PMID- 26090805 OWN - NLM STAT- MEDLINE DCOM- 20160406 LR - 20220330 IS - 1557-9077 (Electronic) IS - 1050-7256 (Linking) VI - 25 IP - 7 DP - 2015 Jul TI - Age and Dose Are Major Risk Factors for Liver Damage Associated with Intravenous Glucocorticoid Pulse Therapy for Graves' Orbitopathy. PG - 846-50 LID - 10.1089/thy.2015.0061 [doi] AB - BACKGROUND: High-dose intravenous glucocorticoid (ivGC) pulse therapy, which is commonly used for Graves' orbitopathy (GO), has been associated with acute liver damage (ALD), resulting in a fatal outcome in a few cases. No certain risk factors for ALD have been established. Consequently, a large retrospective cohort study was performed. METHODS: The relationship between ALD and several potential risk factors was assessed in 1076 consecutive patients with GO given ivGC. ALD was defined as an increase of alanine aminotransferase >/=300 IU/L. RESULTS: Fourteen cases of ALD were recorded, resulting in a morbidity of 1.3%. Thirteen patients recovered and one died, resulting in a mortality of 0.09%. There was a significant, positive correlation of ALD with age and methylprednisolone acetate (MPA) cumulative dose, and ALD was more common (relative risk [RR]=2.8; p=0.05) in patients aged >/=53 years (9/420; 2.14%) than in those aged <53 years (5/656; 0.76%). In patients aged >/=53 years, there was a significant positive correlation of ALD with MPA cumulative dose, and with MPA dose per infusion. Thus, the frequency of ALD in this age group was greater (RR=3.48; p=0.04) in patients with a MPA dose per infusion >/=0.7 g (5/111, 4.5% vs. 4/308, 1.29%). Regardless of age, no cases of ALD were observed for MPA doses per infusion <0.57 g. CONCLUSIONS: Age and MPA dose are significant risk factors for ALD, with the following practical implications. First, the total MPA cumulative dose should not exceed 8.5 g (the average dose in patients without ALD). Second, in patients aged >/=53 years, selection and observation should be quite strict. However, being aged >/=53 years should not be seen as an absolute contraindication to ivGC, especially in patients with severe GO, considering that the risk of ALD, although statistically significant, was relatively low. Third, the MPA dose should not exceed 0.57 g per infusion, a measure to be applied regardless of age. FAU - Sisti, Eleonora AU - Sisti E AD - 1 Department of Clinical and Experimental Medicine, Endocrinology Units, University of Pisa and University Hospital of Pisa , Pisa, Italy . FAU - Coco, Barbara AU - Coco B AD - 2 Hepatology Unit, University Hospital of Pisa , Pisa, Italy . FAU - Menconi, Francesca AU - Menconi F AD - 1 Department of Clinical and Experimental Medicine, Endocrinology Units, University of Pisa and University Hospital of Pisa , Pisa, Italy . FAU - Leo, Marenza AU - Leo M AD - 1 Department of Clinical and Experimental Medicine, Endocrinology Units, University of Pisa and University Hospital of Pisa , Pisa, Italy . FAU - Rocchi, Roberto AU - Rocchi R AD - 1 Department of Clinical and Experimental Medicine, Endocrinology Units, University of Pisa and University Hospital of Pisa , Pisa, Italy . FAU - Latrofa, Francesco AU - Latrofa F AD - 1 Department of Clinical and Experimental Medicine, Endocrinology Units, University of Pisa and University Hospital of Pisa , Pisa, Italy . FAU - Profilo, Maria Antonietta AU - Profilo MA AD - 1 Department of Clinical and Experimental Medicine, Endocrinology Units, University of Pisa and University Hospital of Pisa , Pisa, Italy . FAU - Mazzi, Barbara AU - Mazzi B AD - 1 Department of Clinical and Experimental Medicine, Endocrinology Units, University of Pisa and University Hospital of Pisa , Pisa, Italy . FAU - Vitti, Paolo AU - Vitti P AD - 1 Department of Clinical and Experimental Medicine, Endocrinology Units, University of Pisa and University Hospital of Pisa , Pisa, Italy . FAU - Marcocci, Claudio AU - Marcocci C AD - 1 Department of Clinical and Experimental Medicine, Endocrinology Units, University of Pisa and University Hospital of Pisa , Pisa, Italy . FAU - Brunetto, Maurizia AU - Brunetto M AD - 2 Hepatology Unit, University Hospital of Pisa , Pisa, Italy . FAU - Marino, Michele AU - Marino M AD - 1 Department of Clinical and Experimental Medicine, Endocrinology Units, University of Pisa and University Hospital of Pisa , Pisa, Italy . LA - eng PT - Clinical Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150619 PL - United States TA - Thyroid JT - Thyroid : official journal of the American Thyroid Association JID - 9104317 RN - 0 (Glucocorticoids) RN - 43502P7F0P (Methylprednisolone Acetate) RN - EC 2.3.2.2 (gamma-Glutamyltransferase) RN - EC 2.6.1.1 (Aspartate Aminotransferases) RN - EC 2.6.1.2 (Alanine Transaminase) RN - EC 3.1.3.1 (Alkaline Phosphatase) RN - RFM9X3LJ49 (Bilirubin) RN - X4W7ZR7023 (Methylprednisolone) SB - IM MH - Adolescent MH - Adult MH - Age Factors MH - Aged MH - Alanine Transaminase/blood MH - Alkaline Phosphatase/blood MH - Aspartate Aminotransferases/blood MH - Bilirubin/blood MH - Chemical and Drug Induced Liver Injury/enzymology/*epidemiology/etiology MH - Cohort Studies MH - Dose-Response Relationship, Drug MH - Female MH - Glucocorticoids/administration & dosage/*adverse effects MH - Graves Ophthalmopathy/*drug therapy MH - Humans MH - Infusions, Intravenous MH - Male MH - Methylprednisolone/administration & dosage/adverse effects/*analogs & derivatives MH - Methylprednisolone Acetate MH - Middle Aged MH - Multivariate Analysis MH - Regression Analysis MH - Retrospective Studies MH - Risk Factors MH - Young Adult MH - gamma-Glutamyltransferase/blood EDAT- 2015/06/20 06:00 MHDA- 2016/04/07 06:00 CRDT- 2015/06/20 06:00 PHST- 2015/06/20 06:00 [entrez] PHST- 2015/06/20 06:00 [pubmed] PHST- 2016/04/07 06:00 [medline] AID - 10.1089/thy.2015.0061 [doi] PST - ppublish SO - Thyroid. 2015 Jul;25(7):846-50. doi: 10.1089/thy.2015.0061. Epub 2015 Jun 19.