Graves disease and thyroid eye disease

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Graves disease results from stimulating autoantibodies at the TSH receptor. The thyroid component usually produces diffuse hyperfunction, while orbital fibroblast inflammation and glycosaminoglycan deposition cause thyroid eye disease. The two components can follow different time courses: eye disease may occur during euthyroidism or after thyroid treatment, so a normal thyroid profile does not dismiss new ophthalmic symptoms.

Initial hyperthyroidism management combines symptom control, restoration of euthyroidism and a plan for remission or definitive therapy. Antithyroid drugs avoid immediate gland destruction but can relapse and have rare serious toxicity. Radioiodine is convenient for suitable non-pregnant adults but leads commonly to hypothyroidism and can exacerbate eye disease. Total thyroidectomy gives rapid definitive control but requires an experienced surgeon and carries hypocalcaemia, nerve and operative risks.

Eye management is organised by threat, activity and severity. Mild exposure symptoms may respond to preservative-free lubrication, nocturnal ointment, head elevation and thyroid stabilisation. Moderate-to-severe active disease requires a joint ophthalmology-endocrinology service for immunomodulatory treatment. Optic neuropathy and corneal breakdown are emergencies where visual outcome depends on rapid specialist treatment rather than routine endocrine follow-up.

Key points

Graves disease is TSH-receptor-antibody-mediated hyperthyroidism and may cause diffuse goitre, thyroid bruit, eye disease, dermopathy and rarely acropachy.
Confirm biochemical thyrotoxicosis with TSH, free T4 and free T3, then use TRAb as the NICE-recommended confirmatory test.
A course of carbimazole is commonly used, with NICE describing 12 to 18 months when antithyroid medicine is chosen as definitive treatment in adults.
Radioiodine, antithyroid medicine and surgery each have distinct trade-offs; eye disease, pregnancy plans, goitre size, compression, malignancy concern and relapse risk shape selection.
Before carbimazole obtain baseline full blood count and liver tests; fever, sore throat, mouth ulcers or infection requires stopping the medicine and urgent blood-count assessment.
Thyroid eye disease activity and severity are different: redness and pain indicate activity, whereas diplopia, exposure and optic neuropathy define consequences requiring specialist assessment.
Check acuity, colour vision, pupils, eye movements, corneal exposure and lid closure, not just degree of proptosis.
Smoking cessation and avoidance of second-hand smoke are high-value interventions because smoking worsens eye disease and treatment response.
Radioiodine can worsen active thyroid eye disease and needs specialist selection, with prophylaxis or an alternative strategy when risk is significant.
Pregnancy and planned conception require urgent specialist medication review; radioiodine is contraindicated, and carbimazole carries important MHRA reproductive warnings.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

TSH-receptor autoimmunity

Stimulating autoantibodies activate thyroid TSH receptors, producing diffuse hormone synthesis and gland growth despite suppressed pituitary TSH.

Orbital autoimmune involvement

Related immune activity targets orbital fibroblasts, with inflammation and glycosaminoglycan accumulation affecting extraocular muscles and orbital soft tissues.

Clinical modifiers

Smoking, unstable thyroid status and treatment transitions can influence eye-disease activity, so thyroid and ophthalmic courses do not always move together.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Thyroid receptors are stimulated
Autoantibodies drive new thyroid hormone synthesis and diffuse gland activity independently of normal hypothalamic-pituitary feedback as the process continues.
2
Adrenergic and metabolic effects develop
Excess hormone increases heat production, heart rate, gut activity and tissue catabolism, causing tremor, weight loss, palpitations and weakness.
3
Orbital tissues expand
Inflammation, oedema and glycosaminoglycan deposition enlarge muscles and fat within the fixed bony orbit, causing proptosis, diplopia and exposure.
4
Sight may become threatened
Severe swelling can compress the optic nerve or prevent corneal protection, producing an ophthalmic emergency even when thyroid tests are controlled.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Autoimmune thyroid phenotype

Diffuse smooth enlargement, bruit, tremor, warm skin, tachycardia and proximal weakness support Graves; pretibial dermopathy and acropachy are specific but uncommon extrathyroidal signs.

Mild active eye disease

Grittiness, photophobia, tearing, retro-orbital discomfort, conjunctival redness, lid swelling and pain with eye movement suggest orbital inflammation even before marked proptosis.

Functionally significant disease

Restrictive diplopia, impaired elevation or abduction, troublesome proptosis, exposure symptoms and inability to work or drive because of visual disturbance merit prompt specialist thyroid-eye assessment.

Sight-threatening optic neuropathyRed flag

Reduced central or colour vision, new visual-field defect, relative afferent pupillary abnormality or optic-disc change can result from apical compression, sometimes without dramatic proptosis.

