Galactorrhea

Galactorrhea is the non-puerperal secretion of milk or milk-like discharge from the breast, resulting from dysregulated prolactin signaling on mammary epithelial cells. Prolactin is synthesized and secreted by lactotroph cells of the anterior pituitary, and its regulation is unique among pituitary hormones - it is predominantly under tonic inhibitory control by hypothalamic dopamine (prolactin-inhibiting factor). Dopamine released from tuberoinfundibular dopaminergic (TIDA) neurons in the arcuate nucleus travels via the hypophyseal portal system to the anterior pituitary, where it binds dopamine D2 receptors on lactotroph cell membranes. D2 receptor activation inhibits adenylyl cyclase, reduces intracellular cAMP, and suppresses prolactin gene transcription (Pit-1 transcription factor pathway) and prolactin secretion. Any process that disrupts dopamine synthesis, transport, or D2 receptor signaling will release lactotrophs from tonic inhibition and cause hyperprolactinemia. Prolactinomas (lactotroph adenomas) are the most common functioning pituitary adenoma, accounting for 40-50% of all pituitary tumors. They arise from monoclonal lactotroph proliferation - somatic mutations in genes involved in cell cycle regulation (MEN1, AIP, CDKN1B) have been identified. Microprolactinomas (<10 mm) are far more common than macroprolactinomas (≥10 mm). Prolactin levels generally...