Endocrinology Research Articles

A comprehensive target panel allows to extend the genetic spectrum of neuroendocrine tumors.

Neuroendocrine tumors (NETs) frequently have a genetic basis, and the range of genes implicated in NETs development continues to expand. Application of targeted gene panels (TGP) in next-generation sequencing (NGS) is a central strategy for elucidating novel variants associated with NETs development. In this study, we conducted comprehensive molecular-genetic analyses using TGP on a cohort of 93 patients diagnosed with various NETs subtypes, mainly accompanied by various endocrine syndromes: insulinoma (n=26), pheochromocytoma and paraganglioma (PPGL) (n=38), parathyroid adenoma (n=18, including three with insulinoma), and NETs of other locations (n=14). The TGP encompassed genes linked to diverse NETs and other hereditary endocrine disorders, with subsequent variant classification according to the American College of Medical Genetics and Genomics guidelines. Among the identified variants, 20 were found in genes previously linked to specific tumor types, and 10 were found in genes with a limited likelihood and unclear molecular mechanisms of association with observed NETs. Remarkably, 13 variants were discovered in genes not previously associated with the NETs observed in our patients. These genes, such as ABCC8, KCNJ11, KLF11, HABP2, and APC, were implicated in insulinoma; ZNRF3, GNAS, and KCNJ5 were linked with PPGL; parathyroid adenomas were related to variants in SDHB and TP53; while NETs of other locations displayed variants in APC and ABCC8. Our study demonstrates that utilizing broad TGP in examining patients with various functioning NETs, facilitates the identification of new germinal variants in genes that may contribute to the diseases. The verification of revealed findings requires research in vaster sample.

Select Endocrine Disorders and Exosomes in Early PDAC Diagnosis

Disturbances in carbohydrate metabolism are suggested to be the early symptoms of pancreatic ductal adenocarcinoma (PDAC). The accumulated data suggests that endocrine function-related biomarkers may represent a breakthrough in the early detection of PDAC. Factors which may predispose one to the development of PDAC are insulin resistance and hyperinsulinemia. Elevated insulin levels induce the onset of carcinogenesis by altering the differentiation and function of islet cells through stimulating growth factors, including insulin-like growth factors (IGFs). Impaired β cell function, along with the impact of PDAC-released factors (e.g., adrenomedullin (ADM), IGF-1, and macrophage inhibitory factor (MIF) on pancreatic islets, may contribute to the induction of diabetes associated with PDAC. Recently, exosomes have attracted worldwide attention due to their role in varied features of cell function, particularly in cancer progression. Exosomes comprise of small extracellular vesicles produced by almost all cells. These vesicles contain a vast array of biomolecules, including proteins and microRNAs. Exosomes participate in cancer growth and promote angiogenesis. They promote tumorigenesis and metastasis, and are associated with the acquisition of cancer cells resistant to chemotherapy. Data have been accumulating recently on the role of exosomes in the rapid recognition, prognosis and potential therapy of pancreatic cancer.

BS O02 - Impact of Bariatric surgery on Obesity Indices and Reproductive Hormones: A Prospective Study in Morbidly Obese Women

Abstract Background Obesity, defined by a BMI of 30 kg/m² or higher, is influenced by genetics, socio-economic, and cultural factors. Genetic predispositions affect metabolism and energy regulation, while environmental factors like sedentary lifestyles and poor food environments worsen obesity. Obesity disrupts hormonal balances, impacting sex hormone levels and menstrual cycles, leading to infertility in women. This hormonal imbalance affects oocyte quality and ovulation. Bariatric surgery offers significant weight loss and metabolic improvements, enhancing reproductive hormone profiles and insulin sensitivity. Our study explores how sleeve gastrectomy affects BMI and hormone levels, aiming to understand its impact on obesity management and reproductive health. Method This prospective observational study examines the effects of laparoscopic sleeve gastrectomy on reproductive hormones and ovarian function in 32 morbidly obese women, adhering to Helsinki Declaration ethics. Participants, aged 18-50 with no menopause or chronic illness, consented to the study. Exclusions included those with polycystic ovary syndrome, recent reproductive organ surgery, or recent infertility medications. The study assessed changes in BMI, antral follicles, anti-Müllerian hormone, and reproductive hormones before surgery and at 6 and 12 months post-surgery. Blood samples and transvaginal ultrasounds were conducted preoperatively and at 6 and 12 months postoperatively to monitor outcomes. Results The study involved participants with an average age of 33 and a mean BMI of 42.12. Significant changes were observed post-sleeve gastrectomy at 6 and 12 months (p < 0.001). At 6 months, BMI decreased by 9.24 units, AMH levels dropped from 3 to 2.5 ng/mL, and antral follicle counts in both ovaries declined. By 12 months, BMI decreased by 16.47 units, AMH levels fell to 2 ng/mL, and antral follicle counts further reduced. Hormonal changes included increases in FSH, LH, and estradiol, while SHBG levels rose, and free testosterone levels decreased significantly. Conclusion Individual hormone responses to weight loss and surgery necessitate personalized obesity treatments. Tailoring surgical approaches and care to hormonal profiles can optimize outcomes and reduce complications. Monitoring AMH levels post-surgery can offer insights into reproductive effects, aiding clinical management and counseling for women with obesity-related infertility. We highlight the significant impact of sleeve gastrectomy on physiological parameters in obese individuals, especially regarding reproductive health and metabolic regulation. The findings enhance understanding of the changes associated with bariatric surgery and its potential benefits for metabolic and reproductive health.

