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 ciężkiej i aktywnej orbitopatii tarczycowej z uwzględnieniem zaleceń European Group on Graves’ Orbitopathy (EUGOGO)]

Sawicka-Gutaj N., Stańska A., Stański M., Gruszczyński D., Zawalna N., Pochylski M., Ruchała M.

Graves' disease (GD) and Graves' orbitopathy (GO) are multifactorial disorders with links to the gut microbiome and autoimmunity. It is observed that patients with GD exhibit altered gut microbiome diversity. However, little is known about the role of oral microbiota in GD and GO. This study aims to investigate the impact of oral health and oral sanitation on the clinical course of GO in patients disqualified from glucocorticoid treatment due to oral infections. We reviewed 188 admissions of 127 patients with GO, hospitalized in a tertiary university hospital. Clinical, biochemical, imaging, ophthalmological, and oral health assessment data from each admission were analyzed. Patients excluded from the glucocorticoids (GCs) therapy due to oral foci of infection had the clinical activity score (CAS) reassessed after three months, and they were divided into two groups: with and without improvement. Finishing dental treatment in the meantime was the only factor significantly correlated with improvement in these patients (p = 0.041). The secondary finding was that anti-thyroid peroxidase antibodies titer was significantly higher in the group with oral foci of infection considered as a contraindication for GCs (medians 28.50 vs 128.00; p = 0.026), and those patients were more likely to smoke than the group without oral issues (p = 0.024). The results of our study suggest that monitoring and treating oral diseases may be pertinent in patients with GO and might serve as a supportive treatment strategy for managing the condition. What is known: What is new:

Szybiak-Skora W., Cyna W., Lacka K.

Down syndrome develops due to the presence of supernumerary chromosome 21. This diagnosis is made in approximately 1:800 live births. The tendency to develop autoimmune disorders like idiopathic arthritis, celiac disease, diabetes mellitus type 1, vitiligo and autoimmune thyroid disease is strongly expressed in patients with Down syndrome. Autoimmune thyroid diseases consisting of Hashimoto’s thyroiditis and Graves’ disease are specifically prevalent in patients with Down syndrome. The aim of our study is to collect available data connecting the pathogenesis and clinical course of autoimmune thyroid diseases in patients with Down syndrome of different ages and compare them to control groups. According to published data, the incidence ratio of Hashimoto’s thyroiditis diagnosis in patients with Down syndrome is elevated compared to in age-matched controls without this chromosomal aberration, similarly to Graves’ disease risk, which is also increased in a group of patients with Down syndrome. What is more, both Hashimoto’s thyroiditis and Graves’ disease are diagnosed at an earlier age than in the healthy population and are not correlated with gender or a family history of autoimmune diseases.

Sawicka-Gutaj N., Gruszczyński D., Zawalna N., Nijakowski K., Skiba A., Pochylski M., Sowiński J., Ruchała M.

Abstract Background Graves’ orbitopathy (GO) is an autoimmune disorder of the orbit and retro-ocular tissues and the primary extrathyroidal manifestation of Graves’ disease. In moderate-to-severe and active GO iv glucocorticoids (GCs) are recommended as first-line treatment. The aim was to assess the safety profile of methylprednisolone administered intravenously for three consecutive days at 1 g in patients with active, moderate-to-severe or sight-threatening Graves’ orbitopathy. Methods We retrospectively evaluated 161 medical records of patients with GO treated with high-dose systemic GCs in the Department of Endocrinology, Metabolic Disorders, and Internal Medicine in Poznań between 2014 and 2021. Clinical data included age, gender, laboratory results, activity and severity of GO, smoking status, disease duration, and presented side effects. Results The presence of mild side effects was observed during 114 (71%) hospitalizations. The most common complications were hyperglycemia (n = 95) and elevated aminotransferases (n = 31). Increased levels of aminotransferases were more likely observed in smokers and GO duration above 12 months. Based on the multivariate logistic regression, higher TRAb and CAS values were significantly associated with lower odds of hyperglycemia. In turn, the increased odds of elevated aminotransferases were significantly correlated with higher initial ALT levels, female gender, and GO duration above 12 months. In addition, the multidimensional correspondence analysis (MPA) showed that GO patients who declared smoking and had not l-ornithine l-aspartate applied demonstrated a higher probability of elevated aminotransferases. Conclusions Active GO treatment with high-dose systemic GCs is not associated with serious side effects. Hyperglycemia is the most common steroid-induced complication.

Chichura K.S., Elfers C.T., Salameh T.S., Kamat V., Chepurny O.G., McGivney A., Milliken B.T., Holz G.G., Applebey S.V., Hayes M.R., Sweet I.R., Roth C.L., Doyle R.P.

