Transforming growth factors ß and their signaling pathway in renal cell carcinoma and peritumoral space-transcriptome analysis.

PURPOSE: The aim of the study was to verify hypotheses: Are transforming growth factors TGFß1-3, their receptors TGFßI-III, and intracellular messenger proteins Smad1-7 involved in the pathogenesis of kidney cancer? What is the expression of genes of the TGFß/Smads pathway in renal cell carcinoma (RCC) tissues, peritumoral tissues (TME; tumor microenvironment), and in normal kidney (NK) tissue?. METHODS: Twenty patients with RCC who underwent total nephrectomy were included into the molecular analysis. The mRNA expression of the genes was quantified by RT-qPCR. RESULTS: The study showed that the expression of the genes of TGFß/Smads pathway is dysregulated in both RCC and the TME: TGFß1, TGFß3 expression is increased in the TME in comparison to the NK tissues; TGFß2, TGFß3, TGFßRI, TGFßRIII, Smad1, Smad2, Smad3, and Smad6 are underexpressed in RCC comparing to the TME tissues; TGFßRI, TGFßRIII, and Smad2 are underexpressed in RCC in comparison to the NK tissues. CONCLUSION: On the one hand, the underexpression of the TGFß signaling pathway genes within the malignant tumor may result in the loss of the antiproliferative and pro-apoptotic activity of this cytokine. On the other hand, the overexpression of the TGFß/Smads pathway genes in the TME than in tumor or NK tissues most probably results in an immunosuppressive effect in the space surrounding the tumor and may have an antiproliferative and pro-apoptotic effect on non-neoplastic cells present in the TME. The functional and morphological consistency of this area may determine the aggressiveness of the tumor and the time in which the neoplastic process will spread.

Th17 cytokines and factors modulating their activity in patients with pernicious anemia.

The effects of specific cytokines produced by T cell subsets (such as Th1, Th2, and newly discovered Th17, Treg, Tfh, or Th22) are diverse, depending on interactions with other cytokines, distinct signaling pathways, phase of the disease, or etiological factor. The immunity equilibrium of the immune cells, such as the Th1/Th2, the Th17/Treg, and the Th17/Th1 balance is necessary for the maintenance of the immune homeostasis. If the balance of the T cells subsets is damaged, the autoimmune response becomes enhanced which leads to autoimmune diseases. Indeed, both the Th1/Th2 and the Th17/Treg dichotomies are involved in the pathomechanism of autoimmune diseases. The aim of the study was to determine the cytokines of Th17 lymphocytes as well as the factors modulating their activity in patients with pernicious anemia. The magnetic bead-based immunoassays used (Bio-Plex) allow simultaneous detection of multiple immune mediators from one serum sample. In our study, we showed that patients suffering from pernicious anemia develop the Th1/Th2 imbalance with a quantitative advantage of cytokines participating in Th1-related immune response, the Th17/Treg imbalance with a quantitative advantage of cytokines participating in Treg-related response, as well as the Th17/Th1 imbalance with a quantitative predominance of cytokines participating in Th1-related immune response. Our study results indicate that T lymphocytes and their specific cytokines play an role in the course of pernicious anemia. The observed changes may indicate the immune response to pernicious anemia or be an element of the pernicious anemia pathomechanism.

Update of the diagnostic and therapeutic guidelines for gastro-entero-pancreatic neuroendocrine neoplasms (recommended by the Polish Network of Neuroendocrine Tumours) [Aktualizacja zalecen ogólnych dotyczacych postepowania diagnostyczno-terapeutycznego w nowotworach neuroendokrynnych ukladu pokarmowego (rekomendowane przez Polska Siec Guzów Neuroendokrynnych)].

Continuous progress in the diagnostics and treatment of neuroendocrine neoplasms (NENs), the emerging results of new clinical trials, and the new guidelines issued by medical societies have prompted experts from the Polish Network of Neuroendocrine Tumours to update the 2017 recommendations regarding the management of neuroendocrine neoplasms. This article presents the general recommendations for the management of NENs, resulting from the findings of the experts participating in the Fourth Round Table Conference, entitled "Polish Guidelines for the Diagnostics and Treatment of Neuroendocrine Neoplasms of the gastrointestinal tract, Zelechów, June 2021". Drawing from the extensive experience of centres treating these cancers, we hope that we have managed to formulate the optimal method of treating patients with NENs, applying the latest reports and achievements in the field of medicine, which can be effectively implemented in our country. The respective parts of this work present the approach to the management of: NENs of the stomach and duodenum (including gastrinoma), pancreas, small intestine, and appendix, as well as large intestine.

