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Summary Introduction: Some extrathyroidal cervical cystic lesions can be treated in selected situations by minimally invasive, low-risk method – ultrasound--guided percutaneous ethanol injection therapy (US-PEIT). Here we present 6 cases of neck cysts of various origins – ranula, thyroglossal duct cyst, branchial cleft cyst, midline neck cyst of the pyramidal lobe and dermoid cyst. Method and material: The cohort consisted of 6 patients (mean age 58 ± 13.3 years), who were followed for recurrent cervical cysts located outside the thyroid gland. The cysts were visible, palpable, aesthetically unpleasant and also mechanically compressing the surrounding tissue. After repeated evacuations, they filled in again. The patients repeatedly refused the recommended surgery and demanded an alternative solution. US-PEIT of thyroid cysts is used worldwide as a full-fledged alternative to surgical treatment. We used the same procedure for the treatment of presented neck cysts. Results: The initial volume of cysts was 2–35 mL (mean 17.7 mL); the patients underwent 1–6 sclerotization sessions (mean 3.6). The patients were followed for 12 months; the final volume of solid residue was 0.1–2 mL (mean 1 mL) representing volume reduction by 80–99% (mean 92%). Therapeutic success (volume reduction > 50%) was achieved in all patients. Conclusion: US-PEIT of cervical cysts as an alternative to surgery can be used especially in elderly patients with increased surgical risk or in patients refusing surgery. In middle-aged and older adults, the possibility of a necrotic metastatic lymph node should always be considered. Therefore, a benign cytological examination and an unsuspecting ultrasonographic and CT finding are the basic conditions before performing the ethanol ablation. Key words neck cysts – ultrasound-guided percutaneous ethanol injection therapy

Graves’ orbitopathy (GO) is a serious, progressive eye condition seen in patients with autoimmune thyroid disease. GO is characterized by inflammation and swelling of soft orbital tissues. Adipose tissue produces cytokine mediators called adipokines. The present study focuses on the relationship between serum levels of selected adipokines in patients with GO, comparing them with the control group, and uniquely describes the effect of high-dose systemic corticosteroids (HDSC) on their levels. For the purposes of this study, we collected blood samples before and after the treatment with HDSC from 60 GO patients and 34 control subjects and measured serum levels of adiponectin, AIF-1, A-FABP and FGF-21. Levels of adiponectin significantly differed among the three study groups (ANOVA p = 0.03). AIF-1 levels were also significantly different among the study groups (ANOVA p

Our review summarizes the possible differential diagnoses of hypoglycemia. It confirms the absolute necessity of fulfilling all the three Whipple hypoglycemia criteria. Briefly is mentioned Clinical symptoms of hypoglycemia are briefly mentioned and several ways to classify the hypoglycemic events are offered. Highlighted is the recommended approach to distinguish patients as seemingly ill and healthy and also as hypoglycemia occurring in diabetic and non-diabetic. All the classifications and recommendations are summarized in attached tables and schemes.

Background: Adiponectin, adipocyte fatty acid-binding protein (A-FABP), and fibroblast growth factor-19 (FGF-19) belong to proteins involved in glucose metabolism regulation. The aims of the study were to compare the plasma levels of these proteins in women with early diagnosed gestational diabetes mellitus (GDM) to those in healthy controls and to investigate their changes during pregnancy after early intervention. Methods: The study was undertaken as a case-control study. Early GDM diagnosis was based on repeated fasting plasma glucose ≥5.1 and

Adiponectin, adipocyte fatty acid-binding protein (A-FABP), and fibroblast growth factor-19 (FGF-19) belong to proteins involved in glucose metabolism regulation. The aims of the study were to compare the plasma levels of these proteins in women with early diagnosed gestational diabetes mellitus (GDM) to those in healthy controls and to investigate their changes during pregnancy after early intervention.The study was undertaken as a case-control study. Early GDM diagnosis was based on repeated fasting plasma glucose ≥5.1 andlt;7.0 mmol/L during the first trimester of pregnancy and exclusion of overt diabetes. Age-matched controls comprised healthy pregnant and non-pregnant women. In addition to adipokines, clinical parameters and measures of glucose control were assessed.Women with GDM (Women with GDM showed altered adipokine production even in the first trimester of pregnancy. Early therapeutic intervention not only improved glucose control but also normalized impaired adipokine production.

