Thyroid Brain Map — Endo Unlocked

👋 Returning to practice — secondary care endocrine clinic

Graves' disease: the most common condition you'll see at a new endocrine referral

Graves' disease accounts for approximately 80% of all hyperthyroidism cases referred to secondary care endocrine clinics in the UK. If you've been away — maternity leave, sick leave, OOPR — this is where to start. The management framework has not changed dramatically, but the pregnancy safety guidance around carbimazole vs PTU has been updated, and the TED management pathway now uses a formal Clinical Activity Score. These are the areas most likely to catch a returning clinician out.

Graves' = ~80% of hyperthyroidism referrals to secondary care

Carbimazole teratogenicity — updated ETA 2018/2024 guidance — PTU in T1

TED Clinical Activity Score (CAS) now standard — know the threshold

ATD course is 12–18 months — ~50% relapse rate after stopping

RAI — no evidence of increased cancer, infertility, or birth defects

Always check FT3 — T3 toxicosis can occur with normal FT4

📋 Guidelines

NICE NG145 — Thyroid Disease (2019) BTA Guidelines British Thyroid Foundation ETA Guidelines (EU)

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Key Numbers to Know SCE

For patient counselling and clinical decision-making

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Epidemiology

Prevalence of Graves' diseaseApproximately 1–2% of the UK population. Affects women 5–10× more than men. Peak onset 30–50 years. Accounts for ~80% of all hyperthyroidism in secondary care.

Thyroid eye disease (TED)25–50% of Graves' patients develop TED (Oxford Handbook of Endocrinology and Diabetes). The main modifiable risk factor is smoking — counsel at every visit.

Antithyroid drug outcomes — for patient counselling

Remission after 12–18 months ATD~50% achieve sustained remission after a full course. The other ~50% will relapse, typically within 12 months of stopping treatment.

Relapse risk factorsLarge goitre, very high TRAb at baseline, high FT3/FT4 at diagnosis, male sex, smoking. These patients have lower remission rates and should be counselled about definitive treatment earlier.

Agranulocytosis risk with carbimazole0.2–0.6% with carbimazole (roughly 1 in 170 to 1 in 500) — per MHRA 2019 Drug Safety Update and current British National Formulary. Rate is similar with PTU (0.2–0.5%). Can occur at any time but most commonly in the first 3 months. Potentially fatal if not acted on urgently.

Agranulocytosis risk with PTUSimilar overall risk ~0.03–0.1%. Also carries risk of PTU-induced hepatitis (~0.1–0.3%) and ANCA-associated vasculitis — which is why PTU is not the preferred long-term agent.

Radioiodine (¹³¹I) outcomes

Success rate first dose~75–80% achieve control with a single dose of radioiodine. ~20–25% require a second dose. Most become hypothyroid over months to years — counsel that lifelong levothyroxine is the likely outcome.

Cancer, birth defects, infertilityNo evidence of increased risk of thyroid cancer, other cancers, birth defects in subsequent pregnancies, or infertility in women. Women: avoid pregnancy for 6 months after RAI (UK standard, ATA 2016). Men: ATA 2016 advises 3–4 months before fathering a child (covers one spermatogenesis cycle of approximately 74 days plus safety margin); ETA uses 6 months. Follow local protocol.

💡These numbers are what patients will ask about in clinic. Having them ready — especially the 50% relapse figure and the 75–80% first-dose RAI success rate — allows you to have a genuine shared decision-making conversation about ATD vs RAI vs surgery without appearing to steer.

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Diagnosis SCE

NICE NG145 · BTA · Oxford Handbook of Endocrinology and Diabetes

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Biochemistry — always check both FT4 and FT3

Core TFT pattern↓TSH + ↑FT4 ± ↑FT3. Always check FT3 — T3 toxicosis (↓TSH + normal FT4 + ↑FT3) can occur in early or relapsing Graves'. Missing FT3 leads to underdiagnosis.

Additional blood testsMild normocytic anaemia, mild neutropenia, ↑ESR, ↑Ca²⁺, ↑LFT — all recognised in Graves'. Check at baseline.

TSH receptor antibodies (TRAb)Positive in >95% of Graves'. Confirms autoimmune cause. If TRAb negative and cause unclear — do not assume Graves'. Request thyroid isotope scan before committing to treatment. TRAb level at end of treatment predicts relapse risk.

Clinical features specific to Graves'

General thyrotoxicosis featuresPalpitations, weight loss, heat intolerance, sweating, tremor, diarrhoea, irritability, anxiety, menstrual irregularity, proximal myopathy.

Graves'-specific signsDiffuse smooth goitre (± thyroid bruit on auscultation). Thyroid eye disease (see TED tab). Pretibial myxoedema — non-pitting oedematous plaques on the anterior shin (pretibial area), can extend to feet and ankles. Thyroid acropachy — clubbing + periosteal new bone + soft tissue swelling (rare, extreme manifestation).

When to do isotope scan

TRAb negative + hyperthyroidIsotope scan essential to exclude toxic nodular disease or thyroiditis before starting ATDs. Treating thyroiditis with carbimazole is unnecessary and exposes the patient to agranulocytosis risk without benefit.

TRAb positive but nodular goitreCoexistent nodular autonomy is possible. Scan helps characterise.

💡A thyroid bruit is virtually pathognomonic of Graves' disease — it reflects ↑vascularity from TSH-receptor stimulation. Always auscultate the thyroid in a hyperthyroid patient.

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Antithyroid Drug Treatment SCE

NICE NG145 · Oxford Handbook of Endocrinology and Diabetes

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Starting treatment

Carbimazole — first-line UK (outside pregnancy)Starting dose 20–40mg/24h PO (titration regimen) or carbimazole + levothyroxine simultaneously (block-replace). Both equally effective. Check TFTs every 6 weeks — adjust titration dose to maintain euthyroidism. Once stable, monitor 3-monthly. Continue for 12–18 months total.

Symptom controlPropranolol 40mg 6-hourly for rapid symptom control while awaiting ATD effect. Controls palpitations, tremor, heat intolerance. Also partially blocks T4→T3 conversion.

PTU — use only when carbimazole not suitableReserved for: first trimester of pregnancy (see pregnancy tab), carbimazole allergy, thyroid storm. Not first-line for long-term use due to hepatotoxicity risk and ANCA-associated vasculitis risk.

After 12–18 months — decision point

Low relapse risk — can stop ATDsSmall goitre, TRAb negative at end of treatment, mild initial disease. Monitor TFTs for 12 months after stopping. If remains euthyroid — discharge to GP with relapse advice. Relapse most common in first 6 months.

High relapse risk — discuss definitive treatmentLarge goitre, persistently elevated TRAb, severe initial disease, previous relapse, male sex, smoker. Offer RAI or thyroidectomy proactively rather than waiting for confirmed relapse.

Monitoring on ATDs

TFT monitoringTSH + FT4 + FT3 every 6 weeks until stable, then 3-monthly. Check FT3 — it can remain elevated after FT4 normalises on titration regimen. Do not reduce dose if FT3 still elevated.

TRAb at end of treatmentMeasure TRAb before stopping ATDs. Positive TRAb = higher relapse risk. Use in shared decision-making conversation about definitive treatment.

💡The two ATD regimens (titration vs block-replace) are equally effective for remission rates. Block-replace requires less frequent TFT monitoring and reduces the risk of iatrogenic hypothyroidism. Titration uses a lower total carbimazole dose. Either is acceptable — choose based on patient preference and monitoring reliability.

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Safety — Agranulocytosis & Side Effects SCE

NICE NG145 · BTA · MHRA guidance

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Agranulocytosis — the critical safety issue

Incidence0.2–0.6% with carbimazole; 0.2–0.5% with PTU (MHRA 2019 Drug Safety Update; cross-confirmed by BNF and ATA 2016). Can occur at any time but most common in the first 3 months. Does not appear to be reliably dose-dependent at UK therapeutic doses.

MechanismIdiosyncratic immune-mediated destruction of neutrophils/granulocytes. Results in life-threatening susceptibility to bacterial infection. Can progress to fatal sepsis within hours if not acted on.

Warning symptoms — patient must know theseSore throat · Mouth ulcers · Fever/high temperature · Any signs of infection · Unexplained bruising or bleeding. STOP carbimazole immediately and attend A&E or urgent GP same day for FBC.

What NOT to doDo NOT restart carbimazole if agranulocytosis confirmed. Do NOT switch to PTU — cross-reactivity between carbimazole and PTU for agranulocytosis means PTU is also contraindicated after confirmed agranulocytosis.

Routine FBC monitoring — is it needed?

NICE NG145 positionRoutine FBC monitoring does not reliably prevent agranulocytosis because onset is rapid and unpredictable. NICE NG145 recommends symptom-based vigilance rather than routine monitoring. Patient education is the key safety measure.

Other carbimazole side effects

Rash / urticaria~1–5%. Usually mild. Can try switching to PTU if mild rash — but cross-reactivity occurs in ~50%. Consider definitive treatment if rash occurs.

Arthralgia / arthritisRare. Seronegative. Resolves on stopping.

Cholestatic jaundiceRare with carbimazole. More common with PTU (hepatitis ~0.1–0.3% with PTU — a reason to prefer carbimazole for long-term use).

ANCA-associated vasculitisRare but recognised with PTU specifically. Not with carbimazole. Check ANCA if PTU patient develops unexplained systemic symptoms.

PTU-specific additional risks

HepatotoxicityPTU-induced hepatitis in ~0.1–0.3%. Can be severe, causing fulminant hepatic failure — reason PTU is not preferred for long-term use. Monitor LFTs if any hepatic symptoms on PTU.

Patient information resources — BTA/BTF

Agranulocytosis alert cardGive to all patients starting carbimazole. Available from: btf-thyroid.org/antithyroid-drugs-alert-card

Radioactive iodine informationbtf-thyroid.org — RAI treatment leaflet

Thyroid surgery informationbtf-thyroid.org/thyroid-surgery

Pregnancy and fertilitybtf-thyroid.org/pregnancy-and-fertility

🚨 Agranulocytosis protocol: Patient stops carbimazole → attends A&E or urgent GP → urgent FBC on same day → if confirmed (neutrophils <0.5 × 10⁹/L) → admit, IV antibiotics, haematology review → do NOT rechallenge with carbimazole or PTU → plan definitive treatment (RAI or surgery when recovered).

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Carbimazole in Women of Reproductive Age SCE

ETA 2018 · Updated consensus 2024 · NICE NG145

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The teratogenicity issue — discuss at every clinic visit with women of reproductive age

Carbimazole teratogenicityCarbimazole is associated with a specific embryopathy when taken in the first trimester: aplasia cutis (scalp skin defect), choanal atresia (nasal passage obstruction), oesophageal atresia, and omphalocele. This is believed to occur during organogenesis (weeks 6–10). The risk appears dose-dependent but is not eliminated at low doses. The MHRA Drug Safety Update (February 2019) formally advised that carbimazole should only be used in women of childbearing potential when effective contraception is in place, and recommended that the risks of embryopathy be discussed and documented at every prescription.

PTU and first trimesterPTU does not carry the same structural embryopathy risk and is the preferred antithyroid drug in the first trimester. However, PTU carries its own risk of hepatotoxicity (maternal) and fetal goitre at high doses.

ETA 2018 recommendations (EU guidance — label clearly)

ETA 2018 position (EU guidance)PTU recommended pre-conception and in the first trimester. Acknowledge dose-dependency of carbimazole risk but recommend PTU as the safer first-trimester option. Switch to carbimazole in second and third trimester (PTU hepatotoxicity risk with prolonged use). Source: ETA Guidelines — European Thyroid Journal 2018. ⚠️ This is EU guidance, not UK NICE guidance.

2024 update

Current consensus (2024)PTU first trimester, switch to carbimazole second/third trimester. Low-dose carbimazole may have reduced — but has not eliminated — the teratogenic risk. The switch at end of T1 remains standard practice. Source: ETA/ESE updated position — European Journal of Endocrinology 2024. ⚠️ Label as EU/international consensus guidance.

Practical advice for clinic

All women of reproductive age on carbimazoleAdvise: do not become pregnant on carbimazole without discussing with the endocrine team first. If planning pregnancy — switch to PTU before conception or use contraception until definitive treatment (RAI or surgery) completed and euthyroid on levothyroxine (which carries no teratogenic risk).

If pregnancy confirmed while on carbimazoleSwitch to PTU immediately. Refer to obstetric endocrinology. Do not delay. Target lowest effective ATD dose — aim FT4 at high-normal range to avoid fetal hypothyroidism.

BreastfeedingBoth carbimazole and PTU are compatible with breastfeeding at low doses. Carbimazole ≤20mg/day and PTU ≤200mg/day are considered acceptable. Take dose immediately after feeding. Source: NICE NG145.

💡Document this discussion in every clinic letter for women of reproductive age on carbimazole. It is a medicolegally important conversation. The BTF has a dedicated patient leaflet: btf-thyroid.org/pregnancy-and-fertility

🚨 Carbimazole embryopathy window: weeks 6–10 of pregnancy (organogenesis). This is often before a woman knows she is pregnant. Proactive pre-conception counselling at every clinic visit is essential — not just at initial diagnosis.

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Radioiodine (¹³¹I) SCE

NICE NG145 · Oxford Handbook of Endocrinology and Diabetes

Outcome~75–80% controlled with single dose. Most become hypothyroid over months to years — counsel accordingly. Lifelong levothyroxine is the expected outcome for most patients.

Safety evidenceNo evidence of increased thyroid cancer, other malignancies, birth defects in subsequent pregnancies, or reduced fertility in women. This is well-established evidence — reassure patients confidently.

ContraindicationsPregnancy · Breastfeeding · Active moderate-severe TED (can worsen eye disease — see TED tab) · Planning pregnancy within 6 months.

Active hyperthyroidism — risk of stormCaution in active/severe thyrotoxicosis — RAI can precipitate thyroid storm. Pre-treat with ATDs to achieve near-euthyroidism before RAI. Stop ATDs at least 3–7 days before RAI (ATDs reduce RAI uptake). Resume if needed post-RAI.

TED and RAIRAI can worsen TED — particularly in smokers (25% risk of worsening). In active TED: give steroid cover. EUGOGO 2021 (Bartalena et al, Eur J Endocrinol) recommends prednisolone 0.3–0.5mg/kg/day starting day of RAI, tapering over 3 months. A shorter regimen of 0.2mg/kg for 6 weeks without taper is used in some UK specialist centres. ⚠️ Doses and duration vary between centres — follow local protocol. In inactive TED: no steroid cover needed.

💡Stopping ATDs before RAI: the standard is to stop at least 3–5 days before (some centres stop 1 week before). ATDs reduce radioiodine uptake, reducing efficacy. For patients with severe thyrotoxicosis at risk of storm: pre-treat more thoroughly, confirm near-euthyroid before proceeding.

🚨 RAI + active TED = higher risk of eye deterioration. Always assess TED activity (CAS score — see TED tab) before proceeding with RAI. Refer to ophthalmology if TED active before committing to RAI.

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Thyroidectomy for Graves' SCE

NICE NG145 · Oxford Handbook of Endocrinology and Diabetes

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Operation of choiceTotal thyroidectomy — preferred over subtotal to minimise relapse risk. Lifelong levothyroxine required post-operatively. Starting dose 1.5–2 mcg/kg/day (ATA 2016 Hyperthyroidism Guidelines). In elderly, err towards 1.5 mcg/kg to reduce AF risk.

IndicationsLarge goitre with compressive symptoms (dysphagia, dyspnoea, stridor). Patient preference. Suspicious nodule coexisting. Contraindication to RAI (active TED, pregnancy planning, patient declines). Failed ATDs. Young patients who want definitive treatment.

