Hyperprolactinaemia — structured oral station (12 minutes)

Opening prompt — "What is your interpretation, and what is the most appropriate first step?"

Model response — identify the cause and review the medication list: ^[1]

• "This is a 34-year-old woman on risperidone with secondary amenorrhoea, bilateral galactorrhoea she had not volunteered until asked, and a serum prolactin of 145 ng/mL with low FSH/LH and low oestradiol."
• "The most likely diagnosis is drug-induced hyperprolactinaemia from risperidone, a dopamine D2 antagonist. The prolactin is elevated but below the 200 micrograms per litre threshold typical of a true macroprolactinoma, and there are no headaches or visual symptoms."
• "The first step is NOT to image the pituitary — it is to review with psychiatry and consider switching to a prolactin-sparing antipsychotic — aripiprazole is the consensus-named agent. Starting cabergoline before this review is wrong — escalating a dopamine agonist to treat a problem caused by another dopamine antagonist is illogical and risks worsening the underlying psychiatric condition."
• "I would also exclude pregnancy (β-hCG), confirm the TSH is normal, and discuss with the patient that galactorrhoea is a common and reversible side effect of her medication." ^[1]

Probe 1 — "How do you distinguish true prolactinoma from stalk effect?"

• "By the prolactin-to-mass ratio. A true prolactinoma has a prolactin that is proportional to the tumour size — most patients with a prolactin over 250 micrograms per litre harbour a prolactinoma, over 500 is diagnostic of a macroprolactinoma, and giant prolactinomas over 40 mm usually exceed 1,000."
• "Stalk effect, by contrast, has a disproportionately low prolactin for the mass — under the 200 ng/mL level at which a prolactinoma becomes more probable, with a 97th percentile of 70 ng/mL in one histologically verified series — DESPITE a large pituitary mass. The mechanism is different — a non-functioning pituitary adenoma (most often a gonadotroph or null-cell adenoma) compresses the stalk, interrupting tonic dopamine inhibition of normal lactotrophs. The lactotrophs are intact, just disinhibited."
• "Treatment diverges: true prolactinoma gets cabergoline first-line; stalk effect gets surgery (transsphenoidal decompression), NOT escalating dopamine agonist. Escalating cabergoline in stalk effect would mask the underlying non-functioning tumour's growth by suppressing prolactin without addressing the mass."^[7][8]

Probe 2 — "What about macroprolactinaemia and the high-dose hook effect?"

• "Macroprolactinaemia is a prolactin-IgG complex that is biologically inactive but produces a high assay reading. It is the classic cause of an asymptomatic hyperprolactinaemia with no clinical features. The standard test is polyethylene glycol precipitation; post-PEG recovery below about 40% is consistent with macroprolactinaemia. Big and big-big prolactin were found in around 6% of hyperprolactinaemic samples in a large 2025 series.^[2] The teaching point: screen for macroprolactin when the level is under 200 ng/mL and the clinical or imaging picture is discordant."
• "The high-dose hook effect is the opposite problem — a giant macroprolactinoma with an apparently normal or only mildly elevated prolactin on a two-site immunometric assay. Extremely high prolactin saturates both antibodies and prevents sandwich formation, producing a falsely low reading. Re-measuring after a 1:100 dilution reveals the true value. Clinically, a large pituitary mass with an apparently normal prolactin should raise suspicion; order the dilution before concluding the patient does not have a prolactinoma.^[1][9]"

Probe 3 — "What is the role of MRI pituitary with gadolinium?"

• "MRI pituitary with gadolinium is the imaging standard, and dynamic gadolinium enhancement is important for the initial diagnosis. The indications are confirmed hyperprolactinaemia at diagnosis once drug, renal, thyroid and pregnancy causes are excluded; urgent imaging for headaches or visual field defects; suspected stalk effect; and in psychiatric patients, a prolactin more than ten times the upper limit of normal, mass-effect symptoms, or non-gonadal pituitary hormone deficiency. Gadolinium is used judiciously on follow-up scans."
• "The report must describe the size (micro under 10 mm, macro 10 mm or more, giant over 40 mm), the direction of extension (suprasellar, parasellar, infrasellar), the relationship to the optic chiasm (distance, abutment, compression), the cavernous sinus invasion, and the appearance of the normal pituitary."
• "For any macroadenoma, I would also order full anterior pituitary hormones — cortisol, TSH, free T4, LH/FSH, IGF-1 — and a formal visual field testing (perimetry) if the macroadenoma touches the chiasm."^[1]

Probe 4 — "Cabergoline versus bromocriptine — which is first-line, and why?"

