Treatment options for Cushing disease after unsuccessful transsphenoidal surgery

Abstract

<jats:p>✓Cushing disease is considered an aggressive pituitary endocrinopathy because of the devastating effects from untreated hypercortisolemia. Although they are histologically benign, these adrenocorticotropic hormone (ACTH)-secreting pituitary tumors are associated with significant morbidity and premature death. Currently, transsphenoidal surgery is the primary treatment of Cushing disease associated with an ACTH-secreting pituitary tumor, resulting in remission rates ranging from about 50 to 90%. Some patients, however, will not achieve sustained remission after transsphenoidal surgery and can exhibit persistent or recurrent Cushing disease that requires multimodal treatment to achieve remission. In these patients, options for treatment include repeat transsphenoidal resection, radiation therapy (including conventional fractionated radiation therapy and stereotactic radiosurgery), and medical therapy. Despite undergoing multiple treatment modalities, some patients may ultimately require bilateral adrenalectomy for definitive treatment to eliminate hypercortisolemia associated with Cushing disease. In this article, the authors review the treatment options for patients who have persistent or recurrent Cushing disease after unsuccessful transsphenoidal surgery. The indications, current results reported in the literature, and complications of each treatment modality are discussed.</jats:p>

Repeated transsphenoidal pituitary surgery (TS) via the endoscopic technique: a good therapeutic option for recurrent or persistent Cushing's disease (CD)

“…8 Overall, the remission rates reported after second TS in persistent or recurrent CD seem to be slightly lower than the remission rates reported after first TS which vary from 50% to 90%, but are mostly 70-85%. [3][4][5][6][7][8][9] Nevertheless, the majority of the patients with persistent or recurrent CD can still instantly be cured by repeated TS, and the remission rate we achieved via the endoscopic technique seems to be at least as good as the remission rate achieved by repeated TS via the conventional microscopic technique.…”

“…Remission rates after conventional fractionated radiation therapy range from 56% to 84%. 5,9 However, its usefulness is limited by the delay between therapy and disease control and the 50-100% incidence of hypopituitarism several years after treatment. Additional complications include radiation necrosis, cerebral vasculopathy, damage to surrounding structures and the development of radiation-induced neoplasms.…”

“…13,14 Nowadays the minimally invasive laparoscopic approach is preferred, which has reduced perioperative morbidity significantly. 9,15 However, adrenalectomized patients require lifelong glucocorticoid and mineralocorticoid replacement. The major concern is the development of Nelson's syndrome in 15-46% of the patients.…”

“…Stereotactic radiosurgery, which was introduced more recently, may lead to faster normalization of hormone levels with a lower complication risk than conventional radiotherapy, but long-term follow-up is needed to determine its real value. 5,9,11,12 Bilateral adrenalectomy has a very high success rate of reversing hypercortisolism, ranging from 88% to 100%. Traditionally, open procedures of adrenalectomy were associated with considerable morbidity and mortality.…”

“…Thus far, no consensus exists on which therapy is preferable. 5,9,10 Pituitary radiotherapy has been used to treat persistent or recurrent CD for several decades. Remission rates after conventional fractionated radiation therapy range from 56% to 84%.…”