The co-occurrence of SAT, hypophysitis, and Schnitzler syndrome after COVID-19 vaccination: the first described case.

Subacute thyroiditis (also known as granulomatous thyroiditis, giant cell thyroiditis, de Quervain's disease, or SAT) is an inflammatory disease of the thyroid gland, usually spontaneously remitting, that lasts for weeks to months. However, recurrent forms sometimes occur which may have a genetic basis. In our paper, we have focused on the pathogenetics, symptoms, and treatment of SAT. We have described the 17-month disease course of a woman with persistent recurrent steroid-resistant SAT. SAT was well established and the patient's symptoms were not only recurrent neck pain with fever, but also recurrent chronic urticaria, which are symptoms that fulfil the criteria for the diagnosis of Schnitzler syndrome. Schnitzler syndrome occurred after vaccination with COVID-19 in the mechanism of ASIA syndrome. In our patient, Schnitzler syndrome involved the thyroid gland, causing persistent subacute thyroiditis, and the pituitary gland, causing transient swelling of the pituitary, which, to our knowledge, is the first reported case in the literature. Also unprecedented, as far as we know, is the fact that we performed thyroidectomy in the above patient, which reduced systemic inflammation and caused SAT to resolve, although only the inclusion of anakinra treatment resulted in resolution of the underlying condition.

High-Resolution Imaging of Cones and Retinal Arteries in Patients with Diabetes Mellitus Type 1 Using Adaptive Optics (rtx1).

(1) Background. Diabetes mellitus (DM), called the first non-infectious epidemic of the modern era, has long-term health consequences leading to a reduced quality of life, long-term disabilities, and high mortality. Diabetic retinopathy (DR) is a neurovascular complication of diabetes and accounts for about 80% cases of vision loss in the diabetic population. The adaptive optics (AO) technique allows for a non-invasive in vivo assessment of retinal cones. Changes in number or morphology of retinal cones may be one of the first indicators of DR. (2) Methods. This study included 68 DM1 patients (17 women) aged 42.11 ± 9.69 years with a mean duration of diabetes of 22.07 ± 10.28 years, and 41 healthy volunteers (20 women) aged 41.02 ± 9.84 years. Blood pressure, BMI, waist circumference, and metabolic control measures were analysed. Cones' morphological parameters were examined with a retinal camera with Imagine Eyes adaptive optics (rtx1). Statistical analysis was carried out with IMB SPSS version 23 software. (3) Results. Neither study group differed significantly in age, BMI, blood pressure, or eyeball length. Intraocular pressure (IOP) was statistically significantly higher in DM1 patients but remained within physiological range in both groups. Analysis of cone parameters showed a statistically significant lower mean regularity of cones (Rmean) in the DM1 group compared to control group (p = 0.01), with the lowest value in the group with DM1 and hypertension (p = 0.014). In addition, DM1 patients tended to have fewer cones. (4) Conclusions. Our study revealed abnormalities in cone and vessel parameters and these abnormalities should be considered as risk factors for the development of DR. Complementing an eye examination with AO facilitates non-invasive in vivo cellular imaging of the retina. Lesions like those detected in the eye may occur in the brain and certainly require further investigation.

Could a nonfunctional adrenal incidentaloma be a risk factor for increased carotid intima-media thickness and 10-year cardiovascular mortality based on the SCORE algorithm? A study from a single centre in Poland.

