Prolactinoma and hyperprolactinaemia

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Prolactin is tonically inhibited by hypothalamic dopamine. A lactotroph adenoma releases prolactin autonomously, while any lesion interrupting the stalk can lift dopamine restraint. The magnitude of elevation, tumour volume and clinical context therefore need to be coherent, with assay artefact addressed before an operation is planned.

The cost of prolonged hyperprolactinaemia is primarily hypogonadism. Men may present late with sexual dysfunction, infertility or a large tumour; women often present earlier through cycle change. Bone density can fall in either sex. Direct breast symptoms help recognition but do not measure severity and may be absent in marked disease.

Cabergoline treatment is longitudinal shared decision-making. Dose is titrated against prolactin and MRI rather than symptoms alone, while nausea, postural hypotension, somnolence, impulse-control change and fibrotic or valvular risk are monitored. Withdrawal may be attempted in carefully selected sustained remission, with a plan for biochemical recurrence.

Key points

Hyperprolactinaemia suppresses pulsatile GnRH, reducing LH and FSH and causing amenorrhoea, anovulation, infertility, low libido, erectile dysfunction and bone loss; galactorrhoea is neither necessary nor specific.
Before calling a pituitary tumour, exclude pregnancy, primary hypothyroidism, renal or hepatic disease, chest-wall stimulation and medicines such as antipsychotics, metoclopramide, domperidone, opioids and some antidepressants.
Repeat a modest prolactin under calm sampling conditions and ask the laboratory about macroprolactin when symptoms and result disagree; venepuncture stress can raise the concentration.
A large sellar lesion with only modest prolactin requires assay dilution to exclude the hook effect, while stalk compression usually causes a lesser elevation through lost dopamine inhibition.
Dedicated pituitary MRI, formal fields when the chiasm is threatened and the full pituitary profile complete classification; image only after obvious physiological and medicine explanations are assessed appropriately.
Cabergoline is first-line for most prolactinomas because it lowers hormone and shrinks tumour; a visually compressive macroprolactinoma often improves medically but needs close early objective review.
Dopamine agonists can restore ovulation before menstruation returns, so contraception or planned conception advice must accompany the first prescription.
Transsphenoidal surgery is considered for intolerance, true resistance, selected cystic or compressive disease, CSF leak or patient preference in an experienced pituitary centre.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Prolactin-secreting pituitary adenoma

A lactotroph adenoma releases prolactin autonomously and may also compress normal gland or optic pathways as it enlarges.

Reduced dopamine inhibition

Dopamine-antagonist medicines and pituitary stalk interruption remove tonic hypothalamic restraint, raising prolactin without a lactotroph tumour.

Physiological or systemic elevation

Pregnancy, lactation, stress, hypothyroidism, kidney disease and other systemic contexts can raise prolactin and must be interpreted before imaging.

Analytical macroprolactin

Biologically less active prolactin complexes can produce a high assay result with few compatible symptoms, requiring laboratory clarification.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Prolactin concentration rises
Autonomous secretion or lost dopamine restraint increases circulating prolactin beyond its normal reproductive and lactational context.
2
Gonadotrophin signalling is suppressed
Raised prolactin reduces hypothalamic reproductive drive, lowering LH and FSH and therefore sex-steroid production, ovulation or spermatogenesis.
3
Mass effect may develop
An enlarging adenoma compresses normal pituitary tissue, optic chiasm or cavernous sinus and can create multiple hormone deficits.
4
Bone exposure declines
Chronic sex-steroid deficiency increases bone turnover and gradually reduces bone density in any sex as the process continues.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Female hypogonadism

Oligomenorrhoea, amenorrhoea, anovulation, subfertility, vaginal dryness or low libido can precede headache or radiological diagnosis.

Male hypogonadism

Reduced libido, erectile dysfunction, infertility, lower shaving frequency, gynaecomastia or reduced muscle can reflect prolactin-mediated gonadotrophin suppression.

Galactorrhoea

Milk production outside pregnancy and lactation supports prolactin effect but may occur with medicines or chest stimulation and can be absent in men and oestrogen-deficient women.

Macroadenoma effect

Headache, bitemporal field loss, colour change, diplopia or other pituitary deficits indicate mass effect and increase urgency of imaging and visual assessment.

Medicine association

Temporal relation to dopamine antagonists, antipsychotics, opioids or verapamil can explain the result, but abrupt withdrawal of essential psychiatric therapy is unsafe.

Pregnancy context

Physiological prolactin rises during pregnancy, while a pre-existing macroprolactinoma can enlarge and should be managed from a preconception pituitary plan.

