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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.

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. Najczęściej pierwszą manifestacją 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.

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.

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.

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, Żelechów, 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.

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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.

Pernicious anemia (PA) is an autoimmune hematopoietic disease.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.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.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).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.

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.

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.

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.

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.

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. (Endokrynol Pol 2015; 66 (5): 394–403)

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/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.

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 Żelechów 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.

Wstep: Pierwsza cześc pracy dotyczy ludzi zdrowych — dostarcza dane o stezeniach TGFβ1 i VEGF we krwi (z podzialem i bez podzialu na plec), ich wartości punktowe (godz. 8), średniodobowe stezenie (MDC), pole pod krzywą (AUC; calkowite dobowe wydzielanie), rytm okolodobowy. Druga cześc pracy dotyczy orbitopatii Gravesa (GO). Celem pracy bylo: 1) określenie fizjologicznego wzoru wydzielania TGFβ1 i VEGF; 2) porownanie okolodobowych surowiczych stezen TGFβ1 i VEGF u chorych z nowo rozpoznaną nadczynnością tarczycy i aktywną fazą GO oraz u ludzi zdrowych (H); 3) ocena wplywu wysokodawkowej dozylnej pulsacyjnej terapii metyloprednizolonem (MP) na stezenia TGFβ1 i VEGF we krwi chorych z GO. Material i metody: Przebadano 22 zdrowych (H); 16 pacjentow z nadczynnością tarczycy i GO leczonych MP (6 g/14 dni) obserwowanych okulistycznie. Krew pobierano przed i po 2 tygodniach terapii MP. Stezenia TGFβ1 i VEGF oznaczono metodą ELISA. Wyniki: Nie stwierdzono roznic w stezeniu TGFβ1 i VEGF we krwi miedzy zdrowymi kobietami i zdrowymi mezczyznami — dalszym analizom poddawano wiec grupe zdrowych (H) skladającą sie z kobiet i mezczyzn. Krew pobierano przed i po 2 tygodniach terapii MP. Choc wykazanie braku rytmow okolodobowych stezen TGFβ1 i VEGF we krwi umozliwia zastosowanie ich oceny punktowej to jednak stwierdzono, ze bardziej precyzyjną jest ocena MDC i AUC. Nie wykazano roznicy w TGFβ1 MDC/AUC miedzy GO i H. VEGF MDC/ AUC byly wyzsze u GO niz u H. MP zwiekszyl TGFβ1 MDC/AUC, tym samym u GO po MP, TGFβ1 MDC/AUC byly tez wyzsze niz u H. Nie stwierdzono roznicy w VEGF MDC/AUC podczas MP. MP byl skuteczny u 15/16 chorych. Wnioski: 1. Terapia MP zwieksza MDC i AUC TGFβ1. Skutecznośc MP u chorych z aktywną fazą GO moze byc związana z jego wplywem na stezenia TGFβ1 we krwi, co sugeruje istnienie nieznanego dotąd mechanizmu dzialania glikokortykosteroidow polegającego na zwiekszaniu wydzielania TGFβ1. 2. Podwyzszone stezenia VEGF we krwi u chorych z nadczynnością tarczycy i aktywną fazą GO mogą byc odzwierciedleniem dlugotrwalego procesu autoimmunologicznego w tkankach oczodolu i tarczycy oraz nasilonej angiogenezy w gruczole tarczowym. (Endokrynol Pol 2014; 65 (5): 349–356)

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 Żelechow 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.

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.

W niniejszej pracy przedstawiono uaktualnione zalecenia grupy ekspertow Polskiej Sieci Guzow Neuroendokrynnych dotyczące zasad postepowania w nowotworach neuroendokrynnych zolądka i dwunastnicy z uwzglednieniem gastrinoma . Omowiono epidemiologie, patogeneze i obraz kliniczny tych nowotworow. Przedstawiono zalecenia dotyczące zasad postepowania diagnostycznego, z uwzglednieniem diagnostyki biochemicznej, histopatologicznej oraz lokalizacyjnej. Uwzgledniono takze zasady postepowania terapeutycznego, w tym leczenie endoskopowe i chirurgiczne, oraz omowiono mozliwości leczenia farmakologicznego i radioizotopowego. Przedstawiono takze zalecenia odnośnie monitorowania chorych z NEN zolądka, dwunastnicy z uwzglednieniem gastrinoma .

