Differential diagnosis of thyroid orbitopathy - diseases mimicking the presentation or activity of thyroid orbitopathy.

Thyroid orbitopathy (TO) is the most common cause of orbital tissue inflammation, accounting for about 60% of all orbital inflammations. The inflammatory activity and severity of TO should be diagnosed based on personal experience and according to standard diagnostic criteria. Magnetic resonance imaging (MRI) of the orbit is used not only to identify swelling and to differentiate inflammatory active from non-active TO, but also to exclude other pathologies, such as orbital tumours or vascular lesions. However, a group of diseases can mimic the clinical manifestations of TO, leading to serious diagnostic difficulties, especially when the patient has previously been diagnosed with a thyroid disorder. Diagnostic problems can be presented by cases of unilateral TO, unilateral or bilateral TO in patients with no previous or concomitant symptoms of thyroid disorders, lack of symptoms of eyelid retraction, divergent strabismus, diplopia as the only symptom of the disease, and history of increasing diplopia at the end of the day. The lack of visible efficacy of ongoing immunosuppressive treatment should also raise caution and lead to a differential diagnosis of TO. Differential diagnosis of TO and evaluation of its activity includes conditions leading to redness and/or swelling of the conjunctiva and/or eyelids, and other causes of ocular motility disorders and eye-setting disorders. In this paper, the authors review the most common diseases that can mimic TO or falsify the assessment of inflammatory activity of TO.

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.

Interleukin (IL)-23, IL-31, and IL-33 Play a Role in the Course of Autoimmune Endocrine Diseases.

BACKGROUND: Interleukins (IL)-23, 31, and 33 are involved in the regulation of T helper 17 (Th17)/regulatory T (Treg) cells balance. The role of IL-23, 31 and 33 in non-endocrine autoimmune diseases has been confirmed. Data on the involvement of these cytokines in endocrine autoimmune diseases are limited. OBJECTIVE: This study aimed to determine the involvement of cytokines regulating the T helper 17 (Th17)/regulatory T (Treg) cells axis in the course of autoimmune endocrine diseases. METHODS: A total number of 80 participants were divided into 4 groups: the autoimmune polyendocrine syndrome (APS) group consisting of APS type 2 (APS-2) and type 3 (APS-3) subgroups, the Hashimoto's thyroiditis (HT) group, the Graves' disease (GD) group and the control (C) group. Fifteen cytokines related to Th17 and Treg lymphocytes were determined in the serum of all participants. RESULTS: Higher levels of IL-23 and IL-31 were found in the APS, GD, and HT groups compared to the C group. Higher levels of IL-23 and IL-31 were also observed in the APS-2 group, in contrast to the APS-3 group. Correlation analysis of variables in the groups showed a statistically significant correlation between the cytokines IL-23, IL-31, and IL-33 in the APS and APS-2 groups, but no correlation in the APS-3 and C groups. CONCLUSION: IL-23 and IL-31 are independent factors in the course of HT, GD, and APS-2, in contrast to APS-3. The positive correlation between IL-23 and IL-31, IL-23 and IL-33, and between IL-31 and IL-33 in the APS, APS-2 groups, but the lack of correlation in the APS-3 and C groups may further suggest the involvement of these cytokines in the course of Addison's disease.

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.

Acute adrenal insufficiency secondary to bilateral adrenal haemorrhage.

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[Multiple bone fractures caused by severe hypophosphatemia in the course of the mandible tumour].

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

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

[Optimization of the treatment of moderate to severe and active thyroid orbitopathy considering the recommendations of the European Group on Graves' Orbitopathy (EUGOGO) [Optymalizacja leczenia umiarkowanej do ciezkiej i aktywnej orbitopatii tarczycowej z uwzglednieniem zalecen European Group on Graves' Orbitopathy (EUGOGO)]].

Graves' disease (GB), also known as Basedow's disease, is the most common cause of hyperthyroidism, and thyroid orbitopathy (TO) is its most common non-thyroid manifestation with an incidence of 42.2/million people/year. Based on the guidelines of the European Graves' Orbitopathy Group (EUGOGO), certain management standards presented in our publication should be used to optimize and improve the efficacy of TO treatment. Deciding on the optimal treatment for both hyperthyroidism and TO requires a cooperative team of specialists: endocrinologist, ophthalmologist, radiation therapist, and surgeon, as well as consideration of the risk of relapse and possible complications of the treatment method. The inflammatory activity and severity of TO should be diagnosed based on the investigator's own experience and according to standard diagnostic criteria. Assessment of the inflammatory activity of TO can be performed using the clinical activity score (CAS) and using imaging methods - mainly MRI. The severity of TO is assessed using a seven-grade NOSPECS classification and a three-grade EUGOGO scale. In moderate to severe and active TO, i.v. methylprednisolone pulses are the treatment of choice. It is important to maintain the standard and regimen of treatment. The recommended standard as first-line treatment in most patients with moderate to severe and active TO is the combined use of methylprednisolone i.v. (cumulative dose of 4.5 g over 12 weeks) with concurrent administration of mycophenolate sodium 0.72 g per day for 24 weeks. In more severe forms of moderate to severe and active TO, a higher cumulative dose of methylprednisolone i.v. is recommended as an alternative first-line treatment (7.5 g) as monotherapy starting with a dose of 0.75 g once a week for 6 weeks and 0.5 g for a further 6 weeks. EUGOGO guidelines recommend that in cases of no clinical response after 6 weeks of first-line treatment with i.v. methylprednisolone and mycophenolate, after 3-4 weeks, a second course of i.v. methylprednisolone monotherapy should be started with a higher cumulative dose of 7.5 g. Other second-line treatment options are orbital radiotherapy with or without oral or i.v. systemic glucocorticosteroid therapy, cyclosporine, or azathioprine in combination with p.o. glucocorticosteroid, methotrexate monotherapy, and a group of biologic drugs rituximab, tocilizumab, teprotumumab). Keeping in mind that TO is a sight-threatening disease, we expect, through the treatment applied, to maintain full visual acuity, pain relief, single vision in the useful part of the visual field, and a positive cosmetic effect.