Pancreatic neuroendocrine neoplasms - update of the diagnostic and therapeutic guidelines (recommended by the Polish Network of Neuroendocrine Tumours) [Nowotwory neuroendokrynne trzustki - uaktualnione zasady diagnostyki i leczenia (rekomendowane przez Polska Siec Guzów Neuroendokrynych)].

In this paper, we present the current guidelines for the diagnostics and management of pancreatic neuroendocrine neoplasms (PanNENs) developed by Polish experts providing care for these patients in everyday clinical practice. In oncological diagnostics, in addition to biochemical tests, molecular identification with the use of NETest liquid biopsy and circulating microRNAs is gaining importance. Both anatomical and functional examinations (including new radiopharmaceuticals) are used in imaging diagnostics. Histopathological diagnosis along with immunohistochemical examination still constitute the basis for therapeutic decisions. Whenever possible, surgical procedure is the treatment of choice. Pharmacological management including biotherapy, radioisotope therapy, targeted molecular therapy and chemotherapy are important methods of systemic therapy. Treatment of PanNENs requires a multidisciplinary team of specialists in the field of neuroendocrine neoplasms.

Gastroduodenal neuroendocrine neoplasms including gastrinoma - update of the diagnostic and therapeutic guidelines (recommended by the Polish Network of Neuroendocrine Tumours) [Nowotwory neuroendokrynne zoladka i dwunastnicy z uwzglednieniem gastrinoma - uaktualnione zasady postepowania (rekomendowane przez Polska Siec Guzów Neuroendokrynnych)].

After another meeting of experts of the Polish Network of Neuroendocrine Tumours, updated recommendations for the management of patients with gastric and duodenal neuroendocrine neoplasms, including gastrinoma, have been issued. As before, the epidemiology, pathogenesis and clinical symptoms of these neoplasms have been discussed, as well as the principles of diagnostic procedures, including biochemical and histopathological diagnostics and tumour localisation, highlighting the changes introduced in the recommendations. Updated principles of therapeutic management have also been presented, including endoscopic and surgical treatment, and the options of pharmacological and radioisotope treatment. The importance of monitoring patients with gastric and duodenal NENs, including gastrinoma, has also been emphasised.

Colorectal neuroendocrine neoplasms - update of the diagnostic and therapeutic guidelines (recommended by the Polish Network of Neuroendocrine Tumours) [Nowotwory neuroendokrynne jelita grubego - uaktualnione zasady diagnostyki i leczenia (rekomendowane przez Polska Siec Guzów Neuroendokrynych)].

Colorectal neuroendocrine neoplasm (CRNEN), especially rectal tumours, are diagnosed with increased frequency due to the widespread use of colonoscopy, including screening examinations. It is important to constantly update and promote the principles of optimal diagnostics and treatment of these neoplasms. Based on the latest literature and arrangements made at the working meeting of the Polish Network of Neuroendocrine Tumours (June 2021), this paper includes updated and supplemented data and guidelines for the management of CRNEN originally published in Endokrynologia Polska 2017; 68: 250-260.

Neuroendocrine neoplasms of the small intestine and the appendix - update of the diagnostic and therapeutic guidelines (recommended by the Polish Network of Neuroendocrine Tumours) [Nowotwory neuroendokrynne jelita cienkiego i wyrostka robaczkowego - uaktualnione zasady diagnostyki i leczenia (rekomendowane przez Polska Siec Guzów Neuroendokrynnych)].