• "Cabergoline is first-line, per the Endocrine Society 2011 guideline and the 2023 Pituitary Society consensus. It has superior efficacy — prolactin normalisation in 92% of idiopathic or micro cases and 95% in a placebo-controlled microadenoma study, versus roughly 10% of patients resistant to cabergoline and 25% resistant to bromocriptine — better tolerability, and twice-weekly dosing thanks to its long half-life."
• "The dose: start low (0.25 mg orally twice weekly) and increase stepwise guided by prolactin, first checked 1 month after starting. Frequently employed doses range from 0.5 to 3.5 mg weekly (the FDA-approved maximum is 2 mg weekly; occasional patients have needed up to 11 mg weekly). Take with food or at bedtime to reduce nausea."
• "Bromocriptine is second-line. It is less expensive and has more historical safety data in pregnancy (the reason some clinicians still prefer it for the first 12 weeks of gestation). But the tolerability is worse."^[1][4]

Probe 5 — "She wants to plan a pregnancy. What is your advice?"

• "I would want to review the prolactin and the MRI. If she has a microprolactinoma with stable normoprolactinaemia, the dopamine agonist is stopped as soon as pregnancy is confirmed; pregnancy is usually uneventful with clinical review every 3 months, and the risk of symptomatic tumour growth is 2.6%."
• "If she has a macroprolactinoma, the risk of symptomatic growth is higher — 31% for macroadenomas not previously treated with surgery or radiotherapy, 2.8% if previously treated, and pre-pregnancy transsphenoidal surgery reduces the risk from 21% to 4.7%. Adenoma response to dopamine agonist therapy should be confirmed before conception, and maintenance of dopamine agonist therapy throughout pregnancy is an option for large macroprolactinomas. Recent systematic review data on cabergoline in pregnancy are reassuring (Otis et al, Birth Defects Res 2025) — 1,662 exposed pregnancies with no negative impact on major malformations or spontaneous abortions — and the 2023 consensus notes cabergoline is now preferred by the majority of centres."
• "Macroprolactinoma monitoring in pregnancy means monthly clinical review questioning for mass effects, formal visual field evaluation every 3 months, MRI pituitary WITHOUT gadolinium if growth is suspected — and serum prolactin is NOT measured: it rises physiologically to 150 to 300 micrograms per litre by term and cannot track the tumour. Surgery or delivery if an enlarging adenoma fails to respond to re-initiated dopamine agonist."
• "Breastfeeding is usually not contraindicated, depending on whether treatment reintroduction is needed for mass control. She should be managed jointly with endocrinology and the obstetric team.^[3][6]"

Probe 6 — "When can the dopamine agonist be stopped?"

• "Withdrawal may be considered after at least 2 years of treatment with normoprolactinaemia and substantial tumour volume reduction. The favourable predictors are a low cabergoline maintenance dose, treatment duration over 2 years, marked shrinkage, and no visible tumour remnant on MRI — absence of a residual adenoma is the strongest predictor of staying in remission."
• "About one fifth of patients remain in remission overall; among well-selected patients, roughly 55% of microprolactinomas and 43% of macroprolactinomas achieve ongoing remission — so recurrence is about 45% and 57% respectively even in the best candidates, and 26 to 69% across unselected series. Monitor prolactin every 3 months in the first year, then annually for life, and re-image if prolactin rises or symptoms recur. Recurrence usually responds to dopamine agonist rechallenge, and a second withdrawal attempt can succeed after another 2 to 3 years of therapy."
• "Withdrawal is NOT appropriate in macroprolactinomas with cavernous sinus invasion or chiasmal abutment — the recurrence risk is too high.^[9]"