Pre-operative preparationRender euthyroid before surgery. Where rapid control is needed (e.g. planned surgery in a poorly controlled patient), a short course of propranolol 80mg TDS plus PTU 250mg QDS for approximately 10 days is used by some UK specialist centres. Then add Lugol's iodine (KI 65mg TDS or 0.3ml Lugol's TDS) 10 days pre-op — reduces vascularity, simplifies surgery. PTU must be given ≥1 hour before iodine. Follow local endocrine surgical protocol.

Complications — counsel before surgery

Recurrent laryngeal nerve (RLN) injuryHoarse voice — transient (majority) or permanent (~0.5–1%). Bilateral RLN injury causes stridor — surgical emergency. Risk higher in reoperation or invasive disease.

Hypoparathyroidism → hypocalcaemiaTransient (common, ~20–30%) or permanent (~1–3%). Monitor calcium post-operatively. Symptoms: perioral tingling, muscle cramps, carpopedal spasm, Trousseau's/Chvostek's sign. Treat with calcium + calcitriol if permanent.

Bleeding / haematomaRare but can cause airway compression — emergency re-operation needed. Warn patients to return urgently if neck swelling post-op.

💡Document pre-operative voice assessment (RLN function) formally before thyroid surgery. Post-operative voice change without pre-operative documentation creates medicolegal risk. This is standard practice but easy to omit in a busy pre-op clinic.

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Complications of Thyrotoxicosis SCE

NICE NG196 (AF) · ATA 2016 · NOGG (bone)

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Atrial fibrillationSeen in 10–25% of thyrotoxic patients, and more common in the elderly. Control hyperthyroidism AND anticoagulate if AF present — stroke risk is significant. DOACs (apixaban, rivaroxaban, edoxaban, dabigatran) are first-line per NICE NG196. Warfarin is reserved for mechanical heart valves or moderate-to-severe mitral stenosis. Cardioversion is often deferred until the patient is euthyroid — up to two-thirds revert spontaneously with biochemical control.

Thyrotoxic cardiomyopathy and heart failureParticularly in the elderly. High-output failure predominates early; decompensated systolic failure can follow in prolonged disease. Rate control with beta-blockers is first-line unless acute decompensated heart failure is due to the thyrotoxicosis itself — in that setting propranolol is CONTRAINDICATED and a non-dihydropyridine calcium channel blocker (e.g. verapamil, diltiazem) is used for rate control.

OsteoporosisChronic thyrotoxicosis increases bone resorption and is an independent risk factor for osteoporotic fracture. Assess fracture risk (FRAX, DXA) in all patients with prolonged subclinical or overt thyrotoxicosis — particularly post-menopausal women and men over 50. Treat per NOGG guidance if indicated.

Gynaecomastia and altered SHBGThyrotoxicosis raises SHBG and alters the free oestrogen-to-testosterone ratio — can present as gynaecomastia in men. Usually resolves with biochemical control.

Thyrotoxic periodic paralysisRare but characteristic — episodic flaccid paralysis with hypokalaemia, most commonly in young Asian men. Triggered by carbohydrate load or rest after exercise. Treat the acute attack with cautious potassium replacement and non-selective beta-blockade; definitive treatment is control of the thyrotoxicosis.

💡Two points that catch people out: (1) Propranolol is first-line for adrenergic control but is CONTRAINDICATED in acute heart failure due to thyrotoxicosis — use verapamil instead. (2) Do not rush to cardiovert thyrotoxic AF — restoring euthyroidism alone converts a significant proportion, and stroke risk must be mitigated with anticoagulation in the interim.

🚨 AF in thyrotoxicosis — anticoagulate. Do not wait for euthyroidism. Stroke risk is present from the moment AF is documented, regardless of CHA₂DS₂-VASc score (thyrotoxic AF is treated as intrinsically higher risk in the acute phase).

📋 Guidelines

EUGOGO 2021 (Bartalena et al) NICE NG145 BTF — TED Patient Leaflet ETA Guidelines (EU)

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Thyroid Eye Disease — Overview SCE

EUGOGO · NICE NG145 · Oxford Handbook of Endocrinology and Diabetes

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Incidence25–50% of Graves' patients develop TED. Main risk factor: smoking — advise cessation at every visit. The eye disease does NOT correlate with thyroid status — patient can be euthyroid, hypothyroid, or hyperthyroid at presentation. TED may be the first presenting sign of Graves' disease.

MechanismRetro-orbital fibroblasts express TSH receptors and IGF-1 receptors — targeted by autoimmune response. Glycosaminoglycan accumulation + lymphocyte infiltration → orbital swelling → proptosis, muscle fibrosis, optic nerve compression.

RAI and TEDRAI can worsen TED — especially in smokers (25% risk of worsening after RAI). Radioiodine-induced release of thyroid antigens may amplify orbital autoimmunity. Effect usually transient but can be severe in active disease.

Symptoms to ask about

Mild symptomsEye discomfort, grittiness, ↑tear production, photophobia, pressure sensation behind eyes.

Serious symptoms — urgent ophthalmology referralDiplopia (double vision). ↓visual acuity. Change in colour vision. Afferent pupillary defect → optic nerve compression → sight-threatening emergency. Globe subluxation (eye suddenly 'popping out').

Signs to examine for

SignsExophthalmos (protruding appearance). Proptosis >21mm (eyes protrude beyond orbit — assess from above in same plane as forehead). Lid retraction (white sclera visible above/below iris). Conjunctival oedema (chemosis). Corneal ulceration. Ophthalmoplegia — especially limitation of upward gaze (inferior rectus fibrosis).

Paradox of optic nerve compressionIf anatomical constraints prevent proptosis, optic nerve compression becomes MORE likely — the pressure has nowhere to decompress. A patient with restricted proptosis who develops visual symptoms has a higher risk of optic neuropathy than one with florid exophthalmos. Do not be falsely reassured by absence of proptosis.

💡Ophthalmoplegia in TED is due to inferior rectus and medial rectus fibrosis — not CN III/IV/VI palsy. Upward gaze is most commonly affected first. The restricted eye movement pattern differs from a cranial nerve palsy.

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Clinical Activity Score (CAS) SCE

EUGOGO 2021 (Bartalena et al, Eur J Endocrinol)

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CAS scoring — 1 point each

1. Spontaneous retrobulbar painPain at rest, behind or around the eye (not related to eye movement).

2. Pain on eye movementPain on attempted up, side, or down gaze.

3. Redness of the conjunctivaDiffuse redness of the conjunctiva (covering at least one quadrant).

4. Redness of the eyelidsEyelid redness.

5. Swelling of the caruncleSwelling of the caruncle and/or plica.

6. ChemosisSwelling of the conjunctiva.

7. Swelling of the eyelidsSwelling of the upper or lower eyelid (oedema).

CAS interpretation

CAS 0–2 out of 7Inactive disease. Unlikely to respond to immunosuppression. Manage conservatively. Surgical rehabilitation appropriate for inactive stable disease.

CAS ≥3 out of 7Active disease — likely to respond to immunosuppression. Warrants systemic treatment if significant impact on quality of life. Refer to ophthalmology with TED interest.

Severity grading (EUGOGO)

Grade 1 — MildOcular irritation only. Proptosis <3mm above normal. Minor lid retraction. Intermittent diplopia or none.

Grade 2 — Moderate-severeProptosis ≥3mm above normal. Constant diplopia. Soft tissue swelling (oedema, erythema of lids, chemosis, caruncular swelling). Significant impact on daily activities.

Grade 3 — Sight-threateningOptic neuropathy OR exposure keratopathy. Requires immediate intervention — medical or surgical decompression. Do not delay.

💡CAS ≥3 = active = likely to respond to IV steroids. CAS <3 = inactive = steroids will not help. This distinction matters enormously — giving steroids to inactive TED exposes the patient to steroid side effects with no benefit. Always score the CAS before deciding on treatment.

🚨 Urgent ophthalmology referral triggers: Unexplained ↓acuity · Change in colour vision · Afferent pupillary defect · Corneal opacity · Cornea visible when eyelids closed · Optic disc swelling · Globe subluxation. Do not wait for the next routine appointment.

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TED Management by Severity SCE

EUGOGO 2021 · NICE NG145

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All patients — general measures

Smoking cessationMost important intervention — smoking is the main modifiable risk factor. Document advice at every visit.

Restore and maintain euthyroidismHypo- and hyperthyroidism both worsen TED. Target stable euthyroidism. Avoid post-RAI hypothyroidism specifically — monitor closely after RAI.

Selenium supplementationOral selenium 200mcg daily for 6 months may be beneficial in mild active TED of short duration. Source: EUGOGO; Marcocci et al, NEJM 2011. ⚠️ Evidence is for mild disease only — do not substitute for immunosuppression in moderate-severe disease.

Mild TED (Grade I — CAS <3)

Conservative measuresLubricant eye drops (Clinitas, Hyloforte, Xailin HA). Night-time paraffin-based ointment (Xailin Night, Lacrimal Lube). Sunglasses for photophobia. Avoid dust/dry environments. Elevate head of bed to reduce periorbital oedema. Fresnel prism for diplopia — easy to change as exophthalmos evolves.

Moderate-severe TED (Grade II/III — CAS ≥3)

IV methylprednisolone — first linePulsed IV methylprednisolone: 500mg weekly for 6 weeks, then 250mg weekly for 6 weeks (moderate-severe, CAS ≥3). For severe acute disease: 1g IV daily for 3 consecutive days on PIU, then 250mg IV weekly or oral prednisolone 0.7–1mg/kg. All systemic immunosuppression must be guided by ophthalmology with TED expertise.

Oral steroids — not preferredLess effective than IV pulsed methylprednisolone for active TED. Higher total steroid burden for same effect. Use only if IV not available.

Second-line immunosuppressionMycophenolate mofetil, rituximab (anti-CD20), tocilizumab (anti-IL-6R). Guided by ophthalmology + rheumatology. Rituximab and tocilizumab are emerging biologics with growing evidence for moderate-severe TED refractory to steroids.

Sight-threatening TED (Grade IV)

Urgent surgical or medical decompressionOptic neuropathy or exposure keratopathy requires immediate intervention. Surgical decompression (inferior orbital approach using ethmoidal, sphenoidal, and maxillary sinuses). Orbital radiotherapy for ophthalmoplegia — limited effect on proptosis. Eyelid surgery for cosmesis/function once disease inactive.

💡Early response to IV steroids predicts treatment outcome in TED. If no response after 2–3 pulses, consider second-line therapy. Outcome is inversely related to duration of disease — treat active disease promptly.

📋 Guidelines

NICE NG145 BTA Guidelines ATA Guidelines (US)

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Toxic Multinodular Goitre (MNG) SCE

NICE NG145 · Oxford Handbook of Endocrinology and Diabetes

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EpidemiologyCommonest cause of hyperthyroidism in the elderly and in iodine-deficient areas. Multiple autonomously functioning nodules secreting thyroid hormones independently of TSH regulation. TRAb negative — distinguishes from Graves'.

Most common cause of T3 toxicosisAutonomously functioning nodules preferentially secrete T3 over T4. Always check FT3 in a patient with suppressed TSH and a nodular goitre — normal FT4 does not exclude thyrotoxicosis.

Diagnosis↓TSH + ↑FT3 ± ↑FT4. TRAb negative. Thyroid USS: multiple nodules. Isotope scan: patchy/heterogeneous uptake — areas of increased and decreased function corresponding to hot and cold nodules.

ManagementATDs do NOT induce remission in toxic MNG — they control symptoms while planning definitive treatment. Offer RAI or surgery. Surgery indicated for: compressive symptoms (dysphagia, dyspnoea, stridor), large goitre, patient preference, suspicious nodule.

Iodine-induced thyrotoxicosis (Jod-Basedow)Pre-existing nodular disease + iodine load (contrast media, amiodarone) → unmasking of autonomous function → overt thyrotoxicosis. Preferential T3 secretion common. Can be prolonged and difficult to treat.

💡ATDs in toxic MNG are a bridge to definitive treatment — never the endpoint. If a patient with toxic MNG is on long-term carbimazole without a plan for RAI or surgery, the clinical plan needs reviewing.

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Solitary Toxic Adenoma SCE

NICE NG145 · Oxford Handbook of Endocrinology and Diabetes

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PathophysiologySingle autonomously functioning follicular adenoma producing T3 and T4 independently of TSH. Rest of gland suppressed on isotope scan.

Diagnosis↓TSH + ↑FT3 ± ↑FT4. Isotope scan: solitary hot nodule with suppressed background — pathognomonic pattern. Hot nodule is almost never malignant — FNA not required if isotope scan confirms hot nodule.

ManagementDefinitive treatment: RAI (preferred if no contraindication) or hemithyroidectomy. ATDs control symptoms while planning — not long-term treatment. Hemithyroidectomy preserves contralateral lobe — most patients remain euthyroid without levothyroxine post-operatively.

T3 toxicosis commonMay present with suppressed TSH and normal FT4 — always check FT3. Patient may be symptomatically thyrotoxic with a "normal" TFT profile if FT3 not requested.

💡A hot nodule on isotope scan does not need FNA — malignancy in a hot nodule is exceptionally rare. This is a key SCE and clinical decision point: suppressed TSH + nodule → isotope scan first → if hot → FNA not needed. FNA only if TSH is normal or elevated.

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Amiodarone-Induced Thyroid Disease SCE

Oxford Handbook of Endocrinology and Diabetes · NICE NG145

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Why amiodarone affects thyroid37% iodine by weight. Inhibits T4→T3 conversion (↑FT4, ↓FT3 with normal TSH — early, expected). Half-life 40–55 days — effects persist months after stopping. Always check TFTs at baseline and every 6 months on treatment.

Amiodarone-induced hypothyroidism (AIH)More common in iodine-sufficient areas (UK). Often autoimmune (Wolff-Chaikoff effect + underlying Hashimoto's). Pattern: ↑TSH + ↓FT4. Treat with levothyroxine — continue amiodarone if cardiologically necessary.

AIT Type 1 — iodine excessPre-existing thyroid disease (nodular goitre, latent Graves'). Iodine load unmasks autonomous function. Pattern: ↓TSH + ↑FT4 + ↑FT3. Thyroid vascular on colour Doppler. Treat: high-dose carbimazole.

AIT Type 2 — destructive thyroiditisNo underlying thyroid disease. Direct cytotoxic effect → follicular destruction → hormone leak. Pattern: ↓TSH + ↑FT4 + ↑FT3. Thyroid avascular on colour Doppler. Treat: prednisolone 40mg — rapid response expected.

Mixed AIT (common in practice)Type 1 and Type 2 features coexist. Doppler may not clearly differentiate. Treat with carbimazole + prednisolone together. Reassess response at 4–6 weeks.

💡The Doppler discriminator: AIT1 = vascular (autonomous thyroid tissue), AIT2 = avascular (destroyed follicles). In practice mixed type is common. If uncertain — treat both. Stopping amiodarone is ideal if cardiologically safe but disease can persist for months regardless due to the long half-life.

👋 Returning to practice — hypothyroidism

The commonest thyroid condition — but the complex cases come to you

Hypothyroidism is the commonest thyroid condition overall and the one you'll encounter most in primary care. In secondary care endocrine clinics, most hypothyroid patients are managed in the community — you'll tend to see those with complex or uncertain TFTs, persistent symptoms on adequate replacement, or suspected central hypothyroidism. New hyperthyroid referrals to secondary care are predominantly Graves' disease. This section covers everything from first presentation to the tricky management decisions that come up when patients are referred in.

