Endocrine Abstracts

Introduction: Mitotane is widely used to treat adrenocortical carcinoma (ACC) and remains the mainstay of treatment along with surgery. The aim of this study is to evaluate the adverse side effects of mitotane treatment.

Materials and Methods: This retrospective study included 36 patients with ACC, ENSAT stage I- IV, who were treated with mitotane in an adjuvant or palliative setting. Patients with ENSAT stage IV who died within 6 months after surgery were excluded (n=6). Patient demographic and clinical characteristics, as well as metabolic and hormonal side effects of mitotane, were collected from hospital medical records.

Results: The median age of patients was 48 (18-78) years, 72% of them were female. Twenty-seven patients (75%) received adjuvant mitotane whereas 9 patients (25%) received it in a palliative setting, as monotherapy (n=3) or in combination with chemotherapy (n=6). One patient permanently, and two temporarily, discontinued mitotane treatment due to side effects (severe liver lesion, exfoliative dermatitis and severe gastrointestinal disturbances). Of the remaining 33 patients, all achieved the target mitotane concentration (> 14 mg/L) after median time of 102 days (76-121). In 25 patients (76%), the target mitotane concentration was maintained during > 75% of the treatment period. As for the endocrine toxicity of mitotane, all patients required glucocorticoid substitution, 8 patients (24%) had mineralocorticoid insufficiency, 16 (49%) had central hypothyroidism whereas hypogonadism was observed in 89% of male patients (8/9). In addition, 29% of female patients (7/24) developed ovarian cysts and 15 (46%) patients had dyslipidaemia. Four patients had an Addison crisis during treatment. Fourteen patients (42%) experienced gastrointestinal side effects including nausea, vomiting, diarrhoea and weight loss, while 32 patients (97%) had elevated liver enzymes, predominantly GGT. Twelve patients (36%) had various neurological side effects such as dizziness, decreased ability to concentrate or speech disorders (stutter or aphasia).

Conclusion: Mitotane treatment is associated with a wide spectrum of side effects and their successful management is of paramount importance to improve patient adherence to treatment and avoid drug discontinuation.