Prolactinoma
Commonest functioning pituitary adenoma (~40%). Prolactin-secreting tumour causing hyperprolactinaemia. Presents with galactorrhoea, amenorrhoea/oligomenorrhoea, reduced libido, and infertility. Microprolactinomas (<10mm) are common in women; macroprolactinomas (≥10mm) more common in men. First-line treatment is dopamine agonists (cabergoline), NOT surgery.
Key Facts
Commonest functioning pituitary adenoma (~40%); prolactin (PRL) secretion proportional to tumour size Microprolactinoma (<10mm): common in women (galactorrhoea, amenorrhoea, infertility); PRL usually 1000-5000 mU/L Macroprolactinoma (≥10mm): more common in men (mass effects — headache, visual field loss, hypopituitarism); PRL often >5000 mU/L Important: stalk effect — any large pituitary mass can cause mild PRL elevation (usually <2000 mU/L) by compressing the stalk and preventing dopamine reaching lactotrophs; this is NOT a prolactinoma Hook effect: very large prolactinomas may give falsely NORMAL PRL on immunoassay (antibody saturation); request serial dilutions if macroprolactinoma suspected with 'normal' PRL Treatment: dopamine agonists first-line — cabergoline 0.25-1mg twice weekly (preferred — fewer SE, more effective) or bromocriptine 1.25-7.5mg BD; normalises PRL and shrinks tumour in ~80-90% Surgery (transsphenoidal): only if dopamine agonist intolerant/resistant, or apoplexy/CSF leak
Overview
Key Facts
Prolactinomas are uniquely among pituitary adenomas managed medically first-line. Dopamine agonists are highly effective at both normalising prolactin and reducing tumour size. Surgery is rarely needed.
Epidemiology
Prevalence ~50 per 100,000. Commonest pituitary tumour (~40%). F:M for microprolactinoma ~20:1; macroprolactinoma ~1:1. Peak diagnosis age 20-50.
Aetiology
Sporadic (vast majority). Familial: MEN1 (pituitary adenoma + parathyroid + pancreatic tumour). AIP mutations (familial isolated pituitary adenoma). Lactotroph-specific: somatic mutations in transcription factors.
Pathophysiology
Monoclonal proliferation of lactotroph cells → autonomous prolactin secretion. Prolactin inhibits GnRH pulsatility → hypogonadotrophic hypogonadism (low LH/FSH → low oestrogen/testosterone) → amenorrhoea, anovulation, reduced libido, erectile dysfunction, infertility, osteoporosis (long-term). Prolactin stimulates mammary gland → galactorrhoea.
Clinical Presentation
Women (Usually Microprolactinoma)
- Galactorrhoea (~80%)
- Amenorrhoea/oligomenorrhoea (~90%)
- Infertility (anovulation)
- Reduced libido
- Vaginal dryness
Men (Often Macroprolactinoma — Later Diagnosis)
- Reduced libido, erectile dysfunction
- Infertility (low sperm count)
- Galactorrhoea (uncommon in men — ~20%)
- Gynaecomastia
- Mass effects (macroprolactinoma): headache, bitemporal hemianopia, cranial nerve palsies
- Hypopituitarism (compression of normal pituitary)
Red Flags
- Visual field defect → urgent MRI and visual fields
- Pituitary apoplexy: sudden severe headache, visual loss, meningism, hypopituitarism
- Giant prolactinoma (>4cm, PRL >10,000): more aggressive, may invade cavernous sinus
Differential Diagnosis
| Diagnosis | Key Features | Investigation |
|---|---|---|
| Drug-induced hyperprolactinaemia | Antipsychotics (commonest), metoclopramide, domperidone; PRL usually <3000 | Drug history |
| Stalk effect | Non-functioning pituitary adenoma compressing stalk; PRL <2000 | MRI, PRL level |
| Pregnancy/lactation | Physiological PRL elevation | Pregnancy test |
| Hypothyroidism | TRH stimulates PRL; mild elevation | TFTs |
