European society of endocrinology clinical practice guidelines on the management of adrenocortical carcinoma in adults, in collaboration with the European Network for the study of adrenal tumors

Martin Fassnacht, Olaf M. Dekkers, Tobias Else, Eric Baudin, Alfredo Berruti, Ronald R. De Krijger, Harm R. Haak, Radu Mihai, Guillaume Assie, Massimo Terzolo*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Adrenocortical carcinoma (ACC) is a rare and in most cases steroid hormone-producing tumor with variable prognosis. The purpose of these guidelines is to provide clinicians with best possible evidence-based recommendations for clinical management of patients with ACC based on the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. We predefined four main clinical questions, which we judged as particularly important for the management of ACC patients and performed systematic literature searches: (A) What is needed to diagnose an ACC by histopathology? (B) Which are the best prognostic markers in ACC? (C) Is adjuvant therapy able to prevent recurrent disease or reduce mortality after radical resection? (D) What is the best treatment option for macroscopically incompletely resected, recurrent or metastatic disease? Other relevant questions were discussed within the group. Selected Recommendations: (i) We recommend that all patients with suspected and proven ACC are discussed in a multidisciplinary expert team meeting. (ii) We recommend that every patient with (suspected) ACC should undergo careful clinical assessment, detailed endocrine work-up to identify autonomous hormone excess and adrenal-focused imaging. (iii) We recommend that adrenal surgery for (suspected) ACC should be performed only by surgeons experienced in adrenal and oncological surgery aiming at a complete en bloc resection (including resection of oligometastatic disease). (iv) We suggest that all suspected ACC should be reviewed by an expert adrenal pathologist using the Weiss score and providing Ki67 index. (v) We suggest adjuvant mitotane treatment in patients after radical surgery that have a perceived high risk of recurrence (ENSAT stage III, or R1 resection, or Ki67 >10%). (vi) For advanced ACC not amenable to complete surgical resection, local therapeutic measures (e.g. radiation therapy, radiofrequency ablation, chemoembolization) are of particular value. However, we suggest against the routine use of adrenal surgery in case of widespread metastatic disease. In these patients, we recommend either mitotane monotherapy or mitotane, etoposide, doxorubicin and cisplatin depending on prognostic parameters. In selected patients with a good response, surgery may be subsequently considered. (vii) In patients with recurrent disease and a disease-free interval of at least 12 months, in whom a complete resection/ablation seems feasible, we recommend surgery or alternatively other local therapies. Furthermore, we offer detailed recommendations about the management of mitotane treatment and other supportive therapies. Finally, we suggest directions for future research.

Original languageEnglish
Pages (from-to)G1-G46
JournalEuropean Journal of Endocrinology
Issue number4
Publication statusPublished - 1 Oct 2018


  • Adrenal Cortex Neoplasms/pathology
  • Adrenalectomy
  • Adrenocortical Carcinoma/pathology
  • Antineoplastic Agents, Hormonal/therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols/therapeutic use
  • Catheter Ablation
  • Chemoembolization, Therapeutic
  • Cisplatin/administration & dosage
  • Disease Management
  • Doxorubicin/administration & dosage
  • Endocrinology
  • Etoposide/administration & dosage
  • Europe
  • Humans
  • Mitotane/therapeutic use
  • Neoplasm Metastasis
  • Prognosis
  • Radiotherapy
  • Societies, Medical


Dive into the research topics of 'European society of endocrinology clinical practice guidelines on the management of adrenocortical carcinoma in adults, in collaboration with the European Network for the study of adrenal tumors'. Together they form a unique fingerprint.

Cite this