Context Programmed cell death protein 1/ Programmed cell death protein ligand 1 (PD-1/PD-L1) pathway is a key regulator in T-cell activation and tolerance, limiting effector T-cell function in peripheral tissues. Atezolizumab, an anti-PD-L1, is approved for treatment of some types of advanced cancer. Its main treatment-related side effects are immune-related adverse events (IrAEs) such as thyroid dysfunction and hypophysitis. Autoimmune endocrinopathy can occur as isolated manifestations with only few cases of autoimmune polyendocrine syndromes so far reported. Case We report a case of polyendocrine syndrome type 2, characterized by Addison disease (AD), diabetes mellitus (T1DM) also accompanied by hypophysitis, in a patient treated with atezolizumab. 21-hydroxylase and pituitary antibodies were positive, islet cells antibodies were negative. HLA typing revealed DRB1*04 and DQB1*03 haplotypes, which is associated with increased susceptibility to T1DM and AD. Conclusion the type and severity of IrAEs are different and depend on the monoclonal antibody used. Although the numerous molecular mechanisms inducing autoimmune endocrine diseases are still unclear, a link exists between HLA haplotypes, gene variants involved in immune checkpoints molecules expression and increased susceptibility to autoimmune endocrinopathies. Further studies are needed to identify those susceptible subjects and to adapt therapy to each patient.

Graves' Orbitopathy (GO) is the most frequent extrathyroidal manifestation of Graves' disease (GD). Its ultimate cause remains unclear, but it is commonly considered an autoimmune disorder due to self recognition of autoantigens constitutively expressed by orbital fibroblasts (OFs), and thyroid epithelial cells. High dose intravenous glucocorticoids (ivGC) are the most commonly used treatment for moderately severe and active GO. However, based on the complex pathogenesis of GO, a number of factors may have a protective and maybe a therapeutic role. The use of other medications improving the effect of GC may increase the overall effectiveness of the therapy and reduce GC doses, thereby limiting side effects. Recently, a possible protective role of 3-hydroxy-3-methylglutaryl-coenzyme reductase inhibitors, the so-called statins, and perhaps of lowering cholesterol levels, has been proposed. Thus, statins have been reported to be associated with a reduced frequency of GO in GD patients and in recent cross-sectional and retrospective studies a significant correlation was found between the occurrence of GO and both total and LDL-cholesterol in patients with a GD of relatively recent onset, suggesting a role of cholesterol in the development of GO. Moreover, a correlation was found between the GO clinical activity score and total as well as LDL-cholesterol in untreated GO patients, depending on GO duration, indicating a role of cholesterol on GO activity. Therefore, statin treatment may be beneficial for GO. Here we review this subject, which offers new therapeutic perspectives for patients with GO.

Background Graves’ orbitopathy (GO) is subject to epidemiological and care-related changes. Aim of the survey was to identify trends in presentation of GO to the European Group On Graves’ Orbitopathy (EUGOGO) tertiary referral centres and initial management over time. Methods Prospective observational multicentre study. All new referrals with diagnosis of GO within September–December 2019 were included. Clinical and demographic characteristics, referral timelines and initial therapeutic decisions were recorded. Data were compared with a similar EUGOGO survey performed in 2012. Results Besides age (mean age: 50.5±13 years vs 47.7±14 years; p 0.007), demographic characteristics of 432 patients studied in 2019 were similar to those in 2012. In 2019, there was a decrease of severe cases (9.8% vs 14.9; p<0.001), but no significant change in proportion of active cases (41.3% vs 36.6%; p 0.217). After first diagnosis of GO, median referral time to an EUGOGO tertiary centre was shorter (2 (0–350) vs 6 (0–552) months; p<0.001) in 2019. At the time of first visit, more patients were already on antithyroid medications (80.2% vs 45.0%; p<0.001) or selenium (22.3% vs 3.0%; p<0.001). In 2019, the initial management plans for GO were similar to 2012, except for lid surgery (2.4% vs 13.9%; p<0.001) and prescription of selenium (28.5% vs 21.0%; p 0.027). Conclusion GO patients are referred to tertiary EUGOGO centres in a less severe stage of the disease than before. We speculate that this might be linked to a broader awareness of the disease and faster and adequate delivered treatment.