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The role of reoperation after recurrence of Cushing’s disease

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Surgical failure or recurrence of Cushing’s disease can be treated with medical therapy, radiotherapy, adrenalectomy, and/or repeat transsphenoidal surgery, all of which have their respective benefits and drawbacks. Redo transsphenoidal surgery has been shown to achieve at least short-term remission in about 40–80% of patients and is associated with low rates of morbidity and near-zero mortality, albeit higher rates of postoperative hypopituitarism, diabetes insipidus, and cerebrospinal fluid leak than initial resection. Despite this, recurrence may ensue in 50% of patients. When selecting patient candidates for reoperation, many predictors of postoperative outcomes have been proposed including imaging characteristics, histopathological staining, intraoperative tumor visualization, and tumor size, however no single predictor consistently predicts outcomes. Redo transsphenoidal surgery should be performed by an experienced pituitary surgeon and patients should be followed at a tertiary care center by a multidisciplinary team consisting of an experienced endocrinologist and neurosurgeon to monitor closely for remission and recurrence.

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Background

Cushing’s disease (CD) results from excess secretion of adrenocorticotropic hormone (ACTH) from a pituitary adenoma, leading to hypersecretion of cortisol from the adrenal glands [1]. Prolonged cortisol exposure leads to a host of cardiovascular, musculoskeletal, and neuropsychiatric comorbidities, as well as increased mortality [1,2]. First-line treatment of CD is typically transsphenoidal surgical resection of the ACTH-secreting pituitary adenoma, which has been shown to restore normal

Repeat transsphenoidal surgery

The final option for treatment of recurrent Cushing’s disease, and the focus of this review, is redo transsphenoidal surgery. Reoperation is typically considered based on preoperative imaging findings including visible tumor, tumor size and extension, confirmed histology from first surgery, and the experience of the first surgeon [8]. It has been shown that inappropriate exposure and identification of the adenoma during first surgery is a reliable predictor of surgical failure [22].

Discussion

Cushing’s disease is thought to recur in patients at a rate of up to 50% after first-line treatment with transsphenoidal resection based on current literature [6]. This risk increases with time, with 20–25% of patients experiencing recurrence 10 years postoperatively [8]. Additionally, while initial transsphenoidal surgery results in hormonal remission in a large majority of patients (42–97%), some patients will experience persistence of disease [6]. The most widely used criteria for recurrence

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