| PCOS | Mildly raised PRL in ~20% | Testosterone, USS |
| Macroprolactinaemia | PRL bound to IgG (large complexes); biologically inactive | PEG precipitation test |
Diagnosis / Investigation
Biochemical
- Serum prolactin: microprolactinoma typically 1000-5000 mU/L; macroprolactinoma often >5000 mU/L
- PRL >5000: almost certainly prolactinoma
- PRL 1000-2000: could be stalk effect, drugs, or microprolactinoma
- Hook effect: if large pituitary mass with 'normal' PRL → request serial dilutions
- Macroprolactin screen: PEG precipitation — to exclude macroprolactinaemia (asymptomatic, no treatment needed)
Pituitary Function
- LH, FSH, oestradiol/testosterone (hypogonadism)
- TSH, free T4 (exclude hypothyroidism + assess pituitary function)
- Cortisol (9am), IGF-1
Imaging
- Pituitary MRI (gadolinium-enhanced): size, extension, cavernous sinus invasion
- Visual fields: formal perimetry if macroadenoma/chiasmal compression
Other
- DEXA: if chronic hypogonadism (osteoporosis risk)
- Pregnancy test: in women of childbearing age
Management
First-Line: Dopamine Agonists
- Cabergoline 0.25mg twice weekly initially; titrate to 0.5-1mg twice weekly (max 4.5mg/week); preferred — more effective, fewer SE, twice-weekly dosing
- Bromocriptine 1.25mg OD initially; titrate to 2.5-7.5mg BD; more SE (nausea, postural hypotension)
- Response: PRL normalisation in ~80-90%; tumour shrinkage in ~80% (may be dramatic — check MRI at 3-6 months)
- Side effects: nausea (take with food), dizziness, postural hypotension, fatigue; high-dose cabergoline (Parkinson doses) — cardiac valve fibrosis (not significant at prolactinoma doses)
Duration
- Continue for ≥2 years; then consider withdrawal if: PRL normal, tumour significantly shrunk or not visible on MRI, no immediate fertility plans
- ~30% recurrence after withdrawal; monitor PRL 3-monthly for 1 year, then annually
Surgery (Transsphenoidal)
- Indications: dopamine agonist intolerance/resistance (rare), patient preference, CSF leak, pituitary apoplexy
- Cure rate: ~70-80% microadenoma, ~30-40% macroadenoma
Radiotherapy
- Rarely needed; for aggressive/resistant tumours
Pregnancy
- Stop cabergoline once pregnant (most microprolactinomas remain stable)
- Bromocriptine preferred if DA needed during pregnancy (more safety data)
- Macroprolactinoma: higher risk of expansion during pregnancy; close monitoring (visual fields, symptoms)
Referral Criteria
- Endocrinology: all confirmed prolactinomas
- Neurosurgery: if surgery indicated
- Ophthalmology: visual field assessment for macroadenoma
Prognosis
Microprolactinoma: excellent; DA normalises PRL in ~80-90%; many shrink or resolve. Macroprolactinoma: DA highly effective; visual field improvement in >80%. Recurrence after DA withdrawal: ~30%. Surgery: cure rates lower for macroadenoma. Fertility: restored in majority with DA treatment. Long-term: osteoporosis risk if hypogonadism untreated. Malignant prolactinoma: extremely rare.
Other Relevant Information
PRL Level and Diagnosis
| PRL Level (mU/L) | Likely Diagnosis |
|---|---|
| <1000 | Drugs, stalk effect, hypothyroidism |
| 1000-5000 | Microprolactinoma or stalk effect |
| >5000 | Macroprolactinoma |
| >10,000 | Giant prolactinoma |
| 'Normal' + large mass | Hook effect — request dilutions |
Cabergoline vs Bromocriptine
| Feature | Cabergoline | Bromocriptine |
|---|---|---|
| Dosing | Twice weekly | 2-3× daily |
| Efficacy | Higher (~80-90%) | Lower (~70-80%) |
| Side effects | Fewer | More (nausea, dizziness) |
| Pregnancy safety | Less data | More data (preferred in pregnancy) |
| Cost | Higher | Lower |