INTRODUCTION: Adrenal incidentaloma (AI) secreting small amounts of glucocorticoids may cause morphological and functional changes in the blood vessels. Early stages of cardiovascular remodeling may be observed among asymptomatic patients with AI. But it is unclear whether the nonfunctional adrenal incidentalomas (NFAI) may also be a risk factor for cardiovascular diseases. The aim of this study was to determine the relationship between NFAI, carotid intima-media thickness (CIMT), and cardiovascular risk (CVR) based on Systematic Coronary Risk Evaluation (SCORE) prediction models for Europe. MATERIAL AND METHODS: This study from a single centre in Poland included 48 NFAI patients and 44 individuals in the control group matched for age, sex, and body mass index (BMI). All participants underwent adrenal imaging, biochemical evaluation, measurement of CIMT, and assessment of the 10-year risk of cardiovascular mortality based on the SCORE algorithm. Hormonal evaluation was conducted in AI patients. RESULTS: The NFAI group showed significantly higher sodium (p = 0.02) and glucose levels in the 2-h oral glucose tolerance test (OGTT) (p = 0.04), a higher CIMT (p < 0.01), and a higher CVR calculated according to the SCORE algorithm (p = 0.03). The estimated glomerular filtration rate (eGFR) was higher in the NFAI group (p = 0.015). Hypertension (p < 0.01) and IGT (p = 0.026) were more common in the NFAI group. Statistically significant positive correlations were found between CIMT and age (r = 0.373, p = 0.003), waist circumference (r = 0.316, p = 0.029), diastolic blood pressure (r = 0.338, p = 0.019), and CVR based on the SCORE algorithm (r = 0.43, p = 0.004). There was a statistically significant positive correlation between CIMT and serum cortisol levels after 1 mg dexamethasone suppression test (r = 0.33, p = 0.02). CONCLUSION: Non-functional adrenal adenomas are associated with increased CIMT and CVR. Early stages of cardiovascular remodelling can be observed in asymptomatic NFAI patients.

Do Non-Functional Adrenal Adenomas Affect Metabolic Profile and Carotid Intima-Media Thickness? A Single Centre Study from Poland.

Background: Compared to the general population, among people with adrenal incidentalomas (AIs) the diagnosis of obesity, hypertension, impaired carbohydrate and lipid metabolism is more common. The aformentioned disorders represent typical cardiovascular remodeling risk factors. The study was designed to assess the association between NFAIs, metabolic profile and carotid intima-media thickness (CIMT) as the predictive factor of atherosclerosis. Material: The study included 48 patients with NFAI (16 men, 32 women, mean age 58.6 +/- 9 years) and 44 control participants (15 men, 29 women, mean age 57 +/- 7 years). Both groups were matched for age, gender and BMI. Subjects with history of myocardial infarction, stroke or diabetes mellitus (DM) were excluded. Participants underwent adrenal imaging, biochemical evaluation, and measurement of CIMT. Hormonal evaluation was conducted in AI patients. Results: The NFAI group had significantly higher waist circumference (p < 0.01), higher systolic (p < 0.01) and diastolic blood pressure (p < 0.01), fasting insulin (p = 0.03) and glucose in the 2 h OGTT (p = 0.04) as well as higher CIMT (p < 0.01). Hypertension (p < 0.01) and IGT (p = 0.026) were more common in this group as well. There was a positive correlation between CIMT and cortisol levels in 1 mg dexamethasone suppression test (r = 0.33, p = 0.02). Conclusions: Patients diagnosed with NFAIs, despite normal cortisol inhibition in the 1 mg dexamethasone test, still presented a number of metabolic abnormalities. The assessment of IMT may proove valuable in indicate the presence of early vascular remodelling in asymptomatic patients. The underlying mechanisms of these findings are still unknown, hence further studies are required.

A Brief Look at Hashimoto's Disease, Adrenal Incidentalomas, Obesity and Insulin Resistance-Could Endocrine Disruptors Be the Other Side of the Same Coin?

Hashimoto's disease (HD) is the most common cause of hypothyroidism in developed countries. The exact pathomechanism behind it has not been clearly established; however, an interplay of genetic susceptibility, environmental triggers (including diet) and epigenetic factors seems to be involved. Among the latter, increasingly more attention has been paid to some hormonally active substances, known as endocrine disruptors, which are commonly used worldwide. HD has become a condition widely reported in the media, acting as a culprit for inexplicable weight gain, chronic fatigue or weakness. Nevertheless, the recognition of HD is undeniably increasing and represents a major public health burden. At the same time, improving access to imaging tests has increased the number of incidentally diagnosed adrenal tumors. Above all, the widespread use of chest computed tomography (CT) due to the COVID-19 pandemic has contributed to frequent incidental detection of adrenal lesions. Fortunately, a vast majority of these findings are asymptomatic benign tumors with no excessive hormonal activity, and therefore, they are defined as adrenal incidentalomas (AIs). Interestingly, recent studies have indicated that patients with AIs are more prone to obesity and insulin resistance. Although mutual relationships between the thyroid and the adrenal glands have been studied widely, still, little is known about the possible pathophysiological associations between thyroid autoimmunity and the occurrence of adrenal incidentalomas. This article presents a brief review of the common endocrine disorders with a special focus on the frequently coexisting insulin resistance and/or obesity. Furthermore, in response to the recent growing interest in endocrine disruptors, with their transgenerational epigenetic effects that influence hormonal system function, a concise overview of the topic has also been included.

