Title : Autoimmune signatures in hyperprolactinemia
Abstract:
Background: Hyperprolactinemia is a common endocrine disorder that affects reproductive health and has increasingly been linked with immune dysregulation. Although prolactin is recognized for its immunomodulatory functions, the relationship between elevated prolactin levels and autoimmune activity remains insufficiently understood. This study explored whether specific immune markers are associated with different forms of hyperprolactinemia and whether these changes differ between true hyperprolactinemia and macroprolactinemia.
Methods: A hospital-based observational study included 102 patients with pathological hyperprolactinemia (serum prolactin >100 ng/mL) and 24 healthy controls. Patients were categorized into idiopathic, pituitary adenoma-associated, drug-induced, and secondary hyperprolactinemia. Direct immune markers (IL-2, IL-4, IL-5, and IFN-γ) and indirect autoimmune markers including anti-thyroid peroxidase (anti-TPO), anti-thyroglobulin (anti-Tg), anti-cyclic citrullinated peptide (anti-CCP), VDRL, platelet count, and activated partial thromboplastin time were evaluated using validated laboratory techniques. Statistical comparisons were performed using non-parametric methods.
Results: Serum IL-4 concentrations were consistently higher in patients with hyperprolactinemia than in healthy controls, irrespective of the underlying cause. Anti-TPO antibody levels were also significantly elevated, particularly among patients with idiopathic and drug-induced hyperprolactinemia. In contrast, IL-2, IFN-γ, IL-5, anti-Tg, and anti-CCP did not demonstrate meaningful differences across groups. Furthermore, autoimmune marker profiles were largely comparable between macroprolactinemia and true hyperprolactinemia, suggesting that both conditions share similar immune characteristics.
Conclusion: The findings indicate that elevated IL-4 and anti-TPO antibodies may represent early immunological alterations associated with hyperprolactinemia, even in the absence of overt autoimmune disease. These biomarkers could serve as useful indicators for identifying patients who may benefit from long-term surveillance for autoimmune disorders, particularly autoimmune thyroid disease. The study contributes to a better understanding of the complex interaction between endocrine and immune pathways and highlights the need for integrated clinical monitoring in patients with persistent hyperprolactinemia.

