Endocrine Abstracts

Introduction: : Adrenocortical carcinoma (ACC) is a rare tumor, often with an unfavorable prognosis. The management of ACC is challenging due to its low frequency and limited experience. The objective of this study was to describe the adverse events (AE) in patients diagnosed with ACC treated in the Divisions of Endocrinology and Oncology at the Ramón y Cajal University Hospital (Madrid, Spain) in the last seven years.

Methods: Records of patients with ACC from 2016 to 2022 were retrospectively reviewed including clinical and biochemical data, management and follow up. Only patients with available information about mitotane therapy were included.

Results: A total of 8 patients with ACC (4 females and 4 males; median age at diagnosis 51.2 [38.2–73.9] years) were studied, including 4 hormonally inactive, 3 androgen-secreting and 1 cortisol-secreting ACC. All patients underwent surgery. The ENSAT tumor stage was II in 3 patients, III in 1 patient and IV in 4 patients. 2 patients were treated with mitotane in mononotherapy(stage II) and 6 in combination with other treatments (2 radiotherapy, 5 chemotherapy, 1 immunotherapy and 1 lung metastasis surgery). The median duration of mitotane therapy was 8.0 [3.8–38.6]months (4 patients are still under treatment at the time of analysis, 7 January 2023). During follow-up, all patients achieve the therapeutic range after 5.4 [4–6.1]months of treatment, with a median dose of 4.5 [3-5]gr/day and mitotane levels of 15 [12.4–19.7]mg/dl, except one patient due to therapeutic non-compliance. All patients had at least one AE during mitotane therapy. The time to first AE was 23±8.75 days. The most common AE were digestive and hepatotoxicity in 100%, and neurotoxicity in 63% (n=5). Considering individually, asthenia, hypercholesterolemia and GGT increase were the most common AE (n=8), followed by nausea and anorexia with weight loss (n=7). The AE median number was 14 [9–16]. No correlation was found between the number of AE and the mitotane dose when therapeutic levels were achieved (r=−0.46,P=0.251). Neither with the duration of mitotane therapy (r=0.32,P=0.435) or mitotane plasmatic levels (r=−0.32, P=0.442). After a median follow-up of 17.7 [7.4–84.6] months, 2 patients(stage IV) died and 6 are still alive, including 3 with persistent/recurrent disease. There were two patients with ENSAT II stage treated in monotherapy who had to withdraw mitotane due to neurotoxicity. The time to first ACC recurrence/progression during Mitotane treatment was 18±15.93 months.

Conclusions: The most frequent AE with mitotane were digestive, hepatotoxicity and neurotoxicity, which are not associated with the level, dose or duration of mitotane therapy.