Prognostic value of postoperative day 1 prolactin following prolactinoma resection

OBJECTIVE: The aim of the study was to evaluate the predictive value of postoperative day 1 (POD1) prolactin on long-term hyperprolactinemia normalization following prolactinoma resection. METHODS: The authors retrospectively reviewed 260 prolactinomas that were resected from 1998 to 2020. Patients were classified on the basis of preoperative dopamine agonist (DA) use: the DA-positive group (n = 112 [43.1%]) used DAs < 3 weeks prior to surgery, while the DA-negative group (n = 148 [56.9%]) did not. The prolactin level (ng/ml) was categorized as follows: low normal (0-10 ng/ml for men, 0-12.5 ng/ml for women), high normal (10-20 ng/ml for men, 12.5-25 ng/ml for women), and mildly hyperprolactinemic (20-40 ng/ml for men, 25-50 ng/ml for women). Prolactins were analyzed at 6 time points: POD1, 1 day to 6 weeks, 6-12 weeks, 12 weeks to 6 months, 6 months to 1 year, and > 1 year. The authors identified cases with POD1 normalization, followed by hyperprolactinemia requiring treatment, multiple elevated prolactins, or hyperprolactinemia at latest follow-up, defining rebound hyperprolactinemia as these events that occurred < 1 year of surgery and recurrent hyperprolactinemia as these events that occurred ≥ 1 year after surgery. Remission was defined as persistent normalization during the 1st year. RESULTS: The mean (SD) age was 35.4 (11.4) years. In total, 78.1% (n = 203) of patients were female. In the DA-negative group, 78.9% of mildly hyperprolactinemic patients had persistent elevation, while 90.2% and 37.0% of low- and high-normal patients achieved remission, respectively. For the DA-positive group, 81.8% of mildly hyperprolactinemic DA-positive patients remained with elevated prolactin levels, whereas 72.6% and 50.0% of low- and high-normal patients experienced remission, respectively. Rebound rates were 2.0% versus 33.3% in low-normal versus high-normal DA-negative patients and 12.6% versus 33.3% in low-normal versus high-normal DA-positive patients. Recurrence rates were 7.8% versus 25.9% in low-normal versus high-normal DA-negative patients and 11.6% versus 16.7% in low-normal versus high-normal DA-positive patients. The cumulative incidence rates of rebound (p < 0.001) and recurrent (p < 0.001) hyperprolactinemia varied by group, with low-normal DA-negative patients being the least likely to experience either outcome. For DA-positive (p < 0.001) and DA-negative (p < 0.001) patients, retreatment during the 1st year after surgery was more often required in mildly hyperprolactinemic (47.4% of DA-negative patients vs 81.8% of DA-positive patients) and high-normal (18.5% DA-negative vs 33.3% DA-positive) patients than low-normal patients (1.0% DA-negative vs 18.1% DA-positive). CONCLUSIONS: POD1 prolactin is associated with long-term normalization following prolactinoma resection. However, patients should not be considered cured solely on the basis of the POD1 prolactin level, as rebound hyperprolactinemia can occur, particularly with recent DA use or a high-normal POD1 prolactin level.