Nowotwory neuroendokrynne (NENs) jelita grubego stanowią 20% wszystkich nowotworow neuroendokrynnych. Najczestszą ich lokalizacją jest odbytnica. Nowotwory neuroendokrynne jelita grubego są wykrywane coraz cześciej i liczba ta bedzie wzrastac z uwagi na powszechnośc wykonywania kolonoskopii, w tym badan przesiewowych oraz usuwanie wykrytych zmian. W pracy przedstawiono aktualne zalecenia dotyczące diagnostyki i terapii NEN jelita grubego, z uwzglednieniem diagnostyki biochemicznej, patomorfologicznej, nowych technik obrazowania oraz leczenia endoskopowego, chirurgicznego, farmakologicznego i radioizotopowego. Omowiono takze epidemiologie, charakterystyke kliniczną i monitorowanie leczenia.

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)

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).Three hundred and seventy-two postmenopausal women were included in the study: 114 women had subclinical hypothyroidism (10.0 uIU/mLTSH ≥ 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.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).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.

Soluble intercellular adhesion molecule-1 (sICAM-1) is ranked as one of the endothelial dysfunction markers and factors predicting diseases of the cardiovascular system. The main objective of this study was to assess the serum concentration of sICAM-1 in women with polycystic ovary syndrome (PCOS) and to verify correlations between serum sICAM-1 levels and selected anthropometric, metabolic and hormonal indices. The study assessed 57 women with PCOS (mean age 28.2 +/- 6.4 years). That group was further divided into two subgroups: the first with body mass index (BMI)or =25 kg/m2 (21 women of mean age 27.4 +/- 7.0 years) and the second with BMI25 kg/m2 (36 women of mean age 28.6 +/- 6.0 years). In the control group there were 22 healthy women (mean age of 31.6 +/- 8.5 years). That group again was divided accordingly to BMI into two subgroups: the first with BMI25 kg/m2 (ten women, mean age 30.2 +/- 8.4 years) and the second with BMI25 kg/m2 (12 women, mean age 31.7 +/- 8.7 years). The results demonstrated statistically significantly higher mean concentrations of sICAM-1 in women with PCOS as compared to healthy individuals from the whole control group and also from the control subgroup of women with BMI25 kg/m2. There was no statistically significant difference in sICAM-1 concentration between the PCOS group and the control subgroup with BMIor =25 kg/m2 In conclusion, higher concentrations of sICAM-1 in women with PCOS may confirm the presence of a higher risk for cardiovascular diseases in this group. Further studies are therefore necessary to identify both the factors that are responsible for the increase in sICAM-1 concentration and the clinical usefulness of routine sICAM-1 measurement in females with PCOS.

Summary Objective: To estimate the time it takes for adrenal cortex function in asthmatic patients to return to normal after discontinuation of chronic therapy with systemic glucocorticosteroids (GCs) and to assess the relationship between the duration of the disease, chronic therapy, and the return of the normal adrenal cortex functioning. Materials and methods: The study involved 58 asthmatic patients and 31 healthy volunteers (aged 20–69 years). Adrenal cortex function was evaluated with the Synacthen short test, and determining serum and urinary free cortisol levels after 1, 3, 6, 12, 18, and 21 months following the discontinuation of systemic therapy with GCs. Results: A decreased adrenal reserve was observed 1 month after withdrawal of GCs in 50% of the chronically treated patients. Adrenal cortex function returned to normal in 55% of patients within 6 months, in 24% within 12 months, and in 14% within 15 months of discontinuation of systemic GCs administration. A significant positive correlation between the time taken for return to normal adrenal cortex function and duration of the disease and of GCs therapy was found. Conclusions: Symptoms of adrenal failure may develop in about 50% of asthmatic patients. In the majority of patients treated long term with systemic GCs, adrenal cortex function returns to normal within 6 months following discontinuation of GCs. The time of such return depends on the duration of the disease and of therapy with systemic GCs.

The first part of this paper is related to healthy people and presents concentrations of TGFβ1 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 TGFβ1 and VEGF secretion; 2) to compare the serum TGFβ1 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.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. TGFβ1 and VEGF levels were determined by the ELISA method.No difference was observed in the concentrations of TGFβ1 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 TGFβ1 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 TGFβ1 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 TGFβ1 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.1. MP-therapy increases MDC and AUC of TGFβ1. The effectiveness of MP-therapy in patients with active GO may be related to its influence on TGFβ1 concentrations in blood. The results suggest the existence of a new mechanism of glucocorticoids action, consisting of an increase in the secretion of TGFβ1.2. 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.

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.

