Diagnosis and treatment of refractory pituitary adenomas: a narrative review

Although aggressive pituitary adenomas (PAs) have been proposed and widely discussed for more than a decade, there is no general agreement regarding their definition, diagnosis or management. As one of the largest pituitary centers in China, we have diagnosed and treated more than fifty cases of aggressive PA and 3 pituitary carcinomas in the past 5 years and proposed a new term, i.e., refractory PAs, to define these adenomas. The definitions of aggressive and refractory PAs overlap with each other, though there are some differences between them. We interpret the definition for refractory PA in this review, emphasizing that more attention and early identification of these adenomas are needed. Although temozolomide (TMZ) has been used to treat pituitary carcinomas and refractory PA since 2006, which has significantly improved the prognosis of these patients, treatment of refractory PA is a tremendous challenge for endocrinologists and neurosurgeons. Overall, refractory PA is defined as PA with a Ki-67 labeling index ≥3%, a faster growth rate than that of normal PA, infiltration of surrounding tissues, recurrence or regrowth in the early postoperative period, and continued growth and/or secretion of excessive hormones despite attempts to control it. These criteria for refractory PA are stricter than for aggressive PA. The diagnosis and treatment of refractory PA requires the collaboration of a multidisciplinary team to achieve the best results.