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Management of recurrent and refractory Cushing disease

Abstract

Cushing disease is most frequently caused by pituitary adenomas that secrete adrenocorticotrophic hormone. Transsphenoidal surgery is the treatment of choice in patients with these tumors because of reported remission rates of 69–93%. More challenging for neurosurgeons and endocrinologists, however, is management of the remaining patients whose Cushing disease is refractory to initial transsphenoidal surgery or recurs after initial remission. Here, we review the treatment options and latest surgical, medical, and radiosurgical advances for patients who have persistent or recurrent Cushing disease after transsphenoidal surgery.

Key Points

  • Repeat transsphenoidal surgery is a safe and effective treatment for recurrent and refractory Cushing disease

  • Radiosurgery carries a notable risk of hypopituitarism and takes longer to achieve remission than transsphenoidal surgery but can be considered for Cushing disease for which multiple surgeries have been unsuccessful or that is caused by adenoma in the cavernous sinus

  • Medical therapy that lowers serum cortisol concentrations can be effective in Cushing disease patients in whom remission cannot be achieved with surgery or radiosurgery, and who, therefore, require lifelong treatment; ketoconazole is the most frequently prescribed therapy but mifepristone is currently being studied

  • Adrenalectomy, particularly in the less invasive laparoscopic form, can provide rapid control of refractory hypercortisolemia, but requires MRI surveillance to monitor for adenoma growth before Nelson syndrome develops

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Figure 1: Comparison of dosimetry focus in the sellar contents during proton beam radiosurgery and photon-based radiation therapy.
Figure 2: Mechanisms of action of drugs used to treat hypercortisolemia related to Cushing disease.

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Aghi, M. Management of recurrent and refractory Cushing disease. Nat Rev Endocrinol 4, 560–568 (2008). https://doi.org/10.1038/ncpendmet0947

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