Updated Polish recommendations for the management of patients with neuroendocrine neoplasms (NENs) of the small intestine (SINENs) and of the appendix (ANENs) are presented here. The small intestine, and especially the ileum, is one of the most common locations for these neoplasms. Most of them are well-differentiated and slow-growing tumours; uncommonly - neuroendocrine carcinomas. Their symptoms may be untypical and their diagnosis may be delayed or accidental. Najczesciej pierwsza manifestacja ANEN jest jego ostre zapalenie. Typical symptoms of carcinoid syndrome occur in approximately 20-30% of SINENs patients with distant metastases. In laboratory diagnostics the assessment of 5-hydroxyindoleacetic acid concentration is helpful in the diagnosis of carcinoid syndrome. The most commonly used imaging methods are ultrasound examination, computed tomography, magnetic resonance imaging, colonoscopy and somatostatin receptor imaging. Histopathological examination is crucial for the proper diagnosis and treatment of patients with SINENs and ANENs. The treatment of choice is a surgical procedure, either radical or palliative. Long-acting somatostatin analogues (SSAs) are essential in the medical treatment of functional and non-functional SINENs. In patients with SINENs, at the stage dissemination with progression during SSAs treatment, with high expression of somatostatin receptors, radioisotope therapy should be considered first followed by targeted therapies - everolimus. After the exhaustion of the above available therapies, chemotherapy may be considered in selected cases. Recommendations for patient monitoring are also presented.

Therapeutic difficulties in an aggressive ACTH-secreting pituitary adenoma.

Not required for Clinical Vignette.

Antibodies involved in the development of pernicious anemia and other autoimmune diseases.

INTRODUCTION: Pernicious anemia (PA) is an autoimmune hematopoietic disease. OBJECTIVES: The aim of the study was to determine autoantibodies involved in the pathogenesis of PA and the development of other autoimmune disorders such as connective tissue diseases and celiac disease. We also aimed to assess the potential usefulness of the specific diagnostic and screening tests in patients with PA. PATIENTS AND METHODS: The study group comprised 124 women and men with newly diagnosed PA and 41 healthy controls. Intrinsic factor (IF) antibodies, gastric parietal cell (GPC) antibodies, endomysium antibodies (EmAs), and antinuclear antibodies (ANAs) were determined in blood samples. RESULTS: IF or GPC antibodies were present in 61.3% of patients, GPC antibodies, in 46%, IF antibodies, in 30.6%, IF and GPC antibodies, in 15.3%. There was no difference in the occurrence of ANAs and EmAs between the PA and control groups. However, ANAs were found in 16.1% of patients with PA and in 4.9% of controls. The occurrence of EmAs in both groups was similar (3.2% vs 2.4%); however, it has been shown that patients with IF or GPC antibodies are more prone to be EmA positive (P = 0.009). CONCLUSIONS: Simultaneous determination of IF and GPC antibodies increases the chances of confirming the diagnosis of PA. Also, screening for connective tissue diseases and celiac disease may be considered in patients with PA, due to the presence of ANAs and EmAs in that population.

Pernicious anaemia and endocrine glands antibodies.

INTRODUCTION: The aim of the study was to determine the frequency of occurrence of antibodies participating in the development of endocrine diseases in patients with autoimmune haematopoietic disease, thus documenting the potential suitability of specific diagnostic and screening tests. MATERIAL AND METHODS: The study group consisted of 124 persons (men and women) with newly diagnosed pernicious anaemia (PA) and a control group (C) of 41 healthy people. Antibodies against: intrinsic factor (IFAb), gastric parietal cells (APCA), thyroid peroxidase (TPOAb), thyroglobulin (TgAb), adrenal cortex (AdrenalAb), and pituitary anterior lobe (PituitaryAb) were determined in the blood. RESULTS: 1. The risk of the presence of antibodies against endocrine glands in patients with PA can be classified in order: TPOAb and/or TgAb - 41.1%, TPOAb - 36.3%, TgAb - 25.0%, TPOAb and TgAb - 20.2%, AdrenalAb - 1.6%, PituitaryAb - 0.8%. 2. TPOAb and/or TgAb (mainly TPOAb) are more frequently present in patients with PA, who have IFAb and/or APCA. This correlation is most evident in patients with simultaneous occurrence of IFAb and APCA. 3. Among patients with PA, the simultaneous presence of antibodies IFAb and/or APCA with TPOAb and/or TgAb antibodies is most likely in women over 45 years of age. 4. In group C, 12% had at least one of two antithyroid antibodies (TgAb twice as often as TPOAb), and 2.4% had both. AdrenalAb and PituitaryAb are not found in healthy persons. CONCLUSIONS: In patients with PA, a screening for autoimmune thyroid disease is justified, which should first involve the determination of TPOAb (further TgAb) in the blood. The assessment of antithyroid antibodies should be recommended primarily to patients with PA, who have IFAb and/or APCA, and in particular those with concurrent IFAb and APCA.

