Graves’ orbitopathy (GO) is an autoimmune condition, which is associated with poor clinical outcomes including impaired quality of life and socio-economic status. Current evidence suggests that the incidence of GO in Europe may be declining, however data on the prevalence of this disease are sparse. Several clinical variants of GO exist, including euthyroid GO, recently listed as a rare disease in Europe (ORPHA466682). The objective was to estimate the prevalence of GO and its clinical variants in Europe, based on available literature, and to consider whether they may potentially qualify as rare. Recent published data on the incidence of GO and Graves’ hyperthyroidism in Europe were used to estimate the prevalence of GO. The position statement was developed by a series of reviews of drafts and electronic discussions by members of the European Group on Graves’ Orbitopathy. The prevalence of GO in Europe is about 10/10,000 persons. The prevalence of other clinical variants is also low: hypothyroid GO 0.02–1.10/10,000; GO associated with dermopathy 0.15/10,000; GO associated with acropachy 0.03/10,000; asymmetrical GO 1.00–5.00/10,000; unilateral GO 0.50–1.50/10,000. GO has a prevalence that is clearly above the threshold for rarity in Europe. However, each of its clinical variants have a low prevalence and could potentially qualify for being considered as a rare condition, providing that future research establishes that they have a distinct pathophysiology. EUGOGO considers this area of academic activity a priority.

Background Limited data suggest that treatment with statins is associated with a reduced risk of Graves’ orbitopathy (GO) in patients with Graves’ disease (GD), attributed to the anti-inflammatory rather than to the hypolipemic effects of these medications. The aim of the present study was to investigate whether there is an association between high cholesterol and GO. The primary outcome was the relation between GO and low-density lipoprotein (LDL)-cholesterol. The secondary outcomes were the relation between severity or activity [the clinical activity score (CAS)] of GO and LDL-cholesterol. Methods We conducted a cross-sectional investigation in consecutive patients with GD who came to our observation to undergo radioiodine treatment, a stratification aimed at forming two distinct groups of patients under the same conditions. We enrolled 250 patients, 133 with and 117 without GO. Ophthalmological assessments and serum lipids measurements were performed. Results In multivariate analyses with correction for the duration of hyperthyroidism, a variable that differed between patients with respect to the presence or absence of GO, a correlation between the presence of GO and both total (P=0.01) and LDL-cholesterol (P=0.02) was observed. In patients with hyperthyroidism lasting <44 months, total and LDL-cholesterol were higher (P=0.01 and P=0.008, respectively) among GO patients. In this subgroup, based on the presence/absence of GO, we established cut-off values for total (191 mg/dl) and LDL-cholesterol (118.4 mg/dl), above which an increased risk of GO was observed (total cholesterol RR: 1.47; P=0.03; LDL-cholesterol RR: 1.28; P=0.03). GO severity and CAS did not correlate with serum lipids. However, CAS was found to be higher (P=0.02) in patients with high total cholesterol. When the analysis was restricted to untreated GO patients, we found a correlation between CAS and both total (P=0.04) and LDL-cholesterol (P=0.03), after adjustment for GO duration. Conclusions In patients with a short duration of hyperthyroidism, total and LDL-cholesterol correlate with the presence of GO, suggesting a role of cholesterol in the development of GO. Depending on GO duration, total and LDL-cholesterol correlate with GO activity, suggesting a role of cholesterol in the clinical expression of GO.

Background: According to Rundle's curve, Graves' ophthalmopathy (GO) worsens during an initial phase up to a peak of maximum severity, then improves and reaches a static plateau, with the activity curve preceding the severity curve by a few months. To our knowledge, no studies have tried to replicate Rundle's curve, and very few have investigated the natural history of GO. Here, we studied GO natural history retrospectively and tried to identify factors that may affect it. Methods: A total of 65 patients with untreated GO underwent an eye assessment after a median of seven months after the appearance of GO and then after a median of 40 months. The primary endpoints were the variation of the single GO features and of the NOSPECS score, as well as the overall outcome of GO. The secondary endpoint was the influence of several variables (age, sex, smoking, GO and thyroid disease duration, thyroid treatment, thyroid status, thyroid volume, anti-TSH receptor autoantibodies) on the outcome of GO. Results: The majority of patients had mild, minimally active GO, and only five had a Clinical Activity Score (CAS) >3. There was a significant reduction of CAS ( p 3 at first observation were excluded. At the last observation, 50.8% of patients had improved, 33.8% had remained stable, and 15.4% had worsened moderately or substantially. The overall outcome of GO was not affected by any of the variables under examination. Conclusions: In confirmation of Rundle's observations, untreated GO improves spontaneously with time in the majority of patients, with an activity peak between 13 and 24 months, which may have implications in determining the proper timing of GO treatments.