massoniana. Bioinformatics analysis showed that PmEIL genes contain a highly conserved EIN3 domain and other structural features of acidic, proline-rich and glutamine-rich sites. The molecular evolution tree analysis demonstrated that the EIN3/EIL family was partitioned into three categories (A, B, and C), and the number, type, and distribution of conserved motifs grouped in one category were similar. The results of qRT-PCR indicated that the expression levels of PmEIL genes were markedly elevated in needles compared to other tissues. Through the analysis of expression patterns of the PmEIL genes under various stress treatments, it was found that the PmEIL genes could participate in plant hormone stimulation induction, osmosis, drought and other response processes. In addition, PmEIL is a nuclear localization protein. PmEIL1, PmEIL3, and PmEIL4 are transcriptional activators, while PmEIL2 is a transcriptional suppressor. This research provides a basis for further elucidating the function of EIN3/EIL transcription factors in growth, development and stress response of P. massoniana.

A Neglected Point: Frailty in Older Adults with Differentiated Thyroid Cancer.

This study investigated the risk of frailty in older adults with differentiated thyroid cancer (DTC) and the effect of thyroid- stimulating hormone (TSH) levels on frailty. This single-center, cross-sectional study included 70 DTC patients aged ≥60 years with stable TSH levels during the previous year while receiving levothyroxine. Frailty was assessed using the fried frailty phenotype (FFP). Anterior thigh muscle thickness was measured by ultrasound, and the sonographic thigh adjustment ratio (STAR) index was calculated. Muscle strength was measured using a hand dynamometer. Physical activity was determined by the physical activity scale for the elderly (PASE). The median (interquartile range) age and follow-up time were 65 years (62 to 71) and 11 years (7.0 to 14.2), respectively. The median TSH level was 1.10 μIU/mL (0.49 to 1.62), and 58.6% of patients were prefrail/frail. Muscle mass and strength were reduced in 35.7% and 17.2% of patients, respectively. TSH levels were lower in those with prefrailty/frailty (P=0.002), low muscle mass (P=0.014), and low strength (P=0.037) than in their normal counterparts. TSH levels correlated negatively with FFP (P= 0.001) and positively with the STAR index (P=0.034). TSH below 1.325 μIU/mL was associated with an increased frailty risk (area under the curve=0.719; P=0.001). Low TSH, female sex, low handgrip strength, and low PASE leisure time scores emerged as independent predictors of frailty (P<0.05). Older adults with lower TSH levels due to DTC are at high frailty risk and have low muscle mass and strength. Therefore, TSH targets should be set based on a comprehensive evaluation with consideration of the risk-benefit ratio.

Proof-of-Concept for Long-Term Human Endometrial Epithelial Organoids in Modeling Menstrual Cycle Responses.

Endometrial disorders, such as infertility and endometriosis, significantly impact reproductive health, thus necessitating better models to study endometrial function. Current in vitro models fail to replicate the complexity of the human endometrium throughout the entire menstrual cycle. This study aimed to assess the physiological response of human endometrial organoids (hEOs) to in vitro hormonal treatments designed to mimic the hormonal fluctuations of the menstrual cycle. Endometrial biopsies from three healthy women were used to develop hEOs, which were treated over 28 days with three hormonal stimulation strategies: (1) estrogen only (E) to mimic the proliferative phase, (2) the addition of progesterone (EP) to simulate the secretory phase, and (3) the further addition of cAMP (EPC) to enhance the secretory functions of hEOs. Gene and protein expression were analyzed using qPCR, IHC, and ELISA. The hEOs exhibited proliferation, gland formation, and appropriate expression of markers such as E-cadherin and Ki67. The hormonal treatments induced significant changes in PR, HSD17B1, PAEP, SPP1, and other genes relevant to endometrial function, closely mirroring in vivo physiological responses. The prominent changes were observed in EPC-treated hEOs (week 4) with significantly high expression of uterine milk components such as glycodelin (PAEP) and osteopontin (SPP1), reflecting mid- to late-secretory phase physiology. This model successfully recapitulates human menstrual cycle dynamics and offers a promising platform for studying endometrial disorders and advancing personalized treatments in gynecology.

Comparison of growth hormone stimulation tests in prepubertal children with short stature according to response to growth hormone replacement.

