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Adrenocortical carcinoma: a clinician's update

Nature Reviews Endocrinology volume 7, pages 323–335 (2011)Cite this article

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Abstract

Adrenocortical carcinoma is a rare heterogeneous neoplasm with an incompletely understood pathogenesis and a poor prognosis. Previous studies have identified overexpression of insulin-like growth factor 2 (IGF-2) and constitutive activation of β-catenin as key factors involved in the development of adrenocortical carcinoma. Most patients present with steroid hormone excess, for example Cushing syndrome or virilization, or abdominal mass effects, but a growing proportion of patients with adrenocortical carcinoma (currently >15%) is initially diagnosed incidentally. No general consensus on the diagnostic and therapeutic measures for adrenocortical carcinoma exists, but collaborative efforts, such as international conferences and networks, including the European Network for the Study of Adrenal Tumors (ENSAT), have substantially advanced the field. In patients with suspected adrenocortical carcinoma, a thorough endocrine and imaging work-up is recommended to guide the surgical approach aimed at complete resection of the tumor. To establish an adequate basis for treatment decisions, pathology reports include the Weiss score to assess malignancy, the resection status and the Ki67 index. As recurrence is frequent, close follow-up initially every 3 months is mandatory. Most patients benefit from adjuvant mitotane treatment. In metastatic disease, mitotane is the cornerstone of initial treatment, and cytotoxic drugs should be added in case of progression. Results of a large phase III trial in advanced adrenocortical carcinoma are anticipated for 2011 and will hopefully establish a benchmark therapy. New targeted therapies, for example, IGF-1 receptor inhibitors, are under investigation and may soon improve current treatment options.

Key Points

  • Overexpression of insulin-like growth factor 2 and constitutive activation of β-catenin are key molecular alterations in adrenocortical carcinoma

  • Detailed presurgical endocrine and imaging work-up and an expert surgeon are key prerequisites for a complete resection that offers the best chance of cure

  • Even after radical resection, recurrence rate is high and, therefore, most patients benefit from adjuvant treatment strategies (mitotane with or without radiotherapy)

  • Mitotane is the most effective single drug for adrenocortical carcinoma, but drug monitoring is important and management of adverse events is demanding

  • In advanced disease not amenable to surgery, mitotane is given as monotherapy or in combination with cytotoxic chemotherapy (either etoposide combined with doxorubicin and cisplatin or streptozotocin)

  • To facilitate progress in the treatment of adrenocortical carcinoma, patients should be enrolled in clinical trials

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Figure 1: Pathophysiologically relevant pathways in adrenocortical carcinoma.
Figure 2: Imaging studies performed in a patient with adrenocortical carcinoma.
Figure 3: Disease-specific survival according to tumor stage data from the European Network for the Study of Adrenal Tumors (ENSAT), which includes follow-up data from 566 patients derived from the German adrenocortical carcinoma registry in July 2010.
Figure 4: Treatment of adrenocortical carcinoma amenable to complete resection.
Figure 5: Treatment of advanced adrenocortical carcinoma not amenable to radical surgery.

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Acknowledgements

Work described in this Review was supported by grants of the Deutsche Krebshilfe (grant #107111 to M. Fassnacht), the German Ministry of Research BMBF (grant #01KG0501 to M. Fassnacht and B. Allolio) and the German Research Foundation DFG (grant #FA466/3-1 to M. Fassnacht). C. P. Vega, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the Medscape, LLC-accredited continuing medical education activity associated with this article.

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  1. Department of Internal Medicine I, Endocrine Unit, University Hospital, University of Würzburg, Oberdürrbacher Straße 6, Würzburg, 97080, Germany

    Martin Fassnacht, Matthias Kroiss & Bruno Allolio

  2. Department of Endocrinology, INCa COMETE network, Cochin Hospital, University Paris Descartes, 24 Rue du Faubourg-Saint-Jacques, Paris, 75014, France

    Rossella Libé

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  1. Martin Fassnacht
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All authors researched the data for the article, provided a substantial contribution to discussions of the content, wrote the review and reviewed and edited the manuscript before submission.

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Correspondence to Martin Fassnacht.

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Competing interests

M. Fassnacht and B. Allolio are participating as investigators in clinical trials on the pharmacokinetics of mitotane sponsored by HRA Pharma (France) and on the efficacy of OSI-906 in advanced ACC sponsored by OSI Pharma (USA). The other authors declare no competing interests.

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Fassnacht, M., Libé, R., Kroiss, M. et al. Adrenocortical carcinoma: a clinician's update. Nat Rev Endocrinol 7, 323–335 (2011). https://doi.org/10.1038/nrendo.2010.235

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