AIM OF THE STUDY To assess resource utilization and costs of treatment with lanreotide AUTOGEL 120 mg (ATG120) administered as part of routine acromegaly care in Poland. MATERIAL AND METHODS A multicentre, non-interventional, observational study on resource utilization in Polish acromegalic patients treated with ATG120 at 4 weeks or extended (> 4 weeks) dosing interval. The study recruited adult acromegalic patients treated medically for ≥ 1 year including at least 3 injections of ATG120. Data on dosing interval, aspects of administration, and resource utilization were collected prospectively during 12 months. Costs were calculated in PLN from the public health-care payer perspective for the year 2013. RESULTS 139 patients were included in the analysis. Changes in dosing regimen were reported in 14 (9.4%) patients. Combined treatment was used in 11 (8%) patients. Seventy patients (50%) received ATG120 at an extended dosing interval; the mean number of days between injections was 35.56 (SD 8.4). ATG120 was predominantly administered in an out-patient setting (77%), by health-care professionals (94%). Mean time needed for preparation and administration was 4.33 and 1.58 min, respectively, mean product wastage - 0.13 mg. Patients were predominantly treated in an out-patient setting with 7.06 physician visits/patient/year. The most common control examinations were magnetic resonance imaging of brain and brain stem (1.36/patient/year), ultrasound of the neck (1.35/patient/year), GH (1.69/patient/year), glycaemia (1.12/patient/year), IGF-1 (0.84/patient/year), pituitary-thyroid axis hormone levels assessment (TSH-0.58/patient/year, T4-0.78/patient/year). There were 0.43 hospitalizations/patient/year. For direct medical costs estimated at PLN 50 692/patient/year the main item was the costs of ATG120 (PLN 4103.87/patient/month; 97%). The mean medical cost, excluding pharmacotherapy, was PLN 1445/patient/year (out-patient care - 49%, hospitalization - 23%, diagnostics/laboratory tests - 28%). CONCLUSIONS These results represent the current use of ATG120 in the population of Polish acromegalic patients in a realistic clinical setting. Findings that 50% of patients could be treated with dose intervals of longer than 28 days support the potential of ATG120 to reduce the treatment burden.

Bronchopulmonary neuroendocrine tumours (BP NET) cause many diagnostic and therapeutic problems. There is an ongoing search for biochemical markers of activity of these tumours. The use of polypeptide growth factors seems potentially feasible in establishing the diagnosis, prognosis and treatment of these tumours.We included 41 patients aged 25 to 78 years with histopathologically confirmed typical and atypical bronchopulmonary carcinoid tumours and 20 healthy volunteers. We assessed the levels of specific and non-specific markers of these tumours and of selected growth factors relative to TNM classification.The levels of specific markers (serotonin and its metabolite, 5-hydroxyindoleacetic acid [5HIAA]) and non-specific markers (chromogranin A [CgA]) were significantly higher in patients with atypical carcinoid tumours. The serum levels of hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF) and VEGF receptor-1 (VEGFR-1) were significantly higher in patients with carcinoid tumours versus the control group. The levels of VEGFR-1 closely correlated with TNM classification. No such correlation could, however, be confirmed for the levels of HGF, VEGF or VEGFR-2.Determination of CgA, serotonin and 5HIAA may be useful in the diagnosis of BP NET, particularly in atypical carcinoid tumours, and their levels depend on the presence of distant metastases. Determination of growth factors (VEGF and its receptor, VEGFR‑1, and HGF) may prove useful in the clinical diagnosis of these tumours, while the assessment of VEGFR‑1 expression may be helpful in tumour staging.

Gastroenteropancreatic (GEP) and bronchopulmonary (BP) neurendocrine neoplasms (NENs) are rare and slowly growing tumours. Matrix metalloproteinases (MMPs) degrade extracellular matrix and are responsible for invasion and metastasis. Tissue inhibitors of matrix metalloproteinases (TIMPs) affect the invasiveness of tumour cells and the formation of distant metastases. The aim of this study was to evaluate selected MMPs (MMP2 and MMP9) and their tissue inhibitors (TIMP1 and TIMP2) depending on the pTNM classification, grading, and the occurrence of metastases.The study group consisted of 86 patients with GEP NENs. The control group consisted of 31 healthy volunteers. Serum levels of TIMP1, TIMP2, MMP2 and MMP9 were determined by ELISA (RD Systems) in all the study subjects. The statistical calculations were performed using MedCalc.We observed significant differences in MMP2 and TIMP1 levels between the study group with NENs and the control group. TIMP1 levels were significantly higher in patients with high-grade NEN (NEC, neuroendocrine carcinoma) compared to patients with low-grade tumour (NET G1, neuroendocrine tumours G1) (p 〈 0.017). We also observed a significant correlation between TIMP1 levels and the presence of metastases in the group of patients with GEP NENs, and also higher TIMP1 levels than those in the patients without metastases (p 〈 0.05). We also found a higher likelihood of metastases in patients with GEP NENs with TIMP1 levels exceeding 206.4 ng/mL.Patients with NENs secreted larger quantities of MMP2 and TIMP1. TIMP1 may be considered a marker of metastases in patients with GEP NENs.