Commonest thyroid condition overall and in primary care

Most hypothyroid patients managed in community — secondary care sees the complex cases

TSH alone is not enough — always check FT4 when TSH is abnormal

Symptoms can precede overt biochemical hypothyroidism by years

T3/T4 combination therapy — now discussed, rarely indicated

Subclinical hypothyroidism thresholds remain debated in 2024

Levothyroxine timing matters more than most patients are told

Hashimoto's — TPO antibodies change the conversation, not just the diagnosis

📋 Key Guidelines & References

NICE NG145 — Thyroid Disease (2019) NICE NG145 — Full Guideline PDF ATA Hypothyroidism Guidelines ETA Guidelines

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Primary Hypothyroidism SCE

Diagnosis & causes

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Definition

Overt hypothyroidism↑TSH + ↓FT4. Treat regardless of symptoms.

Subclinical hypothyroidism↑TSH (usually 4–10) + normal FT4. Treatment controversial — see below.

Central hypothyroidism↓FT4 + low/normal TSH. Pituitary or hypothalamic cause. Easy to miss.

Common Causes

Autoimmune (Hashimoto's)Most common. TPO antibodies positive in >90%. Goitre may be present.

Post-radioiodine / post-thyroidectomyPredictable. Lifelong replacement needed.

Drug-inducedAmiodarone, lithium, checkpoint inhibitors, interferon. Always check medication list.

Iodine deficiencyRare in UK. Think of it in patients from endemic areas.

💡Central hypothyroidism is the great mimicker — TSH can appear normal or even slightly elevated. If you suspect pituitary disease, always check FT4 directly. A "normal" TSH does not exclude central hypothyroidism.

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Levothyroxine Treatment SCE

Dosing, monitoring, practical tips

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Starting Dose

Young, healthy adultsTarget full replacement dose is approximately 1.6 mcg/kg/day. NICE NG145 recommends starting at 50–100 mcg/day in most adults, titrated to TSH every 6–8 weeks until target reached.

Elderly or ischaemic heart diseaseStart low: 25–50 mcg. Increase slowly every 6–8 weeks.

PregnancyIncrease dose by 25–30% as soon as pregnancy confirmed. Target TSH in the trimester-specific laboratory reference range where available. If no local trimester-specific range: ETA/BTA 2021 accept TSH <4.0 mU/L throughout pregnancy; ATA 2017 uses the tighter target of TSH <2.5 in T1 and <3.0 thereafter. Document which standard is being applied.

Monitoring

When to recheck TFTs6–8 weeks after any dose change. Annually once stable.

Target TSH0.4–2.5 mU/L for most patients. Symptom-guided within range.

Persistently symptomaticCheck FT3 — consider T3/T4 combination in selected patients (specialist decision).

Practical Pearls

Take on empty stomach30–60 min before food. Coffee, calcium, iron all impair absorption.

Consistency mattersSame time every day. Brand switching can cause instability — advise patients to stick to one brand.

💡The most common reason for persistent symptoms on adequate replacement is absorption issues — check timing, interactions, and consider coeliac screening. Don't just increase the dose.

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Subclinical Hypothyroidism SCE

When to treat — the decision framework

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Treat if ANY of these apply

TSH >10 mU/LTreat regardless of symptoms. Consensus recommendation (NICE NG145, ETA). Observational data support cardiovascular benefit, though RCT evidence (including TRUST trial, NEJM 2017) is less definitive in the elderly.

Symptoms presentTrial of treatment reasonable. Review at 3 months — if no benefit, stop.

Pregnant or planning pregnancyTreat if TSH >4 regardless of TPO status, or TSH >2.5 with positive TPO antibodies (ATA 2017 guidance). ⚠️ Some UK centres and ETA guidelines use 4.0 as the universal threshold. Use trimester-specific laboratory ranges where available.

Positive TPO antibodies + TSH >4Higher progression risk. Treatment reasonable, especially in younger patients.

Heart failure or ischaemic heart diseaseGrowing evidence supports treatment even at lower TSH levels.

Watch and wait if

TSH 4–10, asymptomatic, elderlyEvidence of benefit weaker. Risk of over-treatment (AF, osteoporosis). Recheck in 3–6 months.

💡NICE NG145 (2019) recommends a 3–6 month confirmatory TSH before diagnosing subclinical hypothyroidism — avoid treating a single transient result.

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Hashimoto's Thyroiditis SCE

Beyond the diagnosis

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DiagnosisTPO antibodies (>95% sensitive). Anti-Tg antibodies less specific. Ultrasound shows heterogeneous pattern — not required for diagnosis.

Natural historyMany stay euthyroid for years. ~2–4%/year progression to overt hypothyroidism, faster if TPO strongly positive.

AssociationsOther autoimmune conditions — T1DM, coeliac, vitiligo, pernicious anaemia, Addison's. Screen appropriately.

Symptoms with normal TSHAcknowledge the symptoms are real. Check FT4 and FT3. If TSH and FT4 are genuinely normal, NICE NG145 does not recommend starting levothyroxine — positive TPO antibodies alone are not an indication for treatment in a euthyroid patient. Exclude other causes of fatigue (iron deficiency, vitamin D, B12, coeliac, depression). Be honest with the patient about the evidence.

💡TPO-positive + normal TSH + symptoms = do not start levothyroxine empirically. NICE NG145 is clear on this. The right approach is: exclude other treatable causes, monitor TFTs 6-monthly (higher progression risk), and have an honest shared decision-making conversation about what the evidence does and does not support. Starting treatment without a biochemical indication risks over-replacement and its own harms.

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Thyroid Management in the Elderly NEW

Frailty changes the targets and the risks

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Higher TSH targets in the elderlyObservational data (Leiden 85-Plus, NHANES) consistently show that higher TSH levels in the elderly (up to 7–8 mU/L) are associated with normal or even better outcomes. Over-treatment to a TSH of 0.5–2.0 in a frail 85-year-old increases AF and fracture risk without proven benefit. Target TSH 1–5 mU/L in patients >70, and accept TSH up to 8 mU/L in the very elderly (>80) if asymptomatic.

Subclinical hypothyroidism — do not over-treatThe TRUST trial (NEJM 2017, n=737, mean age 74) showed no benefit of levothyroxine over placebo for subclinical hypothyroidism (TSH 4.6–19.9) in adults ≥65 years. NICE NG145 recommends a watch-and-wait approach for TSH 4–10 in the asymptomatic elderly. Treatment carries real risks: AF, osteoporosis, angina exacerbation.

Starting levothyroxine — go low and slowStart 25mcg in patients >65 or with ischaemic heart disease. Increase by 25mcg every 6–8 weeks. In frail elderly patients, a starting dose of 12.5mcg may be appropriate. Rapid correction can precipitate angina, arrhythmia, or heart failure.

Subclinical hyperthyroidism — do treatUnlike subclinical hypothyroidism, subclinical hyperthyroidism in the elderly (TSH <0.1) does warrant treatment. 3× increased AF risk and doubled fracture risk. Threshold to treat is lower in the elderly — see subclinical hyperthyroidism card.

TSH suppression in DTC follow-upAvoid prolonged full TSH suppression (<0.1) in elderly DTC patients unless actively high-risk. TSH 0.5–2.0 is acceptable for low-risk remission in patients >65. Iatrogenic thyrotoxicosis causes more harm than a slightly relaxed target in this age group.

💡The general principle: in the elderly, the risks of over-replacement consistently outweigh the risks of mild under-replacement. A TSH of 6 in a well 82-year-old does not need treatment. A TSH of 0.8 achieved by aggressive levothyroxine dosing in the same patient may cause AF. Adjust your targets to the patient in front of you.

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TFT Framework SCE

The systematic approach that never fails

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Step 1 — TSH

Normal TSHThyroid function almost certainly normal. Exception: central hypothyroidism (low FT4 + low-normal TSH). Check FT4 if pituitary disease suspected.

↑TSH→ Check FT4. If ↓FT4: overt hypothyroidism. If normal FT4: subclinical hypothyroidism.

↓TSH→ Check FT4 + FT3. If ↑: overt hyperthyroidism. If normal: subclinical hyperthyroidism or non-thyroidal illness.

Step 2 — ↓TSH with normal FT4: don't stop here

⚠️ Always check FT3 when TSH is suppressedA suppressed TSH with normal FT4 is NOT subclinical hyperthyroidism until you have checked FT3. FT3 may be elevated — this is T3 toxicosis. Missing FT3 here is a common and clinically significant error.

Step 3 — Common Pitfalls

T3 toxicosis↓TSH + normal FT4 + ↑FT3. Patient is overtly hyperthyroid clinically despite normal FT4. Commoner in toxic nodular disease, early Graves', iodine excess, and T3-secreting adenomas. Always check FT3 before labelling as subclinical.

Non-thyroidal illness (sick euthyroid)↓TSH, ↓FT3, FT4 variable. Do not treat. Reassess after recovery.

Recovery from hyperthyroidismTSH can remain suppressed for months after FT4 normalises. Don't over-treat.

Assay interferenceBiotin, heparin, heterophilic antibodies — see assay interference card. Repeat if clinically discordant.

💡The rule: whenever TSH is suppressed, always check both FT4 AND FT3. If you only check FT4 and it is normal, you will miss T3 toxicosis. The patient in front of you with palpitations, weight loss and a suppressed TSH but "normal FT4" is not subclinical — check FT3.

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T3 Toxicosis SCE

↓TSH + normal FT4 + ↑FT3 — the missed diagnosis

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DefinitionBiochemical hyperthyroidism driven predominantly by excess T3 rather than T4. TSH suppressed. FT4 normal or even low-normal. FT3 elevated. Patient is clinically thyrotoxic — symptoms are real and can be severe.

Why it happensT3 is the active hormone. The thyroid can preferentially secrete T3 over T4, particularly in: iodine deficiency, autonomously functioning nodules, and some cases of Graves'. T3 has ~3–4× greater biological potency than T4 and acts more rapidly.

When to suspect T3 toxicosis specifically

Toxic multinodular goitreMost common cause of T3 toxicosis. Autonomously functioning nodules often preferentially secrete T3. Always check FT3 in a patient with nodular goitre and suppressed TSH.

Solitary toxic adenomaHot nodule may secrete predominantly T3. Isotope scan confirms autonomous function.

Early or relapsing Graves'At onset of Graves' disease, or in early relapse after ATD withdrawal, T3 may rise before FT4 becomes clearly elevated. Suppressed TSH + symptoms + normal FT4 = check FT3.

Iodine excessJod-Basedow effect in pre-existing nodular disease. Preferential T3 secretion common.

Post-RAI or post-partial thyroidectomyResidual or regenerating thyroid tissue can preferentially secrete T3. FT4 normal, TSH suppressed, patient symptomatic — check FT3.

Exogenous T3 ingestionFactitious thyrotoxicosis with liothyronine. ↑FT3 + ↓FT4 (suppressed by exogenous T3) + ↓TSH. Thyroglobulin undetectable (no endogenous thyroid stimulation).

Management

Treatment same as overt hyperthyroidismATDs (carbimazole/PTU) block T3 and T4 synthesis equally. Beta-blockers for symptomatic relief — propranolol also partially blocks peripheral T4→T3 conversion. Definitive treatment (RAI or surgery) as per underlying cause.

Monitoring on ATDsCheck FT3 as well as FT4 and TSH on treatment. FT4 can normalise before FT3 — don't reduce ATD dose prematurely if FT3 still elevated. Target: normal FT3 + FT4 with rising TSH before dose reduction.

💡T3 toxicosis is most likely to catch you out in two settings: (1) a patient with a nodular goitre and symptoms of thyrotoxicosis but "normal" FT4 — check FT3; and (2) a patient on ATDs whose FT4 has normalised but who remains symptomatic — FT3 may still be elevated. FT3 should be checked at every ATD monitoring visit, not just FT4.

⚠️ Don't discharge as subclinical hyperthyroidism without checking FT3. A suppressed TSH + normal FT4 + symptoms = T3 toxicosis until proven otherwise. Subclinical hyperthyroidism is an asymptomatic finding — if the patient feels unwell, you haven't finished the investigation.

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TFT Assay Interference SCE

Addenbrooke's, Cambridge — Best Pract Res Clin Endocrinol Metab 2013

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Step 1 — Always exclude first

Clinical reappraisalBefore attributing to assay interference, revisit: pregnancy, non-thyroidal illness, recent treatment, drug effects. Most discordant TFTs have a clinical explanation first.

TSH Assay Interference

Heterophilic / human anti-animal antibodies (HAAs)Most important TSH assay pitfall. Two-site immunometric (sandwich) assay uses capture + detection antibodies. HAA cross-linking both = positive interference → falsely HIGH TSH. HAA blocking either = negative interference → falsely LOW TSH. Confirm by: varying result across assay platforms, PEG/protein G treatment removes antibody, non-linear dilution. Seen in Graves' and positive rheumatoid factor.

Macro-TSH complexAnti-TSH immunoglobulin binds TSH — neutralises biological activity but leaves epitopes exposed. Analogous to macroprolactin — artefactually elevated TSH. Rare but important to recognise.

FT4 / FT3 Assay Interference

Heparin — clinically criticalBoth unfractionated and LMWH (including prophylactic doses) cause in vivo activation of lipoprotein lipase → raised NEFAs in vitro → displacement of T4 from TBG binding sites → spuriously ELEVATED FT4 (up to 5-fold). Occurs even with cannula flush doses. Avoid measuring FT4 in heparinised patients; if essential, take sample >10h after last dose and analyse immediately. Use total T4 + TBG instead if needed.

Familial dysalbuminaemic hyperthyroxinaemia (FDH)Variant albumin with increased T4 affinity. Causes spuriously elevated FT4 on one-step immunoassays but normal FT4 on two-step assay or equilibrium dialysis. Patient is clinically euthyroid. TSH normal. Common in Hispanic populations. Autosomal dominant.

Biotin (Vitamin B7)≥5mg/day (common in OTC hair/nail supplements) interferes with biotin-streptavidin based immunoassays → spuriously ↑FT4/FT3 and ↓TSH. Mimics hyperthyroidism biochemically. Patient well, no goitre. Stop biotin 48–72h and repeat.

Anti-iodothyronine antibodiesBind the tracer in competition assays. Can cause spuriously high or low FT3/FT4. Seen in autoimmune thyroid disease. Suspect if total and free hormone results grossly discordant.

Furosemide, aspirin, phenytoin, NSAIDsDisplace T4/T3 from binding proteins → transiently alter free hormone measurement. Furosemide especially relevant at doses >80mg IV. Usually transient.

Structured Algorithm — Best Pract Res Clin Endocrinol Metab 2013

Step 1Clinical reappraisal — exclude pregnancy, NTI, recent treatment, drugs.

Step 2Systematically screen for assay interference — repeat on different platform, PEG precipitation, dilution series.

Step 3Only then consider rare genetic/acquired HPT axis disorders — RTH, TSHoma, MCT8 mutations, selenoprotein deficiency.

💡The heparin effect is the most underrecognised clinical pitfall — especially relevant on AMU, post-cardiac cath, or in any patient on prophylactic LMWH. A patient on dalteparin with a spuriously elevated FT4 and normal TSH is not hyperthyroid. Take sample >10h after last dose. If in doubt, measure total T4 with TBG.

⚠️ Reference: Koulouri O, Moran C, Halsall D, Chatterjee VK et al. Pitfalls in the measurement and interpretation of thyroid function tests. Best Pract Res Clin Endocrinol Metab. 2013;27(6):745–762. Open access.

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Non-Thyroidal Illness (Sick Euthyroid) SCE

The commonest TFT pitfall on the wards

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DefinitionAbnormal TFTs in the context of acute or chronic illness WITHOUT intrinsic HPT dysfunction. A secondary adaptive change — not a primary thyroid disorder. No compelling evidence to treat with TH replacement in the majority.

TFT patternLow/low-normal FT3 (most consistent finding — reduced DIO1 activity), low/low-normal FT4, normal or low (but rarely fully suppressed) TSH. Reverse T3 typically elevated. TSH may rise transiently during recovery — do not treat this.

