Surgical Management of Giant Prolactinomas

Giant prolactinomas (GPs) are rare lactotroph pituitary tumors >4 cm, and are less likely than other prolactinomas to reach remission with dopamine agonist (DA) therapy. Herein our institution’s experience with the surgical management of GPs is described.

Methods:

A retrospective chart review (2003-2018) was conducted on patients with pathology-proven functional prolactinomas. GPs were identified by tumor size on pre-operative imaging. Descriptive statistics were used.

Results:

Of 79 prolactinoma cases, 8 patients (10%) had a GP. The median age was 38 years (range: 20-53) and 6 (75%) were male. All patients presented with symptoms of mass effect. Median maximum tumor dimension was 6 cm (range: 4.6-7.7 cm); all had evidence of optic chiasm compression and cavernous sinus invasion. Of the 7 patients who had pre-treatment lab work, the prolactin level median was 2,500 µg/L (range: 100-13,000 µg/L). All 7 presented with hypogonadism, 2 had adrenal insufficiency, and 2 had central hypothyroidism. Initial cabergoline therapy was given to 6 patients at a median of 2.5 mg/week (range: 1.0-3.5 mg/week) for 6 months. No prolactin level normalized, and tumor diameter decreased by only 4% (range: 35% decrease-30% growth). Transsphenoidal surgery (TSS) was performed in these 6 for DA resistance and/or intolerance. Two patients did not try initial DA therapy because they were not diagnosed as GP upon presentation; both underwent craniotomy instead of TSS. No tumor resections were complete by either surgical approach. All tumors were benign with diffuse prolactin staining. Two tumors co-stained (scattered GH/TSH in one, scattered ACTH in another) but neither had biochemical nor clinical evidence of hormone co-secretion. All had persistence of hyperprolactinemia requiring post-operative DAs. Four patients (50%) reported DA side effects such as psychosis requiring dose decrease (N=2) or discontinuation (N=2). After surgery, all 8 patients had hypogonadism, 5 had adrenal insufficiency, and 7 had central hypothyroidism. Three patients had improved vision. Post-operatively, one patient had a stroke, and two had transient diabetes insipidus. Remission as defined by prolactin normalization occurred in 5 patients at a median time of 36 months (range: 14-63 months) on DA therapy after surgery with a follow up of 3-13 years.

Discussion/Conclusion:

GPs infrequently require surgical resection for DA resistance or intolerance, visual impairment, or pituitary tumor apoplexy. Generally, incomplete resection occurs requiring adjuvant therapy. Given the rarity of surgery for GPs, multi-institutional and/or registry studies may yield clearer guidance on optimal management of this entity.