Gastroenteropancreatic neuroendocrine tumours (GEP NETs) are a heterogenous group of tumours of various clinical presentations. Proliferative activity of tumour cells is an essential parameter determining the course of the disease and affecting the prognosis. The Ki-67 antigen is an important marker of cell proliferation, which shows activity in all the phases of the cell cycle, excluding the G0 phase.To assess the expression of Ki-67 in GEP NETs and to examine the association of Ki-67 with the stage of the tumour (tumour size, presence of metastases) and the hormonal function of the tumour.We included 61 patients with GEP NETs (25 males and 36 females aged between 20 and 82 years [mean age: 56 years]). The proliferative activity was examined in paraffin blocks containing surgically removed tumour samples and in core-needle biopsies of primary and metastatic tumours. The presence of the Ki-67 antigen was assessed by immunohistochemistry using MIB‑1 monoclonal antibodies. Based on the Ki-67 proliferative index we determined the tumour grade. In addition, we determined the tumour stage according to the TNM classification. In all the subjects we determined the levels of the non-specific NET marker (chromogranin A) and of specific NET markers (serotonin, insulin and gastrin in the blood and 5‑hydroxyindoleacetic acid [5‑HIAA] in 24-hour urine).The diagnoses of low-grade (Ki‑67 ≤ 2%), intermediate-grade (Ki-67 3-20%) and high-grade (Ki‑6720%) NET were established in 38, 12 and 11 patients, respectively. Metastatic disease was diagnosed in 36/61 patients. A significantly higher expression of K-67 was observed in patients with metastatic disease (p = 0.01). A positive correlation was demonstrated between Ki-67 and the stage of the disease (p = 0.01) and between the histologic grade of the tumour and the stage of the disease (p = 0.01). No association between Ki-67 and the levels of chromogranin A, serotonin, insulin, gastrin and 5-HIAA was shown. There was also no difference in Ki-67 expression relative to the location of the primary tumour and the tumour size.The Ki-67 proliferative index is an essential parameter predicting the course of GEP-NETs.

Stroke, due to its worldwide prevalence, is not only a medical challenge, but also a serious social problem. Recently, ongoing research has examined whether there are associations between adipose tissue hormones and the risk, mechanisms and course of stroke. The aim of our study was to determine whether there are significant differences in blood concentrations of insulin, adiponectin, leptin, resistin and in insulin resistance among patients in the acute phase of ischaemic stroke, compared to healthy subjects. In addition, we wanted to investigate if those biochemical values show a correlation with the neurological condition of our patients.Adiponectin, leptin, resistin and insulin were measured in patients (n = 69) with first-ever ischaemic stroke (confirmed by CT), using specific electrochemoluminescence, radioimmunoassay and ELISA methods. Neurological evaluation was performed using Barthel ADL index on the day of admission and on the ninth day of hospitalisation. Insulin resistance value was obtained via the HOMA-IR calculator. Data was compared to that of healthy individuals (n = 26).Insulin concentration (51.08 v. 17.02 uU/mL) and HOMA-IR value (6.3 v. 2.2) were significantly higher in the study group. Leptin (14.98 v. 10.47 ng/mL) and resistin (28.92 v. 12.25 ng/mL) levels were elevated among the stroke survivors compared to controls, but no significant difference was noted in adiponectin. Negative correlations of adiponectin level and Barthel score were observed.Hyperinsulinaemia and insulin resistance are involved in the pathogenesis of ischaemic stroke. Hyperleptinaemia and hyperresistinaemia play a role in the mechanism of stroke. The severity of stroke is associated with adiponectin blood concentration.

Endocrine glands are well vascularised and the structure of their vessels facilitates the exchange of various substances, including hormones. These glands are a frequent experimental model in research on VEGF and angiogenesis. VEGF participates in the pathogenesis of diabetes. Diabetic nephropathy is in essence a microvascular disease that develops as a result of a confluence of haemodynamic and metabolic perturbations. Diabetic retinopathy is the commonest microvascular complication of diabetes mellitus and is the leading cause of blindness. In diabetic retinopathy, ischaemic states, and hence tissue hypoxia and angiogenesis, take place. The participation of angiogenesis and VEGF in the pathogenesis of neoplastic disease has been described in many papers. VEGF protein and mRNA have been found in cancers of the thyroid, bronchus, lungs, oesophagus, stomach, colon, liver, breast, ovary, uterus, kidney, and urinary bladder, and in malignant tumours of the brain and bone. There have been many reports of the connections between the degree of VEGF expression and tumour aggression and prognosis in patients. Richly vascularised are GEP NET. In neuroendocrine tumours, strong expression of VEGF, Flt-1 and KDR in relation to the unchanged surrounding tissues has been demonstrated. Depending on the disease entity or the degree of its severity, attempts to apply angiogenic and antiangiogenic therapy have being made. Antiangiogenic therapy (usually regarded as a form of cancer therapy) is based on: 1. inhibitory effects of proangiogenic ligands and their receptors; 2. stimulation or delivery of angiogenesis inhibitors; and 3. direct destruction of neoplastic tumour vasculature.

