37P Estrogen-mimetic effects of mitotane in patients with adrenocortical carcinoma: Focus on this neglected toxicity

Mitotane is the cornerstone of both adjuvant and metastatic treatment of adrenocortical carcinoma (ACC). The side effects of this drug include those related to its estrogenic mimetic action, which has not been well studied. We conducted a retrospective study to assess the rate of menometrorrhagia, endometrial thickness, and ovarian cysts among female ACC patients (F-ACC), as well as gynecomastia among male ACC patients (M-ACC patients) who had been taking mitotane for at least 6 months. Secondary objectives were to examine the correlation between these toxicities and possible clinical factors. 35 F-ACC and 25 M-ACC patients were enrolled; of these, 22 (36.7%) F-ACC and 7 (11.7%) M-ACC patients developed mitotane-related estrogenic effects, respectively. Among F-ACCs, 10 (28.6%) had menometrorrhagia, 8 (22.9%) endometrial thickening, and 13 (37.1%) ovarian cysts. Serum levels of testosterone (p 0.006) and DHEAS (p 0.002) had an inverse correlation with these side effects, but there was no correlation with mitotane plasma concentration, duration of mitotane therapy (p 1.0) and serum levels of LH (p 0.5), FSH (p 1.0), estradiol (p 0.587), cortisol (p 0.234), ACTH (p 0.139), 17-OH progesterone (p 0.381). M-ACC patients developing gynecomastia had higher mitotane concentrations (median: 17 mg/l vs 10 mg/l, p 0.005). Whereas there was no statistically significant correlation between this side effect and serum values of estradiol (p 0.643), testosterone (p 0.222), cortisol (p 1.0), ACTH (p 0.71), 17-OH progesterone (p 0.857) and DHEAS (p 0.143). Women with ACC are particularly susceptible to estrogen-mimetic side effects of mitotane, which are inversely correlated with androgen levels. Serum mitotane levels can affect men's gynecomastia.