Endocrine Abstracts

Background: Mitotane has been used in paliative setting in patients with adrenocortical carcinoma. However, this adrenolytic agent has important toxicities with frequent elevation of cholesterol levels (after a median time of 6 months from mitotane start) and serum aminotransferases. However, there are no published reports of clinically apparent liver injury.

Case presentation: We report a case of a 54 year-old man with history of an 11 cm adrenocortical carcinoma ENSAT IV. Three months after adrenalectomy, imaging studies detected a local recurrence/persistence of disease. At that time, serum aminotransferases were in the reference range and he had a shlight increase lipidic parameters (<2 upper limit of normal - ULN). Mitotane was initiated and titulated to 3g/day after two weeks to a maximum of 4g and was suspended after one month, before the excision of local recurrence. Mitotanemia was 2.3 mg/l (14-20 mg/l) and pre-operatory laboratory tests showed an increase of serum aminotransferases<2×ULN and minor increseas of total cholesterol (TC) and LDL cholesterol (LDL-c). Pos-operative period was complicated by the ocorrence of an acute hepatitis with asthenia, jaundice, and acolic stools.

Biochemically: Maximum levels of total bilirrubin 15×ULN, direct bilirrubin 6×ULN, AST and ALT 15×ULN and coagulopathy. CT and c-LDL levels reached maximum values of 561 mg/dL and 416 mg/dL respectively. Abdominal ultrasound and magnetic resonance cholangiopancreatography excluded hepatic lesions, biliar duct dilatation or obstruction; Viral infections and hepatic auto-imunity were excluded and the hepatic biopsy was compatible with a toxic etiology. We assumed mitotane therapy as the most probable cause.

Conclusions: To our knowledge, this is the first report combining such marked cholesterol elevations and in the shortest period of therapy associated with acute liver failure. This case highlights the serious toxicities of this agent, even in subtherapeutical levels.