The increased incidence of cardiovascular disease in women with polycystic ovary syndrome (PCOS) has prompted researchers to look for indicators of early atherosclerotic changes in these patients. One of the earliest stages of atherogenesis is endothelial cell dysfunction. The aim of this study was to assess the levels of selected plasma markers of endothelial injury [E-selectin, endothelin-1 (ET-1) and von Willebrand Factor antigen (vWF:Ag)] in PCOS women before and after six months of treatment.32 patients with PCOS aged 18-36 years (mean age 25.16 ± 5.80) were included in the study. The control group consisted of 20 healthy women matched for age and body mass. The levels of ET-1, vWF:Ag, E-selectin, fasting glucose, insulin, total cholesterol, HDL and LDL-cholesterol and triglycerides were assessed. In the PCOS group, all these tests were repeated after six months of treatment.The study showed higher levels of vWF:Ag (p = 0.043), E selectin (p = 0.028), insulin (p = 0.044), glucose (p = 0.036) and LDL (p = 0.006) in PCOS patients versus healthy women. A positive correlation was demonstrated between E selectin and glucose (p = 0.0001), triglycerides (p = 0.014) and uric acid (p = 0.008). vWF:Ag levels showed a positive correlation with glucose (p = 0.04) and triglycerides (p = 0.036). A positive correlation was also found between ET-1 and total cholesterol levels (p = 0.012) in PCOS women. After treatment, there was a significant reduction in E-selectin levels from baseline (p = 0.002) and an increase in the levels of HDL (p = 0.0002) and triglycerides (p = 0.033).Elevated levels of vWF:Ag and E selectin in PCOS women suggest endothelial dysfunction in this group of patients. Glucose and triglyceride are significant factors affecting endothelial function in PCOS.

A multitude of mechanisms have been implicated in the pathophysiology of epilepsy.To assess mean daily plasma concentrations of ACTH, cortisol, DHEAS, leu-enkephalin, and beta-endorphin in epileptic patients with complex partial seizures evolving to tonic-clonic in relation to frequency of seizure occurrence (groups with seizure occurrences - several per week and several per year) and duration of the disease (groups less than and more than 10 years). We decided to analyse mean daily values of beta-endorphin and leu-enkephalin because of significant differences in concentrations of these substances in blood during the day.The study was performed on 17 patients (14 males + 3 females; mean age 31.8 yrs) treated with carbamazepine (300-1800 mg/day). The control group consisted of six age-matched healthy volunteers. Blood was collected at 8 a.m., 2 p.m., 8 p.m., and 2 a.m. Intergroup analysis was performed with the use of ANOVA Kruskal-Wallis test.Mean daily concentrations of ACTH and cortisol in the blood of the patients with epilepsy were higher in comparison with those of the healthy volunteers, independently of the frequency of seizures and duration of the disease. Mean daily concentrations of beta-endorphin in the blood of the patients with epilepsy were higher in the groups of patients with more severe clinical course of disease (with more frequently occurring epilepsy seizures and longer duration of the disease) in comparison with healthy subjects. Mean daily concentrations of leu-enkephalin in the blood of the patients with epilepsy were higher in the group of patients with short duration of the disease in comparison with the group with long duration of the disease.1. Pituitary-adrenal axis hyperactivity is observed in patients with clinically active epilepsy, independently of the frequency of seizures and duration of the disease. 2. Changes in endogenous opioid system activity are related to the clinical activity of epilepsy - beta-endorphin concentrations are connected with frequency of seizures and duration of the disease and leu-enkephalin concentrations with duration of the disease. 3. Endogenous opioid peptides might take part in the neurochemical mechanism of human epilepsy. (Pol J Endocrinol 2010; 61 (1): 103-110).