Iron: Not Just a Passive Bystander in AITD.

Autoimmune thyroid disease (AITD) is the most prevalent autoimmune disease all over the world and the most frequent cause of hypothyroidism in areas of iodine sufficiency. The pathogenesis of AITD is multifactorial and depends on complex interactions between genetic and environmental factors, with epigenetics being the crucial link. Iron deficiency (ID) can reduce the activities of thyroid peroxidase and 5'-deiodinase, inhibit binding of triiodothyronine to its nuclear receptor, and cause slower utilization of T3 from the serum pool. Moreover, ID can disturb the functioning of the immune system, increasing the risk of autoimmune disorders. ID can be responsible for residual symptoms that may persist in patients with AITD, even if their thyrometabolic status has been controlled. The human lifestyle in the 21st century is inevitably associated with exposure to chemical compounds, pathogens, and stress, which implies an increased risk of autoimmune disorders and thyroid dysfunction. To summarize, in our paper we discuss how iron deficiency can impair the functions of the immune system, cause epigenetic changes in human DNA, and potentiate tissue damage by chemicals acting as thyroid disruptors.

"Ferrocrinology"-Iron Is an Important Factor Involved in Gluco- and Lipocrinology.

"Ferrocrinology" is the term used to describe the study of iron effects on the functioning of adipose tissue, which together with muscle tissue makes the largest endocrine organ in the human body. By impairing exercise capacity, reducing AMP-activated kinase activity, and enhancing insulin resistance, iron deficiency can lead to the development of obesity and type 2 diabetes mellitus. Due to impaired browning of white adipose tissue and reduced mitochondrial iron content in adipocytes, iron deficiency (ID) can cause dysfunction of brown adipose tissue. By reducing ketogenesis, aconitase activity, and total mitochondrial capacity, ID impairs muscle performance. Another important aspect is the effect of ID on the impairment of thermogenesis due to reduced binding of thyroid hormones to their nuclear receptors, with subsequently impaired utilization of norepinephrine in tissues, and impaired synthesis and distribution of cortisol, which all make the body's reactivity to stress in ID more pronounced. Iron deficiency can lead to the development of the most common endocrinopathy, autoimmune thyroid disease. In this paper, we have discussed the role of iron in the cross-talk between glucocrinology, lipocrinology and myocrinology, with thyroid hormones acting as an active bystander.

Can Iron Play a Crucial Role in Maintaining Cardiovascular Health in the 21st Century?

In the 21st century the heart is facing more and more challenges so it should be brave and iron to meet these challenges. We are living in the era of the COVID-19 pandemic, population aging, prevalent obesity, diabetes and autoimmune diseases, environmental pollution, mass migrations and new potential pandemic threats. In our article we showed sophisticated and complex regulations of iron metabolism. We discussed the impact of iron metabolism on heart diseases, treatment of heart failure, diabetes and obesity. We faced the problems of constant stress, climate change, environmental pollution, migrations and epidemics and showed that iron is really essential for heart metabolism in the 21st century.

Gestational Diabetes Mellitus-Recent Literature Review.