Clinical Effectiveness of Viddha Karma in PCOS: A Case Report

ABSTRACT Polycystic ovary syndrome (PCOS) is a common hormonal disorder affecting women of reproductive age. Ayurveda, an ancient Indian medical system, offers a comprehensive approach to addressing PCOS, including treatments like Viddha Karma. In the case of PCOS, Viddha Karma aims to relieve symptoms and enhance overall well-being. A 27 -year-old unmarried female patient came with complaints of irregular and scanty menses for the past 3-4 years, along with severe abdominal pain during the first 1-3 days of menstruation. She was treated with Shaman Chikitsa and Viddha Karma for 8 months. The patient’s menstrual cycle become regular, the volume of bleeding increased to a normal level, and she experienced a weight reduction of 5 kg. The examination of Viddha Karma principles in the management of PCOS emphasizes its potential as a supplementary treatment that tackles the underlying causes and promotes overall well-being. However, further research and clinical trials are necessary to gain a comprehensive understanding of its effectiveness.

Optimizing Surgical Outcomes: A Case Series on BREAST-V for Treating Breast Asymmetries.

Breast asymmetry occurs when there is a discrepancy in the shape, volume, or positioning of the breasts. Various factors, including unequal development of breast buds, endocrine disorders, chest wall deformities, and surgical or posttraumatic sequelae, can contribute to this condition. Although breast asymmetry is common, clinically severe cases are rare and often require surgical correction because of potential postural, aesthetic, and psychological issues. Accurate assessment of the breast volume is crucial for planning and evaluating surgical interventions. This prospective, non-randomized, interventional study was conducted between 2019 and 2024 at the Breast Reconstruction Section of the Federal University of São Paulo, Brazil. Forty patients with breast asymmetry were evaluated using the BREAST-V, which calculates the breast volume based on three linear measurements. Patients underwent various surgical procedures, including augmentation, reduction mammoplasty, and mastopexy, tailored to their specific type of asymmetry. Preoperative and postoperative breast volumes were compared to assess the effectiveness of surgical correction RESULTS: The study included 40 participants, with an average age of 25.2 years. The mean preoperative breast volumes were 469.6g (right) and 448.8g (left). The postoperative volumes decreased to 338.3g (right) and 331.1g (left), showing an average reduction in asymmetry of 72.9%. The minimal clinically important difference (MCID) for pre-treatment asymmetry was 65.4g. The BREAST-V tool has significant potential for the objective assessment of breast asymmetry. Reliable volumetric measurements can aid in surgical planning and postoperative evaluation, ultimately enhancing the clinical outcomes. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Abstract 4125636: Impaired blood pressure regulation in post-COVID-19 postural orthostatic tachycardia syndrome: novel disease mechanisms beyond sinus tachycardia

