Determinants of liver damage associated with intravenous methylprednisolone pulse therapy in Graves' ophthalmopathy.
BACKGROUND
Intravenous methylprednisolone pulses (IVMP) are more efficacious and better tolerated than oral prednisone in Graves' ophthalmopathy (GO) patients. However, acute and severe liver damage has been reported in sporadic cases during IVMP, resulting in fatal acute liver failure in four patients so far. The mechanism causing the liver damage is incompletely understood.


METHODS
We performed a prospective observational study in 13 patients with dysthyroid optic neuropathy (group A) and in 14 patients with moderately severe GO (group B) who were treated with high-dose (group A) or low-dose (group B) IVMP; cumulative steroid doses were 8.45 g in group A and 4.5 g in group B, and follow-up time was 24 weeks.


RESULTS
Slight increases in serum aminotransferases (in alanine aminotransferase [ALAT] more than in aspartate aminotransferase [ASAT]) were observed, in seven patients exceeding the upper normal limit of 40 U/L. These changes were more prominent in group A than in group B as was also evident from a decrease in ASAT/ALAT ratio in group A but not in group B. Changes in serum aminotransferases occurred especially in the first 6 weeks of IVMP, becoming smaller thereafter with the decrease in steroid dosage. Pretreatment liver steatosis or diabetes were not related to liver damage, but preexistent viral hepatitis was.


CONCLUSIONS
IVMP in GO patients causes dose-dependent liver damage by a direct toxic effect of glucocorticoids on hepatocytes. Nevertheless, IVMP seems to be pretty safe if cumulative doses exceeding 8 g are avoided and liver function is checked before and at regular intervals during pulse therapy.
Le Moli
Rosario
R
Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, The Netherlands.
Baldeschi
Lelio
L
Saeed
Peerooz
P
Regensburg
Noortje
N
Mourits
Maarten P
MP
Wiersinga
Wilmar M
WM
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D049970:Graves Ophthalmopathy / Q000188:drug therapy*; D006801:Humans; D007262:Infusions, Intravenous; D017093:Liver Failure / Q000139:chemically induced*; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage / Q000009:adverse effects*; D008875:Middle Aged; D011446:Prospective Studies
D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D008775:Methylprednisolone