Diagnostic and therapeutic guidelines for gastro-entero-pancreatic neuroendocrine neoplasms (recommended by the Polish Network of Neuroendocrine Tumours).

Progress in the diagnostics and therapy of gastro-entero-pancreatic (GEP) neuroendocrine neoplasms (NEN), the published results of new randomised clinical trials, and the new guidelines issued by the European Neuroendocrine Tumour Society (ENETS) have led the Polish Network of Neuroendocrine Tumours to update the 2013 guidelines regarding management of these neoplasms. We present the general recommendations for the management of NENs, developed by experts during the Third Round Table Conference - Diagnostics and therapy of gastro-entero-pancreatic neuroendocrine neoplasms: Polish recommendations in view of current European recommenda-tions, which took place in December 2016 in Zelechów near Warsaw. Drawing from the extensive experience of centres dealing with this type of neoplasms, we hope that we have managed to develop the optimal management system, applying the most recent achievements in the field of medicine, for these patients, and that it can be implemented effectively in Poland. These management guidelines have been arranged in the following order: gastric and duodenal NENs (including gastrinoma); pancreatic NENs; NENs of the small intestine and appendix, and colorectal NENs.

Gastroduodenal neuroendocrine neoplasms, including gastrinoma - management guidelines (recommended by the Polish Network of Neuroendocrine Tumours).

This paper presents the updated Polish Neuroendocrine Tumour Network expert panel recommendations on the management of neuroendocrine neoplasms (NENs) of the stomach and duodenum, including gastrinoma. The recommendations discuss the epidemiology, pathogenesis, and clinical presentation of these tumours as well as their diagnosis, including biochemical, histopathological, and localisation diagnoses. The principles of treatment are discussed, including endoscopic, surgical, pharmacological, and radionuclide treatments. Finally, there are also recommendations on patient monitoring.

Pancreatic neuroendocrine neoplasms - management guidelines (recommended by the Polish Network of Neuroendocrine Tumours).

This article presents updated diagnostic and therapeutic guidelines for the management of pancreatic neuroendocrine tumours (PNEN), proposed by the Polish Network of Neuroendocrine Tumours. The guidelines contain new data received in the years 2013-2016, which confirm previous recommendations, and have led to modification of previous guidelines or have resulted in the formulation of new guidelines. Biochemical and imaging (anatomical and functional) tests are of great importance in diagnostics, as well as histopathological diagnosis to determine the management of PNEN patients, but they must be confirmed by an immunohistochemical examination. PNEN therapy requires collaboration among the members a multidisciplinary team of specialists experienced in the management of these neoplasms. Surgery is the basic form of treatment in many cases. Further therapy requires a multidirectional procedure; therefore, the rules of biotherapy, peptide receptor radionuclide therapy, molecular targeted therapy, and chemotherapy are discussed.

Neuroendocrine neoplasms of the small intestine and appendix - management guidelines (recommended by the Polish Network of Neuroendocrine Tumours).

This study presents the revised Polish guidelines regarding the management of patients suffering from neuroendocrine neoplasms (NENs) of the small intestine and appendix. The small intestine, especially the ileum, is the most common location for these neoplasms. Most are well differentiated and slow growing. Their symptoms may be atypical, which can result in delayed or accidental diagnosis. Appendicitis is usually the first manifestation of NEN in this location. Typical symptoms of carcinoid syndrome occur in approximately 20-30% of patients suffering from small intestinal NENs with distant metastases. The main cause of death in patients with carcinoid syndrome is carcinoid heart disease. The most useful laboratory test is the determination of chromogranin A, while concentration of 5-hydroxyindoleacetic acid is helpful in the diagnostics of carcinoid syndrome. For visualisation, ultrasound, computed tomography, magnetic resonance imaging, colonoscopy, video capsule endoscopy, double-balloon enteroscopy, and somatostatin receptor scintigraphy may be used. A detailed his-tological report is crucial for the proper diagnostics and therapy of NENs of the small intestine and appendix. The treatment of choice is surgical management, either radical or palliative. The pharmacological treatment of the hormonally active and non-active small intestinal NENs as well as NENs of the appendix is based on long-acting somatostatin analogues. In patients with generalised NENs of the small intestine in progress during the SSA treatment, with good expression of somatostatin receptors, the first-line treatment should be radio-isotope therapy, while targeted therapies, such as everolimus, should be considered afterwards. When the above therapies are exhausted, in certain cases chemotherapy may be considered.