To compare circulating pigment epithelium derived factor (PEDF) levels in type 2 diabetes patients (T2D) with and without metabolic syndrome (MetS+/-) to healthy controls and assess PEDF association with plasminogen activator inhibitor-1 (PAI-1) and von Willebrand factor (vWF) as markers of endothelial dysfunction. Fifty T2D individuals and forty healthy controls were included. PEDF, PAI-1, vWF, anthropological parameters, lipids, and markers of insulin resistance were investigated in all subjects. Compared to controls only MetS+ diabetics had higher PEDF levels [14.2 (10.2-16.0) mg/l vs. 11.1 (8.6-14.4) mg/l; p

Background and aim Diabetes mellitus is a very common metabolic disease with a rising incidence. It is one of the most serious comorbidities in renal transplant recipients. New-onset diabetes after renal transplantation (NODAT) is associated with poor graft function, higher rates of cardiovascular complications and a poor prognosis. Adipocytokines, synthetized by adipose tissue influence metabolic pathways and disorders in various ways. In this review article, we chose the most researched adipocytokines and evaluated their relationship to posttransplant diabetes mellitus. The aim of this paper is to summarize current knowledge and discuss their perspective role in diagnostics or therapy of the new onset diabetes mellitus after transplantation.

In this study we compared levels of selected adipokines between patients with type 2 diabetes (T2D) and healthy individuals and we determined their relationship with early vascular damage markers.Seventy-seven subjects: 56 patients with T2D (34 men and 22 women) and 21 healthy controls (8 men and 13 women) were examined in this cross-sectional study. Selected adipokines [adiponectin, adipocyte fatty acid-binding protein (A-FABP), fibroblast growth factor 21 (FGF-21), C1q/TNF-related protein 9 (CTRP-9), and allograft inflammatory factor-1 (AIF-1)] with possible cardiovascular impact were measured in all participants. To identify markers of vascular damage von Willebrand factor (vWF), plasminogen activator inhibitor-1 (PAI-1) and arterial stiffness parameters were examined in all the subjects.When compared with healthy controls, T2D had significantly higher levels of A-FABP [50.0 (38.1-68.6) vs. 28.6 (23.6-32.9) ng/mL, P 0.0001] and lower levels of adiponectin [5.9 (4.3-9.0) vs. 11.3 (8.7-14.8) μg/mL, P 0.0001]. Differences in other adipokines were not statistically significant. Adiponectin level correlated negatively with vWF levels (ρ = -0.29, P 0.05) and PAI-1 (ρ = -0.36, P 0.05) and A-FABP positively with vWF (ρ = 0.61, P 0.05) and PAI-1 (ρ = 0.47, P 0.05) and augmentation index (ρ = 0.26, P 0.05). Multivariate regression analysis showed independent association between A-FABP and vWF (b = 0.24, P 0.05).Patients with T2D have significantly higher levels of A-FABP and lower levels of adiponectin. These adipokines correlate with indicators of vascular damage and could contribute to cardiovascular risk in patients with T2D. A-FABP may participate in direct endothelium damage.

Endokrinni nebo take Graves-Basedowova orbitopatie (EO) je zavažna, progresivni ocni komplikace asociovana s autoimunitnim onemocněnim stitne žlazy. Typickými přiznaky jsou retrakce horniho vicka, periorbitalni edem, porucha pohyblivosti ocniho bulbu, diplopie, zanětlivý otok měkkých tkani orbity vedouci k protruzi oka a ve važnějsich připadech až ztrata zraku v důsledku utlaku zrakoveho nervu ci poskozeni rohovky. Standardem lecby je kortikoterapie, podani per os je limitovano nežadoucimi ucinky, proto je upřednostňovano podani v podobě intravenozniho pulzu. V roce 2016 bylo vydano jednotne doporuceni European Thyroid Association a European Group on Graves´ Orbithopaty (EUGOGO) pro endokrinni orbitopatii a take doporuceni American Thyroid Association pro lecbu hypertyreozy, ktere zahrnuje lecbu EO.

