Update in adrenocortical carcinoma

J Clin Endocrinol Metab. 2013 Dec;98(12):4551-64. doi: 10.1210/jc.2013-3020. Epub 2013 Sep 30.


Adrenocortical carcinoma (ACC) is an orphan malignancy that has attracted increasing attention during the last decade. Here we provide an update on advances in the field since our last review published in this journal in 2006. The Wnt/β-catenin pathway and IGF-2 signaling have been confirmed as frequently altered signaling pathways in ACC, but recent data suggest that they are probably not sufficient for malignant transformation. Thus, major players in the pathogenesis are still unknown. For diagnostic workup, comprehensive hormonal assessment and detailed imaging are required because in most ACCs, evidence for autonomous steroid secretion can be found and computed tomography or magnetic resonance imaging (if necessary, combined with functional imaging) can differentiate benign from malignant adrenocortical tumors. Surgery is potentially curative in localized tumors. Thus, we recommend a complete resection including lymphadenectomy by an expert surgeon. The pathology report should demonstrate the adrenocortical origin of the lesion (eg, by steroidogenic factor 1 staining) and provide Weiss score, resection status, and quantitation of the proliferation marker Ki67 to guide further treatment. Even after complete surgery, recurrence is frequent and adjuvant mitotane treatment improves outcome, but uncertainty exists as to whether all patients benefit from this therapy. In advanced ACC, mitotane is still the standard of care. Based on the FIRM-ACT trial, mitotane plus etoposide, doxorubicin, and cisplatin is now the established first-line cytotoxic therapy. However, most patients will experience progress and require salvage therapies. Thus, new treatment concepts are urgently needed. The ongoing international efforts including comprehensive "-omic approaches" and next-generation sequencing will improve our understanding of the pathogenesis and hopefully lead to better therapies.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adrenal Cortex Neoplasms / diagnosis
  • Adrenal Cortex Neoplasms / drug therapy*
  • Adrenal Cortex Neoplasms / metabolism
  • Adrenal Cortex Neoplasms / surgery
  • Adrenal Glands / drug effects
  • Adrenal Glands / metabolism
  • Adrenal Glands / pathology
  • Adrenal Glands / surgery
  • Adrenocortical Carcinoma / diagnosis
  • Adrenocortical Carcinoma / drug therapy*
  • Adrenocortical Carcinoma / metabolism
  • Adrenocortical Carcinoma / surgery
  • Animals
  • Antineoplastic Agents, Hormonal / administration & dosage
  • Antineoplastic Agents, Hormonal / pharmacology
  • Antineoplastic Agents, Hormonal / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Chemotherapy, Adjuvant
  • Decision Trees
  • Humans
  • Lymph Node Excision
  • Mitotane / administration & dosage
  • Mitotane / pharmacology
  • Mitotane / therapeutic use
  • Molecular Targeted Therapy*
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / metabolism
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasm Staging
  • Prognosis
  • Recurrence
  • Salvage Therapy


  • Antineoplastic Agents, Hormonal
  • Neoplasm Proteins
  • Mitotane