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

Abstract

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.

Diagnostic Utility of the Prolactin Decrease Rate in the Diagnosis of Mild Hyperprolactinemia

“…Furthermore, 14.5% of the patients in the serial measurement group in the present study had stress-related PRL elevation. In contrast, the stress-induced HP percentages found in other studies were, 28.6% [9], 9% [10], 20% [12] and 24.2% [13].…”

“…Previous studies have also shown that clinical ndings are unreliable in patients with mild HP [9,10]. The most important complaint in previous study populations was oligomenorrhea [10,12]. Likewise, oligomenorrhea was the main complaint of patients with HP in the present study.…”

The utility of rested prolactin sampling in the evaluation of hyperprolactinaemia

“…A study of 53 (94% female) included 25 patients taking medication associated with hyperprolactinaemia and did not exclude macroprolactin interference. 9 A study of 66 (92% female) patients, with sampling over 30 min, reported a normal prolactin result in 45 (68%) patients; however, it did not specifically report the number of patients for whom normalisation occurred on the 30-min (as opposed to initial) sample. 10 Our data add to the existing literature by suggesting that a relatively short rest period of 20-40 min is sufficient to identify patients where initial hyperprolactinaemia is attributable to venepuncture stress (consistent with the described half-life of prolactin 4 ), and by specifically clarifying that serial sampling appears to offer no advantage over a single, rested sample.…”

“…Normalisation with serial sampling has been reported in patients with an initially elevated serum prolactin level. [5][6][7][8][9][10][11] However, the rationale for obtaining multiple samples is unclear. We hypothesised that the use of the final, 'most rested' sample would be sufficient to minimise the impact of venepuncture stress.…”

“…Our protocol is to obtain three samples from an indwelling cannula over a 40‐min period (0, 20 and 40 min). Normalisation with serial sampling has been reported in patients with an initially elevated serum prolactin level 5–11 . However, the rationale for obtaining multiple samples is unclear.…”