Hyperprolactinaemia
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Direct answer
Hyperprolactinaemia is an elevated serum prolactin producing galactorrhoea, oligomenorrhoea or amenorrhoea, infertility, low libido and — when a prolactinoma is the cause — mass effects such as headache and bitemporal visual field loss. Causes divide into physiological (pregnancy, lactation, stress), pharmacological (dopamine D2 antagonists — antipsychotics, metoclopramide, domperidone; oestrogens; verapamil), pathological (prolactinoma — microadenoma under 10 mm, macroadenoma 10 mm or more; stalk disease; hypothyroidism; chronic kidney disease) and the assay artefact macroprolactinaemia. After excluding pregnancy, drugs and hypothyroidism, significant elevations warrant pituitary magnetic resonance imaging. Treatment of prolactinoma is dopamine agonist first — cabergoline 0.25-1 mg twice weekly (more effective and better tolerated than bromocriptine), which shrinks most macroadenomas; surgery is reserved for agonist resistance or apoplexy.
What you must remember
- Symptom split by sex: women — galactorrhoea, amenorrhoea, infertility, osteoporosis risk from hypo-oestrogenism; men — low libido, erectile dysfunction, gynaecomastia, often late diagnosis with macroadenoma.
- Physiological suppression: hypothalamic dopamine tonically inhibits prolactin — hence stalk compression raises it modestly (usually under 200 ng/mL) while prolactinomas push it far higher.
- Level-to-lesion logic (a rule of thumb, not a law): prolactin above 200 ng/mL (about 4000 mIU/L) suggests prolactinoma, with macroadenomas commonly over 500 ng/mL; mild rises with a macroadenoma on imaging suggest stalk effect from a non-functioning adenoma — a distinction that changes management entirely.
- Macroprolactin and the hook effect: macroprolactin (polymeric, biologically inactive) causes spurious elevation — request polyethylene glycol precipitation when the level and the clinical picture disagree; the high-dose hook effect can artefactually lower prolactin in giant prolactinomas — dilute the sample.
- Work-up order: pregnancy test, thyroid-stimulating hormone, renal and liver function, drug history; then MRI pituitary with contrast for significant elevations or any visual/neurological sign; formal visual fields for macroadenoma.
- Therapy of choice: cabergoline 0.25 mg twice weekly titrated (usual range 0.25-1 mg weekly in two doses; up to 2 mg weekly in resistant cases) — shrinkage of macroadenoma, restoration of menses and fertility in most; bromocriptine 2.5-7.5 mg daily preferred when pregnancy is planned because of its longer safety record, then discontinued once pregnancy is confirmed in microprolactinoma.
- Dopamine agonist cautions: echocardiographic surveillance for valvulopathy at high cumulative cabergoline doses; start low to avoid orthostatic hypotension and nausea; monitor visual fields rather than rushing to surgery when a macroadenoma abuts the chiasm, since medical shrinkage is often dramatic.
- When surgery or radiotherapy: resistance or intolerance to agonists, apoplexy with deficits, or cerebrospinal fluid leak — trans-sphenoidal surgery in experienced hands.
Sorting a raised level into its cause
A 29-year-old woman presents with six months of amenorrhoea and milky nipple discharge; she takes domperidone for bloating. Step one clears the obvious: pregnancy test negative; thyroid-stimulating hormone mildly raised at 7 mIU/L — hypothyroidism is itself a cause (thyrotropin-releasing hormone stimulates prolactin), so levothyroxine is started and prolactin repeated in eight weeks. It falls but remains 90 ng/mL, and the domperidone is stopped; a further repeat is planned. Only when two reversible causes are removed and the level stays high does imaging enter: MRI shows a 7 mm microadenoma, and cabergoline 0.25 mg twice weekly restores cycles within two months.
The contrast case is the man with bitemporal field loss, impotence and a prolactin of 30 ng/mL with a 3 cm sellar mass: the mild elevation marks stalk effect, and the tumour is a non-functioning adenoma or other mass — treating it as a prolactinoma wastes time while a compressive lesion needs surgery. Reading the level against the mass size is the single most consequential judgement in the topic, and the exam constructs exactly this mismatch to test it.
Where students slip
The persistent error is treating every raised prolactin with cabergoline on day one: the marks lie in the sequence — pregnancy, thyroid, drugs, macroprolactin, then MRI. Second, the stalk-effect mismatch (big tumour, small prolactin rise) is the trap of every exam bank; the mirror mismatch (no tumour visible, huge prolactin) suggests giant prolactinoma with hook effect — dilute the assay. Third, in pregnancy planning bromocriptine's safety record is longest, and agonists are stopped on confirmation of pregnancy in microprolactinoma, with monitoring in macroadenoma. Fourth, oestrogen-deficiency bone loss in long-standing untreated amenorrhoea is a viva addition. Fifth, cabergoline valvulopathy surveillance is the modern detail that separates updated candidates from older question banks.
Frequently asked questions
What are the commonest causes of hyperprolactinaemia?
Pregnancy and lactation, dopamine-antagonist drugs (antipsychotics, metoclopramide, domperidone), hypothyroidism, prolactinoma, and macroprolactinaemia as an assay artefact.
Which drug is first-line for prolactinoma and at what dose?
Cabergoline 0.25-1 mg weekly in two divided doses, superior to bromocriptine in efficacy and tolerance, with shrinkage of macroprolactinomas in most patients.
What is macroprolactin and why does it matter?
Biologically inactive prolactin aggregates causing spuriously high assays with few symptoms; polyethylene glycol precipitation identifies it and avoids unnecessary imaging and treatment.
Why can a large pituitary tumour cause only mild hyperprolactinaemia?
Stalk compression disconnects the pituitary from hypothalamic dopamine, a "stalk effect" (typically under 200 ng/mL), indicating a non-prolactinoma mass rather than a prolactinoma.
Which dopamine agonist is preferred when pregnancy is planned?
Bromocriptine, with the longest pregnancy safety record, discontinued once pregnancy is confirmed in microprolactinoma, with closer monitoring in macroadenoma.