Growth hormone (GH) stimulation tests are essential tools for diagnosing GH deficiency (GHD). We aimed to compare L-dopa, insulin, and arginine-induced stimulation tests based on response to GH replacement. We retrospectively collected data from a review of patients who underwent the GH stimulation test. A total of 138 patients diagnosed with idiopathic short stature were categorized into group I. The remaining 135 patients, who were diagnosed with GHD and treated for 1 year, were classified into 2 subgroups: group IIa, consisting of patients with an increase of at least 0.5 in height standard deviation score (SDS), and group IIb, patients with an increase of less than 0.5 in height SDS. At the initial visit, group IIa exhibited significantly lower insulin-like growth factor binding protein-3 (IGF-BP3) and higher body mass index (BMI) SDS compared to the other groups. Following 1 year of treatment, group IIb showed significantly lower height SDS, height SDS gain, growth velocity, predicted adult height SDS, weight SDS, and a higher insulin-like growth factor-1 SDS than group IIa. Bone age and IGF-BP3 were inversely associated, and BMI SDS and IGF-BP3 were positively associated with height SDS gain in GHD patients. The specificity and accuracy rates were 50.3% and 70.3% for the L-dopa-induced stimulation test, 72.3% and 86.6% for the insulin tolerance test (ITT), and 64.7% and 87.2% for the arginine-induced stimulation test (ArST). The ArST demonstrated lower specificity compared to the ITT. However, patients undergoing ArST experienced fewer side effects, suggesting that a careful selection of stimulation tests is crucial in diagnosing GHD.

Elucidating the relationship between blood glucose dynamics and growth hormone responses in glucagon stimulation tests among children with short stature

Introduction: The use of glucagon as a provocative agent for growth hormone (GH) assessment is a cornerstone in pediatric endocrinology. Glucagon's role as a GH secretagogue is integral to growth hormone stimulation tests (GHSTs), which diagnose suspected GH deficiency (GHD) in children. These tests are crucial for assessing the hypothalamic-pituitary-adrenal (HPA) axis's integrity. Despite its prevalent use, the exact mechanisms by which glucagon prompts GH release and the impact of ensuing blood glucose (BG) fluctuations are not fully understood. Objectives: This study aims to explore the relationship between GH and BG levels in children with short stature following glucagon administration. Patients and Methods: A retrospective cohort study involved 42 pediatric patients, aged 6 to 11, with short stature. We analyzed GH and BG levels before and after intramuscular glucagon Simulation test (GST). Blood samples were taken at baseline and multiple intervals post-injection. Results: The results revealed that the mean glucose peaked at 60 minutes and declined to a nadir at 120 minutes, which corresponded with a significant rise in GH levels. GH concentrations peaked at 120 minutes post-injection, with 31% of children showing peak GH levels of less than 7 μg/L. Notably, the study found an inverse correlation between BG and GH at peak glucose times, suggesting a complex interplay between glucose dynamics and GH response. Discussion: Our findings indicate a dynamic interrelation between BG and GH post-glucagon injection, challenging traditional interpretations of GST results. The study reinforces the notion that GHST results should be interpreted with consideration of patient-specific factors such as BMI to ensure accurate evaluation of GH reserve and subsequent clinical decision-making. Conclusion: The study corroborates the dynamic nature of GH and glucose responses following glucagon administration and highlights the need for personalized approaches in interpreting GHSTs. Further investigation is warranted to elucidate the mechanisms influencing this complex relationship, which is crucial for accurate diagnosis and management of GHD in children.

Comparison of two strategies of glucocorticoid withdrawal in patients with rheumatoid arthritis in low disease activity (STAR): a randomised, placebo-controlled, double-blind trial

ObjectivesTo compare two strategies—a hydrocortisone replacement strategy and a prednisone tapering strategy—for their success in glucocorticoid discontinuation in patients with rheumatoid arthritis (RA) with low disease activity (LDA).MethodsThe Strategies for glucocorticoid TApering in Rheumatoid arthritis (STAR) study was a double-blind, double-placebo randomised controlled trial including patients with RA receiving a stable dose of glucocorticoid 5 mg/day for ≥3 months and were in LDA for ≥3 months. Patients were randomly assigned in a 1:1 ratio to either replace prednisone with 20 mg/day of hydrocortisone for 3 months, then reduce to 10 mg/day for 3 months before discontinuation or to taper prednisone by 1 mg/day every month until complete discontinuation, contingent on maintaining LDA. The primary outcome was the percentage of patients achieving glucocorticoid discontinuation at 12 months. Other secondary outcomes were proportion of flares, need for additional glucocorticoid use, disease activity, patient-reported outcomes and the results of adrenocorticotropic hormone (ACTH) stimulation tests.ResultsOf the 102 patients randomised in the trial (mean age 62.4 years, 70.6% females), 53 had hydrocortisone replacement and 49 tapered prednisone. At 12 months, 29 patients (55%) in the hydrocortisone replacement group and 23 patients (47%) in the prednisone tapering group achieved glucocorticoid discontinuation (p=0.4). No difference was observed between groups in the secondary outcomes. No cases of acute adrenal insufficiency were observed; however, 17 patients still had an abnormal ACTH stimulation test at 12 months, with no differences between arms.ConclusionA hydrocortisone replacement strategy was not superior to a prednisone tapering strategy for achieving glucocorticoid discontinuation success in patients with RA in LDA.Trial registration numberNCT02997605.

