Hyperprolactinaemia — structured SAQ (15 marks)

(a) Most likely cause and the first step (3 marks)

One mark for the cause; one mark for the prolactin context; one mark for the first step. ^[1]

• Most likely cause: drug-induced hyperprolactinaemia from risperidone, a dopamine D2 antagonist.
• Prolactin context: the prolactin is elevated but below the 200 micrograms per litre level above which a prolactinoma becomes the more probable diagnosis, and well under the ten-times-upper-limit-of-normal mark that would trigger suspicion of a prolactinoma in an antipsychotic-treated patient; there are no clinical features (headaches, visual symptoms) suggesting a macroprolactinoma.
• First step in management: review with psychiatry and consider switching to a prolactin-sparing antipsychotic (aripiprazole — the consensus-named prolactin-sparing agent); do NOT start cabergoline or proceed to MRI before this review. Cabergoline in this context risks worsening the underlying psychiatric condition and is overtreatment if the drug can be switched. ^[1]

(b) Classification of hyperprolactinaemia by mechanism (5 marks)

One mark per mechanism; one mark for the prolactin-to-mass ratio discriminator. ^[1][3][5][7]

• True prolactinoma (autonomous prolactin secretion): microprolactinoma under 10 mm or macroprolactinoma 10 mm or more; the prolactin is proportional to tumour size (most patients with a prolactin over 250 micrograms per litre harbour a prolactinoma, over 500 is diagnostic of macroprolactinoma, and giant prolactinomas over 40 mm usually exceed 1,000 micrograms per litre); cabergoline first-line.
• Stalk effect (non-functioning pituitary adenoma): the most common aetiology is a gonadotroph or null-cell adenoma; the prolactin is modest (under the 200 ng/mL prolactinoma threshold; 97th percentile 70 ng/mL in one histologically verified series) DESPITE a large pituitary mass; treatment is surgery (transsphenoidal decompression), NOT escalating dopamine agonist.
• Drug-induced: dopamine antagonists (antipsychotics — risperidone, amisulpride, haloperidol; antiemetics — metoclopramide, domperidone), methyldopa, verapamil, high-dose oestrogens; the prolactin is usually under 100 micrograms per litre but risperidone and metoclopramide can exceed 200; review with the prescribing clinician, consider switching to a prolactin-sparing agent.
• Physiological: pregnancy, lactation, stress, coitus, sleep, exercise; always exclude pregnancy first.
• Macroprolactinaemia: prolactin-IgG complex (big-big prolactin), biologically inactive; produces high assay readings but no symptoms; PEG precipitation identifies it (post-PEG recovery below 40%); found in around 6% of hyperprolactinaemic samples in a large 2025 series.^[2]
• The prolactin-to-mass ratio is the discriminator: true prolactinoma has prolactin proportional to tumour size; stalk effect has a disproportionately low prolactin for the mass size (under the 200 ng/mL threshold). ^[1]

(c) Indications for MRI pituitary with gadolinium and what the report must include (3 marks)

One mark for the indications; two marks for the report requirements. ^[1]

• Indications for MRI pituitary with gadolinium: confirmed hyperprolactinaemia at diagnosis once drug, renal, thyroid and pregnancy causes are excluded (dynamic gadolinium enhancement is important for initial diagnosis); headaches or visual field defects at any prolactin level (urgent); suspected stalk effect (a large pituitary mass with a disproportionately low prolactin); in psychiatric patients, prolactin more than ten times the upper limit of normal, mass-effect symptoms, or non-gonadal pituitary hormone deficiency; macroprolactinoma follow-up 3 to 6 months after starting a dopamine agonist.
• The report must include: the size of the adenoma (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 presence or absence of cavernous sinus invasion (the Knosp grade stages that invasion when surgery is discussed); the presence of haemorrhage or infarction (relevant if apoplexy is suspected); the appearance of the normal pituitary (compression, displacement).
• Adjunct investigations for any macroadenoma: full anterior pituitary hormones (cortisol, TSH, free T4, LH/FSH, IGF-1) before any surgery or radiotherapy; formal visual field testing (perimetry) for any macroadenoma touching the optic chiasm. ^[1]

(d) Macroprolactinoma in pregnancy (4 marks)

One mark for the pre-conception counselling; one mark for the dopamine agonist continuation; one mark for the monitoring; one mark for the safety data. ^[4][6]

• Pre-conception counselling: confirm adenoma response to dopamine agonist therapy before conception (surgery is considered pre-conception if there is no mass response); discuss the risk of symptomatic tumour growth in pregnancy (2.6% for microadenomas; 31% for macroadenomas not previously treated with surgery or radiotherapy and only 2.8% if previously treated — pre-pregnancy transsphenoidal surgery reduces macroprolactinoma enlargement risk from 21% to 4.7%).
• Dopamine agonist continuation: maintenance of cabergoline (or bromocriptine) therapy during pregnancy is an option for large macroprolactinomas. For microprolactinomas the risk of symptomatic growth is 2.6% and the dopamine agonist is stopped as soon as pregnancy is confirmed.
• Monitoring in pregnancy: for macroprolactinoma, monthly clinical review questioning for local mass effects with formal visual field evaluation every 3 months (formal visual field testing — perimetry, not just confrontation); MRI pituitary WITHOUT gadolinium only if clinically relevant growth is suspected (gadolinium crosses the placenta); serum prolactin is NOT measured in pregnancy; surgery or delivery if an enlarging adenoma does not respond to re-initiated dopamine agonist.
• Dopamine agonist safety: bromocriptine has the largest historical safety database in pregnancy; although bromocriptine might reduce fetal exposure through its shorter half-life, the 2023 Pituitary Society consensus states cabergoline is now preferred by the majority of centres owing to increasing safety data — a systematic review of 1,662 cabergoline-exposed pregnancies found no negative impact on major malformations or spontaneous abortions (Otis et al, Birth Defects Res 2025). Do NOT stop without review.
• Breastfeeding: usually not contraindicated, and can be allowed for a period depending on whether treatment reintroduction is needed for mass control. ^[1][8]