When changes beginAs early as 24h after onset. Seen in sepsis, burns, surgery, malignancy, MI, malnutrition, chronic liver and renal disease.

MechanismReduced hypothalamic TRH secretion; impaired pituitary TSH release; reduced DIO1 (↓T4→T3 conversion); increased DIO3 (↑T4→rT3); altered TH binding capacity. Pro-inflammatory cytokines (IL-1, IL-6, TNF-α) implicated. Leptin reduction in malnutrition impairs hypothalamic TRH directly.

Prognostic significanceMagnitude of T4 decrease correlates with worse outcome. Mortality up to 80% when total T4 falls below 26 nmol/L in ITU patients.

RecoveryTFTs normalise as illness resolves. TSH rises first (may transiently become frankly elevated) — this precedes T4 rise. Avoid diagnosing or treating hypothyroidism in this window.

💡The transient TSH rise during recovery from NTI is a classic trap — do not start levothyroxine. Recheck TFTs 6–8 weeks after the acute illness has resolved before making any thyroid diagnosis. The SCE will give you a patient with elevated TSH 2 weeks after ICU discharge — the answer is to recheck, not to treat.

⚠️ Psychiatric illness: Raised T4 with non-suppressed TSH can be seen in acute major psychiatric illness — typically resolves within 2 weeks. Do not treat. Recheck.

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Drugs & TFTs SCE

What to expect from common medications

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Drugs causing hypothyroidism (↑TSH, ↓FT4)

AmiodaroneHypothyroidism in ~15% (especially women, TPO+ patients). Failure to escape Wolff-Chaikoff effect. Also causes transient ↑TSH and ↑FT4 in first months of treatment — not disease.

LithiumOvert or subclinical hypothyroidism. Also rarely causes thyroiditis (↓TSH, ↑FT4 — usually self-limiting).

Tyrosine kinase inhibitors (TKIs)Sunitinib, sorafenib — primary hypothyroidism (direct thyroid toxicity). Also prodromal thyrotoxic phase with sunitinib.

Bexarotene (Targretin)Inhibits TSHβ transcription → central hypothyroidism (↓TSH + ↓FT4). Used in cutaneous T-cell lymphoma. Significant clinical hypothyroidism common — requires replacement.

Immune modulatorsAlemtuzumab → Graves' disease. Interferon-α → Hashimoto's (with thyrotoxic prodrome) or Graves'. Checkpoint inhibitors (anti-PD1, anti-CTLA4) → thyroiditis, hypothyroidism.

Drugs causing TSH suppression

GlucocorticoidsSuppress hypothalamic TRH → reduced TSH. Usually transient. Clinically significant central hypothyroidism uncommon.

Dopamine / dopamine agonistsIV dopamine infusion suppresses TSH via D2 receptors on thyrotrophs. Combined with NTI in critically ill patients may cause genuine hypothyroidism.

Somatostatin analoguesOctreotide, lanreotide suppress TSH directly. Usually transient. Not clinically significant unless pre-existing HPT axis compromise.

MetforminObservational data suggest metformin lowers TSH in patients with elevated TSH (possibly central effect). Clinical significance unclear — do not adjust levothyroxine dose on TSH alone if newly started on metformin without rechecking.

Drugs affecting T4 absorption / metabolism

↓ Levothyroxine absorptionCalcium, iron, PPIs, sucralfate, aluminium hydroxide, cholestyramine, colestipol, fibre, espresso coffee. Take LT4 30–60 min before food and separate from these by ≥4 hours.

↑ LT4 requirements (enzyme induction)Phenytoin, carbamazepine, phenobarbitone, rifampicin, some TKIs (imatinib) — enhance hepatic metabolism of TH. May need dose increase.

↑ LT4 requirements (↑TBG)Oral oestrogen (not transdermal), raloxifene, tamoxifen, mitotane — increase TBG → more T4 bound → need higher LT4. Common in IVF cycles.

💡A patient on stable levothyroxine whose TSH suddenly rises after starting a PPI, calcium supplement, or oral contraceptive pill has not developed resistance — they have reduced absorption or increased TBG. Check the medication list before increasing the dose. The SCE tests this regularly.

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Anomalous TFTs on Levothyroxine SCE

Why the TFTs don't make sense — structured approach

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Pattern A — Normal TSH, mildly elevated FT4

CauseNormal physiological variant. Some individuals need slightly elevated FT4 to achieve euthyroid TSH — possibly less efficient DIO2-mediated T4→T3 conversion. FT3 typically normal. No action needed.

Pattern B — Elevated TSH despite adequate/high LT4 dose

Poor complianceShort LT4 half-life means intermittent dosing normalises FT4 transiently but fails to suppress TSH. Pattern: ↑TSH + normal or even elevated FT4. A supervised thyroxine absorption test (Walker et al, EJE 2013) can distinguish malabsorption from non-compliance.

MalabsorptionCoeliac disease, achlorhydria, lactose intolerance (lactose is a constituent of some LT4 preparations). Screen for coeliac in unexplained high LT4 requirements.

Drug interactionsSee drugs card above. Always check timing and co-medications before increasing dose.

Increased TBGOral oestrogen, IVF. Review when OCP or HRT started.

RTH on levothyroxineSupraphysiologic LT4 required to normalise TSH, but results in ↑FT4 and ↑FT3. THRB mutation. Rare but important.

Pattern D — Elevated TSH, normal FT4

TSH assay interferenceHeterophilic antibody causing positive TSH interference. FT3 normal. Clinically euthyroid. Request repeat on alternative platform.

💡The formal thyroxine absorption test — acute (6h single supervised dose) plus longer-term (6-week weekly supervised administration) — is the gold standard to distinguish malabsorption from non-compliance when standard assessment fails. Request via endocrine biochemistry.

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Postpartum Thyroiditis SCE

Returning from maternity — know this cold

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Incidence5–10% of women. Higher if TPO antibodies positive pre-pregnancy (25–50%).

PhasesThyrotoxic phase (1–4 months post-delivery) → hypothyroid phase (4–8 months) → recovery (~80%). Can present as either phase alone.

Thyrotoxic phaseDestructive — no role for ATDs. Beta-blockers for symptom control if needed. Distinguish from Graves' (TRAb negative in PPT).

Hypothyroid phaseTreat if symptomatic or breastfeeding — levothyroxine safe in breastfeeding. Review at 12 months — 25% develop permanent hypothyroidism.

💡Women with postpartum depression should have TFTs checked. PPT hypothyroid phase is a common and treatable contributor to postnatal mood symptoms — often missed because the depression is attributed to psychological causes alone.

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De Quervain's Thyroiditis

Painful, self-limiting, often misdiagnosed

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PresentationPainful goitre, fever, elevated ESR/CRP. Preceded by viral URTI. FT4 elevated, TSH suppressed.

Investigations↑ESR (often >50), ↑CRP, low uptake on isotope scan. TPO antibodies negative (distinguishes from Hashimoto's).

TreatmentNSAIDs for mild cases. Prednisolone 40mg for severe pain — rapid response is diagnostic. Beta-blockers for thyrotoxic symptoms.

PrognosisSelf-limiting over weeks to months. Transient hypothyroid phase common. Permanent hypothyroidism in ~5%.

💡The rapid and dramatic response to prednisolone is almost pathognomonic for De Quervain's — if pain doesn't improve within 48 hours of starting steroids, reconsider the diagnosis.

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Checkpoint Inhibitor Thyroiditis NEW

Increasingly common — know the pattern

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IncidenceThyroid dysfunction occurs in 5–20% of patients on anti-PD1/PD-L1 (nivolumab, pembrolizumab, atezolizumab) and up to 25% with combination anti-CTLA4 + anti-PD1 (ipilimumab + nivolumab). Thyroiditis is the commonest endocrine immune-related adverse event (irAE).

Typical patternPainless destructive thyroiditis. Brief thyrotoxic phase (weeks) → hypothyroid phase (usually permanent). Thyrotoxic phase is self-limiting — do NOT start ATDs. Beta-blockers for symptoms if needed. Most patients require lifelong levothyroxine.

TFT monitoringCheck TFTs at baseline, then every 4–6 weeks for the first 6 months of immunotherapy, then every 3 months. More frequently if combination therapy. Source: ESMO Clinical Practice Guidelines 2022.

Key distinction from Graves'Checkpoint inhibitor thyroiditis is destructive (low isotope uptake, TRAb negative). Rarely, checkpoint inhibitors can trigger true Graves' disease (TRAb positive, diffuse uptake on scan) — this is uncommon but requires ATDs. Check TRAb if thyrotoxic phase is prolonged (>8 weeks).

Do NOT stop immunotherapy for isolated thyroiditisGrade 1–2 thyroid irAEs do not require discontinuation of checkpoint inhibitor therapy. Manage the thyroid dysfunction and continue cancer treatment. Only consider holding immunotherapy for severe or life-threatening endocrine irAEs (e.g. adrenal crisis, severe symptomatic thyrotoxicosis).

Always exclude adrenal insufficiencyCheckpoint inhibitors can cause hypophysitis (especially anti-CTLA4) and primary adrenal insufficiency. If a patient on immunotherapy presents with fatigue and low FT4 — check morning cortisol before starting levothyroxine. Starting levothyroxine without excluding cortisol deficiency can precipitate adrenal crisis.

💡Checkpoint inhibitor thyroiditis is now one of the commonest causes of new thyroid dysfunction seen in secondary care. The key clinical action: don't give ATDs (it's destructive, not autoimmune overproduction), check cortisol before starting levothyroxine, and don't stop the cancer treatment.

🔬 Thyroid cancer — returning to practice

What's changed and what catches people out

The management of differentiated thyroid cancer has evolved significantly. Low-risk papillary microcarcinoma may now be managed with active surveillance rather than immediate surgery in selected patients. RAI ablation is no longer routine for all post-thyroidectomy patients — it is risk-stratified. TSH suppression targets are now tailored to recurrence risk. Tg monitoring requires careful attention to anti-Tg antibody interference. MTC requires RET gene testing for all patients — not just familial cases.

RAI ablation — not routine for low-risk DTC (BTA/NICE update)

TSH suppression target depends on recurrence risk category

Anti-Tg Ab interference — trend the antibody, not just the Tg

All MTC patients need RET gene testing — not just familial cases

Focal FDG-PET uptake = 25–50% malignancy risk — investigate urgently

Hot nodule on isotope scan = almost never malignant = no FNA needed

📋 Guidelines

NICE NG145 BTA Thyroid Cancer Guidelines British Thyroid Foundation ETA Guidelines (EU)

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Thyroid Cancer Types — Overview SCE

BTA · Oxford Handbook of Endocrinology and Diabetes

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Papillary thyroid carcinoma (PTC) — ~80%Most common. Well-differentiated. Derived from follicular cells. Spreads via lymphatics → cervical lymph nodes (may be presenting feature). Psammoma bodies on histology. Generally excellent prognosis — 10-year survival >90%. Associated with childhood radiation exposure.

Follicular thyroid carcinoma (FTC) — ~10%Well-differentiated. Follicular cell origin. Spreads haematogenously → lung, bone (lytic metastases), brain. Cannot distinguish from follicular adenoma on cytology — requires histological demonstration of capsular or vascular invasion. Hurthle cell carcinoma is a variant.

Medullary thyroid carcinoma (MTC) — ~5%Derived from parafollicular C cells. Secretes calcitonin (tumour marker). 25% familial — RET proto-oncogene mutations. Associated with MEN 2A and MEN 2B. Does NOT respond to RAI (C cells don't trap iodine). Spreads to cervical and mediastinal nodes.

Anaplastic thyroid carcinoma — ~1–2%Undifferentiated. Most aggressive thyroid cancer. Rapid local invasion, compressive symptoms. Median survival 3–6 months. Presents in elderly patients with rapidly growing, hard, fixed neck mass. Often incurable at diagnosis. Multidisciplinary emergency management needed.

Thyroid lymphoma — rareUsually B-cell Non-Hodgkin's lymphoma. Arises in Hashimoto's thyroiditis background — ↑risk in Hashimoto's patients. Rapidly enlarging goitre in patient with known Hashimoto's = exclude lymphoma. Treated with chemotherapy ± radiotherapy — NOT surgery.

Risk factors for thyroid malignancy

Patient features suggesting malignancyAge <20 or >60 · Male sex · Firm, hard, solitary non-toxic nodule · Rapid growth · Hoarseness of voice · Palpable cervical lymphadenopathy · Microcalcification on USS · Fixation to surrounding structures · Family history thyroid cancer · Previous neck irradiation

💡Hoarseness + thyroid nodule = recurrent laryngeal nerve involvement until proven otherwise = urgent referral. This combination is a red flag for locally invasive malignancy.

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Thyroid Nodule Assessment — U, Thy & TI-RADS SCE NICE

BTA UK standard · ACR TI-RADS (US) — see Nodules tab for full detail

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U Classification (BTA — UK standard)

U1 — NormalNo abnormality. Discharge.

U2 — BenignCharacteristic benign features. FNA not required unless clinical suspicion. Routine follow-up or discharge.

U3 — IndeterminateEquivocal. U3a = low suspicion, U3b = higher suspicion. FNA required. MDT discussion.

U4 — SuspiciousSuspicious for malignancy — microcalcification, irregular margin, hypoechoic, taller-than-wide. FNA + MDT.

U5 — MalignantHighly suspicious or diagnostic. Urgent surgical referral via thyroid cancer MDT.

Thy Classification (BTA — UK standard FNA cytology)

Thy1/1c — Non-diagnosticInadequate sample. Repeat FNA. Thy1c = cystic lesion (inherently low cellularity).

Thy2/2c — Non-neoplasticBenign features. Correlate clinically and radiologically. No further biopsy if no suspicious features.

Thy3a — AtypiaSome atypical features. MDT. Repeat FNA + USS or hemithyroidectomy depending on context.

Thy3f — Follicular neoplasmCannot distinguish follicular adenoma from carcinoma on cytology. Diagnostic hemithyroidectomy required — capsular/vascular invasion only visible on histology.

Thy4 — SuspiciousHigh suspicion. MDT. Hemithyroidectomy ± frozen section or total thyroidectomy.

Thy5 — MalignantDiagnostic of malignancy. MDT. Surgery ± RAI ± radiotherapy depending on tumour type.

USS features — benign vs malignant

Reassuring benign featuresSpongiform/honeycomb · Purely cystic · Egg-shell calcification · Isoechoic/mildly hyperechoic · Peripheral vascularity · Hyperechoic + well-defined halo

Suspicious malignant featuresSolid hypoechoic ± microcalcification · Irregular/spiculated margin · Intranodular vascularity · Absent halo · Taller-than-wide (AP > transverse diameter) · Hypoechoic + absent halo

💡Key rule before FNA: check TSH first. If suppressed → isotope scan before FNA. A hot nodule is almost never malignant → FNA not needed. Performing FNA on a hot nodule wastes resources and creates unnecessary anxiety. Source: BTA / NICE NG145.

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Differentiated Thyroid Cancer — Management SCE

BTA Guidelines · NICE NG145

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Surgical approach — by risk

Low-risk PTC ≤1cm (microcarcinoma)Thyroid lobectomy is acceptable. No RAI needed if well-differentiated, ≤1cm, no angioinvasion, no lymph node involvement. Active surveillance may be appropriate in selected low-risk microcarcinomas — discuss at specialist MDT. TSH target post-lobectomy: 0.3–2 mU/L (no suppression needed).

PTC >1cm or high-risk featuresTotal/near-total thyroidectomy. ± central compartment (level 6) lymph node dissection if nodes involved or high-risk.