Gestational diabetes mellitus (GDM), which is defined as a state of hyperglycemia that is first recognized during pregnancy, is currently the most common medical complication in pregnancy. GDM affects approximately 15% of pregnancies worldwide, accounting for approximately 18 million births annually. Mothers with GDM are at risk of developing gestational hypertension, pre-eclampsia and termination of pregnancy via Caesarean section. In addition, GDM increases the risk of complications, including cardiovascular disease, obesity and impaired carbohydrate metabolism, leading to the development of type 2 diabetes (T2DM) in both the mother and infant. The increase in the incidence of GDM also leads to a significant economic burden and deserves greater attention and awareness. A deeper understanding of the risk factors and pathogenesis becomes a necessity, with particular emphasis on the influence of SARS-CoV-2 and diagnostics, as well as an effective treatment, which may reduce perinatal and metabolic complications. The primary treatments for GDM are diet and increased exercise. Insulin, glibenclamide and metformin can be used to intensify the treatment. This paper provides an overview of the latest reports on the epidemiology, pathogenesis, diagnosis and treatment of GDM based on the literature.

Associations of Dietary-Lifestyle Patterns with Obesity and Metabolic Health: Two-Year Changes in MeDiSH® Study Cohort.

This study aimed to evaluate changes in diet, adiposity, and metabolic outcomes after two years. In all, 358 Polish men aged 19-40 years old participated in the study. Data regarding dietary and lifestyle characteristics as well as family, socio-economic, and demographic status were collected using the food frequency questionnaire KomPAN®. Dietary lifestyle patterns were previously derived from data for 358 men by principal component analysis (PCA). Changes over time were examined in 95 men who returned after two years by calculating relative differences (RD, %) in mean values and markers distribution. Diet quality was described with two predefined scores: pro-Healthy-Diet-Index (pHDI) and non-Healthy-Diet-Index (nHDI). After two years, changes were observed in diet quality and metabolic health markers. No significant changes were observed in family, socio-economic, and demographic status, as well as other lifestyle factors. In the "sandwiches and convenience foods" pattern, an nHDI decrease (RD = -25.3%) was associated with a fasting blood glucose decrease (RD = -6.1%). In the "protein food, fried-food and recreational physical activity" and the "healthy diet, activity at work, former smoking" patterns, pHDI decreases (RD = -13.6% and -14.6%, respectively,) were associated with an adiposity increase. In the "fast foods and stimulants" pattern, no changes in pHDI and nHDI were observed, while adiposity markers and systolic blood pressure worsened. Conclusion: in the two-year perspective, dietary improvement was associated with improved glycemic control, despite no changes in body weight, while worsening of the diet quality or maintenance of unhealthy dietary behaviours were associated with the deterioration of metabolic health.

Will GLP-1 Analogues and SGLT-2 Inhibitors Become New Game Changers for Diabetic Retinopathy?

Diabetic retinopathy (DR) is the most frequent microvascular complication of diabetes mellitus (DM), estimated to affect approximately one-third of the diabetic population, and the most common cause of preventable vision loss. The available treatment options focus on the late stages of this complication, while in the early stages there is no dedicated treatment besides optimizing blood pressure, lipid and glycemic control; DR is still lacking effective preventive methods. glucagon-like peptide 1 receptor agonists (GLP-1 Ras) and sodium-glucose cotransporter 2 (SGLT-2) inhibitors have a proven effect in reducing risk factors of DR and numerous experimental and animal studies have strongly established its retinoprotective potential. Both drug groups have the evident potential to become a new therapeutic option for the prevention and treatment of diabetic retinopathy and there is an urgent need for further comprehensive clinical trials to verify whether these findings are translatable to humans.

Evaluation of Morphological Changes in Retinal Vessels in Type 1 Diabetes Mellitus Patients with the Use of Adaptive Optics.

