Age and Dose Are Major Risk Factors for Liver Damage Associated with Intravenous Glucocorticoid Pulse Therapy for Graves' Orbitopathy | oneGRAVESvoice

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Age and Dose Are Major Risk Factors for Liver Damage Associated with Intravenous Glucocorticoid Pulse Therapy for Graves’ Orbitopathy

key information

source: Thyroid : Official Journal of the American Thyroid Association

year: 2015

authors: Sisti E, Coco B, Menconi F, Leo M, Rocchi R, Latrofa F, Profilo MA, Mazzi B, Vitti P, Marcocci C, Brunetto M, Marinò M


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.

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.

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.

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.

organization: University of Pisa and University Hospital of Pisa, Italy

DOI: 10.1089/thy.2015.0061