Cardiovascular (CV) disease is the primary cause of death in diabetic patients and one of the explanations may be increased arterial stiffness. Arterial stiffness assessment using pulse wave analysis, is a predictive factor of CV events. The aim of this paper is to review the current knowledge of relations between diabetes mellitus and pulse wave analysis. A MEDLINE search was performed to retrieve both original and review articles addressing the relations and influences on arterial stiffness in diabetics. Pulse wave analysis is considered as a gold standard in CV risk evaluation for patients at risk, especially diabetics. Arterial stiffness assessment may be helpful for choosing more aggressive diagnostic and therapeutic strategies, particularly in younger patients to reduce the incidence of CV disease in these patients.

Backgrounds: Adiponectin, adipocyte-fatty acid binding protein (A-FABP), and Wnt1 inducible signaling pathway protein-1 (WISP-1) are adipokines closely associated with insulin resistance. The aim of the study was to compare their levels in women with gestational diabetes (GDM), type 2 diabetes mellitus (T2DM) and healthy controls and determine their relation to metabolic parameters. Methods: Women with GDM, T2DM and healthy women were included in this cross-sectional study. In addition to adipokines, anthropometric, lipid parameters, markers of insulin resistance and glucose control were assessed in all participants. Results: Compared to healthy controls (n = 35) significantly lower levels of adiponectin were detected in women with GDM (n = 50), whereas in women with T2DM (n = 50) higher levels of A-FABP and WISP-1 and lower levels of adiponectin were found. Women with T2DM had also lower levels of adiponectin and higher levels of A-FABP compared to women with GDM. A-FABP and adiponectin were independently associated with levels of triglycerides, HDL-cholesterol and C-peptide insulin resistance index. WISP-1 correlated only with waist circumference. Conclusions: Adverse adipokines production reflecting dysfunctional fat tissue is less presented in women with GDM than in women with T2DM, but more expressed compared to healthy women.

Graves orbitopathy (GO) is an extrathyroidal manifestation of autoimmune thyroid disease. Early treatment with glucocorticoids in appropriately selected patients is recommended for active, moderate to severe, and sight-threatening disease. The recently published European Group on Graves Orbitopathy guidelines re-evaluated the recommended doses of intravenous methylprednisolone (ivMP) in response to the potential for adverse effects. We retrospectively reviewed our patient cohort treated with our ivMP protocol and analyzed the side effects of this treatment when given during hospitalization in our tertiary referral center.Between May 2007 and May 2017, a total of 171 consecutive patients with active, moderate to severe, or sight-threatening GO were treated with ivMP in a cumulative dose of 7.5 grams, given monthly in three hospital sessions. Adverse events were reported using Version 4 of Common Terminology Criteria for Adverse Events.Ninety-two percent of patients who started the treatment were able to finish it; 5% did not finish the study due to adverse events, and 3% did not finish the treatment protocol because of noncompliance. The most common adverse events were asymptomatic changes in laboratory values (liver enzymes), psychiatric disorders, and infectious complications. None of the patients in the study died during the ivMP treatment, including those patients who experienced adverse effects or discontinued the protocol because of noncompliance.High-dose ivMP for active, moderate to severe, and sight-threatening GO, when applied cautiously in carefully selected and monitored patients, is generally safe during the treatment period.AE = adverse effect; CAS = clinical activity score; CTCAE = Common Terminology Criteria for Adverse Events; DM = diabetes mellitus; EUGOGO = European Group on Graves Orbitopathy; GC = glucocorticoid; GO = Graves orbitopathy; ivMP = intravenous methylprednisolone.

INTRODUCTION: Thyroid tissue ectopically located in the ovary can be reported accidentally after adnexectomy, but as a primary cause of hyperthyroidism this diagnosis is rare. The clinical search for a functional ectopic thyroid tissue requires intense clinical focus and a multidisciplinary approach. CASE DESCRIPTION: This case report demonstrates a patient with a history of Graves’ disease who had undergone thyroidectomy combined with postoperative (131)I radioablation. Despite the previous treatment, she developed an outburst of hyperthyroidism ten years later. Only very close follow-up enabled us to disclose the right condition. The ovarian source of thyroid hormone production was removed by laparoscopic adnexectomy and a right sided benign ovarian struma was confirmed. CONCLUSION: Most patients treated by thyroidectomy and radioiodine do not require extended periods of follow-up or postoperative investigations, but when the clinical or laboratory signs change, clinicians should be prepared to perform the necessary re-evaluation in order to provide the best care.