Background: Postural orthostatic tachycardia syndrome (POTS) is a prevalent cardiovascular disorder after COVID-19 infection. Although POTS is characterized by the presence of sinus tachycardia, other hemodynamic disturbances including blood pressure (BP) regulation, remain largely unexplored. Aims: We investigated BP changes using 24-hour ambulatory-BP-monitoring in patients with new-onset POTS after COVID-19 compared with pre-pandemic healthy controls. Methods: We performed a case-control study in 100 verified COVID-19 patients with new-onset POTS (mean age 40.0±12.9 years, 85% women) diagnosed by positive head-up tilt-testing versus 100 healthy controls (mean age 45.0±14.6 years, 70% women) from a population-based cohort with negative active standing test, no history of syncope, orthostatic intolerance, or endocrine disease. We analyzed 24-hour Systolic BP (SBP) and hypotensive SBP episodes (<80, <90, and <100mmHg). Results: Study characteristics are illustrated in the Table . Post-COVID-19 POTS patients had significantly higher nighttime-SBP, but not daytime-SBP, and more daytime SBP hypotensive episodes (<80, <90, and <100 mmHg, Figure ) compared with controls. Non-dipper (34% vs 19%, p<0.001) and reverse dipper patterns (9% vs 0 %, <0.001) were more frequent in post-COVID-19 POTS. In the logistic regression, post-COVID-19 POTS was associated with significantly higher mean 24h SBP (odds ratio (OR) 1.08, 95%CI 1.04-1.11, p<0.001) and nighttime SBP (OR 1.07, 95%CI 1.04-1.10, p<0.001), independently of age and sex. Conclusions: Post-COVID-19 POTS patients demonstrate higher mean 24h and nighttime systolic BP, and show signs of disrupted BP regulation compared with healthy controls. They also have more daytime hypotensive episodes. Future studies are needed to assess if post-COVID-19 POTS patients may benefit from tailored BP therapy.

Abstract 4116692: Cardiovascular Safety of Fertility Therapy: A Systematic Review and Meta-Analysis

Background and Aims: The increasing use of assisted reproductive technology (ART) has raised concerns regarding its long-term cardiovascular safety due to potential hormonal imbalances and pro-thrombotic states. This study aimed to assess the long-term cardiovascular risk associated with fertility treatments in women. Methods: Following PRISMA guidelines, a systematic review and meta-analysis was conducted via MEDLINE (Pubmed) from inception to January 2024. Randomized, cohort or case-control studies were included if fulfilling the following criteria: the association between fertility therapy and the subsequent cardiovascular outcome was reported and conditioned on confounding factors (at least age); the presence of a control group; minimum one-year follow-up. Effect size (ES) estimates of the association between fertility therapy and subsequent cardiovascular disease were pooled using the DerSimonian and Laird random-effects model. Heterogeneity was assessed with the I 2 index. This study is registered with PROSPERO (CRD42024505605). Results: Of 7,298 articles screened, eleven studies were included, encompassing 606,912 women undergoing ART and 70,562,486 controls. The analysis found no increase in the long-term risk of major adverse cardiovascular events (ES=0.97, 95% CI=0.81-1.16, I 2 =89.55%, p=0.73), coronary heart disease (ES=0.88, 95% CI=0.71-1.10, I 2 =24.36%, p=0.26), stroke (ES=1.20, 95% CI=0.96-1.49, I 2 =48.33%, p=0.11), heart failure (ES=0.74, 95% CI=0.60-0.94, I 2 =0.00%, p=0.01), venous thromboembolism (ES=1.03, 95% CI=0.78-1.34, I 2 =54.41%, p=0.85), hypertension (ES=1.08, 95% CI=0.88-1.326, I 2 =94.63%, p=0.46), or diabetes (ES=1.03, 95% CI=0.86-1.22, I 2 =78.44%, p=0.77). Conclusions: ART does not increase the long-term risk of cardiovascular diseases in women. These results support the cardiovascular safety of fertility treatments, though further research into specific ART techniques and extended follow-up is recommended.

Total antioxidant capacity status in non-obese adolescent females with PCOS: a cross-section study

Abstract Background The endocrine disease polycystic ovarian syndrome (PCOS) has a number of complications. Teenagers all over the globe are becoming increasingly concerned about the syndrome. It has been suggested that oxidative stress plays a significant role in the pathogenesis of PCOS. Aim The purpose of the present work was to estimate total antioxidant capacity (TAC) in non-obese adolescents and decide if the TAC could be a potential marker for the prediction and diagnosis of PCOS. Methods Serum samples were collected to assess the levels of follicle stimulant hormone (FSH), luteinizing hormone (LH), serum lipids, and serum total antioxidant capacity (TAC) in 50 non-obese patients with PCOS and 50 controls; correlation analysis was made between serum lipid, hormonal parameters, and TAC. Results Adolescents with PCOS had significantly lower levels of TAC compared with controls and showed significant higher values of LH, FSH, and LH/FSH ratio. There were significant negative correlations between TAC levels with LH, FSH, and LH/FSH. Linear regression analysis revealed statistically significant correlations between TAC and LH and FSH levels in non-obese adolescents with PCOS. Conclusion Serum TAC level was diminished in non-obese PCOS patients and was related to increase of LH/FSH ratio. So, quantification of TAC activity in serum could be of value in assessment of cases at higher risk for development of PCOS, suggesting its possible role in regulating sex hormones and could have potential roles in the etiopathogenesis of PCOS in non-obese adolescent females.

