Obesity - Standards, trends and advances.

Obesity continues to be a significant global health concern, giving rise to various complications. This review article explores the current standards and emerging innovations in diagnosing and treating obesity, including recent disease name change, staging system or therapeutic goals. This narrative review has been based on recent scientific articles from PubMed database, limiting the scope of topics to current standards and upcoming developments and breakthroughs in the diagnosis and treatment of obesity. The educational and informative nature of the review has been maintained in order to make the information presented accessible to both researchers and clinical practitioners. The recognition of diverse obesity phenotypes has prompted a paradigm shift towards a complex and patient-centered approach to diagnosis and therapy. Pharmacotherapy for obesity is evolving rapidly, with ongoing research focusing on novel molecular targets and metabolic pathways. Promising developments include dual or triple incretin analogs, oral incretin drugs, neurotransmitter-based therapies, muscle mass-increasing treatments, and therapies targeting visceral adipose tissue browning. Despite current evidence-based international standards, the field of obesity diagnosis and treatment continues to expand, with new diagnostic tools and pharmacotherapies potentially replacing current practices. Therapeutic management should be tailored to individual patients, considering obesity phenotype, health status, lifestyle, and preferences. Looking ahead, the future holds promising opportunities for obesity management, but further research is required to assess the efficacy and safety of emerging therapies. A multifactorial and personalized approach will be pivotal in addressing the diverse challenges posed by obesity.

Obesity in perimenopause - current treatment options based on pathogenetic factors.

The health of post-menopausal women has become of paramount concern due to the aging of the world's population. Concurrently, the prevalence of obesity among postmenopausal women is expected to increase, presenting a significant public health challenge. Although weight gain during menopause is a well-observed phenomenon, its underlying causes and mechanisms remain incompletely understood. This manuscript reviews the literature to explore potential hormonal factors and pathomechanisms contributing to obesity during perimenopause, aiming to identify pathogenic factors that can guide treatment selection. Menopause-induced hormonal changes, including hypoestrogenaemia, hypergonadotropinaemia, relative hyperandrogenaemia, growth hormone deficiency, leptin resistance, and chronic stress affecting the hypothalamic-pituitary-adrenal axis, have been implicated in the onset of obesity in perimenopausal women. These hormonal fluctuations, alongside lowered daily energy expenditure, lead to metabolic alterations that elevate the risk of developing metabolic disorders and cardiovascular diseases. Weight gain in perimenopausal women is associated with higher total and abdominal adipose tissue and lower lean body mass. Addressing this issue requires individualized behavioural management, supported by effective pharmacological therapy, and, when warranted, complemented by bariatric surgery. Modern obesity treatment therapies have demonstrated safety and efficacy in clinical trials, offering the potential to reduce excess body fat, improve metabolic profiles, lower cardiovascular risk, and enhance the quality and longevity of women's lives. In addition to standard obesity therapies, the article examines different treatment strategies based on obesity's pathogenic factors, which may offer promising options for treating obesity with or without complications in perimenopausal women. One such potential approach is menopausal hormone therapy (MHT), which hypothetically targets visceral obesity by reducing visceral adipose tissue accumulation, preserving metabolically active lean body mass, and improving lipid profiles. However, despite these reported benefits, gynaecological and endocrinological societies currently do not recommend the use of MHT for obesity prevention or treatment, necessitating further research for validation. Emerging evidence suggests that visceral obesity could result from hypoestrogenaemia during perimenopause, potentially justifying the use of MHT as a causal treatment. This highlights the importance of advancing research efforts to unravel the intricate hormonal and metabolic changes that occur during perimenopause and their role in obesity development.

Clinical and Therapeutic Implications of Male Obesity.

The prevalence of obesity, a disorder linked to numerous comorbidities and metabolic complications, has recently increased dramatically worldwide and is highly prevalent in men, even at a young age. Compared to female patients, men with obesity more frequently have delayed diagnosis, higher severity of obesity, increased mortality rate, and only a minority of obese male patients are successfully treated, including with bariatric surgery. The aim of this review was to present the current state of knowledge about the clinical and therapeutic implications of obesity diagnosed in males.

Current Insights into the Potential Role of fMRI in Discovering the Mechanisms Underlying Obesity.

