Background: Dopamine agonists (DA) are the first-line treatment for macroprolactinomas. However, up to 10% of patients fail to respond to medical therapy.
Aim: To assess biochemical resistance rate to DA treatment in a large series of patients with macroprolactinoma and to analyze possibilities to overcome this resistance.
Patients and methods: 195 patients with macroprolactinomas, treated with DA for at least 2 years, were retrospectively reviewed. Serum prolactin levels were measured by chemiluminescence. Tumor dimensions were assessed by computed tomography scan or MRI. Biochemical resistance to DA therapy was defined as failure to achieve normoprolactinemia on DA high dose (Bromocriptine 30 mg/day or Cabergoline up to 3.5 mg/week).
Results: 16 patients (8.2%) resistant to DA were identified: 8 men and 8 women, aged 30.8 ± 16.5 years at diagnosis; median prolactin at diagnosis was 1516.8 ng/ml and average tumor diameter was 3.2 ± 1.6 cm (range: 1−6.8 cm); median follow-up was 11.5 years (range: 2−30). Median cabergoline dose was 7 mg/week (range: 5−15 mg/week). Eight patients underwent pituitary surgery and 11 patients underwent radiotherapy (7 patients underwent both pituitary surgery and radiotherapy). Temozolomide was administered in one patient with aggressive macroprolactinoma, resistant to DA even after neurosurgery and radiotherapy, without improving prolactin levels or tumor shrinkage. None of the patients received Pasireotide. Normalization of prolactin levels occurred in 6 out of 16 patients (37.5%): in 2 patients by increasing CAB dose up to 5 and 9 mg/week, respectively and in 4 patients after pituitary radiotherapy. Two patients were cured at 9 and 10 years after high voltage radiotherapy, respectively. Two patients denied any radical therapy and are currently on high cabergoline dose (10.5 and 7 mg/week), with uncontrolled hyperprolactinemia.
Conclusion: Cabergoline dose escalation and radiotherapy can improve the outcome of macroprolactinomas resistant to DA.