Blood Pressure Regulation in Post-COVID POTS: Beyond Sinus Tachycardia.

Postural orthostatic tachycardia syndrome (POTS) is a frequently diagnosed cardiovascular disorder after COVID-19 infection. POTS is characterized by the presence of excessive sinus tachycardia on standing without a fall in blood pressure (BP). We investigated the BP profile using 24-hour ambulatory BP monitoring in patients with new-onset POTS after COVID-19 compared with prepandemic population-based controls. We performed a case-control study in 100 patients (mean age, 40.0±12.9 years; 85% women) with verified post-COVID-19 new-onset POTS diagnosed by a positive head-up tilt testing versus 100 controls from a population-based cohort with a negative active standing test, no history of syncope, POTS, or endocrine disease (mean age, 42.3±14.0 years; 78% women). Twenty-four-hour BP profile was assessed for circadian BP variation including hypotensive systolic BP (SBP) episodes (<80, <90, and <100 mm Hg). Patients with post-COVID-19 POTS had significantly higher nighttime SBP, but not daytime SBP, and more daytime SBP hypotensive episodes compared with controls. Nondipping (34% versus 19%; P<0.001) and reverse dipping patterns (9% versus 0%; P<0.001) were more frequent in post-COVID-19 POTS. In the logistic regression, patients with post-COVID-19 POTS had significantly higher mean 24-hour SBP (odds ratio, 1.08 [95% CI, 1.04-1.11]; P<0.001) and nighttime SBP (odds ratio, 1.07 [95% CI, 1.04-1.10]; P<0.001), independent of age and sex. Patients with post-COVID-19 POTS demonstrate higher mean 24-hour and nighttime SBP and show disruptions of circadian BP rhythm regulation compared with population-based controls, as well as more daytime hypotensive episodes. Future studies are needed to test whether patients with post-COVID-19 POTS may benefit from tailored BP therapy.

Morbidity rates dynamics among the military women of the Russian Ministry of Defense (2012 to 2021)

Relevance. Extreme military service conditions can reduce functional reserves of the military, provoking early development of occupational disorders.The objective is to study morbidity rates dynamics for the last decade (2012–2021) and evaluate the epidemiological significance of different disease chapters among military women to improve their health status.Methods. The study focused on women serving in the Russian military forces with the aim to analyze their morbidity rates over a decade (2012–2021), as presented in the medical report database (3/MED form) and available publications. Medical and statistical codes for main disease chapters are indicated according to the International Statistical Classification of Diseases and Health Related Problems, 10th revision (ICD-10). Morbidity was calculated per 1,000 military women or in ppm (‰), while mortality was calculated per 100,000 persons or 10–5. The average annual indicators calculated based on absolute data, arithmetic averages, errors (M ± m) are provided in study as well. Trends were assessed using dynamic time serie analysis and a second-order polynomial trend.Results and discussion. The long-term average incidence (total morbidity) was 1653.1 ‰, with primary morbidity – 770.6 ‰, regular follow-up – 186.3 ‰, hospitalization – 347.2 ‰, cases requiring a sick leave due to disability – 898.9 ‰, days of disability-related absence from work – 6964 ‰, dismissal rate – 5.11 ‰, mortality rate – 59.2 ∙ 10–5. Polynomial trends in morbidity tracking indicated decreasing trends, with varying significance of determination coefficients. In terms of their social and epidemiological significance, 8 disease chapters (listed in order of severity according to ICD-10) were the major contributors to the military women morbidity: diseases of the respiratory systems (Chapter X), neoplasms (Chapter II), diseases of the circulatory system (Chapter IX), diseases of the musculoskeletal system and connective tissue (Chapter XIII), diseases of the genitourinary system (Chapter XIV), endocrine, nutritional and metabolic diseases (Chapter IV), injury, poisoning and certain other consequences of external causes (Chapter XIX), diseases of the digestive system (Chapter XI).Conclusion. The diseases presented in the above 8 chapters of the ICD-10 were responsible for 87.8 % of socially and epidemiologically significant morbidities. Thus, timely diagnosis, treatment, rehabilitation, and prevention are required to remarkably improve the health status in military women.

