Abstract
BACKGROUND: Biologically, the monomeric form of prolactin is the most active. In measurement methods, all forms of prolactin are included in the assay; therefore, the presence of macroprolactin, causes a false increase in prolactin and misdiagnosis of hyperprolactinemia. It seems that if an alternative method can be used to check macroprolactin, it would be helpful. The study aims to investigate the urinary level of prolactin and its relationship with serum levels in cases of suspected macroprolactinemia and determine whether these tests can serve as a novel, non-invasive, accessible, and cost-effective tool for diagnosing macroprolactinemia. METHODS: In this cross-sectional study, patients who visited the Tabriz Imam Reza hospital clinic (2020–2021) with elevated prolactin levels. Prolactin and creatinine were checked in the urine and blood samples. After treating the serum with polyethylene glycol to precipitate macroprolactin, serum prolactin was measured again. The patients were divided into two groups. The first group, consisting of 19 individuals, with a recovery rate of more than 60%, formed the hyperprolactinemia group. The second group, comprising 36 individuals with a recovery rate of less than 60%, formed the macroprolactinemia group. RESULTS: The participants in this study were 50 individuals, comprising 10 men and 40 women. The mean urinary prolactin levels in the hyperprolactinemia group are 43.27 ± 15.53, and in the macroprolactinemia group, they are 32.58 ± 16.27. This difference was statistically significant. The median ratio of urinary prolactin to urinary creatinine is 0.03 in the hyperprolactinemia group and 0.02 in the macroprolactinemia group (p<0.05). The median ratio of serum prolactin to urinary prolactin in the hyperprolactinemia group is 32.6, and in the macroprolactinemia group, it is 45.5 (p < 0.01). CONCLUSION: Findings showed that the difference between urinary prolactin in true macroprolactinemic and hyperprolactinemic patients is significant, such that the amount of urinary prolactin in macroprolactinemic patients is less than in hyperprolactinemic patients, and the ratio of serum to urinary prolactin is higher. These parameters can be used to detect macroprolactin in cases of increased serum prolactin level, and this finding could provide a basis for the idea that these parameters can be used as an alternative to the PEG sedimentation test for diagnosing macroprolactin. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12902-025-02052-6.