High Serum Cholesterol Is a Novel Risk Factor for Graves' Orbitopathy: Results of a Cross-Sectional Study.

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: A cross-sectional investigation was conducted in consecutive patients with GD who came under the authors' observation to undergo radioiodine treatment, a stratification aimed at forming two distinct groups of patients under the same conditions. A total of 250 patients were enrolled, 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, cutoff values were established for total (191 mg/dL) and LDL-cholesterol (118.4 mg/dL), above which an increased risk of GO was observed (total cholesterol relative risk: 1.47; p = 0.03; LDL-cholesterol relative risk: 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, a correlation was found 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.

Natural history of graves' orbitopathy after treatment.

Intravenous glucocorticoids are used for Graves' orbitopathy, alone or associated with/followed by additional treatments (orbital radiotherapy, orbital decompression, palpebral or eye surgery). However, the relation between associated/additional treatments and other variables with Graves' orbitopathy outcome following intravenous glucocorticoids is not clear. Thus, the present study was conducted to investigate retrospectively the impact of associated/additional treatments and other variables on Graves' orbitopathy outcome after intravenous glucocorticoids. We evaluated 226 untreated Graves' orbitopathy patients. Following first observation, patients were given intravenous glucocorticoids and re-examined after a median of 46.5 months. The end-points were the relation between Graves' orbitopathy outcome, outcome of NOSPECS score and of the single Graves' orbitopathy features with several variables, including associated/additional treatments. All Graves' orbitopathy features improved significantly after treatment. Overall, Graves' orbitopathy improved in ~60 % of patients (responders), whereas it was stable or worsened in ~40 % of patients (non-responders). Time between first and last observation and clinical activity score at first observation correlated significantly with Graves' orbitopathy outcome. The outcomes of NOSPECS, eyelid aperture, clinical activity score and diplopia correlated with time between the first and last observation. The NOSPECS outcome correlated with gender. The outcomes of proptosis, eyelid aperture and visual acuity correlated with orbital decompression. The outcome of diplopia correlated with orbital radiotherapy. Taking into account the limitations of retrospective investigations, our findings confirm that time (i.e. the natural history of Graves' orbitopathy) is a key factor in determining the long-term outcome of Graves' orbitopathy, radiotherapy is effective for diplopia, and orbital decompression is followed by an amelioration of several Graves' orbitopathy features.

VARIABLES AFFECTING THE LONG-TERM OUTCOME OF GRAVES ORBITOPATHY FOLLOWING HIGH-DOSE INTRAVENOUS GLUCOCORTICOID PULSE THERAPY IN PATIENTS NOT TREATED WITH ORBITAL RADIOTHERAPY.

OBJECTIVE: Intravenous (iv) glucocorticoids (GC) (ivGC) are used for active Graves orbitopathy (GO), but factors affecting GO outcome are poorly understood. We performed a retrospective study to investigate the variables affecting GO after ivGC. METHODS: We evaluated 83 consecutive GO patients treated with ivGC but not orbital radiotherapy (ORT) and re-examined them after a median of 47 months. The endpoints were the relationships between GO outcome or additional treatments with age, sex, smoking habits, thyroid volume, thyroid treatment, time since thyroid treatment, antithyroid-stimulating hormone receptor antibodies (TRAb), GO duration, GO features, and follow-up time. RESULTS: GO features improved after treatment, resulting in moderate and marked amelioration in ~75% and ~41% of patients respectively. By multivariate analysis, a moderate GO improvement correlated with diplopia at first observation, which was more severe in responders. A marked GO improvement correlated with time between first and last observation and time after thyroid treatment, which were longer in responders. This likely reflected the combination of an early effect of GC and a late, spontaneous improvement of GO, as shown by analyses of GO outcome at various time points. Additional treatments after ivGC correlated by multivariate analysis with eyelid aperture, diplopia and NOSPECS score (NOSPECS stands for no GO signs [N], only eyelid sign [O], soft tissue involvement [S], proptosis [P], extraocular motility restriction [E], corneal involvement [C], and sight loss [S]) at first observation, which were more severe in responders. CONCLUSION: Our study shows that response to ivGC increases with time, likely reflecting the known tendency of GO to improve spontaneously, and is more pronounced when GO is more severe to begin with, which is associated with more additional treatments. ABBREVIATIONS: ANOVA = analysis of variance CAS = clinical activity score GC = glucocorticoids GO = Graves orbitopathy 131I = radioactive iodine iv = intravenous ivGC = high-dose intravenous glucocorticoid pulse therapy MMI = methimazole OD = orbital decompression ORT = orbital radiotherapy TRAb = antithyroid-stimulating hormone receptor antibodies.