In patients with mild HP, the serial measurement method combined with the use of PCR and PDR for the diagnosis of prolactinoma and HP offers better management of the diagnostic process than the single measurement method. 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].
It is important to consider whether the serial measurement time period used in a study could affect its results. For example, Whyte et al. [10] used a cannula and extended the measurement period to 120 min; as noted above, they observed a stress-induced HP rate that was lower than the one in the present study (9% vs 14.5%). Although there is no consensus on how long serial measurement should be extended [8]. Tsur et al. [13] found that it PRL returned to normal at 60 min in 86 patients (24%) and at 90 min in 87 patients (24.2%); thus, prolonging the test period did not significantly contribute to the diagnostic process. Meanwhile, previous studies have stated that stress-related PRL elevation stems from a fear of blood drawing [7, 14]. However, the stress-related PRL elevation results in previous studies were similar to that of the present study, which examined blood samples taken using the venous puncture method, suggesting that PRL elevation may be independent of a fear of venous puncture.
Previous studies have also shown that clinical findings 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. In those with stress-induced HP, hirsutism and oligomenorrhea were detected at the same rate; however, oligomenorrhea and galactorrhea were not detected in any of the stress-induced HP patients. However, oligomenorrhea or galactorrhea were found in 36% and 14% of those without HP, respectively. In addition, Whyte et al. [10] found true HP in 17 (60%) of 28 asymptomatic patients. In the present study, HP was detected in 30 (23.3%) of the 129 patients without oligomenorrhea or galactorrhea. True HP can be detected in a significant portion of patients without a clinic, on the other hand HP may not be detected in those patiens with HP symptoms, which suggests that symptoms and clinical signs alone are not reliable in the management of patients with mild HP.
In the present study, PDR and PCR contributed to the diagnosis of HP and prolactinoma; such contributions have not been evaluated in previous studies. A PCR score of 79.4% or higher was present in all HP cases with microadenomas, and a PCR score of 88.2% or higher was present in all HP cases with macroadenomas. The present study’s findings indicated that PCR was better for demonstrating the presence of prolactinoma, while PDR was better for excluding prolactinoma. The ROC analysis revealed that measurements of rPRL, basal and PRL levels at 60 min were similarly reliable in the diagnosis of prolactinoma. As a result, serial PRL measurement should be used instead of single PRL measurement to determine the presence or absence of HP. In addition, since incidental pituitary adenomas are common in the normal population, PCR or PDR scores can guide the diagnosis and treatment of prolactinoma.
Although serial PRL measurement is typically performed in patients with mild HP and a second confirmation with mPRL is performed in cases of clinical uncertainty, the present study shows that these methods can be used together to exclude HP in a significant proportion of patients, regardless of clinical findings. Interestingly, the mPRL rate was higher in the serial measurement group than in the single measurement group, demonstrating the greater accuracy of the serial measurement method. However, similar findings or analyses were not found in the literature.
Although, as mentioned above, the guidelines recommend looking at symptoms and clinical findings first and then requesting mPRL in cases of laboratory and clinical inconsistencies [8], it is difficult to say that clinical findings alone are sufficient for the diagnosis of HP. In the present study, we assumed that routine mPRL was requested from a population of 100 people for the diagnosis of HP. In the serial measurement group, HP was excluded in 37 patients during the first stage (0 min: 22, 60 min: 15). mPRL was requested for the remaining 63 patients, leading to the exclusion of another 43 patients. Thus, these two methods were used to exclude HP in a total of 80 patients. In contrast, in the single measurement group, HP was initially excluded in 17 patients. mPRL was requested for the remaining 83 patients, leading to the exclusion of another 30 patients. Thus, this method excluded a total of 47 patients. In other words, the serial measurement method ultimately led to the exclusion of HP in 33 more patients than the other method (p < 0.001). As such, the use of the serial measurement technique followed by mPRL seems to support more accurate management of patients.
Regarding the limitations of the present study; using venous puncture in the serial PRL measurement method and performing it for 60 minutes may have prevented the detection of stress-induced HP in some patients. In addition, the retrospective nature of the study may have caused difficulties in obtaining patient data and the uneven distribution of the groups; therefore, some important findings may have been overlooked.
In conclusion; the serial PRL measurement method combined with the use of PCR and PDR for the diagnosis of prolactinoma and HP appears to be more reliable than the single measurement method. Furthermore, serial PRL measurement combined with mPRL detection is the most accurate method of HP exclusion.
Headings:
Clinical findings are unreliable in the diagnosis process of patients with mild hyperprolactinemia.
Since incidental pituitary adenomas are common in the normal population, prolactin constant ratio or prolactin decrease rate scores can guide the diagnosis and treatment of prolactinoma.