Category: Pituitary Disorders/Neuroendocrinology
Usually, prolactinomas are very responsive to dopamine agonist therapy, resistance is an infrequent problem occurs in about 10-15% of those treated with cabergoline.
A 39-year-old man was found to have a large suprasellar mass on CT head during the evaluation of a headache and right eye blurry vision. He also has low libido, tiredness, irritable mood, anosmia, cold intolerance, night sweats. On exam, he has right lateral visual field deficit, no signs of acromegaly. MRI Pituitary showed the 6.4x4.7x4.4 cm mass in the sellar, suprasellar regions invading into Right cavernous sinus right side ICA, extending into superior and inferior orbital fissures as well as abutting the medial portions of left cavernous sinus, left ICA, causing mass effect in the midbrain, pons and right mesial temporal lobe, causing compression on the Right Cranial nerves III, V. The pituitary stalk cannot be visualized. Hormonal workup showed inappropriately normal TSH 1.5, low FT4 0.71, prolactin 4700, elevated IGF-1 443(53-331), low testosterone 61 (250-840) but normal ACTH, cortisol, and LH. Cabergoline and levothyroxine were initiated, cabergoline dose was increased from 0.5 mg/wk to 3.5 mg/wk due to lack of response. Baseline ECHO was normal before the dose increase.15 months later he developed CSF leak and had transsphenoidal surgery, tumor debulking with skull base repair. Histology confirmed prolactinoma. After surgery, there was a shrinkage in the tumor size from 6.4 cm to 5.5, 4.7 cm to 4.4 improvements in right eye blurry vision and a decrease in prolactin levels to 2310 from 4700, normalized IGF-1 level. However, 5 months after surgery his prolactin level started rising up to 2858 and his tumor size remained stable even patient had been complaint with cabergoline.
Results : Due to increased prolactin level and stable tumor size, cabergoline dose was increased to 7 mg/wk. 3 months after a dose increase, there was no response in tumor size or prolactin level at that point patient has referred to neurosurgery again. On tumor board discussion the decision was made to repeat TSS, anterior approach with debulking of the accessible tumor and then further evaluation with radiation oncology for possible radiation treatment.
Macroadenomas are more likely to develop dopamine agonist resistance by the decreased number of D2 receptors expressed on resistant prolactinomas.
Conclusion : Overall, control of hyperprolactinemia requires doses of cabergoline ranging from 0.25 to 3 mg/wk; However, occasional patients may require doses up to 11 mg/wk to overcome resistance, caution must be exhibited with protracted use of high dose cabergoline because of the potential risk of cardiac valvular regurgitation.
Endocrine, diabetes and metabolism fellowship
University of Arizona
Jayasree Jonnadula, Endocrine, diabetes and metabolism fellow