Background and Aims: Interest in growth hormone (GH) is inextricably linked to the need for in depth understanding of the somatomedins (insulin-like growth factors) which are polypeptides structurally similar to insulin and with broad physiological activity. To date, the most commonly known is Insulin-Like Growth Factor I (IGF-I). Despite considerable current knowledge of IGF-I, however, its bioactivity is incompletely understood. Measurement of IGF-I is of the utmost importance in the diagnosis and treatment of, for example acromegaly and growth hormone deficiency. The development of recombinant IGF-I, has allowed its use in such cases. Clinical practice, however, shows that few young/adult patients will benefit from treatment with the rIGF-I, mecasermin, given the number of adverse effects found. This review focuses on current knowledge mainly related to IGF-I and the use of its recombinant form (rIGF-I) in clinical practice. Several functions of IGI-II have been elucidated but their clinical significance is unclear.

Currently, there are no reliably effective therapeutic options for metastatic pheochromocytoma (PCC) and paraganglioma. Moreover, there are no therapies that may prevent the onset or progression of tumors in patients with succinate dehydrogenase type B mutations, which are associated with very aggressive tumors. Therefore, we tested the approved and well-tolerated drugs lovastatin and 13-cis-retinoic acid (13cRA) in vitro in an aggressive PCC mouse cell line, mouse tumor tissue-derived (MTT) cells, and in vivo in a PCC allograft nude mouse model, in therapeutically relevant doses. Treatment was started 24 hours before sc tumor cell injection and continued for 30 more days. Tumor sizes were measured from outside by caliper and sizes of viable tumor mass by bioluminescence imaging. Lovastatin showed antiproliferative effects in vitro and led to significantly smaller tumor sizes in vivo compared with vehicle treatment. 13cRA promoted tumor cell growth in vitro and led to significantly larger viable tumor mass and significantly faster increase of viable tumor mass in vivo over time compared with vehicle, lovastatin, and combination treatment. However, when combined with lovastatin, 13cRA enhanced the antiproliferative effect of lovastatin in vivo. The combination-treated mice showed slowest tumor growth of all groups with significantly slower tumor growth compared with the vehicle-treated mice and significantly smaller tumor sizes. Moreover, the combination-treated group displayed the smallest size of viable tumor mass and the slowest increase in viable tumor mass over time of all groups, with a significant difference compared with the vehicle- and 13cRA-treated group. The combination-treated tumors showed highest extent of necrosis, lowest median microvessel density and highest expression of α-smooth muscle actin. The combination of high microvessel density and low α-smooth muscle actin is a predictor of poor prognosis in other tumor entities. Therefore, this drug combination may be a well-tolerated novel therapeutic or preventive option for malignant PCC.

