Prolactin

Prolactin is a single-chain 199-residue polypeptide from pituitary lactotrophs, structurally related to growth hormone and placental lactogen. It is the one anterior pituitary hormone whose default state is release: hypothalamic dopamine reaches the lactotroph by the portal circulation and tonically inhibits it at the D2 receptor. Interrupt the stalk and prolactin rises while every other pituitary hormone falls - the signature of stalk compression.

That inhibitory control explains most of the pharmacology. Dopamine antagonists such as antipsychotics and metoclopramide raise prolactin, while dopamine agonists lower it, which is why cabergoline is first-line for prolactinoma ahead of surgery. Prolactinomas are the commonest functioning pituitary adenoma, and concentrations scale with tumour size, so values above roughly 200 nanograms per millilitre point to a macroadenoma while modest elevations usually reflect drugs, stress, hypothyroidism or the venepuncture itself.

Interpretation therefore turns on magnitude and cause rather than on the flag beside the number. A mildly raised prolactin in someone taking risperidone is explained; the same value with no drug exposure, a headache and a visual field defect is not. Prolactin also suppresses GnRH pulsatility, so hyperprolactinaemia presents as secondary hypogonadism, amenorrhoea or galactorrhoea, and the reproductive complaint usually arrives before anyone measures it.

Two assay artefacts bite in opposite directions. Macroprolactin, a prolactin-immunoglobulin complex that is inert but immunoreactive, gives a raised result in an asymptomatic patient and is excluded by polyethylene glycol precipitation. The hook effect does the reverse: a very large prolactinoma saturates both antibodies in a sandwich assay and reports a falsely low value, so a large sellar mass with unremarkable prolactin must be rerun at dilution.