THE ROLE OF INTRACELLULAR SIGNALING PATHWAYS IN THE DEVELOPMENT OF TROPHIC PATHOLOGIES OF THE LOWER EXTREMITIES AND THEIR REGENERATION UNDER TYPE 2 DIABETES (PART 1)

Introduction. This review article addresses the critical issue of the development and regeneration of chronic trophic ulcers in the context of type 2 diabetes. This pathological process is associated with inhibited cell proliferation, impaired differentiation of various cell types, and disrupted mechanisms that regulate cell death. An analysis of recent scientific literature also highlights the involvement of key intracellular signaling pathways in the development of chronic ulcerative pathologies of the lower extremities, as observed in both experimental animal models and patients with type II diabetes. Despite advancements, this issue remains insufficiently explored in both theory and practice, underscoring its ongoing relevance. The aim of this study is to identify the roles of key signaling pathways—transforming growth factor β (TGF-β), phosphatidylinositol 3-kinase/serine-threonine kinase (PI3K/Akt), and Wnt/β-catenin—in the inflammatory response, regenerative mechanisms, and healing processes of soft tissue damage and trophic ulcers in experimental animals and patients with type II diabetes. Materials and Methods. This study is based on an analysis of current scientific literature that addresses this topic. Results. It has been found out that changes in the content and activity of key molecules of signaling pathways lead to disruption of carbohydrate homeostasis and the occurrence of structural and functional dysfunction in damaged tissues against the background of type II diabetes. These include TGF-β, PI3K, Akt and β-catenin. Analysis of experimental data demonstrated that both under the conditions of type II diabetes development and in the occurrence of chronic ulcers of the lower extremities, against the background of this endocrine disease, there is an increase in the level of TGF-β. At the same time the activity of the PI3K/Akt signaling pathway in the above-mentioned studied groups was reduced. The relationship between the development of type II diabetes and the Wnt/β-catenin signaling pathway has been established. Suppression of its activity was accompanied by impaired regeneration of chronic trophic ulcers in type II diabetes. Conclusion. Thus, the mechanism of type II diabetes and chronic peptic ulcer disease, in the same pathology, is associated with a impaired activity of signaling cascades. This concerns the following cellular systems such as TGF-β, PI3K/Akt and Wnt/β-catenin. They can be considered as potential therapeutic targets for the development of newest methods for the treatment of chronic trophic ulcers in type II diabetes in order to accelerate the recovery process of volumetric tissue damage of the lower extremities.

Aromatic Amino Acid Hydroxylases as Off-Targets of Histone Deacetylase Inhibitors.

The aromatic amino acid hydroxylases (AAAHs) phenylalanine hydroxylase, tyrosine hydroxylase, and tryptophan hydroxylases 1 and 2 are structurally related enzymes that contain an active site iron atom and depend on tetrahydrobiopterin (BH4) as cosubstrate. Due to their important roles in synthesis of serotonin, dopamine, noradrenaline, and adrenaline and their involvement in cardiovascular, neurological, and endocrine disorders, AAAHs have been targeted by substrate analogs, iron chelators, and allosteric ligands. Phenylalanine hydroxylase is also off-target of the histone deacetylase (HDAC) inhibitor panobinostat. To systematically explore the binding of HDAC inhibitors to AAAHs, we screened a library of 307 HDAC inhibitors and structural analogs against tryptophan hydroxylase 1 using a fluorescence-based thermal stability assay, followed by activity assays. Selected hits were enzymatically tested against all four purified human AAAHs. Cellular thermal shift assay was performed for phenylalanine hydroxylase. We show that panobinostat and structurally related compounds such as TB57, which similarly to panobinostat also contains a cinnamoyl hydroxamate, bind to human AAAHs and inhibit these enzymes with high selectivity within the class (panobinostat inhibition (IC50): phenylalanine hydroxylase (18 nM) > tyrosine hydroxylase (450 nM) > tryptophan hydroxylase 1 (1960 nM). This study shows that panobinostat and related hydroxamic acid type HDAC inhibitors inhibit all AAAHs at therapeutically relevant concentrations. Our results warrant further investigations of the off-target relevance of HDAC inhibitors intended for clinical use and provide directions for new dual HDAC/AAAH and selective AAAH inhibitors. These findings may also provide a new mechanistic link between regulation of histone modification, AAAH function, and monoaminergic neurotransmission.

