Surgical Management of Prolactinomas

Background: Nowadays dopamine agonists (DA) are recommended as the treatment of choice for patients with prolactinomas of any size in order to lower prolactine (PRL) levels, decrease tumor size, and restore gonadal function. However, some patients do not adequately respond to DA, and resistance may occur in 20 to 30% of patients treated with bromocriptine and nearly 10 to 20% of those receiving cabergoline. It is known that treatment of prolactinomas with DA is accompanied by relapses of the disease after discontinuation of a treatment in about 50% of cases and a long-term or lifelong medication is required. Recent evidence also supports the use of surgery as first-line therapy for patients with enclosed and not invasive prolactinomas.

Objective: The aim of the study was to evaluate the effectiveness of surgery in achieving remission or biochemical control of the disease.

Methods: We prospectively enrolled 46 consecutive patients with prolactinomas who underwent transsphenoidal surgery (TSS) performed by a highly qualified surgeon. We evaluated the invasiveness of prolactinomas on the Knosp grading scale and measured serum prolactin concentrations on the first postoperative day. Routine histological assessment of the Ki-67 proliferation index was performed. The level of PRL was assessed in the early and in the late postoperative periods. Pituitary MRI with contrast enhancement in 3, 6, and 12 months after surgery was performed.

Among 46 operated patients 32% achieved complete recovery and met the remission criteria during the entire follow-up period. Adenomas, in all patients’ cases who achieved remission, were noninvasive (Knosp 0, 1) and non-aggressive (Ki-67 <3%). The average level of PRL on the first day after surgery was 295.2 mMEd/L (p > 0.1). Biochemical control was achieved in 28%. In this group, 44% had noninvasive adenomas (Knosp 0, 1), 56% had invasive adenomas (Knosp 2, 3). Ki-67 was <3% in all removed tumor tissues. The average value of PRL on the first day after surgery was 1,244 mMEd/L. A significant reduction in the volume of prolactinomas after surgical resection (>80%) made it possible to normalize the level of PRL against the background of lower doses of cabergoline, compared with doses of the drug taken before surgery. Patients who did not achieve postoperative remission and biochemical control accounted for 40% of the total number of patients. This group consisted of individuals with large (> 4 cm) and giant (> 6 cm) invasive tumors (Knosp 3, 4). Ki-67 was mostly ≥3%, which corresponded to a high degree of invasiveness and aggressiveness of the tumor. The average value of PRL on the first day after surgery in this group was 19,348 ± 7,816 mMEd/L. All patients had absolute indications for emergency surgery.

Transnasal transsphenoidal adenomectomy leads to complete postoperative remission in 32% of cases and in 28% of cases it allows to achieve biochemical control of the disease while taking cabergoline. Radiological assessment of prolactinoma invasiveness and early postoperative serum prolactin concentrations are important predictors of early remission after surgery. Given excellent results of TSS and concerns about medical treatment, the scale of indications for TSS as an alternative to DA has increased.

Publication History

Article published online:
07 February 2025