Macroprolactinoma with progressive resistance to high-dose cabergoline
CS Arun1, Dip Mitra3, Steve Ball1, John Hill2, Joanna Lewis3 & Richard Quinton1
True resistance to cabergoline in patients with hyperprolactinaemia has only rarely been reported. We describe a patient with macroprolactinoma who initially responded to cabergoline, but then developed a progressive increase in PRL levels.
A 78-year-old male presenting with headache and left temporal hemianopia was found to have a macroprolactinoma with suprasellar/cavernous sinus extension and panhypopituitarism. The biochemistry dataset revealed central hypothyroidism dating back >5 years. On cabergoline 3.5 mg/wk, PRL fell progressively from 51,299 to 4,833 mU/L over a 7-month period with some tumour shrinkage. However, 14 months after initiation of medical therapy, PRL had risen again to 13,597 with evidence of tumour regrowth, despite a stepwise increase in cabergoline dose to 7 mg/wk. There was little response to octreotide challenge (12,998→8,466) and PRL rose further to 22,227 over the next month. Transsphenoidal surgery (TSS) was limited by severe vascular disease (circle of Willis fed by a single hypertrophic vertebral artery). Histology confirmed lactotroph adenoma with unusually high mitotic index. Post-op PRL was 13,597 and adjuvant fractionated multiportal EBRT was administered, resulting in a nadir PRL 17-months later of 1,665. However, despite cabergoline 10 mg/wk, there has since been tumour regrowth and further rise in PRL, peaking 3-years post TSS/EBRT at 19,606.
It is unusual to develop resistance to cabergoline in patients who are initially sensitive. Due to physical frailty and tumour anatomy, he is not a candidate for further TSS or stereotaxic radiosurgery. Tablet non-adherence is a theoretical possibility, but following periods of supervised twice-weekly administration, we are confident this is not the case. Tachyphylaxis (documented in one previous case) is also a possibility and this could potentially be established by withholding cabergoline for 13 months and then rechallenging. Finally, tumour growth might be E2-driven, in which case a trial of aromatase inhibitor±stopping androgen replacement might be beneficial.