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.

CD4+ cells in autoimmune thyroid disease.

The phenomenon of autoimmunity develops as a result of the triggering factor released by damaged cells. This leads to an infiltration of CD4+ cells involved in stimulating the effector cells cytotoxicity and stimulating the humoral response. One of the most common autoimmune disorders are autoimmune thyroid diseases, including Hashimoto's thyroiditis and Graves's diseases. Helper T lymphocytes, which are divided into Th1, Th2, Tregs, and the relatively new groups Th17, Th22, and Th9, are involved in the pathogenesis of AITD. CD4+ cell subtypes mature and differentiate by specific transcription factors and in a specific interleukin environment. Not only are Th1 and Th2 cells involved in the development of AITD, but also Th17, Th22, and Th9 lymphocytes and their correlation to Tregs lymphocytes. The plasticity of the CD4+ cells is very important, affecting the balance between these cells, as well the factors modulating their phenotypic variability. Patients with AITD have an increased percentage of Th17, Th22, and Th9 cells as well as defective function of Tregs lymphocytes. The balance between Th17 cells (and also other cytotoxic T cells) and Treg cells is also very important. Understanding the role of CD4 cells in the pathogenesis of AITD may be important not only for the development of the knowledge, but also for determining therapeutic targets.

Bilateral testicular infarction as a complication of acute cardiovascular diseases.

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Recurrent tetany in the course of metabolic alkalosis in patient with short bowel syndrome.

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Assessing the blood concentration of new adipocytokines in patients with ischaemic stroke.

INTRODUCTION: Ischaemic stroke (IS) is a disease that is a common cause of death and one of the most common causes of disability in adults. There is a continuous need to conduct stroke pathogenesis studies. A certain role here can be attributed to adipose-derived hormones. The aim of this paper is to assess the blood concentration for selected adipocytokines: omentin-1, irisin, protein-1 related with C1q/TNF (CTRP1), vaspin and nesfatin-1 in IS patients, and an attempt to define their role as risk factors for ischaemic stroke. MATERIAL AND METHODS: The study included 46 patients with ischaemic stroke (27 females, 19 males, average 67.6 years of age). The control group consisted of 32 patients (16 females, 16 males, average 64.1 years of age) who had never had cerebrovascular diseases. RESULTS: The concentration of omentin-1 and CTRP1 in the group of stroke patients was higher than in the control group, whereas the concentrations of nesfatin-1 and irisin was significantly lower than in the control group. The vaspin level was similar in both groups of patients. Statistical analysis using logistic regression allows us to find that CTRP1 can be a significant stroke risk factor. A statistically significant positive correlation was found between the concentration of CTRP1 and NIHSS. However, no correlation between the concentration of other adipocytokines under investigation and the severity of ischaemic stroke was found. CONCLUSIONS: From among the adipocytokines under investigation, higher concentrations of omentin-1 and CTRP1 and lower blood concentrations of nesfatin-1, irisin significantly increase the odds of getting to the group of ischaemic patients. It seems that CTRP1 can be an independent predictive factor of IS.

Therapeutic effect of presurgical treatment with longacting octreotide (Sandostatin® LAR®) in patients with acromegaly.

INTRODUCTION: The aim of this study was to assess the therapeutic effect and the safety of pre-surgical treatment with long-acting octreotide in patients with acromegaly. MATERIAL AND METHODS: This project was conducted in 25 centres across Poland as a non-interventional, multicentre, observational study in patients with acromegaly, in which long-acting octreotide Sandostatin® LAR®) was administered before surgery. They were 148 patients included into the study: 88 females and 60 males aged 18-86 years (51.3 ± 13.4). RESULTS: Eighty patients completed the study (underwent tumour surgery). The CRF included: baseline visit, four follow-up visits every three months before surgery, and two follow-up visits every three months after surgery. Sandostatin® LAR® was administered every four weeks. The efficacy measures were as follows: change of growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels, number of patients fulfilling criteria of cure, and change of adenoma (micro- and macroadenomas) size during the treatment. Normalisation of GH and IGF-1 concentrations were obtained in 42.4 and 49.1% of patients at the end of medical therapy, respectively. Normalisation of GH and IGF-1 concentrations were obtained in 77.9 and 83.8% of patients after surgery, respectively. Reduction of microadenoma size was documented in 58.8% of patients, and in 70% of patients with macroadenomas at the end of medical therapy. In 74.0% of patients no pituitary tumour was shown on MRI after surgery. CONCLUSION: We have shown good surgical outcome in patients with acromegaly after pre-treatment with somatostatin analogue, and good tolerance and safety of the therapy, supporting the national recommendation for pre-surgical treatment with long-acting somatostatin analogues in acromegaly patients.

Can Hashimoto's thyroiditis cause vertigo? [Czy choroba Hashimoto moze byc przyczyna zawrotów glowy?].

Vertigo and balance disorders are common symptoms reported by approximately 15-20% of the adult population worldwide. For many years thyroid diseases have been suspected as the cause of vertigo by ENT physicians. Almost every patient hospitalised due to severe vertigo is investigated for thyroid disease as a suspected cause of acute vestibulopathy. The issue presented in this paper is related to a difficult and poorly understood relationship between autoimmune thyroid disease and peripheral vertigo.

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.