INTRODUCTION: Diabetes mellitus contributes to the development of microvascular complications in the eye. Moreover, it affects multiple end organs, including brain damage, leading to premature death. The use of adaptive optics technique allows to perform non-invasive in vivo assessment of retinal vessels and to identify changes in arterioles about 100 µm in diameter. The retinal vasculature may be a model of the cerebral vessels both morphologically and functionally. Aim. To evaluate morphological parameters of retinal arterioles in patients with type 1 diabetes mellitus (DM1). Material and methods. The study included 22 DM1 patients (13 females) aged 43.00 ± 9.45 years with a mean diabetes duration of 22.55 ± 10.05 years, and 23 healthy volunteers (10 females) aged 41.09 ± 10.99 years. Blood pressure, BMI, waist circumference, and metabolic control markers of diabetes were measured in both groups. Vascular examinations were performed using an rtx1 adaptive optics retinal camera (Imagine Eyes, Orsay, France); the vessel wall thickness (WT), lumen diameter (LD), wall-to-lumen ratio (WLR), and vascular wall cross-sectional area (WCSA) were assessed. Statistical analysis was performed with the application of IMB SPSS version 23 software. Results. The DM1 group did not differ significantly in age, BMI, waist circumference, blood pressure, or axial length of the eye compared to the control group. Intraocular pressure (IOP) in both groups was normal, but in the DM1 group it was significantly higher. The DM1 group had significantly higher WT, WLR, and WCSA. These parameters correlated significantly with the duration of diabetes, but not with IOP. Conclusions. The presented study demonstrates the presence of significant morphological changes in retinal vessels in DM1 patients without previously diagnosed diabetic retinopathy. Similar changes may occur in the brain and may be early indicators of cardiovascular risk, but further investigation is required to confirm that.

Effects of common weight loss plans on diabetes mellitus and cardiovascular risk factors.

Diabetes mellitus is globally considered one of the most common chronic diseases, management of which is critically asscociated with an adequate dietary approach. With overweight and obesity being a global epidemic, choosing the appropriate weight loss plan for patients with diabetes seems to be of particular concern for healthcare professionals. Since diabetes and cardiovascular diseases frequently coexist, modern pharmacological therapeutic models aim at addressing both. Therapeutic targets in diabetic population that address glycemic control, adequate lipid and blood pressure control proves to limit the incidence of cardiovascular events, reduce the risk of chronic complications and improve patients quality of life. Similarly, dietary managment in this population should also concentrate on the reduction of reversible cardiovascular risk factors. Nutritional recommendations for diabetic patients should be individualized to meet their expectations and lifestyle in order to ensure compliance and long-term effects. As diabetic population is more vulnerable to further health risks associated with diet induced metabolic changes, inadequate intake of dietary components and increased cardiovascular risk, nutrition plans should be addressed more carefully in this group.

The potential of using circulating tumour cells and their gene expression to predict docetaxel response in metastatic prostate cancer.

Background: Docetaxel improves overall survival (OS) in castration-resistant prostate cancer (PCa) (CRPC) and metastatic hormone-sensitive PCa (mHSPC). However, not all patients respond due to inherent and/or acquired resistance. There remains an unmet clinical need for a robust predictive test to stratify patients for treatment. Liquid biopsy of circulating tumour cell (CTCs) is minimally invasive, can provide real-time information of the heterogeneous tumour and therefore may be a potentially ideal docetaxel response prediction biomarker. Objective: In this study we investigate the potential of using CTCs and their gene expression to predict post-docetaxel tumour response, OS and progression free survival (PFS). Methods: Peripheral blood was sampled from 18 mCRPC and 43 mHSPC patients, pre-docetaxel treatment, for CTC investigation. CTCs were isolated using the epitope independent Parsortix® system and gene expression was determined by multiplex RT-qPCR. We evaluated CTC measurements for post-docetaxel outcome prediction using receiver operating characteristics and Kaplan Meier analysis. Results: Detection of CTCs pre-docetaxel was associated with poor patient outcome post-docetaxel treatment. Combining total-CTC number with PSA and ALP predicted lack of partial response (PR) with an AUC of 0.90, p= 0.037 in mCRPC. A significantly shorter median OS was seen in mCRPC patients with positive CTC-score (12.80 vs. 37.33 months, HR= 5.08, p= 0.0005), ≥3 total-CTCs/7.5mL (12.80 vs. 37.33 months, HR= 3.84, p= 0.0053), ≥1 epithelial-CTCs/7.5mL (14.30 vs. 37.33 months, HR= 3.89, p= 0.0041) or epithelial to mesenchymal transitioning (EMTing)-CTCs/7.5mL (11.32 vs. 32.37 months, HR= 6.73, p= 0.0001). Significantly shorter PFS was observed in patients with ≥2 epithelial-CTCs/7.5mL (7.52 vs. 18.83 months, HR= 3.93, p= 0.0058). mHSPC patients with ≥5 CTCs/7.5mL had significantly shorter median OS (24.57 vs undefined months, HR= 4.14, p= 0.0097). In mHSPC patients, expression of KLK2, KLK4, ADAMTS1, ZEB1 and SNAI1 was significantly associated with shorter OS and/or PFS. Importantly, combining CTC measurements with clinical biomarkers increased sensitivity and specificity for prediction of patient outcome. Conclusion: While it is clear that CTC numbers and gene expression were prognostic for PCa post-docetaxel treatment, and CTC subtype analysis may have additional value, their potential predictive value for docetaxel chemotherapy response needs to be further investigated in large patient cohorts.