Protocol for a randomized comparative effectiveness trial comparing a very low-carbohydrate diet to DASH diet for polycystic ovary syndrome: the SUPER (Supporting Understanding of PCOS Education and Research) trial

BackgroundPolycystic ovary syndrome (PCOS), the most common endocrine disorder for women of reproductive age, is associated with increased risk for insulin resistance and type 2 diabetes. Current PCOS treatments insufficiently address the spectrum and severity of the disorder, and there is little evidence-based guidance available for lifestyle management of PCOS, especially through nutritional approaches. Some evidence shows that a very low-carbohydrate diet can improve glucose control compared to low-fat or moderate-carbohydrate diets, leading to improved glucose control and insulin levels that may help to treat symptoms of PCOS. This research investigates whether a very low-carbohydrate diet is more effective in improving glucose control and decreasing symptoms of PCOS in comparison to a DASH diet.MethodsThe SUPER study aims to address the gap in knowledge about nutritional advice for people with PCOS through a randomized, comparative effectiveness trial comparing two approaches to glucose control: the dietary approaches to stopping hypertension (DASH) diet, and a very low-carbohydrate (VLC) diet. We will randomize 184 women with PCOS with body mass indexes (BMIs) between 25 and 50 kg/m2 to a VLC or DASH diet. All participants will follow a 24-session, 12-month, online diet, and lifestyle intervention that teaches their assigned diet. Participants will receive nutritional education, support from diet coaches, and education about behavioral strategies to improve dietary adherence. The primary outcome measure is HbA1c, and secondary outcomes include glucose variance, lipid and hormone levels (including total and free testosterone), PCOS symptoms, inflammation (measured by high-sensitivity C-reactive protein), body composition and weight, psychological well-being, and intervention feasibility and acceptability.DiscussionThe SUPER study is a randomized comparative effectiveness trial that compares two promising approaches to glucose control in people with PCOS. The study also aims to assess the effects of each diet on PCOS symptoms. The research addresses an important gap in knowledge regarding nutritional advice for people with PCOS.Trial registrationClinicalTrials.gov NCT05452642. Registered 6 July 2022.

Vitamin D has therapeutic effects on obesity and hyperandrogenemia in PCOS mouse model induced by low dose DHEA and high-fat diet

Polycystic ovary syndrome (PCOS) is the most complex and common reproductive endocrine disease among reproductive age women. This study aimed to investigate the effects of vitamin D (Vit.D) in a PCOS mouse model induced by low dose DHEA and high-fat diet. Prepubertal female mice were divided into 4 groups randomly: control, PCOS, PCOS with low dose Vit.D(LDVD), and PCOS with high dose Vit.D(HDVD) groups (n = 10 per group). PCOS mice were administrated with high-fat diet and subcutaneous injection with 6 mg/kg/day dehydroepiandrosterone throughout the study. After the first 30 days, 1,25(OH)2D3 was intend to be administered by intraperitoneal injection for 40 consecutive days, 1.3 µg/kg/week in LDVD group, and 13 µg/kg /week in HDVD group. However, the mice in HDVD group appeared to be fatigue and anorexic after the Vit.D injections, then all died within two weeks. The body weights and testosterone levels in PCOS group were significantly higher than those in the control and LDVD groups (P < 0.001). The total cholesterol levels in the control group were lower than those in PCOS and LDVD groups (P < 0.001). Further, the ratio of liver to body weight was different among groups (P < 0.001). Our data illustrates that Vit.D has therapeutic effects on obesity and hyperandrogenemia in PCOS mouse model induced by low dose DHEA and high-fat diet. However, over dose of Vit.D is toxic. Further researches are needed to elucidate the mechanisms.

Screening of Optimal Phytoconstituents through in silico Docking, Toxicity, Pharmacokinetic, and Molecular Dynamics Approach for Fighting against Polycystic Ovarian Syndrome.

Polycystic ovarian syndrome (PCOS) is a hormonal disorder caused by excessive secretion of male sex hormones in females. Herbal remedies for PCOS are lightning up as they bypass the adverse effects and are profoundly safe on prolonged usage. The present study included a selection of 34 herbs pursuing biological effects on the uterus, and their major chemical constituents were subjected to a series of in silico techniques using different software. The proteins contributing majorly to the hormonal functions like Human cytochrome P450 CYP17A1 (3RUK), Progesterone (1E3K), and estrogen receptor (1X7R) were selected for the study. Molecular docking studies were performed using AutoDock 1.5.7. The pharmacokinetic properties were predicted using the SwissADME online tool, while toxicity parameters were assessed with OSIRIS toxicity explorer and pkCSM. Molecular dynamics simulations and free energy calculations were performed using the Schrödinger suite. Constituents with a basic steroidal nucleus demonstrated high binding energy values. An analysis of all the in silico techniques showed that Sarsasapogenin from Asparagus racemosus exhibited strong binding energies of -10.88 kcal/mol, -10.51 kcal/mol, and -9.79 kcal/mol with the selected specific proteins. In molecular dynamics simulations, Sarsasapogenin displayed ideal stability, with RMSD fluctuations below 3 Å and RMSF slightly higher than the corresponding peak of apoprotein. Additionally, it showed a favorable druglikeness profile and non-toxic effects across all screened parameters. From the list of the selected constituents, sarsasapogenin was found to be ideal, and further research on it for targeting PCOS is expected to yield promising results.