Follicular carcinomaTotal thyroidectomy. Lobectomy may be sufficient for low-risk FTC ≤2cm with minimal capsular invasion — specialist MDT decision.

Post-operative radioiodine ablation (RRA)

When to give RAI — risk-stratified (BTA/NICE update)Low risk (T1/T2, N0, M0, no aggressive histology): RAI NOT routinely recommended. Intermediate/high risk (T3/T4, N1, M1, vascular invasion, aggressive histology): RAI recommended. Timing: within 3–6 months of thyroidectomy.

TSH stimulation for RAITwo options: (1) Withhold levothyroxine for ≥4 weeks (TSH rises naturally). (2) rhTSH (Thyrogen, thyrotropin alfa) injections — allows RAI without LT4 withdrawal. Thyrogen preferred as avoids hypothyroid symptoms. Both methods equally effective for ablation.

TSH suppression targets — risk-stratified

High recurrence riskTSH <0.1 mU/L — full suppression. Maintained until no evidence of disease, then de-escalated.

Intermediate recurrence riskTSH 0.1–0.5 mU/L — mild suppression.

Low recurrence risk / remissionTSH 0.3–2 mU/L — no suppression. Avoid over-suppression — AF risk, osteoporosis risk, especially in older patients.

Whole body scan (WBS) and follow-up

WBS + stimulated Tg at 9–12 monthsStop LT4 for ≥4 weeks or use Thyrogen. Low recurrence: suppressed Tg <1 µg/L + negative USS + negative WBS = remission. High recurrence risk: stimulated Tg >10 µg/L or positive imaging = persistent/recurrent disease.

💡TSH suppression is not benign — it causes subclinical thyrotoxicosis with associated AF risk (3× increased) and osteoporotic fracture risk. The goal is to suppress only as much as needed based on ongoing risk assessment — not lifelong full suppression for all patients.

📈

Thyroglobulin Monitoring — BTA Principles SCE

BTA Thyroid Cancer Guidelines (2014) · ATA 2015

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Always measure simultaneouslyTSH + Tg + anti-Tg antibodies (TgAb) at every measurement. Do not measure Tg alone — the result is uninterpretable without TSH and TgAb.

Consistency is essentialUse the same laboratory and the same Tg assay long-term. Tg values are not interchangeable between assay platforms — small numerical changes across platforms can lead to false alarm or false reassurance.

FrequencyNo more than 3-monthly routine monitoring. Annually if in confirmed remission.

Stimulated TgOnly needed if basal Tg is undetectable on suppression. Stimulation via TSH withdrawal (≥4 weeks off LT4) or rhTSH (Thyrogen).

Anti-Tg antibody interference — critical

TgAb interferes with Tg immunoassayWhen TgAb is positive, the measured Tg is unreliable — usually falsely low (antibody blocks Tg detection in immunoassay). A "reassuringly undetectable" Tg in a TgAb-positive patient may be spurious. Source: BTA Guidelines.

What to do when TgAb positiveTrend the TgAb level serially. A rising TgAb titre (even with undetectable Tg) may indicate recurrent or residual disease — the antibody is being produced in response to tumour antigen. A falling TgAb suggests remission.

LC-MS/MS for TgMass spectrometry-based Tg measurement is not affected by TgAb interference. Available in specialist centres — use when TgAb interference is suspected and decision-making depends on accurate Tg.

Rising Tg — investigation sequence

Sequential workup1. Neck USS → 2. CT chest → 3. Bone scan → 4. FDG-PET CT. Do not jump to PET first — follow the sequence. PET is reserved for iodine-negative disease where other imaging is negative but Tg is rising.

💡The Tg assay interference trap: a patient with rising TgAb and "undetectable" Tg does NOT have confirmed remission. The antibody is the signal. This is one of the most important and most missed points in DTC follow-up.

🧬

Medullary Thyroid Cancer (MTC) SCE

BTA · ATA 2015 · Oxford Handbook of Endocrinology and Diabetes

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Origin and biologyDerived from parafollicular C cells — not follicular cells. Secretes calcitonin (main tumour marker) and CEA. Does NOT trap iodine → RAI ablation is ineffective. Spreads to cervical and mediastinal lymph nodes and liver.

Epidemiology25% familial (RET proto-oncogene mutations). 75% sporadic — but ALL sporadic cases should still have germline RET testing as de novo mutations occur. Associated with MEN 2A (phaeochromocytoma + primary hyperparathyroidism) and MEN 2B (phaeochromocytoma + marfanoid habitus + mucosal neuromas — no hyperparathyroidism).

Initial evaluation

At diagnosisUSS thyroid + FNA + plasma calcitonin. Check CEA. Screen for phaeochromocytoma BEFORE surgery (plasma/urinary metanephrines) — operating on undiagnosed phaeochromocytoma can be fatal. Check serum calcium (exclude hyperparathyroidism).

Genetic testingGenetic counselling + RET gene mutation analysis for ALL patients — not just those with family history. If RET mutation confirmed → screen all first-degree relatives.

Surgery

OperationTotal thyroidectomy + level 6 (central compartment) lymph node dissection. Lateral neck dissection if lateral nodes involved. Levothyroxine replacement post-op (TSH suppression NOT needed — MTC is not TSH-driven).

Prophylactic thyroidectomy in RET carriers

MEN 2B — highest risk RET mutationProphylactic thyroidectomy by age 1 year. Most aggressive MTC — early and complete thyroidectomy is potentially curative.

MEN 2A — high risk RET mutationProphylactic thyroidectomy before age 5. Timing guided by specific RET codon mutation — some high-risk codons require earlier surgery.

Lower risk RET mutationsCan monitor calcitonin and operate when elevated. Specialist MDT decision based on specific mutation.

Follow-up

Lifelong calcitonin + CEA monitoringCalcitonin is the primary tumour marker. CEA doubling time is the best predictor of disease progression. Stimulated calcitonin test (pentagastrin or calcium infusion) for borderline cases — see dynamic testing tab.

Systemic therapy for metastatic MTCVandetanib or cabozantinib (RET tyrosine kinase inhibitors) — approved for symptomatic/progressive metastatic MTC. Selpercatinib (selective RET inhibitor) for RET-mutant MTC — specialist oncology.

GLP-1 receptor agonists and C-cell tumoursGLP-1 RAs (semaglutide, liraglutide, tirzepatide) carry an FDA boxed warning regarding thyroid C-cell tumours based on rodent data (dose-dependent C-cell hyperplasia and MTC in rats and mice). No causal link established in humans to date — post-marketing surveillance ongoing. GLP-1 RAs are contraindicated in patients with personal or family history of MTC or MEN 2. Clinically relevant given overlap between T2DM/obesity patients and thyroid clinic populations.

💡Always exclude phaeochromocytoma before thyroid surgery in any patient with MTC or suspected MEN 2. Operating on an unsuspected phaeochromocytoma causes hypertensive crisis — potentially fatal. This is a non-negotiable pre-operative step.

🚨 MTC + surgery without phaeochromocytoma screen = potentially fatal. Screen plasma/urinary metanephrines before every operative intervention. If phaeochromocytoma confirmed — adrenalectomy first, then thyroid surgery after adequate α-blockade.

🚨

Anaplastic Thyroid Cancer SCE

Oxford Handbook of Endocrinology and Diabetes · BTA

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Clinical presentationRapidly enlarging, hard, fixed neck mass. Almost always in patients >60 years. Compressive symptoms: stridor, dysphagia, hoarseness. Often incurable at presentation due to local invasion.

PrognosisMedian survival 3–6 months from diagnosis. Most aggressive thyroid malignancy. 6-month survival <20%.

ManagementUrgent MDT referral. BRAF V600E mutation testing — present in ~40%. BRAF V600E+ patients may respond to dabrafenib + trametinib (BRAF + MEK inhibitor combination) — FDA approved, emerging evidence. Palliative radiotherapy ± surgery for airway protection. Clinical trial enrolment where possible.

Airway emergencyIf stridor present → urgent airway assessment. May require emergency tracheostomy or stenting. Involve ENT/thoracics early.

💡Anaplastic thyroid cancer is one of the most aggressive solid tumours in oncology. The clinical challenge is managing the rapid airway compromise and providing realistic prognosis information while ensuring MDT involvement and clinical trial access. BRAF testing is now essential at diagnosis.

🚨 Stridor in a patient with rapidly enlarging thyroid mass = airway emergency. Do not wait for MDT. Secure the airway first, investigate second.

🔭

FDG-PET Incidental Thyroid Findings SCE

BTA Guidelines

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Focal FDG uptakeMalignancy risk 25–50%. Investigate with USS + FNA. Urgent secondary care referral. Do not dismiss as incidental — nearly half are malignant.

Diffuse FDG uptakeReported in 0.6–3.3% of population. Usually represents thyroiditis (most commonly Hashimoto's). Lower malignancy risk. Arrange USS + TFTs + TPO antibodies. Lower urgency but still requires clinical follow-up.

💡As PET scanning becomes increasingly prevalent in oncology follow-up, incidental thyroid findings are more common. Focal = urgent investigation. Diffuse = TFT + USS + thyroid antibodies. Document clearly in correspondence and ensure appropriate follow-up is arranged.

🤰

Thyroid in Pregnancy SCE

The complete framework

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Physiological Changes

TSH in pregnancyTSH reference ranges differ by trimester. T1: 0.1–2.5. T2: 0.2–3.0. T3: 0.3–3.5 (approximate — use lab-specific ranges).

hCG effecthCG stimulates TSH receptor → transient TSH suppression in T1, especially with hyperemesis. Usually no treatment needed.

TBG increase↑TBG → ↑total T4. Use free T4 reference ranges validated for pregnancy trimesters.

Hypothyroidism in Pregnancy

Known hypothyroidismIncrease levothyroxine by 25–30% as soon as pregnancy confirmed. Target TSH within trimester-specific lab reference range where available; if unavailable, ETA/BTA 2021 accept <4.0 mU/L throughout, ATA 2017 uses <2.5 in T1. Check TFTs every 4 weeks in T1, then 4–6 weekly thereafter.

New diagnosis in pregnancyStart levothyroxine promptly. Consequences of untreated hypothyroidism include impaired fetal neurodevelopment.

Hyperthyroidism in Pregnancy

Graves' in pregnancyPTU preferred in T1 (carbimazole associated with aplasia cutis). Switch to carbimazole in T2. Target FT4 at high-normal range — avoid hypothyroidism in fetus.

TRAb monitoringCheck at booking and at 30–34 weeks. High TRAb in T3 → risk of neonatal Graves. Liaise with neonatology.

Gestational thyrotoxicosishCG-driven, associated with hyperemesis. TRAb negative. Self-limiting. Beta-blockers for symptoms if needed. No ATDs.

💡The PTU-to-carbimazole switch in T2 is a classic SCE question. PTU is used in T1 because carbimazole is teratogenic (aplasia cutis, choanal atresia). PTU has hepatotoxicity risk with long-term use — switch to carbimazole after the organogenesis period.

🧪 Dynamic thyroid testing

When static TFTs aren't enough

Dynamic thyroid tests are used when the diagnosis can't be made on standard TFTs alone — either because the result is borderline, the clinical picture doesn't fit, or you need to characterise the underlying pathophysiology. These tests come up regularly in the SCE and in complex clinic patients. Know when to use them, what they measure, and how to interpret them.

TRH stimulation test — now rarely used but still tested in SCE

T3 suppression test — historical but conceptually important

Perchlorate discharge test — for organification defects

Isotope scanning — essential for nodule and thyroiditis workup

T3/T4 combination therapy — debated, Cambridge group research on DIO2 polymorphism

Thyroid hormone resistance — know the biochemical pattern

📋 Key References

NICE NG145 — Thyroid Disease Koulouri et al. Best Pract Res Clin Endocrinol Metab 2013 ATA Guidelines ESE Position Statements

🧪

TRH Stimulation Test SCE

Beck-Peccoz et al, Eur Thyroid J 2013 · Oxford Handbook of Endocrinology and Diabetes

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Indications

1. Assess TSH reserveRarely needed now — sensitive TSH assays have replaced this for most clinical questions.

2. Pituitary vs hypothalamic TSH deficiencyLocalise the lesion in central hypothyroidism — hypothalamic cause gives a delayed peak; pituitary cause gives a flat response.

3. TSHoma vs thyroid hormone resistanceThe most clinically important current use. TSHoma = flat response. RTH = exaggerated response.

Preparation

No overnight fast requiredDrug: 200mcg TRH (Protirelin 200mcg in 0.2ml). IV cannula required. 3 × red-top vacutainers (6ml per sample).

⚠️ Thyroxine must be stopped 3 weeks beforeBecause of this requirement, the TRH test is rarely performed in patients already on levothyroxine.

Side effects — warn the patient

Transient symptoms after injectionMetallic taste in the mouth, flushing, mild nausea. Patient should be on a recliner or bed during the test.

Method

Step 1Site IV cannula.

Step 2Take baseline bloods for TSH and T4.

Step 3Inject TRH slowly IV over 2 minutes. Flush cannula.

Step 4Take samples for TSH at t = 30 mins and t = 60 mins only.

Interpretation

Normal responseTSH rises to >5 mU/L. The 30-minute value must exceed the 60-minute value — this is the normal peak pattern.

Flat response → TSHomaBlunted or absent TSH rise. Seen in 90% of TSHomas. The autonomous tumour is not under TRH regulatory control.

Exaggerated response → RTHTSH rises markedly above normal. Pituitary thyrotrophs are responding normally to TRH but are resistant to thyroid hormone feedback — so the response is exuberant.

Delayed peak (60 min > 30 min)Suggests hypothalamic disease — TRH secretion is impaired, but the pituitary itself can still respond. Seen rarely in thyroid and pituitary disease also.

💡The two rules to memorise: (1) Normal = rise >5 mU/L, peak at 30 minutes. (2) TSHoma = flat. RTH = exaggerated. The test is rarely used now for routine hypothyroidism — its main value is in the TSHoma vs RTH distinction, and in localising the cause of central hypothyroidism when MRI is inconclusive. Source: Beck-Peccoz P et al. Eur Thyroid J 2013;2(2):76–82.

☢️

Thyroid Isotope Scanning SCE

Tc-99m pertechnetate & I-123 — when and why

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Indications

Thyroid nodule with suppressed TSHExclude autonomously functioning (hot) nodule before FNA — hot nodules are almost never malignant. FNA not needed if hot.

Hyperthyroidism — cause unclearDifferentiates Graves' (diffuse uptake), toxic MNG (patchy uptake), toxic adenoma (focal hot area with suppressed background), and thyroiditis (very low/absent uptake).

Ectopic thyroid tissueLingual thyroid, substernal goitre extent, thyroglossal cyst with functioning tissue.

Post-thyroidectomy DTC follow-upI-131 whole body scan to detect residual or metastatic differentiated thyroid cancer after thyroidectomy ± ablation.

Patterns to know

Diffuse increased uptakeGraves' disease. Homogeneous. Sometimes pyramidal lobe visible.

Patchy/nodular uptakeToxic multinodular goitre. Irregular areas of increased and decreased uptake.

Solitary hot noduleToxic adenoma. One area of uptake, rest of gland suppressed.

Very low/absent uptakeThyroiditis (De Quervain's, postpartum, silent), exogenous thyroid hormone, recent iodine load.

💡Recent iodine load (contrast CT, amiodarone) suppresses isotope uptake for weeks to months — always check timing. A thyroiditis pattern on scan in someone who recently had IV contrast may simply reflect iodine saturation, not true thyroiditis.

🔬

Perchlorate Discharge Test

Organification defects — rare but tested

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PrincipleRadioiodine is given and uptake measured. Perchlorate is then given — it blocks further iodide trapping. In normal thyroid, trapped iodide has already been organified (bound to thyroglobulin) so perchlorate causes little discharge. In organification defect, unbound iodide is released — >10% discharge is positive.