// Ying Pang 1 , Chunzhang Yang 2 , Jan Schovanek 3 , Herui Wang 4 , Petra Bullova 5 , Veronika Caisova 1 , Garima Gupta 1 , Katherine I. Wolf 1 , Gregg L. Semenza 6 , Zhengping Zhuang 4 and Karel Pacak 1 1 Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA 2 Neuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA 3 Department of Internal Medicine III-Nephrology, Rheumatology, and Endocrinology, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic 4 Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA 5 Department of Molecular Medicine, Institute of Virology, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovak Republic 6 McKusick-Nathans Institute of Genetic Medicine and Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA Correspondence to: Karel Pacak, email: // Keywords : anthracyclines, paraganglioma, pheochromocytoma, metastatic, hypoxia-inducible factors Received : January 13, 2017 Accepted : March 03, 2017 Published : March 15, 2017 Abstract Pheochromocytomas (PHEOs) and paragangliomas (PGLs) are rare, neuroendocrine tumors derived from adrenal or extra-adrenal chromaffin cells, respectively. Metastases are discovered in 3-36% of patients at the time of diagnosis. Currently, only suboptimal treatment options exist. Therefore, new therapeutic compounds targeting metastatic PHEOs/PGLs are urgently needed. Here, we investigated if anthracyclines were able to suppress the progression of metastatic PHEO. We explored their effects on experimental mouse PHEO tumor cells using in vitro and in vivo models, and demonstrated that anthracyclines, particularly idarubicin (IDA), suppressed hypoxia signaling by preventing the binding of hypoxia-inducible factor 1 and 2 (HIF-1 and HIF-2) to the hypoxia response element (HRE) sites on DNA. This resulted in reduced transcriptional activation of HIF target genes, including erythropoietin ( EPO ), phosphoglycerate kinase 1 ( PGK1 ), endothelin 1 ( EDN1 ), glucose transporter 1 ( GLUT1 ), lactate dehydrogenase A ( LDHA ), and vascular endothelial growth factor ( VEGFA ), which consequently inhibited the growth of metastatic PHEO. Additionally, IDA downregulated hypoxia signaling by interfering with the transcriptional activation of HIF1A and HIF2A . Furthermore, our animal model demonstrated the dose-dependent suppressive effect of IDA on metastatic PHEO growth in vivo . Our results indicate that anthracyclines are prospective candidates for inclusion in metastatic PHEO/PGL therapy, especially in patients with gene mutations involved in the hypoxia signaling pathway.

Introduction: Glucocorticoids represent the therapy of choice for active and moderate-to-severe Graves' orbitopathy (GO). In some patients, rituximab, a monoclonal antibody against the cluster of differentiation (CD) 20 receptor of B-lymphocytes, can serve as a second-line or an alternative treatment. The effect of very low-dose of rituximab on the clinical activity of GO and corresponding clinical or laboratory changes is reported. Material and methods: Changes of Clinical Activity Score (CAS) for GO, proptosis, levels of thyroid-stimulating hormone receptor antibodies, and depletion of CD19+ and CD20+ B-lymphocytes were determined in ten patients (two men and eight women) with active moderate-to-severe GO treated with a single 100-mg dose of rituximab. Correlations between differences of clinical and laboratory parameters were performed. Results: A significant decrease of CAS was found during subsequent examinations compared to the baseline values. A significant depletion of CD19+ and CD20+ B-lymphocytes was detected after rituximab administration. Differences between follow-up and baseline levels of CD20+ positively correlated with differences in CAS after six (p < 0.05) and 12 months (p < 0.01). Differences in CD19+ levels correlated with differences in CAS after 12 months (p < 0.05) of the treatment. Two patients developed dysthyroid optic neuropathy (DON) requiring orbital decompression. No other rituximab side effects were reported during the whole study duration. Conclusions: A single very low-dose of rituximab appears to be very well tolerated and effective enough to reduce clinical activity in active moderate-to-severe GO patients without impending DON.

Percutaneous Ethanol Injection Therapy (PEIT) of parathyroid adenoma under ultrasound guidance is individually used as an alternative procedure in management of primary hyperparathyroidism in polymorbid elderly patients with increased surgical risk. The treatment is also suitable for patients who already underwent surgery of the thyroid gland, and any other surgery is associated with a higher risk of postsurgical complications. We present a case of a 92-year-old male patient, who underwent thyroidectomy for papillary thyroid carcinoma three years ago. Part of the regular annual follow-up visits was also ultrasonography, which showed a solitary parathyroid adenoma at the site of the removed thyroid gland. Given the underlying condition, polymorbidity and age of the patient, the PEIT method was successfully used in the therapy. The coincidence of adenoma and papillary thyroid carcinoma is also interesting.

