Hyperprolactinemia: NP Workup

Prolactin is secreted by lactotroph cells in the anterior pituitary and is unique among pituitary hormones in being under tonic inhibitory control by dopamine from the tuberoinfundibular pathway. Dopamine acts on D2 receptors on lactotrophs, inhibiting both prolactin synthesis and secretion. Any interruption of this dopaminergic inhibition causes hyperprolactinemia. Causes are classified as: physiological (pregnancy — estrogen stimulates lactotroph hyperplasia; lactation; stress; sleep), pharmacological (most common pathological cause — antipsychotics, metoclopramide, and other D2 receptor blockers; SSRIs; verapamil), and pathological (prolactinoma — micro < 10 mm or macro ≥ 10 mm; stalk effect — any sellar/suprasellar mass compressing the pituitary stalk interrupts dopamine delivery, causing mild hyperprolactinemia < 200 ng/mL; hypothyroidism — TRH stimulates prolactin; CKD — reduced prolactin clearance). The degree of prolactin elevation helps differentiate: mild (25-100 ng/mL) suggests medication, stalk effect, hypothyroidism; moderate (100-250) may be microprolactinoma or stalk effect; markedly elevated (> 250) is virtually diagnostic of macroprolactinoma. The 'hook effect' — a laboratory artifact — can cause falsely low prolactin in very large macroprolactinomas; serial dilution of the sample corrects this.