Dopamine Agonists in Endocrine Disease

Dopamine agonists suppress prolactin and are first-line for prolactinoma and symptomatic hyperprolactinaemia. Cabergoline is the usual choice, with bromocriptine used in pregnancy planning and where cost matters. They also have secondary roles in acromegaly and Cushing disease.

Mechanism. They stimulate D2 receptors on lactotroph cells, inhibiting prolactin synthesis and release and shrinking the tumour.

Pharmacokinetics. Cabergoline has a half-life of 63 to 69 hours (twice weekly dosing) and good D2 selectivity. Bromocriptine has a half-life of 3 to 6 hours and is given twice daily. Both are cleared by the liver through CYP3A4.

Cabergoline. Start 0.25 mg twice weekly, increase by 0.25 mg twice weekly every 4 weeks based on the prolactin response, usual maintenance 0.5 to 1 mg weekly (maximum usually 3 mg weekly; higher doses in resistant tumours under specialist care). Fewer side effects and better efficacy.

Bromocriptine. Start 1.25 mg at bedtime with food, increase by 1.25 mg every 3 to 7 days to 2.5 to 7.5 mg daily in 2 to 3 doses (maximum 15 mg daily in prolactinoma). Most experience in pregnancy.

Quinagolide. Non-ergot, limited availability.

• Prolactinoma: cabergoline normalises prolactin in 80 to 90% and shrinks macroadenomas. Treat micro- and macroadenoma and symptoms such as galactorrhoea, infertility and hypogonadism.
• Drug-induced hyperprolactinaemia: stop the cause if possible; if an antipsychotic must continue, cabergoline at low dose is used with specialist input.
• Post-partum lactation suppression: cabergoline 1 mg single dose within 24 hours of delivery; avoid in hypertension or pre-eclampsia.
• Acromegaly and Cushing disease: cabergoline as adjunct (for example 0.5 mg weekly up to 3 mg weekly).
• Withdrawal attempt: consider after 2 years of normal prolactin and no visible tumour remnant on MRI; recheck prolactin at 3 months and then every 6 to 12 months.

Special groups. Pregnancy: stop dopamine agonist when pregnancy is confirmed in microprolactinoma; in macroadenoma with visual risk, continue or consider surgery before conception. Breastfeeding: lowers milk supply; avoid. Children: specialist use. Older adults: orthostatic hypotension. Liver impairment: reduce the dose. Regional: bromocriptine is cheaper and widely available; cabergoline cost and supply vary.

Adverse effects. Nausea, dizziness, orthostatic hypotension, headache, nasal congestion, constipation, impulse control disorders (gambling, hypersexuality), psychosis, cerebrospinal fluid leak after tumour shrinkage, and, at high or prolonged doses, cardiac valve fibrosis.

Contraindications. Uncontrolled hypertension, pre-eclampsia, pre-existing valvular heart disease or fibrotic conditions (cabergoline), severe psychosis, and ergot hypersensitivity.

Interactions. Antipsychotics, metoclopramide and domperidone oppose effect. Macrolides and azole antifungals raise levels. Antihypertensives add hypotension.

Monitoring. Prolactin 1 month after starting and after each dose change, then every 3 to 6 months; MRI at 3 to 12 months in macroadenoma and visual fields at baseline; echocardiography before and during treatment at over 3 mg weekly or prolonged use; mood and behaviour.

Referral and escalation. Visual loss, pituitary apoplexy, resistant tumour, pregnancy, or impulse control disorder.