Statins may increase the risk of liver dysfunction in patients treated with steroids for active graves' orbitopathy.
BACKGROUND
Intravenous glucocorticoids (IVGC) administered at high doses for the treatment of active moderate-severe Graves' orbitopathy (GO) may induce liver toxicity. Cumulative doses should not exceed 8 g and strict monitoring of liver function is recommended to avoid potentially life-threatening side effects. The 3-hydroxy-3-methylglutaryl-coenzyme reductase inhibitors, also known as statins, are employed to prevent major cardiovascular events. Patients with active GO, requiring immunosuppression with IVGC, are often treated with statins also.


OBJECTIVE
We studied a 64-year-old man and a 58-year-old woman who developed significant liver toxicity after moderate doses of IVGC (methylprednisolone 2.3 g and 5 g in patients 1 and 2, respectively) and concomitant administration of statins.


METHODS
Liver function tests were monitored every two weeks. Hepatitis virus markers and serology for autoimmune hepatitis were negative. At the occurrence of liver dysfunction (5-fold increase of serum aspartate aminotransferase/alanine aminotransferase concentrations), in patient 1 we stopped simvastatin indefinitely and discontinued IVGC for 2 weeks, whereas in patient 2, ongoing treatment with rosuvastatin was discontinued 3 weeks after IVGC therapy.


RESULTS
In patient 1, off simvastatin, liver function remained normal after resuming IVGC. In patient 2, a further increase of the aminotransferase values was observed 3 weeks after IVGC discontinuation, with a progressive normalization only after statin withdrawal.


CONCLUSIONS
Our study shows that statins, when concomitantly employed with methylprednisolone, may be a cause of liver dysfunction during IVGC in active GO. An accurate pharmacological history of all patients who are candidates for IVGC treatment is suggested to identify subjects at risk for hepatotoxicity.
Graves' Orbitopathy Center, Endocrine Unit (D.C., G.V., I.C., P.B.-P., M.S.), Ophthalmology (N.C.), Department of Gastroenterology and Hepatology (R.D.), Pathology Unit, and Department of Pathophysiology and Transplantation (M.M., U.G.), Fondazione Ca' Granda IRCCS, Ospedale Maggiore Policlinico and University of Milan, 20122 Milan, Italy.
Danila
D
Covelli
Guia
G
Vannucchi
Irene
I
Campi
Nicola
N
Currò
Roberta
R
D'Ambrosio
Marco
M
Maggioni
Umberto
U
Gianelli
Paolo
P
Beck-Peccoz
Mario
M
Salvi
D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology*; D005260:Female; D005938:Glucocorticoids / Q000009:adverse effects* / Q000627:therapeutic use; D049970:Graves Ophthalmopathy / Q000188:drug therapy*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008775:Methylprednisolone / Q000009:adverse effects* / Q000627:therapeutic use; D008875:Middle Aged; D019821:Simvastatin / Q000009:adverse effects* / Q000627:therapeutic use
D005938:Glucocorticoids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin; D008775:Methylprednisolone