Red flags requiring action

Acute severe headache, visual loss, ophthalmoplegia or reduced consciousness suggests pituitary apoplexy and requires emergency cortisol and neurosurgical management.
Rapidly progressive visual field or acuity deficit from a macroadenoma needs same-day pituitary review and cannot wait for slow outpatient dose titration.
A large lesion with low cortisol, hypotension, vomiting, hyponatraemia or hypoglycaemia may have ACTH deficiency requiring immediate glucocorticoid protection.
Clear rhinorrhoea developing after rapid dopamine-agonist tumour shrinkage can represent CSF leak and needs urgent skull-base assessment because of meningitis risk.
Severe headache or new visual symptoms during pregnancy in a patient with macroprolactinoma requires urgent endocrine, obstetric and neuro-ophthalmic evaluation.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
Repeat serum prolactinFirst step
Why
Confirm persistence and judge the magnitude under conditions that minimise transient stress elevation.
Interpretation and limitations
Relate the result to sex, pregnancy, symptoms, medicines and assay range; serial values from the same laboratory help treatment follow-up.
02
Macroprolactin screen
Why
Detect immunoreactive high-molecular-weight prolactin when laboratory elevation and clinical phenotype are discordant.
Interpretation and limitations
A predominance of macroprolactin may explain few biological symptoms, but monomeric prolactin and imaging indications still need correct laboratory reporting.
03
Diluted prolactin assay
Why
Exclude high-dose hook artefact when tumour size greatly exceeds the reported hormone concentration.
Interpretation and limitations
A dramatic rise after dilution reclassifies the lesion as macroprolactinoma and can change first-line treatment from surgery to dopamine agonist.
04
Pregnancy thyroid renal and liver tests
Why
Identify physiological and systemic causes that should be addressed before tumour attribution.
Interpretation and limitations
Primary hypothyroidism raises TRH-driven prolactin, reduced renal clearance elevates concentrations, and pregnancy makes usual reference interpretation inappropriate.
05
Dedicated pituitary MRI
Why
Define adenoma size, chiasm relationship, cavernous invasion and alternative stalk or sellar pathology.
Interpretation and limitations
Micro- or macroadenoma classification supports monitoring, but imaging does not prove secretion; correlate with diluted prolactin and the remaining axes.
06
Full pituitary and visual assessment
Why
Detect compressive deficits and establish safe baseline function before therapy.
Interpretation and limitations
Cortisol has immediate priority; formal fields are required for optic contact, and testosterone or oestradiol with gonadotrophins quantifies hypogonadism.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Medicine-induced hyperprolactinaemia

Dopamine-antagonist exposure with a temporally coherent rise suggests a pharmacological cause, but medicines should not be stopped unsafely.

Stalk-effect elevation

A non-prolactin sellar mass can raise prolactin by interrupting dopamine delivery, usually with imaging and hormone findings disproportionate to secretion.

Primary hypothyroidism

Low thyroid hormone increases hypothalamic stimulation and can raise prolactin; the high TSH and low free T4 pattern identifies gland failure.

Macroprolactinaemia

Marked assay elevation with limited biological symptoms may reflect macroprolactin rather than active monomeric hormone excess.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01CONFIRMRaised prolactin resultFirst stepA laboratory concentration is above the reference range without an established prolactinoma.

1Check pregnancy, symptoms, stress, breast or chest stimulation, thyroid, renal and hepatic function and every relevant prescription or recreational drug.
2Repeat modest elevations and request macroprolactin evaluation when biology and concentration do not align.
3If a large lesion or mass symptoms are present, obtain diluted prolactin urgently to exclude the hook effect and assess all pituitary axes.
4Arrange dedicated MRI and specialist referral when persistent monomeric elevation, significant symptoms or tumour concern remains.

02STARTDopamine-agonist treatmentA symptomatic microprolactinoma or macroprolactinoma is confirmed and medicine is appropriate.

1Discuss goals, pregnancy plans, contraception, baseline cardiac or fibrotic history, mental health and medicines that antagonise dopamine action.
2Begin low-dose cabergoline with food using the specialist schedule and titrate from prolactin, vision and imaging rather than chasing rapid biochemical normality.
3Review a compressive macroadenoma early with formal fields and urgent access for headache, clear rhinorrhoea or worsening sight.
4Continue the lowest effective dose, documenting adverse effects and the SmPC or local echocardiography surveillance plan.

03PREGNANCYConception and pregnancyA person with prolactinoma wishes to conceive or becomes pregnant during dopamine-agonist therapy.

1Before conception, document tumour size, fields, pituitary reserve and a plan for stopping or continuing medicine based on individual growth risk.
2Explain that fertility can return before regular cycles and coordinate cabergoline decisions with the specialist team rather than using a blanket rule.
3During pregnancy, monitor clinically for headache and visual change; routine prolactin concentrations do not reliably track tumour enlargement.
4Investigate new symptoms urgently with pregnancy-appropriate MRI and multidisciplinary endocrine-obstetric-neurosurgical care.