Is there a relationship between the prevalence of autoimmune thyroid disease and diabetic kidney disease?

Autoimmune thyroid disease (AITD) is more common among diabetes mellitus (DM) patients and may impact its microvascular complications. The present study aimed to assess the relationship between AITD and the prevalence of diabetic kidney disease (DKD) in patients with diabetes mellitus type 1 (DM1). Anthropometric parameters, parameters of metabolic control of DM, thyreometabolic status, and the UACR were assessed. DKD was diagnosed if patients' UACR level was ≥30 mg/g or eGFR level was <60 mL/min. This study involved 144 patients with DM1 aged 36.2 ± 11.7 years: 49 men and 95 women. Significant differences in creatinine, eGFR, and UACR levels were found in patients with DKD. fT3 concentration was significantly lower among DKD patients. A significantly higher probability of DKD was found in DM1 patients with lower fT3 levels. Patients with DM1 and AITD had significantly lower creatinine levels than the control group. However, the study did not show any significant relationship between AITD and the occurrence of DKD in patients with DM1. Significantly lower fT3 concentrations in DKD patients may be caused by metabolic disorders in the course of DKD and require further cohort studies in a larger population of patients with DM1 and AITD.

The Safety of Pharmacological and Surgical Treatment of Diabetes in Patients with Diabetic Retinopathy-A Review.

BACKGROUND: Diabetes mellitus (DM) is a non-infectious pandemic of the modern world; it is estimated that in 2045 it will affect 10% of the world's population. As the prevalence of diabetes increases, the problem of its complications, including diabetic retinopathy (DR), grows. DR is a highly specific neurovascular complication of diabetes that occurs in more than one third of DM patients and accounts for 80% of complete vision loss cases in the diabetic population. We are currently witnessing many groundbreaking studies on new pharmacological and surgical methods of treating diabetes. AIM: The aim of the study is to assess the safety of pharmacological and surgical treatment of DM in patients with DR. MATERIAL AND METHODS: An analysis of the data on diabetes treatment methods currently available in the world literature and their impact on the occurrence and progression of DR. RESULTS: A rapid decrease in glycaemia leads to an increased occurrence and progression of DR. Its greatest risk accompanies insulin therapy and sulfonylurea therapy. The lowest risk of DR occurs with the use of SGLT2 inhibitors; the use of DPP-4 inhibitors and GLP-1 analogues is also safe. Patients undergoing pancreatic islet transplants or bariatric surgeries require intensive monitoring of the state of the eye, both in the perioperative and postoperative period. CONCLUSIONS: It is of utmost importance to individualize therapy in diabetic patients, in order to gradually achieve treatment goals with the use of safe methods and minimize the risk of development and progression of DR.

The Transcriptomic Landscape of Prostate Cancer Development and Progression: An Integrative Analysis.

Next-generation sequencing of primary tumors is now standard for transcriptomic studies, but microarray-based data still constitute the majority of available information on other clinically valuable samples, including archive material. Using prostate cancer (PC) as a model, we developed a robust analytical framework to integrate data across different technical platforms and disease subtypes to connect distinct disease stages and reveal potentially relevant genes not identifiable from single studies alone. We reconstructed the molecular profile of PC to yield the first comprehensive insight into its development, by tracking changes in mRNA levels from normal prostate to high-grade prostatic intraepithelial neoplasia, and metastatic disease. A total of nine previously unreported stage-specific candidate genes with prognostic significance were also found. Here, we integrate gene expression data from disparate sample types, disease stages and technical platforms into one coherent whole, to give a global view of the expression changes associated with the development and progression of PC from normal tissue through to metastatic disease. Summary and individual data are available online at the Prostate Integrative Expression Database (PIXdb), a user-friendly interface designed for clinicians and laboratory researchers to facilitate translational research.

