NICE vs SIGN: Management of Hyperthyroidism (2025) - A Clinical Comparison
This guide provides a detailed, factual comparison of the National Institute for Health and Care Excellence (NICE) and the Scottish Intercollegiate Guidelines Network (SIGN) guidelines for the management of hyperthyroidism. While both aim to standardise high-quality care across the UK, there are nuanced differences in their recommendations that clinicians should be aware of. This comparison focuses on the core principles, key divergences, and practical implications for clinical practice in the UK setting.
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Diagnosis and Initial Assessment
Both guidelines agree on the fundamental steps for diagnosing hyperthyroidism: a combination of clinical assessment, thyroid function tests (TFTs), and identification of the underlying aetiology.
- NICE (NG231): Emphasises a pragmatic approach. Recommends a single measurement of serum TSH as the initial test. If TSH is suppressed (<0.1 mU/L), free T4 and T3 should be measured. NICE provides clear pathways for interpreting different TFT patterns (e.g., overt hyperthyroidism, subclinical hyperthyroidism, T3 toxicosis). For aetiology, they recommend TSH-receptor antibodies (TRAb) as the first-line investigation for Graves’ disease, noting its high sensitivity and specificity, which can often avoid the need for a radionuclide scan.
- SIGN (SIGN 164): Similarly recommends initial TSH measurement. SIGN places a stronger emphasis on the clinical context and the value of additional investigations. While TRAb is also recommended for diagnosing Graves’ disease, SIGN more explicitly discusses the role of thyroid ultrasound and radionuclide scanning in cases where the diagnosis is uncertain, or a toxic nodule is suspected.
Key Difference: The main distinction is one of emphasis. NICE strongly advocates for TRAb testing to confirm Graves’ disease, potentially streamlining diagnosis. SIGN provides a more detailed discussion of scenarios where imaging is crucial, offering a broader diagnostic toolkit for complex presentations.
Treatment Strategies
This is the area with the most significant differences in philosophy and recommendation strength.
Antithyroid Drugs (ATDs): Carbimazole
- NICE: Recommends Carbimazole as the first-line ATD for all patients, including in pregnancy (with important caveats, see below). This is a change from previous guidance and is based on a comprehensive review of safety data. The block-and-replace regimen is advised against; titration is the recommended strategy for all patients.
- SIGN: Also recommends Carbimazole as the first-line drug. However, SIGN continues to present both the titration and block-and-replace regimens as viable options, acknowledging that block-and-replace may be preferred in certain situations where monitoring adherence or TFTs is difficult.
Key Difference: NICE has taken a firmer stance against the block-and-replace regimen, recommending titration for everyone. SIGN offers more flexibility, allowing clinician and patient preference to influence the choice of regimen. This is a major practical takeaway for clinicians.
Definitive Therapy (Radioiodine and Surgery)
- Both Guidelines agree on the indications for definitive therapy: drug intolerance, relapse after a course of ATDs, and patient preference.
- NICE: States that radioiodine or surgery should be offered as an alternative first-line treatment to ATDs, if appropriate. This places definitive therapies on a more equal footing with long-term drug treatment from the outset.
- SIGN: Presents radioiodine and surgery more traditionally as options after a trial of ATDs, particularly for Graves’ disease. The guidance is less explicit about offering them as first-line equivalents.
Key Difference: NICE promotes a more patient-centric model where definitive treatment can be discussed as a primary option, potentially reducing the time to permanent control. SIGN’s pathway is more sequential.
Special Situations
Pregnancy and Breastfeeding
- NICE: Recommends Carbimazole as the first-line ATD in pregnancy, including in the first trimester. This is a significant shift. They advise using the lowest effective dose and monitoring closely. Propylthiouracil (PTU) is suggested as an alternative if Carbimazole is not tolerated.
- SIGN: Maintains the traditional recommendation: Propylthiouracil (PTU) should be used in the first trimester due to a historically perceived lower risk of teratogenicity, with a potential switch to Carbimazole after organogenesis is complete. Both drugs are considered safe during breastfeeding.
Key Difference: This is the most critical divergence for obstetric physicians and endocrinologists. NICE's position on Carbimazole is based on newer evidence suggesting the risk of teratogenicity is very low and similar between the two drugs, while Carbimazole may be more effective. SIGN's more cautious approach reflects an older evidence base. Clinicians must be aware of both positions.
Thyroid Eye Disease (TED)
- Both guidelines stress the importance of informing patients with Graves’ disease about the symptoms of TED and referring urgently to a dedicated TED service if active, moderate-to-severe disease is suspected.
- NICE: Specifically advises that patients with active TED should be offered surgery or ATDs rather than radioiodine, as radioiodine can potentially exacerbate TED, unless steroid cover is provided.
- SIGN: Provides similar advice but offers more detailed grading of TED activity and severity to guide referral and treatment decisions.
Practical Clinical Flow: A Synthesis
A pragmatic UK pathway synthesising both guidelines would be:
- Diagnosis: Clinical suspicion → Check TSH. If suppressed, check fT4/fT3. If pattern suggests hyperthyroidism, check TRAb to confirm/rule out Graves’ disease. Use ultrasound/scan if TRAb negative or nodules palpable.
- First-Line Discussion: Discuss all options: a 12-18 month course of ATD (using a titration regimen, per NICE preference) vs. definitive therapy (radioiodine or surgery) as a potential first-line choice (per NICE), or after drug treatment (per SIGN).
- Pregnancy: Be aware of the conflicting guidance. A UK-wide consensus may still favour PTU in the first trimester, but NICE's recommendation for Carbimazole is strong and evidence-based. Decision should be made in a specialist multidisciplinary setting.
- Monitoring & Follow-up: Monitor TFTs regularly during ATD treatment. After treatment, monitor for relapse annually for at least the first few years.
Frequently Asked Questions (FAQs)
1. Which guideline should I follow in England? In Scotland?
In England and Wales, follow NICE NG231. In Scotland, follow SIGN 164. However, understanding the rationale behind both is valuable, especially for managing patients from different UK nations or in complex cases.
2. What is the single biggest practical difference in day-to-day management?
The recommendation on ATD regimen. NICE advises against block-and-replace, recommending a titration regimen for all patients. SIGN allows for either, giving clinicians more flexibility.
3. How should I manage a pregnant woman with hyperthyroidism given the conflicting advice?
This requires careful shared decision-making. Discuss the evidence behind both guidelines with the patient. In practice, many tertiary centres may still use PTU in the first trimester due to longstanding caution, but NICE's position on Carbimazole is robust. Management must involve close liaison between endocrinology and obstetric teams.
4. Is radioiodine really a first-line option now?
According to NICE, yes, it should be discussed as an alternative to ATDs from the beginning for appropriate patients (e.g., those not planning pregnancy, without active TED). SIGN's pathway is more traditional, typically reserving it for after drug treatment fails or is not tolerated.
5. Are the guidelines likely to be harmonised in the future?
While there is a move towards UK-wide guidelines, differences currently remain. SIGN is in the process of being integrated into NICE, but for now, these are separate publications. Future updates may see greater alignment.
Source Links
- NICE Guideline NG231 (2025): Hyperthyroidism: diagnosis and management
- SIGN Guideline 164 (2025): Management of thyroid disease (Hyperthyroidism is a key part of this document).