Positive result indicatesOrganification defect — failure of thyroid peroxidase (TPO) to incorporate iodide into tyrosine residues. Causes congenital hypothyroidism, Pendred syndrome.

Pendred syndromeAutosomal recessive. SLC26A4 (pendrin) gene mutation. Sensorineural deafness + goitre + partial organification defect. Cochlear malformation on CT (Mondini dysplasia / enlarged vestibular aqueduct).

💡Pendred syndrome is the most common cause of syndromic congenital deafness — accounting for up to 10% of hereditary hearing loss. The thyroid dysfunction is variable and sometimes mild. A young patient with goitre and deafness should prompt this diagnosis.

🔄

Thyroid Hormone Resistance (RTH) vs TSHoma SCE

Beck-Peccoz et al 2009 · Koulouri et al 2013 — the critical distinction

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The shared biochemical pattern — both cause:

↑FT4 + ↑FT3 + non-suppressed (normal or elevated) TSHCalled "central hyperthyroidism" or "inappropriate TSH secretion." Cannot be distinguished on TFTs alone. Both conditions can present with goitre. Both can follow inappropriate thyroid ablation. Clinical approach is mandatory before treatment.

RTH (TRβ resistance)

MechanismLoss-of-function mutation in THRB gene (chromosome 3). TRβ2 predominant in pituitary — pituitary resistant to T3 negative feedback. TRα1 (heart, CNS, muscle) relatively spared — hence tachycardia and neurological features.

Incidence~1 in 40–50,000 live births. 80% dominantly inherited; 20% de novo mutations. THRB sequencing confirms in 85% — 15% THRB-negative RTH exists.

Generalised RTH (GRTH)Both pituitary and peripheral tissues resistant. Usually euthyroid clinically despite elevated TH. May have goitre, ADHD features, tachycardia (TRα-mediated).

Pituitary RTH (PRTH)Pituitary resistant, peripheral tissues relatively sensitive → peripheral thyrotoxicosis with unsuppressed TSH. Clinically hyperthyroid. Hardest to distinguish from TSHoma.

TSHoma

PrevalenceRarest pituitary adenoma — <2% of all adenomas, ~1/million population. Prevalence increasing as diagnosis improves. 76% are macroadenomas at diagnosis. 30% had prior inappropriate thyroid ablation — which drives further tumour expansion (cf. Nelson's syndrome).

Mixed adenomas~25% co-secrete GH (most common) or prolactin. GH co-secretion may mask thyrotoxic symptoms with acromegalic features.

Differential Diagnosis — Key Tests (Beck-Peccoz 2009)

α-GSU (alpha-subunit) and α-GSU/TSH molar ratioElevated α-GSU in >80% TSHomas. Normal in RTH (<2%). Calculate molar ratio: α-GSU (μg/L) ÷ TSH (mU/L) × 10. Ratio >1.0 strongly favours TSHoma. Normal in RTH. Note: elevated ratio also seen in some postmenopausal women — interpret in clinical context.

SHBG (sex hormone-binding globulin)Hepatic marker of thyroid hormone action via TRβ1. Elevated in TSHoma (peripheral hyperthyroid state) — mean ~124 nmol/L. Normal in pituitary RTH — mean ~56 nmol/L. Most discriminatory single biochemical marker. Confounders: oral oestrogen, liver disease, insulin resistance, obesity, GH excess (co-secreting TSHoma).

ICTP (bone resorption marker)Carboxyterminal cross-linked telopeptide of type I collagen. Elevated in TSHoma (bone is thyroid hormone-sensitive). Normal in pituitary RTH. Less commonly used but adds discriminatory value.

TRH test (200μg IV)TSH rise <1.5-fold = strongly suggests TSHoma (occurs in 80–90% of macroTSHomas). RTH patients show exuberant TSH rise — typically >5-fold. Blunted response also seen in some microTSHomas. Safe and easy to perform. Use TRH test in combination with T3 suppression for maximum diagnostic power.

T3 suppression test (Werner's test)80–100μg T3/day for 8–10 days. TSHoma: TSH never fully suppressed (100% of cases). RTH: qualitatively abnormal (TSH not fully suppressed) but quantitatively differs — partial suppression seen. Contraindicated in elderly and cardiac disease. Use TRH test if T3 suppression contraindicated.

Somatostatin analogue trial — diagnostic AND therapeutic2-month trial of long-acting octreotide LAR or lanreotide: TSHoma — FT4/FT3 normalises in >95%. RTH — no significant change in FT4/FT3. Useful in problematic cases where T3 suppression and TRH test are inconclusive. Beck-Peccoz 2009: chronic SRL response is highly discriminatory (acute response similar in both).

Pituitary MRIMacroadenoma = strong evidence for TSHoma. However: 15% are microadenomas (easily missed on standard MRI — dynamic MRI or functional imaging may be needed); pituitary incidentalomas are common; RTH with thyrotroph hyperplasia can cause pituitary enlargement (reversible with LT4). Family history of similar TFTs = RTH.

THRB gene sequencingConfirms RTH in 85%. Positive in first-degree relatives = RTH (familial TSHoma not documented). Negative does not exclude RTH.

Treatment of TSHoma

First lineTrans-sphenoidal adenomectomy. Restore euthyroidism first with ATDs or somatostatin analogues pre-operatively — but note pre-op SRL normalises TSH making post-op monitoring harder.

Medical — somatostatin analoguesOctreotide LAR or lanreotide Autogel. FT4/FT3 normalises in >95%. Tumour shrinkage in ~40%. Option if surgery declined or contraindicated. Monitor for cholelithiasis and glucose intolerance.

RadiotherapyIf surgery contraindicated or declined. ≥45 Gy fractionated or stereotactic gamma knife (10–25 Gy single dose).

💡The α-GSU/TSH molar ratio calculation is simple and should be done in every case of central hyperthyroidism: α-GSU (μg/L) ÷ TSH (mU/L) × 10. A ratio >1 in a non-postmenopausal patient strongly favours TSHoma. Combined with SHBG and TRH test, you can usually distinguish RTH from TSHoma without resorting to T3 suppression.

🚨 Never ablate the thyroid before excluding TSHoma. Thyroid ablation in a TSHoma patient removes the negative feedback — TSH rises further, driving rapid tumour expansion and possible invasion. This is the most dangerous diagnostic error in thyroid endocrinology. Beck-Peccoz 2009: 30% of TSHoma patients had prior inappropriate thyroid ablation. Reference: Beck-Peccoz P, Persani L et al. Best Pract Res Clin Endocrinol Metab. 2009;23:597–606.

🧬

T3/T4 Combination Therapy Debate 2024

DIO2 polymorphism · BTA/ETA 2023 guidance

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The clinical problemUp to 10–15% of patients on adequate levothyroxine replacement (normal TSH, normal FT4) continue to report significant symptoms — fatigue, cognitive impairment, low mood, weight gain. This is a real and poorly understood phenomenon.

The DIO2 hypothesisResearch from the University of Cambridge has contributed significantly to understanding why some patients feel unwell on LT4 alone. The type 2 deiodinase (DIO2) enzyme converts T4 to T3 in peripheral tissues. A common polymorphism in the DIO2 gene (Thr92Ala) impairs local T3 generation — these patients may have tissue-level hypothyroidism despite normal serum TFTs. This group may preferentially benefit from T3/T4 combination therapy.

T3/T4 combination — the evidenceMultiple RCTs have shown mixed results — some patients report clear quality of life benefit, others show no difference. The overall evidence is insufficient to recommend combination therapy routinely. However, published research and ETA/BTA position statements acknowledge a subset of patients with persistent symptoms may warrant a carefully monitored trial.

Current guidance (BTA/ETA 2023)Consider combination LT4/LT3 only in specialist setting, for patients with persistent symptoms on LT4 with normal TSH, after exclusion of other causes. DIO2 genotyping not currently recommended in routine practice but may guide future personalised therapy.

Practical prescribing — UK contextIf trialling combination: use slow-release T3 (Thybon Henning 20mcg in UK on named patient basis via specialist pharmacy, or liothyronine tablets — now available as generic, significantly cheaper than previously). NICE NG145 does not recommend routine T3/T4 combination but acknowledges it may be considered in specialist settings. Many UK CCBs/ICBs have local prescribing policies restricting liothyronine initiation to secondary care. Target FT3 within reference range. Reduce LT4 dose to avoid over-replacement. Review at 3 months — if no subjective benefit, discontinue. NICE October 2025 surveillance confirmed no update to liothyronine recommendations despite lower costs.

💡The DIO2 Thr92Ala polymorphism is carried by approximately 12% of the population in homozygous form. Research suggests these patients have altered hypothalamic-pituitary-thyroid axis setpoint and genuinely different tissue thyroid hormone kinetics. This is not a psychosomatic complaint — it is a biological mechanism for persistent symptoms. Acknowledging this to patients is itself therapeutic.

⚠️ T3 prescribing risks: Short half-life causes peaks and troughs — palpitations, anxiety. Cardiovascular risk in elderly and those with AF or IHD. Osteoporosis risk with over-replacement. Use slow-release T3 where available. Monitor FT3, not just TSH.

📉

T3 Suppression Test SCE

Historical — but the principle is examined

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PrincipleExogenous T3 (liothyronine 60–100mcg/day for 10 days) is given. This suppresses pituitary TSH and should reduce thyroidal radioiodine uptake to <50% of baseline in a normal thyroid. Autonomous thyroid tissue is not suppressible.

Normal responseUptake suppressed to <50% of baseline. Normal thyroid — pituitary-thyroid axis intact.

Abnormal (non-suppressed)Autonomous function — Graves', toxic nodule. Uptake remains >50% despite exogenous T3. The thyroid is not under TSH control.

Why it's rarely done nowSensitive TSH assays and TRAb measurement have replaced it for most clinical questions. Carries cardiac risk from exogenous T3 in older patients. Mainly of historical and conceptual importance.

💡The T3 suppression test is the conceptual basis for understanding autonomous thyroid function. The same principle underpins why we use isotope scanning to look for hot nodules — autonomously functioning tissue is by definition non-suppressible.

🚨 Thyroid emergencies — returning to practice

Rare but high-stakes — know the sequence cold

Thyroid storm and myxoedema coma are rare but carry 10–60% mortality. They are most likely to present via the medical take or ITU. The management sequences have specific rules about order — PTU before iodine in thyroid storm, hydrocortisone before thyroid hormone in myxoedema coma. These sequences are both SCE favourites and real clinical safety issues. If you've been away, review both carefully.

Thyroid storm: PTU before iodine — always, minimum 1 hour gap

Propranolol CONTRAINDICATED in thyrotoxic heart failure — use verapamil

Myxoedema coma: hydrocortisone before levothyroxine

Passive rewarming only in myxoedema coma — active = vasodilation + cardiovascular collapse

T3 IV carries cardiac risk — use PO/NG route in myxoedema coma

Both require HDU/ITU + early endocrinology involvement

📋 Guidelines

NICE NG145 BTA Guidelines British Thyroid Foundation

🚨

Thyroid Storm Emergency SCE

Burch-Wartofsky Score & management · Oxford Handbook verified

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Investigations — check all of these

BloodsTSH, T4, T3, U&E (often ↓Na⁺), FBC, liver function, calcium, glucose, cortisol, infection screen (blood and urine cultures).

OtherCXR (infection, cardiac), ECG (AF, rate), precipitants/sequelae screen.

Precipitants

Common triggersSurgery, infection, iodine load, RAI, trauma, non-compliance with ATDs, labour.

Burch-Wartofsky Score ≥45 = Storm

Temperature37.2–37.7°C = 5pts | 37.8–38.3 = 10pts | 38.4–38.8 = 15pts | 38.9–39.4 = 20pts | ≥39.4 = 25pts

CNS effectsAgitation = 10 | Delirium/psychosis/extreme lethargy = 20 | Seizure/coma = 30

GI-hepaticDiarrhoea/nausea/abdominal pain = 10 | Unexplained jaundice = 20

HR (bpm)100–109 = 5 | 110–119 = 10 | 120–129 = 15 | 130–139 = 20 | ≥140 = 25

Heart failureMild = 5 | Moderate = 10 | Severe (pulmonary oedema) = 20

Precipitant identifiedPositive = 10pts

Management — in sequence

1. IV access + seek endocrinology adviceRefer to critical care. This is a multi-team emergency.

2. Propranolol 40–80mg QDS PO (up to 320mg/day)Controls adrenergic symptoms AND blocks peripheral T4→T3 conversion. BNF maximum for thyrotoxicosis: 40mg QDS. Higher doses (80mg TDS–QDS) are used in thyroid storm in some UK specialist protocols — follow local guidance. IV only if PO/NG not possible: 1–2mg IV over 10 min (rarely needed). ⚠️ CONTRAINDICATED if acute heart failure is due to thyrotoxicosis — use rate-controlling calcium channel blocker instead (e.g. verapamil).

3. PTU (propylthiouracil) — loading dose then maintenanceLoading dose 500–1000mg PO/NG/PR, then 250mg every 4 hours (ATA 2016 Hyperthyroidism Guidelines — thyroid storm section). Preferred over carbimazole in storm — blocks synthesis AND peripheral T4→T3 conversion. Give ≥1 hour before iodine.

4. Hydrocortisone 200mg IV initiallyThen 100mg TDS or prednisolone 20mg TDS. Benefits: blocks T4→T3 conversion, autoimmune effect in Graves', protects adrenal reserve (relative adrenal insufficiency common).

5. Supportive measuresTreat infection (antibiotics). Monitor blood glucose — correct hypoglycaemia (100mL 20% glucose IV over 15 min). Active cooling. IV fluids only if volume deplete — risk of pulmonary oedema. Nutritional support. Critical care if cardiovascular or respiratory support needed.

Specialist endocrinology — after steps above

Lugol's iodine — AT LEAST 1 HOUR after PTUPotassium iodide solution (100mg/mL) plus iodine (50mg/mL): 0.3mL PO TDS. Blocks T4 and T3 release (Wolff-Chaikoff). Must give PTU at least 1 hour beforehand — if iodine given first, it provides substrate for new hormone synthesis before the block is in place, potentially worsening the storm.

Cholestyramine 3–4g TDS/QDSReduces enterohepatic circulation of thyroid hormone — accelerates hormone clearance. Useful adjunct in severe cases or when other measures are insufficient.

MonitoringTitration of thionamide guided by liver function (PTU hepatotoxicity risk) and neutrophil count (agranulocytosis). Tapering of glucocorticoid treatment once stable.

🚨 HDU/ITU admission. Mortality 10–30% even with treatment. Propranolol is CONTRAINDICATED in thyrotoxic heart failure — use verapamil instead. PTU must be given BEFORE iodine by at least 1 hour. Consider plasmapheresis if refractory to all measures.

💡Two sequence rules that must be memorised: (1) PTU before iodine — always, by at least 1 hour. (2) Check for heart failure before giving propranolol — if thyrotoxic cardiomyopathy is present, β-blockade will worsen it. Verapamil is the rate-control alternative in this situation.

🌡️

Myxoedema Coma Emergency SCE

Rare but deadly — Oxford Handbook verified

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Signs & symptoms

Classic featuresHypothyroid appearance, hypothermia, bradycardia, hypercapnia (respiratory failure), hypotension, hyporeflexia, hypoglycaemia, hyponatraemia, altered consciousness.

"Myxoedema madness"Psychosis can occur — do not attribute solely to psychiatric cause. Seizures and coma represent the most severe end of the spectrum.

PrecipitantsInfection (most common), MI, stroke, trauma, cold exposure, drugs (opioids, sedatives, anaesthesia), non-compliance with levothyroxine.