Leptin and adiponectin are involved in the pathogenesis of several autoimmune diseases. Very little is known about adipocytokine production in autoimmune thyroid diseases. Interleukin-6 (IL-6) plays an important role in the inflammatory and autoimmune processes.The aim of this study was to assess the serum levels of leptin, adiponectin, and IL-6 in postmenopausal euthyroid women with Hashimoto's thyroiditis and compared them with concentrations in control women. Ninety-eight euthyroid women with Hashimoto's thyroiditis were enrolled in the study. The diagnosis was confirmed with elevated thyroid peroxidise autoantibody (TPOAb) levels in serum and typical hypoechogenic pattern on thyroid ultrasound. The control group, matched for body mass index (BMI), consisted of 105 healthy postmenopausal euthyroid women. Serum levels of leptin, adiponectin, IL-6, thyroid-stimulating hormone (TSH), free thyroxine (fT(4)), and TPOAbs were determined.When compared with controls, the women with Hashimoto's thyroiditis were characterized by significantly elevated serum concentrations of IL-6, whereas concentrations of leptin and adiponectin were not different. Hashimoto's thyroiditis patients had significantly higher serum levels of TSH than the controls. The simple linear regression analyses of the Hashimoto's thyroiditis group and all of the studied women indicated that serum leptin levels correlated positively with BMI, waist to hip ratio (WHR), TSH, and IL-6 and negatively with adiponectin. No correlation was observed between serum adiponectin and TSH, fT(4), or TPOAbs. There were no associations between serum IL-6 levels, TPOAbs, and TSH levels; however, positive correlations between IL-6 and BMI, WHR, and leptin were observed. TSH correlated positively with leptin, age, and TPOAbs.Hashimoto's thyroiditis is characterized by an increased production of IL-6 but does not have a direct influence on leptin or adiponectin serum levels. The correlations between TSH and leptin demonstrated in this study highlight the need for future investigations. (Pol J Endocrinol 2010; 61 (1): 112-116).

Pathogenesis of colonic lesions in patients with acromegaly remains still unclear. There are suggestions that apart from somatotropin axis hormones (GH and IGF-1), other agents also take part in this process. Molecular and animal studies indicate a vital role of hyperinsulinemia in development of colorectal neoplasms.To evaluate a relation between insulin level, insulin resistance and its anthropometric markers and colorectal lesions in patients with acromegaly.The study consisted of 40 patients with active, newly diagnosed acromegaly; 24 women and 16 men aged from 24 to 77 years (mean age 50.1, SD+/-12.1). The analysis included the results of somatotropin axis function (GH and IGF-1 level), carbohydrate metabolism assessment (fasting serum glucose and insulin levels, oral glucose tolerance test, HOMA-IR for insulin resistance), the results of anthropometric measurement (BMI, WHR) and colonoscopy.Colon pathologies (60 polyps and 2 flat lesions) were discovered in 19 (47.5%) patients with acromegaly, 8 of them had multiple polyps. Hyperplastic polyps were revealed in 11 (27.5%), while adenomas in 8 (20%) acromegalics. Patients with colorectal lesions were found to have higher WHR then subjects with normal colon (p=0.033). Positive correlation between the number of hyperplastic polyps in the patients with multiple changes in the colon and IGF-1 (p=0.025), insulin level (p=0.005) and HOMA-IR (p=0.001) was found. Multiple adenomas correlated positively with insulin level (p=0.007), HOMA-IR (p=0.006) and BMI (p=0.015).The study results show a relation between hyperinsulinemia, insulin resistance and colon pathologies in acromegaly. Fasting insulin level and HOMA-IR correlate positively with the number of hyperplastic polyps and adenomas in acromegalic patients with multiply colorectal lesions.

Prolonged glucocorticoids administration is the most common cause of secondary osteoporosis. It is estimated that 30% to 50% of chronic glucocorticoids users experience vertebral or hip fractures. The highest bone loss (up to 30% in some studies) is observed in the first six months of treatment. Only a minority of patients who take chronic glucocorticoids receive optimal osteoporosis diagnosis, prevention, and/or treatment. The aim of this paper is to present the pathophysiology of glucocorticoid-induced osteoporosis, as well as some guidelines on diagnostic, preventive and therapeutic strategies for this disorder in an effort to promote the greater awareness of it.

Chromogranin A (CgA) is a non-specific marker of neuroendocrine tumors (NET) and is important in monitoring the disease course and NET treatment.Usefulness of suppression test of CgA secretion with octreotide in diagnosis and predicting the therapy outcome in NET patients.The study included 32 patients with NET of gastrointestinal tract, lung and of unknown origin. CgA level in blood plasma on fasting, before and 30, 60, 90 and 120 minutes after subcutaneous administration of 100 mug octreotide, was determined in all patients. The subjects were divided into two subgroups with relation to CgA level and to the results of somatostatin receptor scintigraphy (SRS).Statistically significant CgA decrease after octreotide administration in all study time points and positive results of SRS were found in the patients with the elevated CgA level. No statistically significant decrease of CgA level after octreotide was found in the group with normal CgA levels. In this group, 13 patients had a negative result of SRS, and somatostatin receptors expression was found in one patient. Tolerance of somatostatin analogs (SSA) therapy was very good.Octreotide suppression test with CgA level assessment in NET patients is a simple, straightforward examination, providing information on the predicted response to the applied SSA and the data on initial clinical tolerance of those agents. This examination can also be a screening test useful in planning the treatment with SSA in patients with NET.