Obesity is becoming one of the major global health concerns. This chronic disease affects around 650 million people worldwide and is an underlying cause of a number of significant comorbidities. According to the World Health Organization (WHO) report on obesity from 2022, this disorder became the fourth leading cause of deaths in Europe. Thus, understanding the mechanisms underlying obesity is of essential importance to successfully prevent and treat this disease. The aim of this study was to review the current insights into the potential role of fMRI in discovering the mechanisms underlying obesity on the basis of recent scientific literature published up to December 2022 and searches of the PubMed, Google Scholar and Web of Science databases. The literature assessed indicated that a growing body of evidence suggests that obesity leads to changes in both structure and connectivity within the central nervous system. Emerging data from recent functional magnetic resonance imaging (fMRI) studies prove that obese individuals present an increased motivational drive to eat as well as impaired processing in reward- and control-related brain regions. Apart from this, it is clear that fMRI might be a useful tool in detection of obesity-induced changes within the central nervous system.

Diagnosis and Non-Invasive Treatment of Obesity in Adults with Type 2 Diabetes Mellitus: A Review of Guidelines.

Obesity, a chronic disease with multifactorial etiopathogenesis, is characterized by excessive accumulation of adipose tissue. Obesity prevalence is growing globally at an alarming rate. The overwhelming majority of obesity cases are caused by inappropriate lifestyles, such as overconsumption of food and inadequate physical activity. Metabolic and biochemical changes due to increased adiposity resulted in numerous comorbidities, increased all-cause mortality, and reduced quality of life. T2DM (type 2 diabetes mellitus) and obesity have many common pathogenetic points and drive each other in a vicious cycle. The aim of this article is to review obesity management guidelines and highlight the most important points. Management of both obesity-related and T2DM complications incur enormous expenses on healthcare systems. It is, therefore, paramount to provide streamlined yet custom-tailored weight management in order to avoid the negative ramifications of both diseases. Efficient obesity treatment leads to better diabetes control since some antidiabetic medications support weight reduction. Obesity treatment should be overseen by a multi-disciplinary team providing indispensable information and individually tailored regimens to patients. Weight management should be multimodal and consist chiefly of MNT (medical nutrition therapy), physical activity, and lifestyle changes. A comprehensive approach to obesity treatment may give tangible results to quality of life and comorbidities.

Basics of prevention and management of iodine-based contrast media-induced thyroid dysfunction - position paper by the Polish Society of Endocrinology.

Medical practice involves a high number of radiological examinations using iodinated contrast media (ICM). Therefore, it is crucial for doctors of different specialties to be aware of possible adverse effects associated with ICM use. The most common and well characterized adverse effect is contrast-induced nephropathy, whereas thyroidal adverse reactions remain a diagnostic and therapeutic dilemma. ICM-induced thyroid dysfunction represents a highly heterogenous group of thyroid disorders. Due to supraphysiological iodine concentration, ICM can induce both hyper- and hypothyroidism. In most cases, the ICM-induced thyroid dysfunction is oligo- or asymptomatic, mild, and transient. In rare cases, however, the ICM-induced thyroid dysfunction may be severe and life threatening. Recently, the European Thyroid Association (ETA) Guidelines for the Management of Iodine-Based Contrast Media-Induced Thyroid Dysfunction were published. The authors advise an individualized approach to prevention and treatment of ICM-induced thyroid dysfunction, based on patient's age, clinical symptoms, pre-existing thyroid diseases, coexisting morbidities, and iodine intake. There is a geographic variation of ICM-induced thyroid dysfunction prevalence, which is linked to iodine intake. The prevalence of ICM-induced hyperthyroidism, which may pose a serious therapeutic challenge, is greater in countries with iodine deficiency. Poland is a region with a history of iodine deficiency, contributing to an increased prevalence of nodular thyroid disease, especially in the elderly. Therefore, the Polish Society of Endocrinology has proposed national, simplified principles of ICM-induced thyroid dysfunction prevention and treatment.

Branched-chain amino acids as a novel biomarker of metabolic disturbances in women with polycystic ovary syndrome - literature review.