04RESISTInadequate response or intoleranceProlactin and tumour fail to improve on a tolerated regimen, or adverse effects prevent treatment.

1Verify diagnosis, adherence, dose, assay, medicine antagonists and whether the lesion is truly a prolactinoma rather than stalk effect.
2Optimise dopamine agonist under the pituitary specialist while monitoring vision and impulse-control, psychiatric and cardiovascular harms.
3Discuss transsphenoidal surgery for genuine resistance, intolerance, progressive compression, CSF leak or informed patient preference.
4Reserve radiotherapy and oncological options for aggressive refractory disease after expert pathology and multidisciplinary review.

Key medicines and prescribing safety3 treatments · regimens, roles and cautions

Activate lactotroph D2 receptors, lower prolactin, restore gonadal function and shrink most prolactinomas.

Cabergoline

The current SmPC starts hyperprolactinaemia treatment at 0.5 mg weekly in one or two doses, with gradual specialist titration to response.

Give with food and review postural hypotension, nausea, somnolence, impulse-control or psychiatric effects; use baseline and follow-up cardiac-fibrosis assessment according to SmPC and local policy.

Provide an alternative dopamine agonist for prolactin suppression and tumour control.

Bromocriptine

Use a low starting dose with food and increase slowly under the current BNF regimen when cabergoline is unsuitable or a pregnancy pathway favours it.

Nausea, postural hypotension, headache, sleepiness and psychiatric effects can limit adherence; check interactions and avoid abrupt unsupervised changes around pregnancy.

Protect symptoms, sexual function and bone when hypogonadism persists despite appropriate tumour-directed treatment.

Sex-hormone replacement

Use an individual testosterone or oestrogen-based regimen only after tumour, fertility, contraception and contraindication review with the pituitary team.

It can obscure assessment of gonadal recovery and is not fertility induction; use agent-specific cancer, thrombotic, haematocrit, prostate and uterine safeguards.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Infertility and sexual dysfunction

Suppressed gonadotrophins cause anovulation, amenorrhoea, low testosterone, reduced libido, erectile dysfunction and impaired fertility across sexes.

Low bone density

Prolonged prolactin-related sex-steroid deficiency increases bone turnover, reduces skeletal strength and can eventually increase fragility-fracture risk.

Visual loss

A large adenoma can compress the optic chiasm, producing progressive bitemporal field loss and, later, acuity impairment.

Other pituitary deficits

Mass compression can reduce ACTH, TSH or other pituitary secretion, with cortisol deficiency carrying immediate safety significance.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Follow prolactin at a specialist-defined interval through titration, using the same laboratory where possible and avoiding interpretation detached from dose timing and adherence.
Repeat MRI according to initial size and biochemical response, earlier if headache, vision or cranial nerve function worsens.
Use serial formal fields for chiasmal compression until stable recovery is documented; subjective visual improvement is insufficient.
Ask patients and, where appropriate, carers about gambling, compulsive spending, hypersexuality, binge eating, sleep attacks and mood change on dopamine agonists.
Apply the current SmPC or documented specialist echocardiography plan and investigate dyspnoea, cough, oedema or cardiac signs for fibrotic complications.
Review cycles, sexual function, contraception, fertility, pregnancy intent and bone health because prolactin normalisation does not guarantee full gonadal recovery.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

The assay can invert logic

At extreme prolactin concentration, antibody saturation can yield a falsely low-looking value, making a secreting giant tumour resemble stalk effect.

Fertility precedes menses

Ovulation may resume before the first visible period after treatment, so preconception or contraception discussion cannot wait for cycle recovery.

Prolactin is poor in pregnancy

Physiological concentrations rise and do not correlate reliably with tumour size, making symptoms and visual assessment more useful for enlargement.

Psychiatric medicines need partnership

Stopping an antipsychotic abruptly can cause major relapse; endocrinology and psychiatry should weigh substitution, observation and tumour evidence together.

Shrinkage can uncover a leak

Rapid macroadenoma involution may open a pre-existing skull-base defect, so clear unilateral rhinorrhoea after cabergoline is an urgent warning rather than rhinitis.

11Common pitfallsFrequent interpretation and management errors.

01
Do not diagnose prolactinoma from one mildly high stressed sample without pregnancy, medicine, thyroid, renal and macroprolactin assessment.
02
Do not mistake a falsely modest hook-effect result for stalk compression when MRI shows a very large pituitary lesion.
03
Do not discontinue an essential antipsychotic without the treating mental-health team merely to normalise prolactin.
04
Do not start cabergoline without explaining that fertility can return before menstruation and agreeing contraception or conception plans.
05
Do not rely on serum prolactin to monitor tumour size during pregnancy or ignore new headache and visual change.
06
Do not label apparent dopamine-agonist failure until adherence, tolerability, assay, diagnosis and a genuinely optimised specialist dose are reviewed.