Colorectal neuroendocrine neoplasms - management guidelines (recommended by the Polish Network of Neuroendocrine Tumours).

Neuroendocrine neoplasms/tumours (NENs/NETs) of the large intestine are detected increasingly often, especially rectal tumours, which is probably associated with the widespread use of screening colonoscopy. There is a growing body of evidence supporting the thesis that the NENs of the rectum and the NENs of the colon are two different diseases. Rectal NENs are usually small lesions, of low to moderate histological malignancy, associated with good prognosis, and most may be treated endoscopically. NENs of the colon, however, are often aggressive, poorly differentiated, associated with a poor or uncer-tain prognosis, and require surgical treatment. The management guidelines regarding these groups of patients are constantly changing. On the basis of the recent literature data and conclusions reached by the working meeting of the Polish Network of Neuroendocrine Tumours (December 2016), this study completes and updates the data and management guidelines regarding colorectal NENs published in Endokrynologia Polska 2013; 64: 358-368.

Transcriptional activity of TGFß1 and its receptors genes in thyroid gland.

INTRODUCTION: Determination of gene-candidates' profile expression responsible for fibrosis, immunosuppression, angiogenesis, and neoplasia processes in the pathogenesis of thyroid gland disease. MATERIAL AND METHODS: Sixty-three patients underwent thyroidectomy: 27 with non-toxic nodular goitre (NG), 22 with toxic nodular goitre (TNG), six with papillary cancer (PTC), and eight with Graves' disease (GD). In thyroid tissues, transcriptional activity of TGFbeta1 and its receptors TGFbetaRI, TGFbetaRII, and TGFbetaRIII genes were assessed using RT-qPCR (Reverse Transcriptase Quantitative Polymerase Chain Reaction). Molecular analysis was performed in tissues derived from GD and from the tumour centre (PTC, NG, TNG) and from peripheral parts of the removed lobe without histopathological lesions (tissue control). Control tissue for analysis performed in GD was an unchanged tissue derived from peripheral parts of the removed lobe of patients surgically treated for a single benign tumour. RESULTS/CONCLUSIONS: Strict regulation observed among transcriptional activity of TGFb1 and their receptor TGFbetaRI-III genes in control tissues is disturbed in all pathological tissues - it is completely disturbed in PTC and GD, and partially in NG and TNG. Additionally, higher transcriptional activity of TGFb1 gene in PTC in comparison with benign tissues (NG, GD) and lower expression of mRNA TGFbRII (than in TNG, GD) and mRNA TGFbetaRIII than in all studied benign tissues (NG, TNG, GD) suggests a pathogenetic importance of this cytokine and its receptors in PTC development. In GD tissue, higher transcriptional activity of TGFbetaRII and TGFbetaRIII genes as compared to other pathological tissues was observed, indicating a participation of the receptors in the pathomechanism of autoimmune thyroid disease (AITD). TGFbeta1 blood concentrations do not reflect pathological processes taking place in thyroid gland. (Endokrynol Pol 2016; 67 (4): 375-382).

Associations between metabolic syndrome, serum thyrotropin, and thyroid antibodies status in postmenopausal women, and the role of interleukin-6.