Polycystic ovary syndrome (PCOS) is a common, heterogeneous endocrine disorder which effects 5-10% of reproductive-age women. Recently, an association between PCOS and an increased risk of developing metabolic disturbances, such as insulin resistance, prediabetes, type 2 diabetes mellitus as well as obesity has been emphasised. Branched-chain amino acids (BCAAs), including valine (Val), leucine (Leu) and isoleucine (Ile), are a group of essential amino acids that cannot be synthesized in human body and need to be obtained from food. Several recent studies provide evidence that plasma BCAAs also serve as crucial nutrient signals and metabolic regulators. Interestingly, latest metabolomics analysis shows abnormalities in amino acid catabolism and biosynthesis in patients with PCOS, particularly in BCAAs. A growing body of evidence proves that elevated levels of BCAAs may have adverse effects on metabolic health leading to the development of insulin resistance, prediabetes, type 2 diabetes mellitus and obesity both in human and animal models. The aim of this review is to assess the current state of knowledge about the potential role of BCAAs as a novel biomarker of metabolic disturbances in women with polycystic ovary syndrome based on recent scientific literature published up to July 2021 and searches of the PubMed, Google Scholar, and Web of Science databases.

Link between Insulin Resistance and Obesity-From Diagnosis to Treatment.

Insulin resistance (IR) has become a common health issue in medical practice. There are no detailed data on IR prevalence, but it is an increasing problem due to its close association with obesity. However, IR is not considered as a separate nosological entity and the diagnostic criteria are not well defined, which leads to overdiagnosis of IR and an inappropriate approach. This review aims to summarize the available literature on IR pathophysiology, its relationship with obesity, as well as diagnostic methods, clinical presentation and treatment. Excessive energy intake results in cell overload that triggers mechanisms to protect cells from further energy accumulation by reducing insulin sensitivity. Additionally, hypertrophied adipocytes and macrophage infiltration causes local inflammation that may result in general inflammation that induces IR. The clinical picture varies from skin lesions (e.g., acanthosis nigricans) to metabolic disorders such as diabetes mellitus or metabolic-associated fatty liver disease. There are numerous IR laboratory markers with varying sensitivities and specificities. Nutrition changes and regular physical activity are crucial for IR management because a reduction in adipose tissue may reverse the inflammatory state and consequently reduce the severity of insulin resistance. In cases of obesity, anti-obesity medications can be used.

Efficacy, Safety, and Immunogenicity of Biosimilar Insulin Aspart Premix SAR341402 Mix 70/30 Compared with Originator Insulin Aspart Mix 70/30 in Adults with Diabetes (GEMELLI M): A Subgroup Analysis by Prior Type of Premix Insulin.

INTRODUCTION: We compared the efficacy, safety, and immunogenicity of biosimilar insulin aspart premix SAR341402 Mix 70/30 (70% intermediate SAR341402 protamine and 30% rapid SAR341402 solution) (SARAsp-Mix) with its originator NovoMix 30 insulin aspart mix (NN-Mix) in adults with type 1 or type 2 diabetes switching from different premix insulin analogs. METHODS: This phase 3, randomized, open-label, multinational, 26-week trial (GEMELLI M) enrolled 402 participants with type 1 or type 2 diabetes. At randomization, participants switched from their prestudy premix insulin NovoMix 30 (n = 341) or Humalog Mix 25/Liprolog Mix 25 (n = 61) to equivalent (1:1) doses of either SARAsp-Mix or NN-Mix at least twice daily (1:1 randomization). In this subgroup analysis, efficacy measures [change in hemoglobin A1c (HbA1c), daily insulin dose], and safety outcomes [hypoglycemia incidence, adverse events (including hypersensitivity and injection site reactions), anti-insulin aspart antibodies] of SARAsp-Mix were compared with those of NN-Mix separately according to the participants' prestudy premix insulin. RESULTS: At week 26, change from baseline in HbA1c (primary efficacy endpoint) was similar between SARAsp-Mix and NN-Mix in those participants pretreated with NovoMix 30 [least squares (LS) mean difference 0.05%, 95% confidence interval (CI) -0.195% to 0.289%] or Humalog Mix 25/Liprolog Mix 25 (LS mean difference 0.28%, 95% CI -0.279% to 0.830%) (P value for treatment-by-subgroup interaction = 0.46). In both subgroups, safety outcomes, including immunogenicity, and changes in daily insulin doses were similar between treatments over 26 weeks. CONCLUSIONS: Efficacy, safety, and immunogenicity profiles of SARAsp-Mix are similar to NN-Mix over 26 weeks in adults with diabetes irrespective of prior type of premix insulin. TRIAL REGISTRATION: EudraCT number 2017-000092-84.

