Relationship between serum cholesterol and Graves' orbitopathy (GO): a confirmatory study.

BACKGROUND: It has been suggested that high cholesterol represents a risk factor for Graves' orbitopathy (GO). In a recent cross-sectional study, a correlation between cholesterol and the presence of GO was found in patients with a Graves' disease (GD) of recent onset. To confirm this observation, we conducted a retrospective investigation in consecutive patients with GD. The primary outcome was the relationship between the presence of GO and low-density lipoprotein (LDL)-cholesterol. METHODS: The design entailed the inclusion of consecutive patients with a GD of recent onset, with or without GO, who came to our observation to receive radioiodine over a period of 6 months, and a stratification aimed at having two homogeneous group of patients in terms of thyroid function. A total of 86 patients fulfilled the inclusion and evaded the exclusion criteria. All patients underwent an ophthalmological assessment and serum lipids were measured. RESULTS: Serum levels of LDL-cholesterol were significantly higher in patients with GO (135.3 ± 41.3 mg/dL) compared with those without GO (106.6 ± 23.9 mg/dL, P = 0.0007). In a similar manner, serum levels of total cholesterol were higher in patients with GO (211.6 ± 44.0 mg/dL) than in those without GO (176.0 ± 27.2 mg/dL, P = 0.0001). There was no relationship between GO severity and activity and cholesterol. There was no relationship between GO and high-density lipoprotein-cholesterol or triglycerides. CONCLUSIONS: Our study confirms a relationship between the presence of GO and cholesterol in patients with GD of recent onset. Whether lowering of cholesterol ameliorates, GO remains to be established.

Statins are not a risk factor for liver damage associated with intravenous glucocorticoid pulse therapy for Graves' orbitopathy.

OBJECTIVE: Acute liver damage (ALD) is associated with high-dose intravenous (iv) glucocorticoid (GC) (ivGC) pulse therapy in ~1 % of patients for Graves' orbitopathy (GO). It has been proposed that statins may increase the risk of ALD. Here we investigated the frequency of ALD according to the assumption of statins in a large retrospective cohort study. METHODS: We studied 1076 consecutive patients with GO given ivGC. ALD was defined as an increase in alanine aminotransferase ≥300 U/l. RESULTS: At the time of ivGC, 62 patients were taking statins and 1014 were not. The frequency of ALD has been reported to be 1.2 cases/100,000 statins users and 1300/100,000 in GO patients given ivGC. Thus, the expected frequency of ALD in patients given both statins and ivGC is 1560/100,000. Transferring these data to our series, one would have expected at least 0.96 cases of ALD (~one case), in the 62 patients given both ivGC and statins. However, no cases of ALD were observed in patients given statins, and the previously reported 14 cases of ALD in this series were seen in patients who were not taking statins. CONCLUSIONS: The lack of observation of cases of ALD in patients given ivGC and statins is quite reassuring. Although caution should be applied to any patient candidate to ivGC treatment and this should be particularly accurate in patients given statins, our findings somehow justify the use of ivGC in patients under statins, although further studies in larger cohorts are needed to confirm our conclusions.

Long-term outcome of Graves' orbitopathy following high-dose intravenous glucocorticoids and orbital radiotherapy.

OBJECTIVE: Intravenous (iv) glucocorticoids (GC) (ivGC) and orbital radiotherapy (ORT) are commonly used in active Graves' orbitopathy (GO), with favorable outcomes in up to 80% of patients. However, little is known on the factors that may affect GO outcome in the long term, an issue that we investigated here. METHODS: We studied retrospectively 96 untreated patients with GO, identified out of 787 consecutive patients who came to our GO Clinic for a follow-up visit between September 2010 and June 2013. After the first observation, patients were treated with ivGC and ORT and were then re-examined after a median period of 55.5 months. The primary end-point was the possible relation between GO outcome and several individual variables. RESULTS: Exophthalmometry, eyelid aperture, CAS, diplopia and visual acuity (the latter only in patients with an initial reduction) improved significantly after treatment. Overall, 67.7% of patients had improved and were considered as responders, whereas the remaining (29.1% stable and 4.5% worsened) were considered as non-responders. Age, smoking, thyroid volume, thyroid treatment, serum anti-TSH receptor autoantibodies and individual GO features at first observation did not affect the outcome of GO, which, in contrast, was affected by gender and by the time elapsed between first and last observation. Thus, the prevalence of responders was higher in females (76.4 vs 48% in males, P = 0.02) and the time elapsed between first and last observation was greater in responders (58 vs 39 months in non-responders, P = 0.02). Whereas the prevalence of responders and non-responders was similar up to 36 months, there was an increase in responders beginning between 37 and 48 months and reaching a peak of ~80% between 61 and 72 months, to plateau thereafter. CONCLUSIONS: Given the limitations of retrospective investigations, our study confirms that the combination of GC and ORT is effective in GO and shows that females have greater chances to respond to treatment. The notorious tendency of GO to improve spontaneously with time most likely contributes the long-term outcome of the eye syndrome.