Dopamine agonist and tamoxifen combination therapy for a prolactin-secreting pituitary tumor resistant to dopamine agonist monotherapy: Case report and review

Background: The majority of prolactin-secreting pituitary macroadenomas are effectively managed with dopamine-agonist therapy alone. Although surgical resection and radiotherapy are second- and third-line treatment options, there remains a paucity of therapies for when these options fail. Case description: We report a woman with a dopamine-agonist resistant macroprolactinoma. She initially presented at 49-years old with irregular menses, a prolactin of 63.1 ng/mL, and a hypoenhancing, 11.5 mm by 15.6 mm by 7.0 mm mass in the left sella. The tumor failed to shrink with bromocriptine. She underwent partial tumor resection with postoperative Gamma Knife radiosurgery. The residual tumor gradually progressed, warranting a second subtotal tumor resection 4 years later with postoperative fractionated radiation. Again, the tumor progressed, and 3 years later, she developed recurrent epistaxis, third nerve palsy, vision loss, and epilepsy. Despite switching to cabergoline therapy and increasing the dose to 4 mg/week, her prolactin rose to 1267 ng/mL. As a palliative measure, a third subtotal tumor resection controlled her epistaxis, and a craniotomy resolved her epilepsy. Despite cabergoline 4 mg/week, the tumor again progressed. Due to the trophic effect of estrogens on lactotrophs and the patient's massive obesity with potential for extraglandular estrogen synthesis, we hypothesized that abnormal estrogen signaling may be contributing to the tumor's growth and dopamine-agonist resistance. Tumor immunohistochemistry demonstrated a prolactin-secreting pituitary tumor that lacked estrogen receptor alpha but stained moderately for estrogen receptor beta. Tamoxifen was added to her cabergoline treatment regimen. Her prolactin decreased to 3 ng/mL over 8 months as the medications were tapered, and her MR scans revealed no residual tumor for the next 14 years until her death of unrelated causes. Conclusions: This case report suggests that tamoxifen's therapeutic effect on a dopamine-agonist resistant macroprolactinoma is not mediated through estrogen receptor alpha but possibly through estrogen receptor beta.