Dopamine Agonist-Resistant Microprolactinoma-Mechanisms, Predictors and Management: A Case Report and Literature Review.

OBJECTIVE: Prolactinomas are the most common type of functional, hormone-secreting pituitary adenomas that account for about 40% of total pituitary adenomas. Typical clinical presentations include loss of menstrual periods (amenorrhea) and galactorrhoea in women and sexual dysfunction in men. Prolactinomas are preferentially treated with dopamine agonists and respond to such therapy with hormonal normalisation and tumour shrinkage. However, about 10-20% of prolactinomas are resistant to dopamine agonists. The management of dopamine agonist-resistant prolactinomas poses a therapeutic challenge and includes several possible approaches. DESIGN AND METHODS: In this study, we present a case report of a woman diagnosed with microprolactinoma at the age of 27 who did not fully respond either to treatment with dopamine agonists nor to transsphenoidal surgery. This was followed by a review of literature on the current state of knowledge about the mechanisms, predictors, and management of dopamine agonist-resistant prolactinomas on the basis of recent scientific literature published up to November 2021 and searches of the PubMed, Google Scholar, and Web of Science databases. RESULTS AND CONCLUSIONS: The exact mechanisms underlying dopamine agonists' resistance in lactotroph tumours are not fully understood, yet refractory prolactinomas pose a great challenge in everyday clinical practice. Several predictive factors that contribute to poor response to medical treatment have been identified, among them the elevated Ki-67 index. Recently, various alternative medical treatments have been considered, but their usefulness remains to be evaluated. A return of menses can serve as a first clinical indication of successful medical treatment.

Biosimilar Insulin Aspart Premix SAR341402 Mix 70/30 Versus Originator Insulin Aspart Mix 70/30 (NovoMix 30) in People with Diabetes: A 26-Week, Randomized, Open-Label Trial (GEMELLI M).

INTRODUCTION: This study compared the efficacy, safety, and immunogenicity of biosimilar insulin aspart premix SAR341402 Mix 70/30 (SARAsp-Mix) with European-approved insulin aspart mix 70/30 - NovoMix® 30 (NN-Mix) in people with type 1 (T1D) or type 2 diabetes (T2D). METHODS: This 26-week, open-label, phase 3 trial enrolled 402 people with T1D (n = 105) or T2D (n = 297) previously treated with premix insulin, who were randomized (1:1) to SARAsp-Mix (n = 204) or NN-Mix (n = 198). RESULTS: After 26 weeks, the least squares (LS) mean [median] change in HbA1c from baseline was similar in both treatment groups (SARAsp-Mix - 0.55% [- 0.60%]; NN-Mix - 0.64% [- 0.60%]). The LS mean difference for SARAsp-Mix versus NN-Mix was 0.08%, with the upper bound of the two-sided 95% confidence interval (- 0.139 to 0.303) slightly above the prespecified noninferiority margin of 0.3%. Noninferiority of SARAsp-Mix over NN-Mix was not demonstrated in the primary intent-to-treat analysis, primarily because of one extreme outlying value impacted by the COVID-19 pandemic in the SARAsp-Mix group. Noninferiority was achieved in all secondary analyses, including prespecified per-protocol supportive and COVID-19 sensitivity analyses, as well as post hoc sensitivity analyses. Other efficacy endpoints, insulin dosages, anti-insulin aspart antibody response, hypoglycemia, and adverse events were similar between groups. CONCLUSIONS: The totality of evidence indicates that SARAsp-Mix provides effective glycemic control with a similar safety and immunogenicity profile to NN-Mix in people with diabetes treated for 26 weeks. TRIAL REGISTRATION: EudraCT number 2017-000092-84.