Corneal emergencyRed flag

Lagophthalmos, severe pain, photophobia, epithelial defect, ulceration or a cloudy dry cornea indicates exposure-related threat and requires immediate ocular protection plus same-day ophthalmology.

Relapse or treatment toxicity

Recurrent palpitations and weight loss after a medicine course suggests relapse; fever, sore throat, mouth ulcer, jaundice or severe abdominal pain while taking carbimazole instead raises an adverse-drug emergency.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
TSH, free T4 and free T3First step
Why
Establish severity and follow biochemical response to treatment.
Interpretation and limitations
Suppressed TSH with raised peripheral hormone confirms overt thyrotoxicosis; early monitoring should follow free hormones because TSH may remain suppressed after control improves.
02
TSH-receptor antibodies
Why
Confirm Graves autoimmunity and inform selected reproductive or relapse questions.
Interpretation and limitations
Positive TRAb supports Graves. Negative results do not absolutely exclude it; NICE suggests technetium scintigraphy when diagnostic uncertainty remains and imaging is safe.
03
Baseline full blood count and liver tests
Why
Assess suitability and create a reference before antithyroid treatment.
Interpretation and limitations
Unexpected neutropenia or significant hepatic dysfunction needs endocrine or haematology discussion; subsequent testing is symptom-triggered rather than routine in an asymptomatic patient.
04
Structured eye examination
Why
Detect exposure, motility restriction and optic nerve dysfunction at presentation.
Interpretation and limitations
Document acuity, colour desaturation, pupils, fields by confrontation, ocular movements, diplopia, lid closure and corneal staining; any optic or corneal threat needs same-day review.
05
Orbital imaging
Why
Define apical crowding, muscle enlargement or an alternative orbital diagnosis.
Interpretation and limitations
CT or MRI is specialist-directed for suspected optic neuropathy, unilateral or atypical disease, surgical planning or diagnostic uncertainty; imaging must not delay urgent ophthalmic treatment.
06
ECG and cardiac assessment
Why
Find arrhythmia or heart failure caused by sustained hormone excess.
Interpretation and limitations
Atrial fibrillation, ischaemia or decompensation needs treatment alongside thyroid control, including independent stroke-risk and anticoagulation assessment.
07
Pregnancy assessment and reproductive history
Why
Select safe antithyroid and definitive options and plan TRAb surveillance.
Interpretation and limitations
Possible pregnancy stops radioiodine planning and triggers urgent specialist review of medicine; previous definitive treatment does not remove fetal relevance of circulating TRAb.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Toxic nodular disease

An irregular nodular gland with patchy or focal uptake and absent Graves eye signs suggests autonomous nodules rather than diffuse receptor autoimmunity.

Destructive thyroiditis

Painful or painless release of stored hormone produces low uptake and does not respond mechanistically to antithyroid synthesis blockade.

Orbital cellulitis

Fever, severe unilateral pain and infective orbital signs favour cellulitis, which needs urgent antimicrobial and ophthalmic assessment.

Other orbital mass

Marked asymmetry, atypical progression or a discrete imaging lesion suggests tumour or inflammation unrelated to Graves disease.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01New GravesConfirm and stabilise hyperthyroidismFirst stepClinical and biochemical findings suggest Graves disease without storm.

1Measure TRAb, document cardiac and eye status, check pregnancy possibility and obtain baseline full blood count and liver tests before thionamide treatment.
2Use BNF-checked carbimazole and symptom control under the local pathway, with explicit infection, liver, pancreatitis and reproductive safety-netting.
3DefinitiveMonitor free hormones initially, then discuss a 12-to-18-month medicine course or definitive radioiodine or surgery according to relapse risk and patient priorities.

02Eye triageProtect sight before grading cosmeticsAny eye symptom occurs in current or previous Graves disease.

1Check acuity, colour vision, pupils, visual fields, motility, diplopia, lid closure and corneal integrity, comparing both eyes and documenting change.
2Arrange same-day ophthalmology for optic-nerve indicators or corneal breakdown; provide immediate lubrication and mechanical protection when closure is incomplete.
3Refer non-emergency active or functionally significant disease to a combined thyroid-eye service while supporting smoking cessation and stable euthyroidism.

03Definitive choiceMatch treatment to the whole patientDefinitiveRelapse, preference, toxicity or disease features prompt definitive therapy discussion.

1Review active eye disease, smoking, pregnancy timetable, goitre compression, suspicious nodules, antithyroid reactions, surgical fitness and likelihood of medicine remission.
2Avoid radioiodine in pregnancy and generally when active eye disease makes worsening unacceptable; involve specialists regarding glucocorticoid prophylaxis in selected risk settings.
3If surgery is chosen, render the patient safely euthyroid where possible, refer to a high-volume thyroid team and plan lifelong levothyroxine monitoring after total thyroidectomy.