ASSESSMENT OF THYROID FUNCTION DISORDERS AMONG THE SUBJECTS ATTENDING CENTRAL LABORATORY OF A TERTIARY CARE HOSPITAL: AN OBSERVATIONAL, CROSS-SECTIONAL STUDY

Objective: Thyroid disorders are the most common endocrine disorders worldwide and India is not an exception. Several factors may determine the prevalence of thyroid dysfunction including age, gender, geographical and ethnic background, and most importantly iodine intake. Therefore, data related to thyroid disorders from one population cannot be extrapolated to another. In this study, we aimed to assess the disorders of thyroid function among the subjects attending the central laboratory of a tertiary care hospital. Methods: This observational, cross-sectional study was conducted in the Department of Pharmacology and the Department of Biochemistry of the same institute over a period of 3 months. All subjects of either sex attending the central laboratory of the institute for estimating thyroid function on their outpatient visit during the study period were included. Subjects who were on any medications known to alter the thyroid hormone status or diagnosed with a thyroid disorder and/or on therapy were excluded. A pre-designed and pre-tested data collection form was used for taking interviews to collect relevant data including sociodemographic characteristics, comorbid conditions, thyroid illness, and investigational reports. Results: A total of 132 subjects were included in the study. The majority of them were female (72.27%) and residents of urban areas (52.27%). The most common comorbid conditions and presenting symptoms were hypertension (25.76%) and fatigue (46.97%), respectively. The majority of the subjects were found to be euthyroid (81.81%). About 18.19% of the study subjects were having thyroid disorders, most commonly subclinical hypothyroidism (SCH) (13.64%), followed by primary hypothyroidism (2.27%), secondary hyperthyroidism (1.52%), and subclinical hyperthyroidism (0.76%). Thyroid disorders were mainly found in females, such as primary hypothyroidism (66.67%), SCH (66.67%), and subclinical hyperthyroidism (100%). The majority of the thyroid disorders were found in the age group of 26–50 years (20.27%), where females were found to have more primary hypothyroidism (3.17%), and SCH (12.70%). Conclusion: The findings of our study call for a review of current practices regarding thyroid disorders to include active screening of thyroid function among the subjects at greater risks and an emphasis on regular monitoring of the thyroid status.

A review of vitamin D deficiency and vitamin D receptor polymorphisms in endocrine related disorders.

The endocrine system is a complex network of glands that produce and release hormones that regulate various physiological processes. In the past few decades, the human skin has been identified as an important peripheral endocrine organ that is the main site for the synthesis of vitamin D through exposure to sunlight. Mutations in downstream vitamin D-related gene pathways are associated with disease development. The vitamin D receptor (VDR) gene, which regulates the pleiotropic effects of vitamin D, has been extensively studied in adult populations. Several studies have reported the prevalence of vitamin D deficiency in children and adolescents. With changes in socioeconomic status and lifestyle, vitamin D-deficient individuals are prone to developing the disease at a young age. However, geographical and racial differences affect the association between VDR gene polymorphisms and vitamin D endocrine disorders, explaining the non-consensus effects of polymorphisms and their association with disease development across populations. In this review, we discuss the connection between the vitamin D endocrine system and polymorphisms in the gene encoding VDR in children and adolescents, focusing on its effects on growth, puberty, insulin resistance, and the immune system.