MicroRNAs as Biomarkers for Coronary Artery Disease Related to Type 2 Diabetes Mellitus-From Pathogenesis to Potential Clinical Application.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease with still growing incidence among adults and young people worldwide. Patients with T2DM are more susceptible to developing coronary artery disease (CAD) than non-diabetic individuals. The currently used diagnostic methods do not ensure the detection of CAD at an early stage. Thus, extensive research on non-invasive, blood-based biomarkers is necessary to avoid life-threatening events. MicroRNAs (miRNAs) are small, endogenous, non-coding RNAs that are stable in human body fluids and easily detectable. A number of reports have highlighted that the aberrant expression of miRNAs may impair the diversity of signaling pathways underlying the pathophysiology of atherosclerosis, which is a key player linking T2DM with CAD. The preclinical evidence suggests the atheroprotective and atherogenic influence of miRNAs on every step of T2DM-induced atherogenesis, including endothelial dysfunction, endothelial to mesenchymal transition, macrophage activation, vascular smooth muscle cells proliferation/migration, platelet hyperactivity, and calcification. Among the 122 analyzed miRNAs, 14 top miRNAs appear to be the most consistently dysregulated in T2DM and CAD, whereas 10 miRNAs are altered in T2DM, CAD, and T2DM-CAD patients. This up-to-date overview aims to discuss the role of miRNAs in the development of diabetic CAD, emphasizing their potential clinical usefulness as novel, non-invasive biomarkers and therapeutic targets for T2DM individuals with a predisposition to undergo CAD.

Presenting symptoms and endocrine dysfunction in Rathke cleft cysts - a two-centre experience.

INTRODUCTION: Rathke cleft cysts (RCC) arise as developmental abnormalities of the pituitary gland and are usually diagnosed incidentally. However, they may present with headaches, visual impairment, or pituitary dysfunction. Rathke cleft cysts are poorly described in the Polish literature. We aimed to characterize presenting symptoms, associated endocrine dysfunction, and concomitant disorders in the Polish population of patients with RCC. MATERIAL AND METHODS: We performed a retrospective analysis of medical records of 102 patients diagnosed with RCC between 2006 and 2021 at Heliodor Swiecicki Clinical Hospital in Poznan and Independent Public Clinical Hospital No. 4 in Lublin. RESULTS: The cohort was 72% female, with a mean age of 43 years. The median maximal cyst diameter was 7 mm. The majority of subjects were overweight or obese and presented lipid profile or glucose disturbances. Common presenting symptoms included headache, vertigo, and visual impairment. Less frequently we observed sexual dysfunction, irregular menses, galactorrhoea, or fatigue. Hormonal abnormalities were identified in 30% of patients, with hyperprolactinaemia being the commonest endocrinopathy (23%). Pituitary function in patients with RCC did not correlate with cyst size. Both concomitant pituitary adenomas and pineal cysts were diagnosed in 3% of patients. A considerable proportion of subjects were diagnosed with Hashimoto's thyroiditis and multinodular goitre. CONCLUSIONS: RCCs occur mostly in females and may result in a variety of symptoms and hormonal dysfunction. Patients require a full clinical and endocrine evaluation regardless of the cyst diameter. We report a substantial co-occurrence of RCC and metabolic disorders and primary thyroid diseases, which requires further investigation.

Neutrophil-to-Lymphocyte, Platelet-to-Lymphocyte Ratios, and Systemic Immune-Inflammation Index as Potential Biomarkers of Chronic Inflammation in Patients with Newly Diagnosed Acromegaly: A Single-Centre Study.

Acromegaly is a rare disease caused by overproduction of growth hormone (GH) by a pituitary adenoma, and consequently increased insulin-like growth factor 1 (IGF-1) concentration. The GH/IGF-1 axis and immune cells interactions are hypothesized to be involved in subclinical inflammation. This retrospective study aimed to investigate the differences in neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR) ratios, and systemic immune-inflammation index (SII) in GH-secreting adenomas compared with non-functioning pituitary adenomas (NFPAs) concerning clinical and radiological findings. After evaluation of 665 patients with pituitary tumors, 62 individuals with newly diagnosed acromegaly and 134 with NFPAs were enrolled in the analysis. The control group consisted of 120 healthy individuals. Fifty-eight patients with acromegaly were re-evaluated after medical or surgical therapies. NLR, PLR, SII values, and neutrophil count were significantly higher (p ≤ 0.001), whereas lymphocyte count was lower in acromegaly than in NFPAs (p = 0.001). No significant differences between NFPAs and controls were observed in analyzed ratios. Higher preoperative NLR, PLR, SII values were found in patients who failed to achieve a cure with surgery (p < 0.05). Although NLR, PLR, and SII values were significantly higher in acromegaly, these indices cannot be used to discriminate GH-secreting pituitary tumors from NFPAs. Treatment of acromegaly decreased the value of NLR and SII, but it requires further studies to consolidate the real clinical role of these inflammation-related ratios.

