NICE vs SIGN: Management of Hyperprolactinaemia (2025)

This guideline comparison provides a factual, UK-focused overview of the National Institute for Health and Care Excellence (NICE) Clinical Knowledge Summary (CKS) on Prolactinoma and Hyperprolactinaemia (last revised May 2023) and the Scottish Intercollegiate Guidelines Network (SIGN) guideline Management of Prolactinoma and Hyperprolactinaemia (SIGN 169, published May 2023). Both are key reference documents for UK clinicians in 2025. While their core principles are aligned, there are nuanced differences in emphasis and practical detail.

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Diagnosis and Initial Assessment

The initial approach to confirming pathological hyperprolactinaemia is similar, but the guidelines differ in their emphasis on specific steps.

NICE CKS

• Confirmation: Stresses the need to confirm elevated prolactin with a repeat sample, ensuring it is taken under optimal conditions (fasting, no strenuous exercise, minimal stress, ideally mid-morning).
• Macroprolactinaemia: Explicitly recommends testing for macroprolactin if the assay routinely reports total prolactin without correction, particularly in asymptomatic patients or those with discordant symptoms.
• Imaging: Advises pituitary MRI for confirmed hyperprolactinaemia not explained by medication, renal failure, or hypothyroidism. Also recommends MRI if macroprolactinaemia is confirmed but the patient has symptoms or pituitary dysfunction.

SIGN 169

• Confirmation: Similarly emphasises a correctly taken repeat sample. Provides a clear threshold: a single prolactin level >5000 mU/L is highly suggestive of a prolactinoma and may not require repetition before imaging.
• Macroprolactinaemia: Also recommends screening, particularly in patients with asymptomatic hyperprolactinaemia or discordant clinical features.
• Imaging: Provides more specific imaging guidance. Recommends pituitary MRI for:
  • Prolactin >1000 mU/L where the cause is not obvious.
  • Symptomatic patients with lower prolactin levels if no other cause is found.
  • Patients with pituitary dysfunction or mass effect symptoms regardless of prolactin level.

Key Difference: SIGN provides more granular, threshold-based guidance for when to proceed to MRI, which can be more practical for decision-making. NICE offers a broader principle.

Treatment Strategies

Both guidelines agree on dopamine agonists (DAs) as first-line therapy for symptomatic micro- and macroprolactinomas, but differ in agent preference and monitoring nuances.

NICE CKS

• First-line Agent: Recommends a dopamine agonist (cabergoline or bromocriptine). Notes that cabergoline is often preferred due to its better efficacy and side-effect profile.
• Treatment Aim: Focuses on controlling symptoms (e.g., restoring gonadal function, stopping galactorrhoea) and reducing tumour size.
• Monitoring: Advises measuring prolactin 1 month after starting treatment and after each dose change, then every 6-12 months once stable. Suggests repeating MRI 1-3 years after starting DAs for macroprolactinomas, or if prolactin rises or new symptoms develop.

SIGN 169

• First-line Agent: Strongly recommends cabergoline as the first-choice DA over bromocriptine, citing superior tolerability, efficacy, and convenience.
• Treatment Aim: Defines biochemical targets: aim for a normal prolactin level. For macroprolactinomas, a normal level may not be achievable, so the goal is a >50% reduction.
• Cardiac Monitoring: Includes specific advice regarding cabergoline and valvular heart disease risk. Recommends:
  • Using the lowest effective dose to maintain normal prolactin.
  • Informing patients of the potential risk.
  • Considering baseline echocardiography for patients on long-term, high-dose therapy (>2 mg/week) or if pre-existing valve disease exists.

Key Difference: SIGN's stronger endorsement of cabergoline and its detailed guidance on cardiac monitoring represent a significant practical difference. NICE mentions the risk but is less prescriptive about echocardiography.

Special Situations

Asymptomatic Microprolactinoma / Idiopathic Hyperprolactinaemia

• NICE: Suggests observation without treatment is a reasonable option, with annual prolactin monitoring.
• SIGN: Aligns with this, stating treatment is not required for asymptomatic patients and observation is appropriate.