USING ARTIFICIAL INTELLIGENCE FOR BIOMARKER ANALYSIS IN CLINICAL DIAGNOSTICS

Introduction. Artificial intelligence (AI) technologies are becoming crucial in clinical diagnostics due to their ability to process and interpret large volumes of data. The implementation of AI for biomarker analysis opens new opportunities in personalized medicine, offering more accurate and individualized approaches to disease diagnosis and treatment. The relevance of this review stems from the need to systematize recent advances in AI application for biomarker analysis, which is critical for early diagnosis and prediction of chronic non-communicable diseases (NCDs). Material and methods. The analysis of peer-reviewed scientific publications and reports from leading research centers over the past five years was conducted. Studies on the application of AI algorithms for analyzing genomic, proteomic, and metabolomic biomarkers were reviewed, including machine learning methods and deep neural networks. Special attention was paid to the integration of multi-marker panels for improving the accuracy of diagnosis and prediction of cardiovascular, digestive, respiratory, endocrine system diseases, as well as oncological and neurodegenerative pathologies. Results. The application of AI has significantly increased the sensitivity and specificity of diagnostics, especially in complex cases requiring analysis of multiple disease parameters. The effectiveness of AI has been demonstrated in early diagnosis of lung, breast, and colorectal cancer, prediction of cardiovascular complications and NCDs progression, including diabetes mellitus and Alzheimer’s disease. AI’s significant contribution to the discovery of new biomarkers, optimization of personalized treatment, and improvement of therapeutic strategies has been noted. Conclusion. The use of AI in biomarker analysis has become a significant breakthrough in medical diagnostics, particularly in oncology, cardiology, and neurodegenerative diseases. The technology allows integration of data about various biomarkers and contributes to creating more accurate models for disease diagnosis and prediction. Further development is associated with technology advancement and overcoming ethical and regulatory barriers, which will expand AI capabilities in clinical practice.

Acrylamide-induced hypothalamic-pituitary-gonadal axis disruption in rats: Androgenic protective roles of apigenin by restoring testicular steroidogenesis through upregulation of 17β-HSD, CYP11A1 and CYP17A1

Acrylamide (ARL) exposure induces significant toxicity to the hypothalamic-pituitary-gonadal (HPG) axis, leading to detrimental effects on behavior, neuroendocrine functions, steroidogensis, oxidative stress, inflammation, hormonal balance, sperm quality, and histopathological integrity in rats. This study investigates the protective role of oral apigenin (API; 10 or 20 mg/kg/day for 28 days) against ARL-induced toxicity in the HPG axis of male Wistar rats. Behavioral assessments revealed that ARL exposure impaired motor coordination and balance, as evidenced by increased landing foot splay distance and gait score. ARL-induced toxicity elevated brain Tau protein levels and disrupted hypothalamic GnRH levels, both mitigated by API. ARL triggered oxidative/nitrosative stress, reducing GSH contents and increasing MDA and NO levels in brain and testicular tissues, which were reversed by API. Hormonal imbalance, marked by decreased serum testosterone, FSH, and LH levels, was corrected by API. API enhanced semen quality parameters, with elevation in sperm count concentration and the percentages of both progressive motility and individual motility. It also normalized testicular PS and PC content, enhanced testicular cellular energy and restored seminal amino acid. The repression of testicular steroidogenesis-related enzymes CYP11A1, CYP17A1, and 17β-HSD following ARL exposure was alleviated by API administration. API also mitigated the inflammatory effects of ARL by reducing the expression of p–NF–κB p65 and TNF-α in testicular tissue. Histopathological examinations showed that API reduced neuronal and testicular degeneration, improving spermatogenesis. These findings suggest that API confers significant protective effects against ARL-induced HPG axis toxicity by restoring testicular steroidogenesis through the upregulation of 17β-HSD, CYP11A1, and CYP17A1, potentially due to its antioxidant, anti-inflammatory, and neuroprotective properties.

Septo-optic dysplasia plus: A case report for reviewing and recognizing this condition

Septo-optic dysplasia is a congenital neurological condition with multifactorial etiology, characterized by septum pellucidum agenesis and/or corpus callosum dysgenesis, hypoplasia of the chiasm or optic nerves, and hormonal dysfunction with pituitary or hypothalamic alterations. Diagnosis requires two of these criteria and magnetic resonance is the imaging test of choice. Most cases present with abnormalities of cortical development in the form known as septo-optic dysplasia plus. While seizures and neurodevelopmental disorders are the dominant neurological manifestations, this entity is highly heterogeneous and has multiple clinical and radiological findings to consider. We present the case of a 35-year-old man with a history of cranioencephalic trauma in childhood and remission for refractory focal epilepsy associated with cognitive deficit. During the initial examination, the simple cranial tomography showed septum pellucidum agenesis and corpus callosum dysgenesis. Brain magnetic resonance imaging revealed agenesis of the septum pellucidum, irregularity and anomalous thickening of the cerebral cortex in frontal lobes and perisylvian region, heterotopic gray matter in frontal lobes and left fronto-insular region, mild supratentorial ventriculomegaly, atypical appearance of the corpus callosum rostrum, and hypoplasia of the chiasm and optic nerves. Although agenesis of the septum pellucidum was the key finding in this case, it is not present in all patients. The relevance of magnetic resonance imaging for the detailed evaluation of other involved structures, highlighting optic nerve hypoplasia, is fundamental in the radiologist’s diagnostic workup and this entity recognition.