Investigations

Bloods↑↑TSH, ↓free T4, ↓free T3 (confirms diagnosis). U&E (often ↓Na⁺), glucose, cortisol (exclude concurrent adrenal insufficiency), FBC, ABG (hypercapnia), infection screen: blood and urine cultures. CXR.

Treatment — in order

1. Seek endocrinology advice · refer to critical careHDU/ITU admission. Secure airway, O₂ if hypoxic.

2. Hydrocortisone 100mg IV — give FIRSTAssume relative cortisol deficiency until tests prove otherwise. Give BEFORE thyroid hormone replacement — levothyroxine accelerates cortisol metabolism and can precipitate Addisonian crisis if given first. Continue until cortisol result known.

3. Thyroid hormone replacementOption A — Liothyronine (T3) 5–10mcg PO/NG, repeat/titrate depending on response and cardiac status. Preferred by some because T4 conversion to T3 may be severely impaired in critical illness. PO/NG route preferred — IV T3 carries higher cardiac risk but is used in some specialist centres when enteral absorption is unreliable (ATA 2014 position statement). Option B — Thyroxine (T4) 25–75mcg/day PO/NG. Lower cardiac risk. Slower onset. T4→T3 conversion may be unreliable in severe illness — monitor FT3 as well as FT4. ⚠️ Whichever route and preparation: start low, go slow, monitor cardiac status closely. This is a specialist decision — always involve endocrinology.

4. Correct hypoglycaemia100mL 20% glucose IV over 15 minutes if hypoglycaemic. Monitor glucose closely.

5. Supportive carePassive rewarming only — NOT active. Active rewarming causes peripheral vasodilation and cardiovascular collapse. Treat infection (antibiotics empirically if infection suspected). IV fluids carefully — risk of pulmonary oedema. Correct hyponatraemia cautiously. Establish on oral thyroxine before discharge.

🚨 Mortality 30–60% even with treatment. Hydrocortisone MUST be given before thyroid hormone replacement. T3 IV carries increased cardiac risk — use PO/NG route. Active rewarming is dangerous — passive only.

💡The choice between T3 and T4 in myxoedema coma is genuinely debated. The argument for T3 (liothyronine PO/NG) is that severely ill patients may not convert T4 to T3 efficiently — so giving T4 may not raise tissue T3 adequately. Whichever you use, give it via PO/NG not IV, go low and slow, and monitor cardiac status closely. This is a specialist decision — always involve endocrinology.

📋 Thyroid nodule assessment

Three classification systems — know which is UK standard

The BTA U classification and Thy cytology grading are the UK standard systems. ACR TI-RADS is a US-developed points-based system increasingly used in some UK centres alongside BTA U classification — but it is not a NICE or BTA mandated system in the UK. When you see a radiology report using TI-RADS terminology, it is ACR (US) classification. Always document which system has been used in your clinical correspondence.

U classification — BTA UK standard for USS reporting

Thy classification — BTA UK standard for FNA cytology

TI-RADS — ACR (US) points-based system, used in some UK centres

Suppressed TSH + nodule → isotope scan first, before FNA

Hot nodule → almost never malignant → no FNA needed

📋 Guidelines

NICE NG145 BTA Guidelines ETA Guidelines (EU) ACR TI-RADS (US)

🔬

U Classification — USS Reporting SCE

BTA UK standard · British Thyroid Association

▼

U1 — NormalNo abnormality identified. Normal thyroid tissue. No action needed.

U2 — BenignCharacteristic benign features — e.g. simple cyst, spongiform nodule, colloid nodule with comet-tail artefacts. Routine follow-up or discharge as appropriate. No FNA needed unless symptomatic.

U3 — Indeterminate / equivocalEquivocal features — cannot confidently categorise as benign or malignant. Subdivided: U3a (low suspicion, follicular lesion possible) and U3b (higher suspicion). FNA required. Discuss in MDT.

U4 — SuspiciousSuspicious features for malignancy — irregular margins, microcalcification, taller-than-wide shape, marked hypoechogenicity, abnormal vascularity. FNA + MDT discussion.

U5 — MalignantHighly suspicious or radiologically diagnostic of malignancy. Urgent surgical referral via thyroid cancer MDT. FNA to confirm histological type if not already done.

Important principle before FNA

Check TSH first — alwaysIf TSH is suppressed → isotope scan before FNA. A hot nodule on scan is almost never malignant and does not require FNA. Performing FNA on a hot nodule wastes resources and creates unnecessary patient anxiety. Source: BTA / NICE NG145.

💡U2 nodules with compelling symptoms (e.g. rapid growth, compressive symptoms, cosmetic concern) may still warrant clinical action despite benign USS features. Clinical context always overrides the USS classification.

🧫

Thy Classification — FNA Cytology SCE

BTA UK standard · British Thyroid Association Guidelines

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Thy1 — Non-diagnosticInsufficient material for diagnosis. Repeat FNA to obtain adequate sample. Thy1c = cystic lesion where adequate cellularity is inherently difficult.

Thy2 — Non-neoplasticAdequate sample. Features of non-neoplastic tissue — normal thyroid, colloid nodule, thyroiditis. Correlate with clinical and USS findings. If no suspicious features — no further biopsy needed. Thy2c = cystic with non-neoplastic features.

Thy3a — Atypia / follicular lesion of undetermined significanceSome atypical features but insufficient for neoplasm category. Discuss in MDT. Options: repeat FNA + USS, or proceed to hemithyroidectomy depending on clinical context.

Thy3f — Follicular neoplasmCellular follicular patterned lesion — could be follicular adenoma or follicular carcinoma. Cytology CANNOT distinguish between them (requires capsular invasion on histology). Diagnostic hemithyroidectomy required.

Thy4 — Suspicious of malignancySignificant nuclear or architectural atypia suspicious but not diagnostic. MDT discussion. Usually diagnostic hemithyroidectomy ± frozen section, or total thyroidectomy if suspicion very high.

Thy5 — MalignantDiagnostic of malignancy. Discuss in thyroid cancer MDT. Treatment according to tumour type — usually total thyroidectomy for PTC, MTC, or anaplastic. Lymphoma may be treated without surgery.

💡Thy3f is the classification that most confuses trainees — follicular adenoma and follicular carcinoma look identical on cytology. Malignancy can only be confirmed by histological demonstration of capsular or vascular invasion. This is why hemithyroidectomy (not FNA alone) is needed for Thy3f.

🇺🇸

ACR TI-RADS — Points-Based Classification SCE

⚠️ ACR (US system) — used in some UK centres alongside BTA U classification

▼

⚠️ Important — this is a US (ACR) classification system

ACR TI-RADS status in UKTI-RADS (Thyroid Imaging Reporting and Data System) was developed by the American College of Radiology (ACR). It is not mandated by NICE or BTA in UK practice. However, some UK radiology departments use TI-RADS alongside or instead of BTA U classification. When you see TI-RADS on a report — it is ACR (US) guidance. BTA U classification remains the UK standard.

ACR TI-RADS — scoring categories

TR1 — Benign (0 points)No suspicious features. No FNA needed. No follow-up required.

TR2 — Not suspicious (2 points)Mild features. No FNA needed. No follow-up typically required.

TR3 — Mildly suspicious (3 points)FNA if ≥2.5cm. Follow-up USS if ≥1.5cm.

TR4 — Moderately suspicious (4–6 points)FNA if ≥1.5cm. Follow-up USS if ≥1.0cm.

TR5 — Highly suspicious (≥7 points)FNA if ≥1.0cm. Follow-up USS if ≥0.5cm.

ACR TI-RADS — how points are scored

CompositionCystic/spongiform = 0 · Mixed cystic-solid = 1 · Solid/nearly solid = 2

EchogenicityAnechoic = 0 · Hyperechoic/isoechoic = 1 · Hypoechoic = 2 · Very hypoechoic = 3

ShapeWider-than-tall = 0 · Taller-than-wide = 3

MarginSmooth/ill-defined = 0 · Lobulated/irregular = 2 · Extrathyroidal extension = 3

Echogenic fociNone/large comet-tail = 0 · Macrocalcification = 1 · Peripheral (rim) calcification = 2 · Punctate echogenic foci = 3

Comparison: BTA U vs ACR TI-RADS

BTA U classificationUK standard. Radiologist assigns U1–U5 based on overall gestalt assessment of features. Simpler, faster, widely used in NHS.

ACR TI-RADSUS standard. Points-based — more standardised and reproducible across operators. Better inter-observer agreement data. Used in some UK centres, particularly those with US-trained radiologists or academic centres.

ETA guidelines (EU)ETA 2023 updated guidelines for thyroid nodule management use a slightly different risk stratification framework. ⚠️ Label as EU guidance when citing. ETA guidelines are available at: eurothyroid.com/guidelines/eta_guidelines.html

💡In practice: if your radiologist uses TI-RADS, ask them to also provide the BTA U category for your thyroid MDT discussion — this ensures consistency with UK MDT documentation standards. Document which classification system was used in your correspondence.

⭐ SCE exam preparation

High-yield tables and facts — SCE Reference

This section contains the highest-yield SCE material in table format — the things most likely to appear as single best answer questions. Content is cross-checked against the Oxford Handbook of Endocrinology and Diabetes and current NICE, BTA, ATA and ETA guidelines. Use this for rapid review in the weeks before your exam.

🧬

Embryology, Physiology & TBG SCE

Oxford Handbook of Endocrinology and Diabetes · NICE · ATA

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Embryology — exam favourites

First endocrine gland to developThe thyroid. Appears at day 24 of gestation. Origin: endodermal epithelium on floor of developing pharynx + lateral pharyngeal pouches. Thyroglossal duct connects foetal thyroid to tongue — obliterated by 8–10 weeks.

C cell (parafollicular cell) originTraditionally stated as neural crest (ultimobranchial body, 5th pharyngeal pouch). Newer evidence suggests endodermal germ cell progenitors. The SCE may test either — know both positions.

TSH structure — subunit question

TSH subunitsGlycoprotein with α and β subunits linked by non-covalent bonds. The α subunit is COMMON to TSH, FSH, LH, and hCG. The β subunit confers SPECIFIC biological activity and receptor specificity. This is definitively established and is not debated.

TSH stimulationTRH, opioids, arginine-vasopressin, GLP-1, leptin.

TSH inhibitionThyroid hormones, dopamine agonists, gastrin, somatostatin, glucocorticoids, growth hormone.

TBG — what increases and decreases it

↑ TBG (→ ↑ total T4/T3, free hormones usually normal)Newborn · Oestrogen · Tamoxifen · Hepatitis A / chronic active hepatitis · Biliary cirrhosis · Oral contraceptive pills · Pregnancy

↓ TBG (→ ↓ total T4/T3, free hormones usually normal)Androgens · Large-dose steroids / Cushing's · Chronic liver disease · Severe systemic illness · Active acromegaly · Nephrotic syndrome · Phenytoin

Thyroglobulin (Tg) — key SCE distinction

Low Tg + thyrotoxicosis= Thyrotoxicosis factitia (exogenous thyroid hormone ingestion). Tg is suppressed because there is no endogenous thyroid stimulation.

High Tg + low isotope uptake= Thyroiditis (endogenous hormone release from damaged follicles). The thyroid is not being stimulated — uptake is low — but hormone is leaking from destruction.

💡The Tg distinction is a high-yield SCE question. Low Tg + suppressed TSH + no goitre = factitious. High Tg + suppressed TSH + tender thyroid = thyroiditis. The isotope scan confirms: uptake absent in both, but the Tg separates them.

⚗️

Deiodinase Enzymes SCE

Oxford Handbook of Endocrinology and Diabetes · NICE · ATA

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D1 — Liver, muscle, kidneysOuter + inner ring deiodination of T4. Activity increased in hyperthyroidism. Responsible for much of peripheral T4→T3 conversion.

D2 — Neurons, heart, skeletal muscle, brown adipose tissueOuter ring deiodination: T4 → T3. The MAIN activating enzyme in humans. Critically important in the hypothalamus (negative feedback). DIO2 gene encodes D2. Thr92Ala DIO2 polymorphism reduces thyroid hormone signalling → may cause localised/tissue hypothyroidism despite normal serum TFTs.

D3 — Placenta, embryo, proliferative/cancer cellsInner ring deiodination: T4 → reverse T3 (inactive). Protects placenta and fetus from excess T3/T4. Overexpressed in cancer cells — contributes to sick euthyroid syndrome in malignancy.

💡D2 is the main activating enzyme — this is the most commonly tested deiodinase fact. D3 is the inactivating enzyme — it produces reverse T3 (rT3), not active T3. Elevated rT3 in NTI is due to D1 inhibition (less rT3 cleared) combined with D3 upregulation.

☢️

RAIU Pattern — Causes of Thyrotoxicosis SCE

Oxford Handbook of Endocrinology and Diabetes · NICE · ATA

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Normal / Increased RAIU

CausesGraves' disease · Toxic nodular / multinodular goitre · Trophoblastic disease (hydatidiform mole) · TSH-producing pituitary adenoma (TSHoma) · Resistance to thyroid hormone (RTH)

Near-absent / very low RAIU

CausesPainless/silent thyroiditis · AIT Type 2 (amiodarone-induced destructive thyroiditis) · Subacute (de Quervain's) thyroiditis · Iatrogenic / factitious thyrotoxicosis · Struma ovarii

Practical scan pearls

Before scanStop carbimazole before scan — allows TSH recovery for adequate uptake. Recent iodine contrast (within 1–2 months) can falsely lower uptake — always ask about recent imaging.

Scan patternsGraves' = diffuse homogeneous uptake ± pyramidal lobe. Toxic MNG = patchy irregular uptake. Solitary toxic adenoma = focal hot nodule, rest of gland suppressed.

💡The RAIU table is a high-yield SCE topic. The key distinction: low uptake + thyrotoxicosis = destructive process (thyroiditis, factitious) or struma ovarii. High uptake + thyrotoxicosis = autonomous thyroid stimulation (Graves', toxic nodule, TSHoma, trophoblastic disease).

📊

RAI — Detailed Reference Table SCE

Oxford Handbook of Endocrinology and Diabetes · NICE · ATA

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Onset of effect4 weeks to 6 months for full effect. Do not declare treatment failure until at least 6 months post-RAI.

Hypothyroidism>80% develop hypothyroidism by 4 months. Falling FT4 is the marker for initiating levothyroxine. Counsel all patients that lifelong levothyroxine is the expected outcome.

ATD timing around RAIStop ATDs at least 1 week before RAI. Restart 3–7 days post-RAI if high risk of storm. ⚠️ PTU specifically causes radio-resistance (sulphydryl group mechanism) → higher RAI failure rate. Carbimazole is preferred ATD if pre-treating before RAI.

GO risk15–20% worsening or de novo GO. Give steroid cover if active GO. EUGOGO 2021: prednisolone 0.3–0.5mg/kg/day, taper over 3 months. Some UK centres use a shorter 0.2mg/kg regimen for 6 weeks without taper. ⚠️ Follow local protocol — doses vary between centres.

Fertility — womenDelay conception at least 6 months post-RAI (UK standard).

Fertility — men (ATA vs ETA)ATA (US): avoid fathering a child for 3–4 months. ETA (EU): 6 months. ⚠️ These are different guidance sources — label accordingly in exam answers.

💡PTU radio-resistance is a classic SCE question. PTU's sulphydryl group scavenges free radicals generated by radioiodine — reducing its effectiveness. This is why carbimazole is preferred over PTU when pre-treating before planned RAI.

⚠️ PTU → radio-resistance. If a patient on PTU fails RAI, consider whether inadequate radioiodine uptake was due to PTU radio-resistance rather than true treatment failure.