Copeptin as a novel biomarker of cardiometabolic syndrome.

Arginine vasopressin (AVP), which is also called antidiuretic hormone (ADH), is a neurohormone synthetized from a pre-pro-hormone precursor in the supraoptic and paraventricular nuclei of the hypothalamus in response to increased plasma osmolality and decreased blood volume. AVP exerts several effects by binding to three different receptors: V1aR, V1bR, and V2R. In recent years, it has been suggested that increased plasma concentration of AVP may play a causal role in the development of type 2 diabetes, the metabolic syndrome, renal dysfunction and cardiovascular disease by influencing glucose homeostasis and lipid metabolism through several possible mechanisms involving V1aR and V1bR. V1aR located in the liver is involved in hepatic glycogenolysis and gluconeogenesis. V1bR, found in the pituitary gland and pancreas, mediates secretion of adrenocorticotrophic hormone (ACTH), insulin, and glucagon. However, AVP's clinical use as a biomarker is limited due to its short half-life in plasma (16-20 minutes), small size, and poor stability, which make direct measurement difficult. Copeptin, the biologically inactive, stable, C-terminal part of pro-vasopressin, is co-secreted with AVP in equimolar amounts and thus is considered an adequate and clinically useful surrogate marker of AVP. The aim of this review is to assess the current state of knowledge about the potential role of copeptin as a novel biomarker of cardiometabolic syndrome on the basis of recent scientific literature published up to December 2020 and searches of the PubMed, Google Scholar, and Web of Science databases.

Influence of SARS-CoV-2 infection on thyroid gland function: The current knowledge.

The paper summarizes the current knowledge about the influence of SARS-CoV-2 on the thyroid gland and benign thyroid diseases, with emphasis on the situation in Poland. Based on the latest scientific literature published up to May 1, 2021 and the PubMed, Google Scholar, EMBASE and Web of Science database searches, keywords related to SARS-CoV-2 and its impact on the thyroid gland and benign thyroid diseases were searched. COVID-19-related thyroid disorders include non-thyroid syndrome, hypothyroidism and thyrotoxicosis. The authors paid special attention to the treatment of thyroid disease during the pandemic. The emphasis was on radioiodine therapy, which is of high clinical value due to the lower risk of neutropenia or agranulocytosis. It is currently unknown whether COVID-19 may lead to de novo thyroid dysfunction or if it can aggravate an existing thyroid disease. Patients with uncontrolled thyrotoxicosis are in a risk group for complications (e.g., cytokine storm) from any infection (especially from SARS-CoV-2 infection). Moreover, this group of patients should receive more extensive care, bearing in mind the neutropenia from taking antithyroid drugs, which may mask the symptoms of COVID-19.

Selected thyreology problems during the COVID-19 pandemic. Hypothyroidism and hyperthyroidism - did anything change?

On March 11, 2020, the World Health Organisation (WHO) observed the scale of epidemic risk and declared the state of the COVID-19 pandemic. Most countries, including Poland, implemented national and local emergency management plans to deal with the imminent threat of SARS-CoV-2 infection, one of the most serious in this century, according to many experts. In the era of pandemic, during which an epidemiological regime and social distancing are constantly recommended, and routine medical care and planned surgical procedures have been postponed or significantly reduced, patients and their physicians have to struggle on a daily basis with difficult access to diagnostic and therapeutic procedures. This is a great challenge for both groups. The aim of this study is to assess the current state of knowledge about thyreological diseases during the COVID-19 pandemic and to provide indications for the introduced therapeutic changes on the basis of recent scientific literature published up to December 2020 and searches of the PubMed, Google Scholar, EMBASE, and Web of Science databases, which searched for keywords related to SARS-CoV-2 and its influence on thyreology problems. The main focus was on diagnostic and therapeutic differences in the era of the COVID-19 pandemic, bearing in mind the most common endocrinopathies, i.e. hypothyroidism and hyperthyroidism, as well as advantages and disadvantages and possibilities of using telemedicine in the common practice of a specialist physician.

