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.

Quercetin decreases proliferation of orbital fibroblasts and their release of hyaluronic acid.

BACKGROUND: Inhibition of fibroblast (FB) proliferation and hyaluronic acid (HA) production may be a therapeutic approach to Graves' ophthalmopathy (GO). The flavonoid quercetin has a wide range of activities, including reduction of FB growth. AIM: To investigate the effects of quercetin in orbital FB from GO patients and control subjects. METHODS: Primary cultures of orbital FB were treated with quercetin or with its glycosides rutin and quercitrin. Cell proliferation, necrosis, apoptosis, HA production, and cell cycle were measured. RESULTS: Beginning at a 30 µM concentration, quercetin, but not rutin and quercitrin, reduced cell proliferation, with no difference between GO and control FB. The effect of quercetin on proliferation was due to necrosis and cell cycle blockade, whereas apoptosis was unaffected. Quercetin reduced HA in the cell media, with no difference between GO and control FB. CONCLUSIONS: Quercetin reduces cell proliferation and HA release in orbital FB. Whether these initial findings have any potential for the use of quercetin in the clinical practice remains to be established.

Chlorinated pesticides and PCB content in thermal aquaculture of sturgeon (Acipenser naccarii).

One hundred sturgeon (Acipenser naccarii) with an initial weight of about 80 g each were fed on wet pellets (3% of live weight) for about 2 years and bred in part of the cooling water of a thermoelectric power station. Every 3 months five fish were sacrified and muscle samples were collected. Pesticide and PCB concentrations were measured by high resolution gas chromatography coupled with high resolution mass spectrometry (GC-MS) in the multiple ion detection mode. The mean levels of PCBs and DDT metabolites after 24 months of breeding were 28.4 +/- 2.1 micrograms/kg d.w. respectively. Values were negligible compared with those observed in other fish species living in the River Po. Furthermore, a remarkable growth of fishes was observed owing to the use of cooling water.