The utility of prolactin serial sampling and the best prolactin cut-offs associated with persistent hyperprolactinemia

BACKGROUND: A single prolactin sampling is recommended for the diagnosis of hyperprolactinemia. We aimed to study the utility of the prolactin serial sampling and to determine the best cut-offs associated with persistent hyperprolactinemia. METHODS: Retrospective study of hyperprolactinemic patients [referral prolactin (rPRL)] that underwent prolactin serial samplings. Prolactin at 0 minutes (PRL0′), 20 to 30, and 40 to 60 minutes. The lowest of these last 2 was defined as nadir prolactin (nPRL). Persistent hyperprolactinemia was defined as nPRL above normal. We excluded patients under dopamine receptor agonists. Receiver-operating characteristic (ROC) curves were used to determine the best rPRL and PRL0′ cut-offs predicting persistent hyperprolactinemia. RESULTS: We studied 53 patients (3 males). Median rPRL 48.0 ng/mL (39.5–72.5), PRL0′ 34.3 ng/mL (18.0–50.8) and nPRL 29.5 ng/mL (11.4–44.4). PRL0′ was elevated in 35 (66.0%) patients and in 7 of them a normal nPRL was reached; therefore 28 (52.8%) had persistent hyperprolactinemia. The area under curve (AUC) for the association between rPRL and persistent hyperprolactinemia was 0.70 (95%CI: 0.56–0.84); best cut-off: 53.4 ng/mL [sensitivity 53.6%, specificity 80.0%, positive predictive value (PPV) 75.0%, and negative predictive value (NPV) 60.6%]. In the 35 patients with elevated PRL0′, the AUC was 0.92 (95%CI: 0.81–1.00); best cut-off: 35.2 ng/mL (sensitivity 85.7%, specificity 85.7%, PPV 60.0%, and NPV 96.0%). CONCLUSIONS: Approximately 1/3 of the patients reached a normal PRL0′. In an additional 20%, prolactin normalized after serial samplings. Patients with rPRL >53.4 ng/mL had 75% probability of having persistent hyperprolactinemia and those with PRL0′ <35.2 ng/mL had a 96% probability of not having persistent hyperprolactinemia.