Pregnancy Planning and Management

• Both Guidelines advise stopping dopamine agonists once pregnancy is confirmed due to the low risk to the foetus, which is well-established for bromocriptine and cabergoline.
• SIGN provides more structured advice:
  • For microprolactinomas: Stop DA and monitor clinically for symptoms of tumour enlargement (severe headaches, visual disturbances).
  • For macroprolactinomas: Strongly recommend discussing the risks of tumour growth (15-30%) before pregnancy. Advise a pre-pregnancy debulking surgery or continuing DAs as potential strategies. If DAs are stopped, rigorous visual field monitoring every 1-3 months during pregnancy is essential.

Medication-Induced Hyperprolactinaemia

• NICE: Recommends checking prolactin before starting antipsychotics if possible. If elevated on medication, consider switching to a prolactin-sparing antipsychotic (e.g., aripiprazole) in liaison with psychiatry.
• SIGN: Offers similar advice but adds that if switching medication is not feasible, adding a DA (typically low-dose aripiprazole) can be considered, but this should only be done by a specialist with psychiatric input due to the risk of worsening psychosis.

Key Difference: SIGN provides more detailed, risk-stratified management pathways for macroprolactinomas in pregnancy and a specific, cautious approach to managing antipsychotic-induced hyperprolactinaemia.

Practical Clinical Flow and Takeaway Points

Unified Diagnostic Pathway (NICE & SIGN)

1. Confirm: Repeat prolactin under optimal conditions. Exclude secondary causes (medication, hypothyroidism, renal impairment).
2. Consider Macroprolactin: Especially if asymptomatic or symptoms are discordant.
3. Image: Proceed to pituitary MRI if prolactin is persistently elevated >1000 mU/L (SIGN) or unexplained (NICE), or if pituitary dysfunction/mass effect symptoms are present.

Unified Treatment Principles

• Treat symptomatic patients and those with macroprolactinomas.
• Cabergoline is the preferred first-line dopamine agonist.
• Asymptomatic microadenomas can be observed.

Key Practical Takeaways for 2025

• Follow SIGN for Specificity: For clear thresholds (e.g., when to MRI) and detailed management in complex cases (pregnancy, antipsychotic use), SIGN 169 is more prescriptive.
• Follow NICE for Principles: NICE CKS provides a robust, general overview that is consistent with good practice.
• Cardiac Monitoring is Key: Adopt SIGN's pragmatic approach to discussing cabergoline risk and considering echocardiography for long-term, high-dose users.
• Pregnancy Requires a Plan: For women with macroprolactinomas, pre-conception counselling and a clear monitoring plan are essential, as outlined in detail by SIGN.

Frequently Asked Questions (FAQs)

1. Which guideline should I follow in England? In Scotland?

In England and Wales, NICE guidance is the standard. In Scotland, SIGN is predominant. However, as both documents were updated in 2023 and are largely congruent, clinicians across the UK can confidently use either. The SIGN document often provides more detailed procedural guidance which can be valuable regardless of location.

2. What is the single most important difference?

The most significant practical difference is SIGN's specific and strong recommendation on cabergoline-associated cardiac monitoring, advising consideration of echocardiography for specific patient groups, which is less emphasised in NICE.

3. How should I manage a patient on an antipsychotic who has symptomatic hyperprolactinaemia?

Both guidelines recommend liaison with psychiatry. The first step is to consider switching to a prolactin-sparing agent (e.g., aripiprazole). SIGN cautiously notes that adding a DA can be a specialist option if switching fails, but this carries a risk of exacerbating psychosis and must be managed within a specialist mental health team.

4. When can treatment for a microprolactinoma be stopped?

Both guidelines suggest considering dose reduction or withdrawal of dopamine agonists after 2-3 years of sustained normal prolactin and no visible tumour on MRI, particularly for microprolactinomas. This should be done with careful monitoring for recurrence.

5. Is cabergoline safe in pregnancy?

Yes. Data from over two decades, consolidated in both guidelines, show no increased risk of congenital abnormalities or adverse pregnancy outcomes with cabergoline (or bromocriptine) exposure during the early weeks of gestation. The standard practice remains to stop the drug once pregnancy is confirmed for other clinical reasons (managing tumour growth).

Source Links

• NICE Clinical Knowledge Summary: Prolactinoma and Hyperprolactinaemia (Last revised May 2023). [View on NICE website]
• SIGN Guideline 169: Management of Prolactinoma and Hyperprolactinaemia (Published May 2023). [Download PDF]