AbstractMechanisms underlying long-term sustained weight loss and glycemic normalization after obesity surgery include changes in gut hormone levels, including glucagon-like peptide 1 (GLP-1) and peptide YY (PYY). We demonstrate that two peptide biased agonists (GEP44 and GEP12) of the GLP-1, neuropeptide Y1, and neuropeptide Y2 receptors (GLP-1R, Y1-R, and Y2-R, respectively) elicit Y1-R antagonist-controlled, GLP-1R-dependent stimulation of insulin secretion in both rat and human pancreatic islets, thus revealing the counteracting effects of Y1-R and GLP-1R agonism. These agonists also promote insulin-independent Y1-R-mediated glucose uptake in muscle tissue ex vivo and more profound reductions in food intake and body weight than liraglutide when administered to diet-induced obese rats. Our findings support a role for Y1-R signaling in glucoregulation and highlight the therapeutic potential of simultaneous receptor targeting to achieve long-term benefits for millions of patients.

Enders J., Elliott D., Wright D.

Significance: Diabetic peripheral neuropathy (DPN), a complication of metabolic syndrome, type I and type II diabetes, leads to sensory changes that include slow nerve conduction, nerve degeneration, loss of sensation, pain, and gate disturbances. These complications remain largely untreatable, although tight glycemic control can prevent neuropathy progression. Nonpharmacologic approaches remain the most impactful to date, but additional advances in treatment approaches are needed. Recent Advances: This review highlights several emerging interventions, including a focus on dietary interventions and physical activity, that continue to show promise for treating DPN. We provide an overview of our current understanding of how exercise can improve aspects of DPN. We also highlight new studies in which a ketogenic diet has been used as an intervention to prevent and reverse DPN. Critical Issues: Both exercise and consuming a ketogenic diet induce systemic and cellular changes that collectively improve complications associated with DPN. Both interventions may involve similar signaling pathways and benefits but also impact DPN through unique mechanisms. Future Directions: These lifestyle interventions are critically important as personalized medicine approaches will likely be needed to identify specific subsets of neuropathy symptoms and deficits in patients, and determine the most impactful treatment. Overall, these two interventions have the potential to provide meaningful relief for patients with DPN and provide new avenues to identify new therapeutic targets.

Olejarz M., Szczepanek-Parulska E., Ostałowska-Klockiewicz A., Antosik P., Sawicka-Gutaj N., Helak-Łapaj C., Stopa M., Ruchala M.

BackgroundThe aim of the study was to evaluate the differences in clinical profile, laboratory parameters, and ophthalmological signs, and symptoms between patients with high IgG4 Graves orbitopathy and patients with normal IgG4 Graves orbitopathy.MethodsThis was a prospective observational study. We recruited adult patients with Graves Orbitopathy(GO) referred to our clinic for further diagnostics and treatment. Eventually, 60 patients with GO were enrolled in the study. All patients underwent ophthalmological assessment, magnetic resonance imaging (MRI) of the orbits, and laboratory tests, including IgG4 serum concentration measurement. High IgG4 GO was diagnosed if the IgG4 concentration exceeded 135 mg/dl. We used both the clinical activity score (CAS) and magnetic resonance imaging (MRI) to assess the activity of GO. Eventually, active GO was defined according to MRI results.ResultsAmong 60 GO patients, 15 (25%) patients had elevated IgG4 levels. Patients in the high IgG4 group had a higher prevalence of active GO by MRI than patients with normal IgG4 (100% vs. 64.44%, P=0.006). They also had a higher eosinophile count in peripheral blood, a lower bilirubin level, a more frequent lower eyelid retraction, and a lower prevalence of glaucoma. There were no statistically significant differences between the groups in CAS. Patients with active GO, had higher median IgG4 level [89.95 (55.48; 171.1) vs 43.45 (32.48; 49.68) mg/dl, P<0.001]. The receiver operating characteristic (ROC) analysis for IgG4 as a marker of active GO revealed the following results: AUC 0.848 for the cut-off value of 54.2 mg/dl, sensitivity 79.5%, specificity 87.5%, positive predictive value 94.6%, negative predictive value 59.1%.ConclusionsWe demonstrated that IgG4 is a marker of GO activity. Certain differences in the clinical profile of patients with high IgG4 GO, and normal IgG4 GO were observed. More data is needed to establish whether patients with high IgG4 GO are GO patients with particularly active disease or actually represent a distinct clinical entity related to IgG4-Related Disease.