Insulinomas are the most common functioning endocrine tumors of pancreas. Approximately 10% are multiple, less than 10% can be malignant and 5-10% associated with the MEN-1 syndrome. Insulinomas are the most common cause of hypoglycemia resulting from endogenous hyperinsulinism. The aim of this lecture is to present the up-to-date information concerning the prevalence, diagnosis and treatment of insulinoma.

Polypeptide growth factors form a potent class of extracellular signal molecules in the regulation of cellular differentiation and proliferation. Disturbances in the expression of growth factors influence the normal pathway of differentiation and lead to cellular transformation and tumour progression. Contemporary medical studies report that various growth factors such as those for platelet-derived growth factor, vascular endothelial growth factor, epidermal growth factor, hepatocyte growth factor and insulin-like growth factor are expressed in gastroenteropancreatic neuroendocrine tumours (GEP/NET). Polypeptide growth factors have great significance in the growth, progression and development of metastases by various tumours. We describe the role of growth factors in GEP/NET on the basis of the available reports of medical research.

Ghrelin is a natural ligand of the growth hormone secretagogue receptor and has been shown to be a potent stimulant of GH secretion. It has also orexigenic effects and regulates energy homeostasis. Recent studies claim that ghrelin influences the androgen level and probably takes part in PCOS pathomechanism. The aim of the study was an assessment of ghrelin level in plasma in women with PCOS before and after the treatment and ghrelin's influence on androgen level change.The study included 25 women with the diagnosed PCOS (mean age 25.3+/-4.05 yr). The tests were done twice: before the treatment and after 6-month therapy with Diane 35 (cyproterone acetate 2 mg with ethinylestradiol 35 mug). Following hormones were measured: ghrelin, free testosterone, androstendione, dehydroepiandrosterone sulfate, 17-OH-progesterone and estradiol.The received results in both groups were compared with the control group (11 healthy women, mean age 26.0+/-2.6 yr). No statistically significant differences in ghrelin levels before (187.8+/-8.1 fmol/ml) and after the therapy (185.6+/-9.5 fmol/ml) were found. Similar results were received when two groups of women compared with the control (186.5+/-8.7 fmol/ml). No correlations between ghrelin and androgen levels were confirmed.Final conclusion is that there is no direct impact of ghrelin level on PCOS pathogenesis, however, its role in development of obesity, hyperinsulinemia and insulin resistance co-occurring with metabolic disorders syndrome cannot be excluded.

Acromegalics have an increased risk of colorectal neoplasm. The aim of this study was to establish the association between acromegaly and colorectal lesions.The study included 51 patients with active acromegaly: 30 women and 21 men (average age 52.95 +/- 13.49 years). Growth hormone (GH), insulin-like growth factor I (IGF-I), prolactin (PRL), thyreothropin (TSH), thyroxine (FT4) were measured in the serum when patients were hospitalized for their first diagnosis of acromegaly, before starting the treatment. All patients underwent colonoscopy--in the first phase conventional in white light; in the second phase fluorescence colonoscopy. Autofluorescence of colonic mucosa was assessed by illumination with monochromatic light. Green fluorescence is characteristic for normal colonic mucose, whereas red fluorescence occur in pathological lesions. Material to histopathological examination was taken from every pathological colorectal lesion.Using conventional colonoscopy we detected colonic polyps in 21 acromegalic patients (41.17%). Polyps with red fluorescence were found in 7 (13.7%) acromegalics and with green fluorescence in 16 (31.37%) cases of these patients. Histological diagnoses of colorectal lesions are adenoma, hyperplastic and inflammatic polyps. The number of colorectal polyps was dependent on IGF-I, fT4 and sex.Acromegaly is associated with high prevalence of colorectal pathology, mainly hyperplastic polyp and adenoma. There is a relationship between number of colorectal polyps and serum IGF-I levels in acromegaly. Adenomas and hyperplastic polyps were associated with higher levels of IGF-I.

Neuroendocrine tumors are frequently associated with other primary malignancies. Plasmablastic lymphoma is a rare, aggressive neoplasm, derived from large B-cell, associated with human immunodeficiency virus infection. Plasmablastic lymphoma cells share many cytomorphologic and immunophenotypic features with plasmablastic cells, causing some diagnostic problems. We present a unique case of coexisting two very uncommon neoplasms: plasmablastic lymphoma and neuroendocrine carcinoma in 54-years-old men. This is the first report of caecum localization of plasmablastic lymphoma. Presented case images diagnostic problems in rare neoplasms.