Metastatic pheochromocytoma continues to be an incurable disease, and treatment with conventional cytotoxic chemotherapy offers limited efficacy. In the present study, we evaluated a novel topoisomerase I inhibitor, LMP-400, as a potential treatment for this devastating disease. We found a high expression of topoisomerase I in human metastatic pheochromocytoma, providing a basis for the evaluation of a topoisomerase 1 inhibitor as a therapeutic strategy. LMP-400 inhibited the cell growth of established mouse pheochromocytoma cell lines and primary human tumor tissue cultures. In a study performed in athymic female mice, LMP-400 demonstrated a significant inhibitory effect on tumor growth with two drug administration regimens. Furthermore, low doses of LMP-400 decreased the protein levels of hypoxia-inducible factor 1 (HIF-1α), one of a family of factors studied as potential metastatic drivers in these tumors. The HIF-1α decrease resulted in changes in the mRNA levels of HIF-1 transcriptional targets. In vitro, LMP-400 showed an increase in the growth-inhibitory effects in combination with other chemotherapeutic drugs that are currently used for the treatment of pheochromocytoma. We conclude that LMP-400 has promising antitumor activity in preclinical models of metastatic pheochromocytoma and its use should be considered in future clinical trials.

Drug repurposing or repositioning is an important part of drug discovery that has been growing in the last few years for the development of therapeutic options in oncology. We applied this paradigm in a screening of a library of about 3,800 compounds (including FDA-approved drugs and pharmacologically active compounds) employing a model of metastatic pheochromocytoma, the most common tumor of the adrenal medulla in children and adults. The collection of approved drugs was screened in quantitative mode, testing the compounds in compound-titration series (dose-response curves). Analysis of the dose-response screening data facilitated the selection of 50 molecules with potential bioactivity in pheochromocytoma cells. These drugs were classified based on molecular/cellular targets and signaling pathways affected, and selected drugs were further validated in a proliferation assay and by flow cytometric cell death analysis. Using meta-analysis information from molecular targets of the top drugs identified by our screening with gene expression data from human and murine microarrays, we identified potential drugs to be used as single drugs or in combination. An example of a combination with a synergistic effect is presented. Our study exemplifies a promising model to identify potential drugs from a group of clinically approved compounds that can more rapidly be implemented into clinical trials in patients with metastatic pheochromocytoma or paraganglioma.

Background Succinate dehydrogenase subunit B (SDHB) mutations are associated with aggressive pheochromocytoma (PHEO)/paraganglioma (PGL) behavior, often resulting in metastatic disease and fatal outcomes. These tumors are often larger, extra-adrenal, and contain lower catecholamine concentrations than other hereditary PHEOs/PGLs. This study evaluated the size and age at diagnosis of primary SDHB-related PHEOs/PGLs as independent predictors of their metastatic behavior and outcome (survival). Methods One hundred six patients with SDHB mutation-related PHEO/PGL were included in this retrospective study. The recorded largest diameters, locations, and patient ages at initial diagnosis of SDHB-related primary tumors were analyzed in the context of time to metastasis and patient survival. Results First, the development of metastatic disease in patients with primary tumors ≥4.5 cm was significantly earlier than in patients with smaller tumors (P = 0.003). Second, patients with primary tumors larger than 5.5 cm also had worse overall survival than patients with smaller tumors (P = 0.008). Third, age at initial diagnosis was found to be an independent predictor of patient survival (PHEOs: P = 0.041; PGLs: P

Several guidelines often exist on the same topic, sometimes offering divergent recommendations. For the clinician, it can be difficult to understand the reasons for this divergence and how to select the right recommendations. The aim of this study is to compare different guidelines on the management of atrial fibrillation (AF), and provide practical and affordable advice on its management in the acute setting. A PubMed search was performed in May 2014 to identify the three most recent and cited published guidelines on AF. During the 1-week school of the European School of Internal Medicine, the attending residents were divided in five working groups. The three selected guidelines were compared with five specific questions. The guidelines identified were: the European Society of Cardiology guidelines on AF, the Canadian guidelines on emergency department management of AF, and the American Heart Association guidelines on AF. Twenty-one relevant sub-questions were identified. For five of these, there was no agreement between guidelines; for three, there was partial agreement; for three data were not available (issue not covered by one of the guidelines), while for ten, there was complete agreement. Evidence on the management of AF in the acute setting is largely based on expert opinion rather than clinical trials. While there is broad agreement on the management of the haemodynamically unstable patient and the use of drugs for rate-control strategy, there is less agreement on drug therapy for rhythm control and no agreement on several other topics.