Current Knowledge on Graves' Orbitopathy.

(1) Background: Graves' orbitopathy (GO) is an autoimmune inflammation of the orbital tissues and the most common extra-thyroid symptom of Graves' disease (GD). Mild cases of GO are often misdiagnosed, which prolongs the diagnostic and therapeutic process, leading to exacerbation of the disease. A severe course of GO may cause permanent vision loss. (2) Methods: The article presents an analysis of GO-its etiopathogenesis, diagnostics, current treatment and potential future therapeutic options based on a review of the currently available literature of the subject. (3) Results: Current treatment of the active GO consists predominantly in intravenous glucocorticoids (GCs) administration in combination with orbital radiotherapy. The growing knowledge on the pathogenesis of the disease has contributed to multiple trials of the use of immunosuppressive drugs and monoclonal antibodies which may be potentially effective in the treatment of GO. Immunosuppressive treatment is not effective in patients in whom a chronic inflammatory process has caused fibrous changes in the orbits. In such cases surgical treatment is performed-including orbital decompression, adipose tissue removal, oculomotor muscle surgery, eyelid alignment and blepharoplasty. (4) Conclusions: Management of GO is difficult and requires interdisciplinary cooperation in endocrinology; ophthalmology, radiation oncology and surgery. The possibilities of undertaking a reliable assessment and comparison of the efficacy and safety of the therapeutic strategies are limited due to the heterogeneity of the available studies conducted mostly on small group of patients, with no comparison with classic systemic steroid therapy. The registration by FDA of Teprotumumab, an IGF1-R antagonist, in January 2020 may be a milestone in future management of active GO. However, many clinical questions require to be investigated first.

Chronic Microvascular Complications in Prediabetic States-An Overview.

A prediabetic state is a major risk factor for the development of diabetes, and, because of an identical pathophysiological background of both conditions, their prevalence increases parallelly and equally fast. Long-term hyperglycemia is the main cause inducing chronic complications of diabetes, yet the range of glucose levels at which they start has not been yet unequivocally determined. The current data show that chronic microvascular complications of diabetes can be observed in patients with abnormal glucose metabolism in whom glycaemia is higher than optimal but below diagnostic criteria for diabetes. Prediabetes is a heterogenous nosological unit in which particular types are differently characterized and show different correlations with particular kinds of complications. Analysis of the latest research results shows the need to continue studies in a larger population and can imply the need to verify the currently employed criteria of diagnosing diabetes and chronic complications of diabetes in people with prediabetes.

Thyroid dysfunction in patients with diabetic retinopathy.

Thyroid disease and diabetes mellitus (DM) are the most common endocrinopathies in clinical practice that interact with each other. On the one hand, thyroid hormones regulate carbohydrate metabolism and pancreas functions, and on the other hand DM affects the function and work of the thyroid gland. Diabetic retinopathy (DR) is a highly specific neurovascular complication of both type 1 and type 2 DM, which is a significant cause of vision loss on a global scale. In DM, the internal blood-retinal barrier is the earliest to be damaged, and changes in neuroretina result from the loss of its adaptation to metabolic disorders. Patients with DM have a higher incidence of thyroid disease compared to people without DM. The coexistence of DM with thyroid disease leads to endothelial damage, and the degree of its dysfunction has a significant impact on the course of macro- and microangiopathic complications in patients. There are few reports in the literature about the impact of thyroid disease and substitution of levothyroxine preparations on the development and course of DR in patients with DM. It is unknown whether the fact that patients with unrecognised hypothyroidism are not treated with levothyroxine preparations disrupts thyroid hormone homeostasis to the extent that it may contribute to a higher incidence of DR. This review discusses recent clinical trials for thyroid dysfunction in patients with DR.