To our knowledge, this study involved the largest study population of 140 patients with newly diagnosed and cabergoline-treated bioactive prolactinoma with a PRL ≥ 1000 ng/mL, regardless of tumor size, and demonstrated that hypopituitarism is significantly associated with cabergoline non-responsiveness and cabergoline-induced CSF rhinorrhea. The gene discussed is PRL; the disease is neoplasm.