Prolactinoma

Overview

•Dopamine from hypothalamus tonically inhibits prolactin via D2 receptors on lactotrophs - remove this brake (tumour, drug, stalk compression) and prolactin rises

•Excess prolactin suppresses GnRH → reduced LH/FSH → hypogonadotropic hypogonadism (amenorrhoea, infertility, low testosterone)

•Prolactin also acts directly on breast tissue → galactorrhoea

Presentation

•Headache - expansion within sella stretches diaphragma sellae; bifrontal or retro-orbital

•Bitemporal superior quadrantanopia - tumour grows upward, compressing inferior fibres of optic chiasm first (inferior fibres carry superior temporal visual field information)

•Bitemporal hemianopia - complete chiasmal compression with larger tumours; patients bump into things at the periphery

•Galactorrhoea - inappropriate milk production; more common in women

•Amenorrhoea/infertility - women present earlier; men present later with larger tumours and more mass-effect features

•Hypopituitarism - large tumours compress normal pituitary (low TSH, ACTH, GH, FSH, LH)

⚠️

The COCP can mask amenorrhoea caused by a prolactinoma. A woman on the pill with absent periods, or who never had regular periods before starting it, should have prolactin measured regardless.

Investigations

🥇 First-line

•serum prolactin - levels >5000 mIU/L strongly favour macroprolactinoma over drug-induced causes; exclude pregnancy first

•TFTs and renal function - exclude hypothyroidism and renal failure as secondary causes

•medication review - dopamine antagonists (antipsychotics, metoclopramide, domperidone) are a common reversible cause

•full anterior pituitary profile (IGF-1, cortisol, TSH/fT4, LH, FSH, testosterone/oestradiol) - assess for hypopituitarism

•formal visual field assessment (Goldmann or Humphrey perimetry) - mandatory if MRI shows suprasellar extension

🏆 Gold standard

•MRI pituitary with gadolinium - confirms tumour size, location, suprasellar extension; distinguishes prolactinoma from non-functioning adenoma

⚠️

Hook effect: at very high prolactin concentrations (>10,000 mIU/L), immunoassays may give a falsely low result due to antibody saturation. If a large pituitary mass is present but prolactin appears only mildly raised, request a diluted sample - missing this could lead to unnecessary surgery on a giant prolactinoma.

Differential Diagnosis

🎯

Distinguishing prolactinoma from stalk compression is critical: prolactinoma (prolactin typically >5000 mIU/L) is managed medically; non-functioning adenoma causing stalk effect (prolactin usually <2000 mIU/L) usually requires surgery.

Management

🥇 First-line

•cabergoline (dopamine D2 agonist) - preferred; once or twice weekly dosing, better tolerability, greater efficacy; typical starting dose 0.5 mg twice weekly, titrated to response

•First-line alternative: bromocriptine - daily dosing, more side effects (nausea, postural hypotension); preferred in pregnancy (more safety data)

🥈 Second-line

•transsphenoidal surgical resection - if dopamine agonist intolerance/resistance, acute visual deterioration despite medical therapy, cystic tumour, or patient preference

🥉 Third-line

•stereotactic radiosurgery (e.g. Gamma Knife) - residual or recurrent tumour after surgery

•Therapy can often be withdrawn after 2 years of normal prolactin if MRI shows no residual tumour; monitor prolactin after cessation as rebound hyperprolactinaemia occurs in a proportion

💡

In women seeking pregnancy: stop dopamine agonist once pregnancy is confirmed in microprolactinoma (low growth risk). In macroprolactinoma, tumour may expand during pregnancy (oestrogen stimulates lactotrophs) - specialist input essential; bromocriptine preferred if treatment must continue.

Complications

•Osteoporosis - prolonged hypogonadism reduces bone mineral density; mostly reversible with treatment

•Progressive visual loss - chiasmal compression; typically improves rapidly with cabergoline as tumour shrinks

•Pituitary apoplexy - haemorrhage/infarction into tumour; sudden severe headache, ophthalmoplegia, visual loss; neurosurgical emergency

•Dopamine agonist side effects - nausea, postural hypotension, impulse control disorders (gambling, hypersexuality at higher doses); cardiac valvulopathy at high cumulative doses