BackgroundMost of pituitary adenomas (PAs) are slow-growing benign tumors which can be cured or controlled by conventional therapies, including surgery, medical treatment or radiotherapy. A small set of PAs, usually known as aggressive PAs or refractory PAs, present with more aggressive behavior and lead to poorer prognosis than classical PAs. MethodsWe retrospectively analyzed the clinical and pathological characteristics of 44 patients who were diagnosed with refractory PAs by a multidisciplinary team (MDT). All the patients' demographic characteristics, radiological findings, Knosp grade, treatment details and clinical outcomes were abstracted from the medical records. Additionally, 44 patients with nonrefractory PAs (NRPAs) matched for age and gender were selected to serve as the control group. ResultsDespite using all combined treatments including surgery, radiotherapy and conventional medical treatments, all the refractory PAs showed tumor progression or hormone hypersecretion which caused increased morbidity and mortality and remained challenging to management. Compared with those of the non-refractory PAs, the tumor size, invasive rate and tumor growth rate (TGR) were significantly higher in the refractory PAs. TGR >2.2% per month may be considered as a preoperative indicator of refractoriness. The Ki-67 index in the refractory PAs were all >= 3%. EGFR, but not MMP2 or MMP9, was significantly overexpressed in refractory PAs compared with the corresponding levels in nonrefractory PAs. ConclusionRefractory PAs are unresponsive to surgery, radiotherapy and conventional medical treatments with a poor prognosis. Moreover, a TGR >= 2.2% per month, Ki-67 index >= 3% and EGFR overexpression may be independent predictors of clinical refractoriness.