🎯

Graves' — Treatment Choice Framework SCE

NICE NG145 · ATA 2016 · Oxford Handbook of Endocrinology and Diabetes

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Relapse risk factors — high risk = counsel about definitive treatment

High relapse risk featuresYounger age (<40) · Male gender · Smoking · Larger goitre · Orbitopathy · Higher FT3/FT4 at diagnosis · Higher TRAb (TBII) titre. Relapse rate >50% after ATD therapy overall.

Treatment modality — when to favour each

ATDs preferred when:Women with mild disease, small goitre, low/negative TRAb · Pregnancy · Care home residents · Moderate–severe active GO (RAI contraindicated, surgery higher risk)

RAI preferred when:Women planning pregnancy >6 months post-RAI · Co-morbidities (high surgical risk) · ATD contraindication or side effects · CHF · Periodic thyrotoxic hypokalaemic paralysis

Surgery preferred when:Large/compressive goitre (≥80g) · Suspected malignancy · Large nodule >4cm · Co-existing hyperparathyroidism · High TRAb titre · Moderate–severe active GO (RAI contraindicated)

💡The SCE frequently asks about the interaction between GO and treatment choice. Key rule: active moderate-severe GO is a relative contraindication to RAI (worsens GO). ATDs or surgery are preferred. If RAI must be used — give steroid cover.

👁️

GO — Signs by Stage & New Treatments SCE

EUGOGO 2021 · NICE NG145

▼

Clinical signs by severity stage

Mild stage signsLid retraction — EARLIEST and MOST COMMON sign of GO. Lid lag (Von Graefe's sign). Widened palpebral fissure (Dalrymple's sign). Lagophthalmos (incomplete eye closure). Corneal dryness. Chemosis. Keratoconjunctivitis.

Moderate stage signsExtraocular muscle involvement. Inferior rectus MOST COMMONLY affected → vertical diplopia on upgaze. Medial rectus second most common. May be asymmetric.

Severe / sight-threatening signsProgressive exophthalmos. Restrictive myopathy. Optic neuropathy at orbital apex. Loss of visual acuity. Visual field defects. RAPD (afferent pupillary defect). Loss of colour vision. → EMERGENCY — urgent decompression.

Pathogenesis — SCE depth

MechanismOrbital fibroblasts express TSH-R AND overexpress IGF1-IR. TRAb + IGF1-IR signalling act synergistically. Orbital infiltration with lymphocytes, plasmocytes, mastocytes → cytokine release → hyaluronan synthesis → oedema + lipogenesis → ↑orbital volume → proptosis + muscle compression.

Lacrimal glandsExpress TSH-R → anti-TSH-R antibodies cause lacrimal inflammation → dry eyes. This is why dry eye symptoms are an early and common feature of GO.

New treatments — biologics

Teprotumumab (anti-IGF1-IR monoclonal antibody)FDA approved (US, 2020) and MHRA approved (UK, May 2025) for moderate-to-severe TED. Targets the IGF1-IR pathway that synergises with TRAb in orbital fibroblasts. Significant evidence for reducing proptosis and diplopia (OPTIC trial: 83% proptosis response vs 10% placebo). NICE technology appraisal for NHS reimbursement is in progress (ID6432). Side effects include hyperglycaemia, hearing loss, and infusion reactions. Contraindicated in pregnancy.

Rituximab (anti-CD20)2nd line for moderate-severe GO unresponsive to IV steroids. Avoid if impending dysthyroid optic neuropathy (DON) or long disease duration. Evidence from EUGOGO-supported trials.

Tocilizumab (anti-IL-6R)Emerging evidence for moderate-severe GO. Used in some specialist centres for refractory disease.

Selenium — important caveats

Selenium 200mcg daily — ETA 2016 (EU)Recommended ONLY for mild GO of SHORT duration. Not recommended for moderate-severe disease. Not a substitute for immunosuppression. ⚠️ EU guidance — ETA 2016.

💡Lid retraction is the earliest and most common sign of GO — not proptosis. Inferior rectus is the most commonly affected muscle — causing limitation of upgaze and vertical diplopia. These two facts are tested frequently in the SCE.

📉

Subclinical Hyperthyroidism — Treatment Decisions SCE

NICE NG145 · Oxford Handbook of Endocrinology and Diabetes

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DefinitionNormal FT4 + low TSH. Two subgroups: suppressed TSH (<0.1 mU/L) = higher risk; low TSH (0.1–0.4 mU/L) = lower risk. Confirm with repeat TFT: 2–6 weeks if high-risk; 3–6 months if low-risk before deciding on treatment.

Treatment decision matrix

Age >65 + TSH <0.01TREAT — increased cardiovascular morbidity/mortality, AF risk, osteoporosis.

Age <65 + co-morbidities + TSH <0.01TREAT.

Age >65 + TSH 0.01–0.04Consider treatment.

Age <65 + co-morbidities + TSH 0.01–0.04Consider treatment.

Age <65, asymptomatic + TSH <0.01Consider treatment vs observe — balance benefits vs risks.

Age <65, asymptomatic + TSH 0.01–0.04Observe. Repeat TFT at 3–6 months.

💡Subclinical hyperthyroidism increases AF risk 3-fold and doubles osteoporotic fracture risk. The threshold to treat is lower in the elderly and those with cardiovascular disease. Don't ignore a suppressed TSH in an elderly patient — even without symptoms.

🔢

Anti-TPO & Nodule Referral Criteria SCE

NICE NG145 · BTA · Oxford Handbook of Endocrinology and Diabetes

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Anti-TPO antibody prevalence

Hashimoto's thyroiditis90–95% anti-TPO positive. TPO is a 105 kDa glycoprotein that catalyses iodine oxidation and thyroglobulin tyrosyl iodination. Majority of anti-TPO antibodies produced by thyroid-infiltrating lymphocytes.

Graves' disease70–80% anti-TPO positive. Note: anti-TPO has no established role in Graves' pathogenesis — the key antibody in Graves' is TRAb. Anti-TPO presence in Graves' reflects co-existing autoimmune thyroid inflammation.

Normal individuals10–15% anti-TPO positive. These individuals have higher risk of developing thyroid dysfunction over time, particularly postpartum thyroiditis.

Thyroid nodule referral — from primary care

Routine (non-urgent)Unchanged lump with no risk factors · Non-palpable nodules <1cm found incidentally · Gradual enlargement over months.

Non-urgent secondary care referralAbnormal TFT · Sudden onset pain in lump · Rapid painless enlargement over weeks.

Urgent (2-week wait) — NICE NG12Unexplained hoarseness + cervical lymphadenopathy · Thyroid nodule in a child. Source: NICE NG12 (Suspected cancer: recognition and referral), not NG145.

Same day / emergencyStridor — airway compromise. Admit immediately.

FDG-PET incidental thyroid findings

Focal FDG uptakeInvestigate with USS + FNA. Malignancy risk 25–50%. Urgent secondary care referral.

Diffuse FDG uptakeReported in 0.6–3.3% of population. Usually represents thyroiditis. Lower malignancy risk — correlate clinically and arrange USS.

💡FDG-PET incidental findings are increasingly common as PET scanning becomes more prevalent in oncology. Focal uptake = high malignancy risk = investigate urgently. Diffuse uptake = usually thyroiditis = lower urgency but still needs USS.

🔬

Thyroid Cancer — SCE High-Yield Reference SCE

BTA Guidelines · ATA 2015

▼

USS features — benign vs malignant

Benign featuresSpongiform/honeycomb pattern · Purely cystic · Egg-shell (rim) calcification · Isoechoic/mildly hyperechoic · Peripheral vascularity · Hyperechoic + well-defined halo.

Malignant features (papillary/medullary)Solid hypoechoic nodule ± microcalcification · Irregular margin · Intranodular vascularity · Absent halo · 'Taller than wide' (AP diameter > transverse) · Hypoechoic + absent halo.

Follicular lesionsHyperechoic + well-defined halo = more likely benign. Hypoechoic + absent halo = suspect carcinoma. Cannot distinguish follicular adenoma from follicular carcinoma on USS or cytology — requires histology.

Poor prognostic factors in DTC

Poor prognosis indicatorsAge <10 or >40 · Male gender · Poor cellular differentiation · Vascular invasion · Larger tumour size · Lymph node involvement or distant metastasis.

Post-treatment Tg monitoring (BTA)

Key principlesAlways measure TSH + Tg + TgAb simultaneously. Use same laboratory and assay long-term (consistency essential). Anti-Tg antibodies interfere with Tg assay — if positive, trend the antibody level itself (rising TgAb may indicate recurrence even when Tg appears undetectable).

Rising Tg workup sequenceNeck USS → CT chest → bone scan → PET-CT (sequential — do not jump to PET first).

Medullary thyroid cancer (MTC)

Always screen for MEN2Genetic counselling + RET gene mutation analysis for all MTC patients. Screen for MEN 2A (phaeochromocytoma + primary hyperparathyroidism) and MEN 2B.

Prophylactic thyroidectomy timingMEN 2A: before age 5. MEN 2B: by age 1 year (most aggressive — earliest intervention). Lifelong calcitonin monitoring post-surgery.

💡'Taller than wide' on ultrasound — this means the AP diameter exceeds the transverse diameter when measuring the nodule in cross-section. It is a strong predictor of malignancy and features in both BTA U classification and ACR TI-RADS scoring.

🤰

Block & Replace in Pregnancy — SCE Specific SCE

Oxford Handbook of Endocrinology and Diabetes · NICE · ATA

▼

Block and replace is CONTRAINDICATED in pregnancy — with ONE exceptionBlock and replace (ATD + levothyroxine) is NOT used in pregnancy because carbimazole crosses the placenta and suppresses the fetal thyroid, while levothyroxine does NOT cross the placenta — the fetus cannot be protected from ATD-induced hypothyroidism by the maternal levothyroxine.

The ONE exception — isolated fetal hyperthyroidismTRAb can persist for years after RAI and cross the placenta → isolated fetal hyperthyroidism in a euthyroid mother (e.g. after previous thyroid ablation). In this situation only: carbimazole crosses the placenta to control fetal hyperthyroidism, while levothyroxine prevents maternal hypothyroidism. Block and replace is the ONLY indication for this regimen in pregnancy.

Why levothyroxine doesn't cross the placentaThyroid hormones are highly protein-bound and require specific transporters for placental transfer. T4 crosses the placenta in very small amounts — insufficient to protect the fetus from ATD-induced hypothyroidism. This is why titration regimen (lowest effective ATD dose) is used in pregnancy rather than block-replace.

💡This is one of the most nuanced and frequently tested pregnancy-thyroid questions in the SCE. The rule is simple: block and replace is contraindicated in pregnancy EXCEPT when treating isolated fetal hyperthyroidism due to maternal TRAb in a euthyroid mother.

🚨 RAI scan is absolutely CONTRAINDICATED in pregnancy — this is unconditional. No clinical circumstance justifies thyroid isotope scanning in a pregnant woman.

📋

Graves' Disease Clinic Letter Template

Endo Unlocked standard template · Customise for each patient

▼

It was a pleasure meeting you at the Endocrinology Clinic today.

Diagnosis:

Diagnostic Investigations:
TSH receptor antibody:
Thyroid ultrasound:

Current Medication:
Carbimazole

You are currently clinically and biochemically euthyroid (normal thyroid function), and you report feeling well from a thyroid symptom perspective.

Recent Investigations:
TSH: _____ mU/L (0.27–4.20)
Free T4: _____ pmol/L (11.9–21.6)
Free T3: _____ pmol/L (3.10–6.80)

These results are excellent and show your Graves' disease is well controlled on your current dose.

Medication Plan:
☐ Continue carbimazole _____ mg once daily for the next 3 weeks
☐ Then reduce to carbimazole _____ mg on alternate days (one day on, one day off)
☐ Continue taking your tablets until you hear from our department

⚠️ Important Safety Information — Agranulocytosis:
We discussed the rare but serious risk of agranulocytosis (severe reduction in white blood cells) with carbimazole. If you develop any of the following, STOP carbimazole immediately and contact your GP or attend A&E urgently for a blood test:
• Sore throat · Mouth ulcers · High temperature/fever · Any signs of infection · Unexplained bruising or bleeding

Monitoring for Relapse:
If you develop any of the following, please contact us sooner or arrange a blood test with your GP:
Palpitations · Diarrhoea · Tremor · Irritability or anxiety · Weight loss · Increased sweating · Heat intolerance

Long-Term Treatment Plan:
We aim to continue carbimazole for 18 months in total. Treatment expected to finish around: _____________

After stopping carbimazole:
• TFTs monitored for 1 year
• If remains euthyroid → discharged to GP with relapse advice
• If Graves' relapses → restart carbimazole + discuss definitive treatment

Definitive Treatment Options (if relapse occurs):
☐ Radioactive iodine therapy
☐ Thyroid surgery (thyroidectomy)
☐ Long-term low-dose carbimazole

Follow-Up:
Blood tests: TSH, Free T4, Free T3 before next appointment
☐ Telephone clinic appointment in _____ weeks
☐ Face-to-face appointment in _____ weeks

Patient Information Discussed/Provided:
☐ Carbimazole and agranulocytosis safety information
☐ Radioactive iodine treatment information
☐ Thyroid surgery information
☐ British Thyroid Foundation resources
☐ Pregnancy and fertility advice (if applicable)

Please do not hesitate to contact our department if you have any questions, concerns, or symptoms of relapse before your next appointment.

Important Resources:

BTF — Antithyroid Drugs Alert Card
BTF — Thyroid Eye Disease
BTF — Thyroid Surgery
BTF — Radioactive Iodine Treatment
BTF — Pregnancy and Fertility

💡This template covers the MHRA-required agranulocytosis safety information, relapse monitoring, and treatment planning. Customise the doses and timeframes for each patient. Always document that BTF leaflets were provided — this has medicolegal importance.

⚠️

Patient Safety Information — Agranulocytosis

For all patients starting carbimazole or PTU · Give at first clinic visit

▼

⚠️ Important Safety Information: Agranulocytosis

Carbimazole can rarely cause a serious condition called agranulocytosis — a severe drop in white blood cells that normally fight infection. This typically occurs in the first few months of treatment but can happen at any time.

STOP carbimazole immediately and contact your GP or attend A&E urgently if you develop:

• Sore throat
• Mouth ulcers
• Fever or high temperature
• Signs of infection
• Unexplained bruising or bleeding

You will need an urgent blood test (FBC) to check your white blood cell count.

For the BTF alert card: btf-thyroid.org/antithyroid-drugs-alert-card

Teratogenic Risk — Carbimazole vs PTU

⚠️ ETA 2018 recommendations (EU guidance):

• PTU recommended pre-conception and in the first trimester
• Switch to carbimazole in second and third trimester (PTU hepatotoxicity risk with prolonged use)
• Carbimazole associated with embryopathy in weeks 6–10 (aplasia cutis, choanal atresia, oesophageal atresia)

2024 updated consensus:

PTU first trimester, switch to carbimazole second/third trimester. Low-dose carbimazole may have reduced — but not eliminated — risk. This remains EU/international consensus guidance.

All women of reproductive age on carbimazole: discuss contraception and pre-conception planning at every clinic visit. Document the conversation.

BTF leaflet: btf-thyroid.org/pregnancy-and-fertility

🔗

Patient Information Resources

BTA and BTF — verified working links

▼

British Thyroid Foundation (BTF) — patient leaflets

Antithyroid drugs alert cardbtf-thyroid.org/antithyroid-drugs-alert-card — Give to ALL patients starting carbimazole or PTU.

Thyroid eye diseasebtf-thyroid.org/thyroid-eye-disease-leaflet

Radioactive iodine treatmentbtf-thyroid.org — RAI treatment

Thyroid surgerybtf-thyroid.org/thyroid-surgery

Pregnancy and fertilitybtf-thyroid.org/pregnancy-and-fertility