INTRODUCTION: The prevalence of metabolic syndrome increases after menopause; however, the role of concomitant subclinical hypothyroidism has not been completely elucidated. The aim of the study was to identify associations between thyrotropin, immune status, inflammation, and metabolic syndrome in postmenopausal women. The specific goals were: to assess thyrotropin (TSH) and interleukin-6 (IL-6) concentrations in the serum of subclinical hypothyroid postmenopausal women with and without metabolic syndrome and compare them with euthyroid controls; to test whether immune status is related to metabolic syndrome in postmenopausal women and determine the role of IL-6; to examine the relationships between TSH and different features of metabolic syndrome: insulin resistance, waist circumferences, waist-to-hip ratio (WHR), BMI, metabolic parameters (triglycerides, total cholesterol and high-density lipoprotein cholesterol), and inflammatory cytokines (IL-6). MATERIAL AND METHODS: Three hundred and seventy-two postmenopausal women were included in the study: 114 women had subclinical hypothyroidism (10.0 uIU/mL > TSH ≥ 4.5 uIU/mL, normal fT4), and 258 women were in euthyreosis (TSH 0.35-4.5 uIU/mL, normal fT4); both groups were matched by age. Anthropometric measurements were conducted (BMI, waist circumference, WHR) and blood pressure was measured. In all subjects the following were assessed in serum: lipid profile, glucose, insulin, TSH, fT4, thyroid antibodies (T-Abs) - TPO-Abs, TG-Abs, and IL-6 concentrations. RESULTS: The prevalence of metabolic syndrome was 49.12% in subclinical hypothyroid women and 46.89% in euthyroid women. However, the proportion of subjects with one or two abnormalities was significantly higher in the subclinical hypothyroid group (45.61%) than in the euthyroid group (32.17%). When we compared subclinical hypothyroid women with and without metabolic syndrome, subjects with metabolic syndrome had higher BMI, abdominal circumferences, WHR, and HOMA-I. They presented higher systolic and diastolic blood pressure. Serum concentrations of cholesterol, triglycerides, fasting glucose, IL-6, TSH, T-Abs were also higher and serum cHDL was lower. There were no significant differences in fT4 concentrations. A similar comparison was made for euthyroid women with and without metabolic syndrome. Higher BMI, waist circumference, WHR, HOMA-I, and systolic blood pressure were observed in subjects with metabolic syndrome. Serum concentrations of TSH, triglycerides, glucose, and IL-6 were also higher, but the concentration of cHDL was significantly lower. There were no significant differences in fT4, T-Abs, cholesterol levels, and diastolic pressure. When we compared euthyroid women T-Abs (+) and T-Abs (-), the prevalence of metabolic syndrome was similar (48.68% vs. 46.15%). There were no differences in BMI, waist circumference, WHR, lipid profile, glucose, and HOMA-I, fT4. However, thyroid autoimmunity was associated with elevated TSH and IL-6 levels. When we analysed subclinical hypothyroid women with and without thyroid autoimmunity, there were no significant differences in glucose and lipid profile. However, Hashimoto`s subjects were more obese, had higher waist circumference, WHR, HOMA-I, and higher prevalence of metabolic syndrome. Serum concentrations of TSH and IL-6 were also higher and fT4 was lower. Among all of the women, serum TSH concentration was significantly correlated with BMI, waist circumference, WHR, systolic blood pressure, cholesterol, triglycerides, and TPO-Abs. When the variables of subjects with upper quartile of TSH were compared with lower quartile of TSH, we found significantly higher BMI, waist circumference, WHR, increased concentration of IL-6, cholesterol, triglycerides, and T-Abs, and concentrations of cHDL and fT4 were lower. OR for metabolic syndrome in subjects with upper quartile TSH vs. lower quartile was 1.35 (95% confidence interval [CI] 1.10-1.60). CONCLUSIONS: Our study confirms that metabolic syndrome in both euthyroid and subclinical hypothyroid women is connected with obesity, visceral fat accumulation, and higher TSH and IL-6 concentrations. Immune thyroiditis is associated with higher TSH and IL-6 levels. Obese subclinical hypothyroid women with Hashimoto`s thyroditis have a higher prevalence of metabolic syndrome when compared with subclinical hypothyroid women without thyroid autoimmunity. It is possible that in the crosstalking between subclinical hypothyroidism and metabolic syndrome, enhanced proinflammatory cytokine release in the course of immunological thyroiditis plays a role.

Transforming growth factor ß1 (TGFß1) and vascular endothelial growth factor (VEGF) in the blood of healthy people and patients with Graves' orbitopathy--a new mechanism of glucocorticoids action?