Neutrophil-to-Lymphocyte, Monocyte-to-Lymphocyte and Platelet-to-Lymphocyte Ratios in Relation to Clinical Parameters and Smoking Status in Patients with Graves' Orbitopathy-Novel Insight into Old Tests.

Graves' orbitopathy (GO) is an autoimmune disease with a chronic inflammatory background. Smoking behavior is the main environmental factor responsible for the transition of this major extra thyroidal manifestation of Graves' disease (GD) from the subclinical to the overt form. Complete blood count-derived parameters are suggested to be novel inflammatory indices. The aim of this retrospective study was to investigate the association between neutrophil-to-lymphocyte (NLR), monocyte-to-lymphocyte (MLR), and platelet-to-lymphocyte ratios (PLR) with selected clinical parameters and smoking status in 406 GD patients with (n = 168) and without GO (n = 238). The control group consisted of 100 healthy individuals. The activity of GO was graded according to Clinical Activity Score. Significantly higher white blood cells (WBC), neutrophil, and NLR (p < 0.05) values were observed in GD patients with GO compared with those without GO. PLR values were significantly higher in GO patients than in the controls. WBC (6.81 ± 1.56 vs. 5.70 ± 1.23) and neutrophils (3.89 ± 1.06 vs. 3.15 ± 0.95) count was higher in active GO patients than in those with inactive GO. Positive correlation (p < 0.05) between CAS score and WBC, neutrophil and monocyte count, and NLR was found. Smoking was associated with higher WBC (p = 0.040), neutrophil (p = 0.049), PLR (p = 0.032) values. Multivariate analysis revealed that WBC, NLR may be risk factors for GO development. WBC, neutrophil, NLR and PLR values seem to be useful tools in the assessment of inflammation in GD.

Pancreatic neuroendocrine tumours in patients with von Hippel-Lindau disease.

Von Hippel-Lindau disease is a highly penetrant autosomal genetic disorder caused by a germline mutation in the tumour suppressor gene, manifesting with the formation of various tumours, including neuroendocrine tumours of the pancreas. The incidence of the latter is not very high, varying from 5% to 18%. To compare, haemangioblastomas and clear cell renal carcinoma are present in 70% of von Hippel-Lindau patients and are considered the main prognostic factors, with renal cancer being the most common cause of death. However, pancreatic neuroendocrine tumours should not be neglected, considering their malignant potential (different to sporadic cases), natural history, and treatment protocol. This paper aims to review the literature on the epidemiology, natural history, treatment, and surveillance of individuals affected by pancreatic neuroendocrine tumours in von Hippel-Lindau disease.

Toll-Like Receptors-2 and -4 in Graves' Disease-Key Players or Bystanders?

Graves' disease (GD) is an autoimmune disease that affects the thyroid. The development of autoimmunity is associated with innate immune responses where the prominent role plays Toll-like receptors (TLRs). The aim of our study was to assess the relationship between the expression levels of TLR-2 and TLR-4 on CD4+ and CD8+ T as well as CD19+ B lymphocytes in patients with GD and selected clinical parameters. The study group consisted of 32 women with GD, the control group consisted of 20 healthy women. Immunophenotyping was performed using the flow cytometry and cytokines concentrations were assessed using ELISA assay. The mean percentage of CD4+/TLR-2+ and CD8+/TLR-2+ T cells in patients with GD was higher than in the control group (p < 0.0001). After obtaining euthyroidism, the mean percentage of CD4+/TLR-2+ T cells in patients with GD decreased (p < 0.0001). The expression level of TLR-2 on CD4+ T lymphocytes correlated with serum FT3 concentration in patients with GD (r = 0.47, p = 0.007). The mean percentage of CD8+/TLR-2+ T cells in patients with GD before treatment compared to patients with GD after obtaining euthyroidism was higher (p = 0.0163). Similar findings were found for TLR-4. Thus the TLR-2 and TLR-4 can be a prognostic marker for Graves' disease.