Bilateral adrenal hemorrhage in a postpartum woman with multiple thromboemboli: A case report

BackgroundBilateral adrenal hemorrhage is a rare but often a fatal cause of primary adrenal insufficiency that can result in adrenal crisis if not identified and managed appropriately.Case presentationWe present a case of a 27-year-old Caucasian female who was admitted to the hospital 17 days postpartum with pleuritic chest and flank pain, shortness of breath and nausea. Computed tomography imaging confirmed multiple thromboemboli including pulmonary emboli and noted bilateral bulky adrenal glands. She was managed for infection and pulmonary emboli; however, she complained of persistent headaches, nausea, and vomiting despite appropriate management. Radiology re-review found the computed tomography imaging was consistent with bilateral adrenal hemorrhage in hindsight. Subsequent endocrine evaluation with hypothalamic–pituitary–adrenal axis interrogation and adrenocorticotropic hormone (Synacthen) stimulation testing confirmed resultant primary adrenal insufficiency. She required urgent intravenous hydrocortisone and was subsequently discharged on oral adrenal replacement therapy and anticoagulation.ConclusionsDelay in identification and treatment of adrenal insufficiency can lead to catastrophic outcomes. This case highlights the challenge of diagnosing bilateral adrenal hemorrhage and resultant adrenal insufficiency as patients may not present with the classic risk factors, signs, symptoms, and electrolyte derangements.

Association of FSHR gene polymorphism with fertility of Holstein cows

Relevance. The view of the mechanisms of hormonal regulation of the ovarian cycle of cows has allowed the development of a large number of synchronization programs. An active search is underway for biomarkers related to the fertility of cows, as well as to identify animals with a high ovarian response to the injection of exogenous gonadotropins. The aim of the work is to study the polymorphism of the FSHR gene and its association with reproduction indicators in black-and-white Holstein dairy cows.Results. Based on the results of genotyping cows (n = 128) using the FSHR gene, the frequency of occurrence of the CC genotype was determined at the level of 0.601, the CG genotype — 0.360, GG — 0.031. It was found that for productive insemination, animals with the CG genotype require fewer inseminations. At the same age, the frequency of insemination of heifers with the CG genotype was 1.43, with the CC genotype — 1.60. After the first calving, the animals with the CG genotype responded more actively to hormonal stimulation in the postpartum period. The interval from the first to fruitful insemination in cows with the CG genotype was 34.7 days, in cows with the CC genotype — 57.2 days (p &lt; 0.05). The number of pregnant cows with the CG genotype re-inseminated after natural hunting was 2.1 times higher than the number of cows with the CC genotype (66.7% and 31.2%). It is assumed that exogenous hormone injection has a stimulating effect on the hypothalamus-pituitary-gonad system in cows with the CG genotype.

Effects of Ovarian Stimulation with Gonadotropins in the Conditions of Chronic Psychosocial Stress on the Quality of Murine Oocyte

Chronic psychosocial stress may negatively affect the female reproductive system. Meanwhile, the effect of ovarian stimulation with gonadotropins during stress on the quality of oocytes remains poorly studied. The purpose of this work was to investigate the effects of chronic psychosocial stress on the quality of murine cumulus-oocyte complexes during natural estrus cycle, as well as during ovarian stimulation with exogenous gonadotropins; the latter is an important part of modern assisted reproductive technologies. The results of the study demonstrate that psychosocial stress does not affect the number of ovulating oocytes, but worsens their quality, i. e. reduces the percentage of mature oocytes. In addition, stressed mice exhibited the increased accumulation of reactive oxygen species in oocytes, which is accompanied by the enhanced rate of apoptosis in cumulus cells. Hormonal stimulation of the ovaries with gonadotropins alleviates the negative changes associated with the psychosocial stress, normalizing the level of reactive oxygen species in oocytes and reducing the rate of apoptosis in cumulus cells.