INTRODUCTION: The first part of this paper is related to healthy people and presents concentrations of TGFß1 and VEGF in blood (with and without dividing data with respect to sex), their single measurement values (at 8 am), Mean Daily Concentrations (MDC), Area Under the Curves (AUC; total daily secretion), and circadian rhythm. The second part of the work is related to Graves' orbitopathy (GO). The aim of the study were: 1) to determine the physiological pattern of TGFß1 and VEGF secretion; 2) to compare the serum TGFß1 and VEGF circadian profile in newly diagnosed thyreotoxic patients with active GO and healthy controls (H); and 3) to estimate the influence of high-dose intravenous methylprednisolone pulse therapy (MP) on TGFb1 and VEGF blood levels in GO. MATERIAL AND METHODS: Twenty-two healthy (H) subjects and 16 hyperthyroid GO patients were treated with MP (6 g/14 days) and followed up by ophthalmological assessment. Blood was collected before and after 2 weeks MP-therapy. TGFß1 and VEGF levels were determined by the ELISA method. RESULTS: No difference was observed in the concentrations of TGFß1 and VEGF in the blood of healthy women and men - in further analysis, a combined healthy male and female cohort was used (H). While the absence of circadian rhythms in the concentrations of TGFß1 and VEGF allows the application of a single measurement approach, MDC and AUC measurements were found to be more precise. There were no differences in TGFß1 MDC/AUC between GO and H. VEGF MDC/AUC in GO were higher than in H. MP-therapy increased TGFb1 MDC/AUC, thus in GO after MP, the TGFß1 MDC/AUC were higher than in H. There were no differences in VEGF MDC/AUC during MP-therapy. MP-therapy was effective in 15/16 patients. CONCLUSIONS: 1. MP-therapy increases MDC and AUC of TGFß1. The effectiveness of MP-therapy in patients with active GO may be related to its influence on TGFß1 concentrations in blood. The results suggest the existence of a new mechanism of glucocorticoids action, consisting of an increase in the secretion of TGFß1.2. The elevated serum VEGF in thyreotoxic patients with active GO may reflect long-standing autoimmune processes in orbital and thyroid tissues and intensified angiogenesis in the thyroid gland.

Relationships between adiponectin, sex hormone binding globulin and insulin resistance in hyperthyroid Graves' disease women.

INTRODUCTION: Adiponectin and sex hormone binding globulin (SHBG) play a role in glucose metabolism. Hyperthyroidism has an impact on carbohydrate metabolism and could affect insulin resistance. The aim of this study was to assess the associations between insulin resistance, adiponectin and SHBG among hyperthyroid Graves` disease (GD) women. MATERIAL AND METHODS: The study was undertaken in 60 women with hyperthyroidism in the course of GD; 32 healthy women matched by BMI and age formed the control group. The concentrations of: free thyroxine (fT4), free triiodothyronine (fT3), thyroid-stimulating hormone (TSH), SHBG, insulin, adiponectin and glucose were measured, and the homeostasis model assessment (HOMA-I) was calculated. RESULTS: Compared to euthyroid subjects, hyperthyroid GD women had elevated glucose, fT4, fT3, adiponectin and SHBG concentrations, but there were no differences in HOMA-I. When we explored the relations between adiponectin as well as SHBG with glucose and HOMA-I, we observed that HOMA-I was associated with adiponectin and SHBG only in the control group, and in hyperthyroidism there were no such connections. We found positive associations between adiponectin, SHBG, fT4 and fT3 in the GD group. CONCLUSIONS: Elevated concentrations of adiponectin and SHBG were observed in hyperthyroidism but they were not related to insulin resistance.

Gastroduodenal neuroendocrine neoplasms including gastrinoma - management guidelines (recommended by the Polish Network of Neuroendocrine Tumours).

This paper presents the updated Polish Neuroendocrine Tumour Network expert panel recommendations on the management of neuroendocrine neoplasms (NENs) of the stomach and duodenum, including gastrinoma. The recommendations discuss the epidemiology, pathogenesis and clinical presentation of these tumours as well as their diagnosis, including biochemical, histopathological and localisation diagnosis. The principles of treatment are discussed, including endoscopic, surgical, pharmacological and radionuclide treatment. Finally, recommendations on patient monitoring are given.