It is well known that there is a higher prevalence of cardiovascular risk factors and metabolic syndrome (MS) in postmenopausal women. Recently it has become evident that adiponectin and leptin secreted by adipose tissue may be involved in the pathophysiology of MS.was to assess the effects of the menopause on the relationships between adiponectin and leptin and different cardiovascular and metabolic risk factors.A total of 56 postmenopausal women and 75 premenopausal subjects were enrolled in this study. We measured blood pressure, BMI, waist circumference and WHR, triglycerides (TG), high density lipoprotein cholesterol (cHDL) levels and fasting glucose and applied the oral glucose tolerance test (OGTT). Women were categorised as having 0, 1, 2, 3 or more risk factors. The presence of at least 3 abnormalities was defined as MS. Serum was assayed for adiponectin and leptin by the radioimmunoassay (RIA) method.A decline in adiponectin was related to an increased number of MS variables in postmenopausal and premenopausal women. Postmenopausal women with MS had significantly lower adiponectin concentrations than premenopausal women with MS. Serum adiponectin concentrations were inversely correlated to leptin in postmenopausal women. In premenopausal women no clear relationships were found between serum leptin and the number of metabolic disturbances. In contrast to young women, postmenopausal women showed an increase in leptin secretion with a growing number of MS elements. Compared to premenopausal women with MS, postmenopausal women with MS had higher levels of leptin. We found associations between leptin and different risk factors, mainly in the postmenopausal group. When the presence of MS was used as a dependent variable (yes/no) and adiponectin, leptin and menopause status as independent factors, adiponectin and leptin remained significant variables related to MS.The significant role of adiponectin in the pathophysiology of MS in premenopausal and postmenopausal women is confirmed in this study. Leptin is correlated with several MS components but this adipocytokine appears to play a role only in postmenopausal women.

Females with polycystic ovary syndrome (PCOS) are characterized by several metabolic abnormalities that favor the development of atherosclerosis. Atherosclerosis is possibly a chronic inflammatory process, and the markers of the inflammatory state, such as C-reactive protein (CRP) and fibrinogen may be useful to assess the global risk of developing cardiovascular diseases. These proteins might be helpful in finding females with subclinical atherosclerosis. The purpose of this study was to assess the serum CRP and fibrinogen concentrations in young females with PCOS and to clarify the possible correlations between their levels and selected anthropometric, metabolic and hormonal indices. Study assessed a group of 57 females with PCOS (mean age 28.2±6.4 years). That group was further divided into two subgroups: the first with body mass index (BMI)≤25 (21 females of mean age 27.4±7.0 years) and second with BMI>25 (36 females of mean age 28.6±6.0 years). In the control group there were 22 healthy females (mean age 31.6±8.5 years). That group was again divided into two subgroups: the first with BMI≤25 (10 females, mean age 30.2±8.4 years) and second with BMI>25 (12 females, mean age 31.7±8.7 years). Results demonstrated statistically significantly higher CRP concentration in females with PCOS compared to healthy individuals in both BMI subgroups. PCOS females showed also higher plasma insulin levels. There was, however, no statistically significant difference in fibrinogen concentrations. The hormonal profile of females with PCOS seems to influence the concentration of CRP and fibrinogen in different ways. This was evident in the positive correlation between plasma fibrinogen and androstenedione and in the lack of correlation between CRP and androgens and in the positive correlation between CRP and estradiol and the negative correlation between fibrinogen and estradiol. In conclusion, high CRP concentration in females with PCOS probably speaks for a higher risk for cardiovascular diseases.

Anxiety accompanies patients at all stages of severe somatic diseases as well in the course of diagnostic procedures. It affects significantly quality of life of these patients and their relations with their physicians. It may also induce or exacerbate wide range of somatic complaints.Evaluation of usefulness of anxiolytic therapies in patients with diagnosed neoplastic diseases. Comparison of anti-anxiety and antidepressant effects of alprazolam and diazepam in patients treated with systemic chemotherapy.Final analysis included 45 patients with various malignancies randomly assigned to receive alprazolam 3 x 0.5 mg or diazepam 3 x 2 mg. Anti-anxiety effects of both drugs was evaluated four times during the 21-day follow-up period at one week intervals with help of Clinical Global Impression scale (CGI), Hamilton Anxiety Rating Scale (HARS), Hospital Anxiety and Depression Scale (HADS). Analysis of these questionnaires was performed with Mann-Whitney test and Wilcoxon test.Statistically significant reduction of anxiety was found in both study groups. Alprazolam was proven to be significantly more effective than diazepam in reduction of anxiety (HARS, HADS) and depressive symptoms accompanying anxiety (HADS). Alprazolam vs. diazepam showed better tolerance by patients.Alprazolam effectively reduced anxiety in patients suffering from malignant diseases. Alprazolam was found to reduce depressive symptoms in patients with neurotic disorders whereas no effects of this kind were observed for diazepam.