Prolactinoma

Prolactinoma is a lactotroph pituitary adenoma and the most common functioning pituitary tumour. It causes hyperprolactinaemia with hypogonadism, galactorrhoea and, in macroadenomas, mass effect.

Women usually present with microadenomas in their reproductive years, whereas men more often present with macroadenomas. Microadenoma is under 10 mm, macroadenoma 10 mm or more, and giant adenoma 40 mm or more.

Prolactin tracks tumour size. Over 200 micrograms/L (about 4000 mIU/L) strongly suggests a prolactinoma, and 100 to 200 micrograms/L is intermediate. Under 100 micrograms/L fits drugs, stalk compression or a small tumour.

Pathophysiology.

Autonomous prolactin secretion suppresses hypothalamic pulsatile gonadotrophin releasing hormone, causing low LH, FSH and sex steroids.

Dopamine agonists act on lactotroph D2 receptors to lower prolactin and shrink the tumour. In macroprolactinomas the assay hook effect can give a falsely low value, so dilute the sample.

• Women: oligomenorrhoea or amenorrhoea, galactorrhoea, infertility, hot flushes and vaginal dryness.
• Men: low libido, erectile dysfunction, infertility, rarely gynaecomastia or galactorrhoea.
• Both: reduced bone density. Macroadenomas: headache, bitemporal visual field loss, cranial nerve palsies and hypopituitarism.

Red flags.

• Visual loss or sudden severe headache (apoplexy).
• Clear nasal fluid after starting treatment (cerebrospinal fluid leak as the tumour shrinks).

• Prolactin on two samples, pregnancy test, thyroid function, kidney function, and a drug history. Upper reference is about 25 micrograms/L (500 mIU/L).
• Exclude macroprolactin with polyethylene glycol precipitation if prolactin is raised without symptoms.
• Pituitary MRI with contrast. Visual fields and the other pituitary axes for macroadenomas.
• Prolactin under about 2000 mIU/L (94 micrograms/L) with a macroadenoma suggests stalk compression rather than prolactinoma.

Differential diagnosis.

• Drug induced (antipsychotics such as risperidone, metoclopramide, domperidone, some antidepressants, opioids).
• Pregnancy, breastfeeding, hypothyroidism and chronic kidney disease.
• Stalk effect from a non-functioning macroadenoma, craniopharyngioma or other sellar mass.
• Macroprolactinaemia, polycystic ovary syndrome and chest wall stimulation.

• Cabergoline first line: start 0.25 mg twice weekly (or 0.5 mg once weekly) and increase by 0.25 mg twice weekly every 4 weeks. Usual 0.25 to 1 mg twice weekly, up to 3 mg weekly, with higher doses only under specialist supervision. Take with food at night.
• Adverse effects: nausea, postural hypotension, impulse control disorders and psychiatric effects. Valve disease occurs at high doses, so obtain echocardiography before and during prolonged high dose treatment. Avoid in uncontrolled hypertension and fibrotic valve disease.
• Bromocriptine is an alternative and preferred when pregnancy is planned: 1.25 mg at night, increased to 2.5 mg two to three times daily.
• Surgery for resistance, intolerance, apoplexy or visual loss that does not improve on treatment. Radiotherapy for residual tumour.
• Consider withdrawal after at least 2 years of treatment with normal prolactin and no visible tumour (or marked shrinkage), with prolactin every 3 months in the first year after stopping.

Special groups. Pregnancy: stop the dopamine agonist at confirmed pregnancy in microadenoma. Macroadenoma carries a higher risk of enlargement; discuss surgery before conception or continuing treatment, and check visual fields each trimester. Men: measure testosterone and replace it if low after prolactin normalises.

Monitoring. Prolactin every 3 months until stable then yearly. MRI at 3 to 6 months, then yearly for macroadenomas. Visual fields if mass effect.

Referral and escalation. Endocrinology for all cases and neurosurgery for visual compromise or resistance.