Macroprolactinoma with Secondary Resistance to Dopamine Agonists: A case Report and Review of the Literature

Background: Resistance to dopamine agonists is not uncommonly seen in prolactinomas. However, development of resistance to dopamine agonists after an initial period of robust treatment response is rare, and only 39 cases have been reported in the past four decades. We describe a Chinese man with this rare condition and explored the postulated mechanisms that may explain this phenomenon. We compiled similar cases that were previously reported and compared their etiology, progress, and response to treatment. On the basis of these cases, we derived a list of differential diagnoses to consider in patients with secondary resistance to dopamine agonists.

Case Presentation: A 63-year-old Chinese man presented with blurred vision and was subsequently diagnosed with a macroprolactinoma. He had initial response to cabergoline but developed secondary resistance to it after 5 years. The prolactinoma continued to grow, and his serum prolactin remained markedly elevated despite adherence to escalating dosages of cabergoline up to 6 mg/week. The patient finally underwent transsphenoidal surgery and was found to have a sparsely granulated lactotroph tumor with Ki-67 index of 5%. Postoperatively, there was improvement in his serum prolactin level, although he still required treatment with cabergoline at 6 mg/week.

Conclusions: Surgery can facilitate disease control in patients with prolactinomas that develop secondary resistance to dopamine agonists. Malignant prolactinoma is an important differential diagnosis in this group of patients, especially when serum prolactin remains markedly elevated despite resolution or stability of the primary pituitary lesion, suggesting a metastatic source of prolactin secretion.