Elevated Endocan Signals Endothelial Dysfunction in Hyperprolactinemia Patients

Hyperprolactinemia is recognized beyond its reproductive consequences as a potential driver of cardiovascular risk, linked to reduced nitric oxide production, direct vasoconstriction, dyslipidemia, and increased carotid intima-media thickness. Yet traditional cardiovascular biomarkers often fail to capture early vascular injury in this population. This study sought to investigate whether endocan—a soluble dermatan sulfate proteoglycan secreted by vascular endothelium and an emerging biomarker of endothelial dysfunction—is altered in hyperprolactinemic patients.

Researchers enrolled 39 treatment-naive hyperprolactinemic patients of various etiologies and 39 age-, sex-, and BMI-matched healthy controls at Kırıkkale University Faculty of Medicine between December 2023 and June 2024. Both groups were non-smokers, free of chronic disease, and not pregnant. Serum endocan was measured via sandwich ELISA (Elabscience kit), while a comprehensive panel including lipids, CRP, fasting glucose, insulin, HOMA-IR, HbA1c, thyroid function, and CBC was assessed using validated automated analyzers. Anthropometric data including BMI and waist circumference were also recorded.

Despite well-matched baseline characteristics, serum endocan levels were significantly higher in the hyperprolactinemic group (p=0.028). Strikingly, no significant differences were found between groups in lipid profiles, CRP, glucose metabolism markers, or inflammatory indices—suggesting endocan may detect subclinical endothelial stress before conventional markers become abnormal. Mean prolactin was 45.90 ± 2.72 ng/mL in patients versus 12.07 ± 0.46 ng/mL in controls, and 66% of patients fell in the mild hyperprolactinemia range (≤50 ng/mL). Within the patient group, endocan correlated positively with waist circumference, body weight, and BMI, and negatively with WBC count, hinting at interplay between adiposity, immune modulation, and endothelial activation.

The biological plausibility is supported by prolactin's known effects on vascular endothelium: it suppresses nitric oxide synthesis, promotes vasoconstriction, and stimulates endothelial proliferation—mechanisms that collectively drive endocan release. The fact that elevated endocan appeared even in mildly hyperprolactinemic patients is clinically notable, as this subgroup is often considered lower risk and may not receive early intervention.

The authors acknowledge important limitations: the study is small (n=78 total), cross-sectional, and limited to a single center. Causal inference cannot be drawn, and the study does not track cardiovascular outcomes. Nonetheless, the results provide a first-of-its-kind signal that endocan may serve as an earlier, more sensitive vascular biomarker in hyperprolactinemia, warranting larger prospective trials with clinical endpoint data.