Prolactin (PRL) Test

The Prolactin Test measures serum prolactin, the anterior pituitary hormone responsible for lactation and, at pathological concentrations, for suppression of gonadotrophin-releasing hormone and consequent hypogonadism. It is ordered in the assessment of galactorrhoea, menstrual disturbance, infertility, unexplained hypogonadism or erectile dysfunction, and suspected pituitary disease, and to monitor patients with known prolactinoma. Interpretation rests on distinguishing three broad explanations for a raised result, in roughly descending order of frequency. Physiological and stress-related elevation is common and mild: prolactin rises with sleep, exercise, nipple stimulation, and the stress of venepuncture itself, and a modest elevation frequently resolves on a calm repeat sample. Drug-induced hyperprolactinaemia is the commonest pathological cause and is substantially more frequent than prolactinoma — antipsychotics, particularly risperidone and amisulpride, along with metoclopramide, domperidone, some antidepressants, and opioids all antagonise dopaminergic inhibition. Pituitary and hypothalamic disease accounts for the remainder, including prolactinoma and stalk compression by non-functioning masses, which raises prolactin by interrupting dopamine delivery rather than by secreting it. Primary hypothyroidism and chronic kidney disease should also be excluded, since both raise prolactin through separate mechanisms. Two analytical phenomena deserve particular attention because both lead to management error. Macroprolactin — prolactin complexed with immunoglobulin G — is immunoreactive but biologically inert, and inflates the measured value in patients with no true hyperprolactinaemia. It accounts for a meaningful proportion of raised results, and failing to identify it leads to unnecessary pituitary imaging and dopamine agonist therapy in patients who require neither; polyethylene glycol precipitation identifies it and should be requested where hyperprolactinaemia is unexplained or discordant with the clinical picture. The high-dose hook effect runs in the opposite direction and is the more dangerous of the two: in a very large macroprolactinoma, prolactin concentrations can be high enough to saturate both capture and detection antibodies in a sandwich immunoassay, producing a falsely low or even normal result. A patient with a large sellar mass and an unremarkable prolactin may therefore have a prolactinoma that would respond to medical therapy rather than a non-functioning adenoma requiring surgery, and serial dilution of the specimen resolves the question.