Precision Medicine in Prolactinomas: From Bench to Bedside

Lactotroph adenomas (prolactinomas, PRLomas) are the most frequently diagnosed pituitary neuroendocrine tumors and originate from anterior pituitary lactotroph cells. Excess prolactin secretion is the defining feature and typically leads to reproductive/endocrine dysfunction; when lesions enlarge, symptoms related to local compression may also occur. In clinical practice, microadenomas are reported predominantly in women, whereas men more often present with macroadenomas, a distribution that may relate to differences in symptom recognition and time to diagnosis. Current mechanistic data support a multifaceted model in which estrogen-related signaling, inherited or acquired genetic/epigenetic alterations, and dysregulated pathways, including PI3K/AKT/mTOR and RAS/RAF/MEK/ERK, intersect to promote tumor growth and functional activity. Patients therefore present along a spectrum, ranging from hypogonadism, infertility, and sex-specific manifestations to visual compromise, cranial neuropathies, or hypopituitarism in advanced disease. Dopamine agonists (DAs), particularly cabergoline, remain the standard first-line therapy; however, endoscopic surgery is increasingly used in selected patients (e.g., wellcircumscribed microadenomas and carefully chosen macroadenomas in experienced centers). For aggressive, DA-resistant, or malignant PRLomas, temozolomide remains the main systemic salvage option, and immunotherapy is being explored in early-phase settings. A precision approach will likely depend on integrating molecular stratification with clinical behavior to individualize treatment sequencing and improve long-term control and quality of life.