Abstract
Proper selection of patients to avoid hepatic adverse events with IV GC for GO is addressed by Wichary and Gasińska (6) in their careful observational study published in this issue of Thyroid. They measured a number of parameters, including viral hepatitis serologies and liver enzymes, before and 2 days following a course of IV GC in 30 euthyroid patients with active GO. Although minor hepatic function abnormalities are commonly seen with IV GC, the researchers found no significant increases in mean levels of liver enzymes. While the study group was perhaps not large enough to capture the hepatic morbidity associated with the therapy, it is reassuring that seven patients with pretreatment serology suggesting past history of hepatitis B did not have reactivated liver disease. An earlier prospective observational study of 27 GO patients treated with IV GC found frequent and small increases in serum aminotransferases that were dose dependent (7). This study also found that elevations in alanine aminotransferase levels exceeding the upper normal limit during therapy were associated with evidence of prior viral hepatitis. Since severe hepatic complications were not observed in either series, it is unclear whether mild elevations of liver enzymes during or prior to therapy are a risk factor for acute liver failure. No patient was found pretherapy to have evidence of new or recent hepatitis (i.e., presence of anti–hepatitis B core immunoglobulin M), which would, of course, represent a definite contraindication to IV GC therapy.
What are the practical clinical implications of the current study and others regarding adverse events associated with IV GC therapy in GO? First, it appears that the risk–benefit ratio for this therapy in patients with active moderately severe to severe GO, especially of short duration, is favorable overall. This of course assumes accurate assessment of disease severity and activity and suggests that the therapy should be administered only in centers having expertise in the evaluation and treatment of patients with GO. Next, although the optimum treatment protocol has yet to be defined in a randomized controlled trial, some reasonable parameters for therapy are that single doses not be greater than 0.5 g, cumulative totals not exceed 8.0 g, and consecutive day dosing be avoided except in the treatment of sight-threatening disease (2). These guidelines were suggested because significant hepatotoxicity has only occurred in patients treated with more frequent or larger cumulative doses. A commonly used regimen is 500 mg methylprednisolone weekly for 6 weeks followed by 250 mg weekly for 6 weeks, for a cumulative dose of 4.5 g. Investigational studies prior to therapy should include assessment of liver function and hepatocellular integrity with consideration of hepatic ultrasound to investigate morphology. In addition, measurement of viral markers for both past and recent hepatitis, antinuclear autoantibodies, and fasting serum glucose levels are recommended. Contraindications to therapy include evidence of recent viral hepatitis, significant hepatic dysfunction, severe cardiovascular morbidity, severe hypertension, inadequately managed diabetes, and glaucoma (2). Liver enzymes, glucose levels, and blood pressure are best monitored monthly during treatment. Experience with the treatment suggests that if a patient does not benefit from the treatment after 6 weeks of high-dose therapy, a full 12-week course is not warranted (8). Finally, oral GC remains a reasonable, although less effective, alternative to IV GC that might be considered when IV infusions are not logistically possible or the patient prefers the oral route.