04PregnancyUrgent specialist reproductive planPregnancy is possible, confirmed or planned during Graves treatment.

1Confirm pregnancy promptly and contact endocrine-obstetric services; do not stop necessary treatment abruptly without a replacement plan because uncontrolled disease also harms mother and fetus.
2Review carbimazole and propylthiouracil timing, use the lowest effective specialist-selected dose and avoid block-and-replace or radioiodine during pregnancy.
3Arrange gestation-specific thyroid and TRAb surveillance plus fetal assessment according to the current regional maternal-medicine protocol.

Key medicines and prescribing safety4 treatments · regimens, roles and cautions

Suppresses new hormone synthesis and supports remission or preparation for definitive treatment.

Carbimazole for Graves hyperthyroidism

The adult starting total is commonly 15 to 40 mg daily in the current BNF, selected by biochemical severity; subsequent titration or block-and-replace requires the agreed endocrine regimen.

Baseline blood count and liver tests are required. Stop for infection symptoms pending urgent count; discuss pregnancy, effective contraception, hepatic injury and pancreatitis, and check live MHRA warnings.

Reduces adrenergic tremor and palpitations until thyroid hormone production is controlled.

Propranolol for short-term symptom relief

Use a BNF-verified oral regimen commonly within 10 to 40 mg three or four times daily, titrated to symptoms and pulse while monitoring blood pressure.

Avoid in asthma, significant conduction disease, marked hypotension and decompensated low-output failure. It does not treat autoimmunity, prevent relapse or replace separate atrial-fibrillation management.

Protects the exposed ocular surface and relieves dryness in mild thyroid eye disease.

Preservative-free ocular lubricant

Use drops regularly through the day and lubricating ointment at night according to the ophthalmic product and symptom severity; increase protection if closure is incomplete pending review.

Lubrication does not treat optic neuropathy or deep orbital inflammation. Pain, reduced vision, colour change, corneal defect or lagophthalmos requires urgent ophthalmology rather than repeated self-treatment.

Treats active moderate-to-severe orbital inflammation or sight-threatening disease under specialist supervision.

Intravenous glucocorticoid for active severe eye disease

Pulse selection and cumulative exposure are determined only by the specialist thyroid-eye multidisciplinary protocol after liver, cardiovascular, infection, glucose and psychiatric risk assessment.

Do not initiate a generic ward regimen. High cumulative exposure can cause serious hepatic, cardiovascular, metabolic, infectious and psychiatric harm; optic neuropathy may also need urgent decompression.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Thyrotoxic cardiac disease

Persistent hormone excess can cause atrial fibrillation, heart failure and ischaemic stress, particularly in older patients or those with underlying cardiac disease.

Dysthyroid optic neuropathy

Apical orbital crowding can compress the optic nerve, causing colour desaturation, field loss and permanent visual impairment without rapid specialist treatment.

Corneal breakdown

Proptosis and incomplete lid closure expose the cornea, leading to ulceration, infection and sight loss when lubrication and closure are inadequate.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Follow free T4 and free T3 during early antithyroid titration, allowing for delayed TSH recovery and adjusting only through the agreed treatment strategy.
At every contact ask about fever, sore throat, mouth ulcers, bruising, jaundice, pruritus, dark urine and severe abdominal pain while carbimazole continues.
Document visual acuity, colour perception, diplopia, corneal symptoms and lid closure over time; advise immediate review for any rapid deterioration.
Record smoking status and offer evidence-based cessation support repeatedly, as stopping remains a disease-modifying intervention for the orbit.
After antithyroid withdrawal, provide relapse symptoms and scheduled thyroid tests; after radioiodine or total thyroidectomy, monitor for and replace expected hypothyroidism.
Review contraception and conception timing at each relevant visit, because medicine and radioiodine plans can become unsafe when circumstances change.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Orbit and thyroid can diverge

Eye inflammation may begin or worsen when biochemical status is normal, so new visual symptoms deserve examination rather than reassurance from a recent TSH.

Activity differs from severity

Redness, swelling and pain describe inflammatory activity; diplopia, exposure and optic-nerve compromise describe impact. Both dimensions guide specialist treatment.

Proptosis is not the sight test

Apical muscle crowding can damage the optic nerve with modest forward displacement. Colour desaturation, acuity, pupils and fields are higher-value danger checks.

Radioiodine needs orbital context

Eye activity, smoking and other risk factors influence whether radioiodine is appropriate and whether specialist glucocorticoid cover is considered.

TRAb can outlive the gland

Antibodies can persist after surgery or radioiodine and cross the placenta, so previous definitive treatment does not remove pregnancy-related antibody assessment.

11Common pitfallsFrequent interpretation and management errors.

01
Describing every prominent eye as cosmetic without testing vision, colour and cornea.
02
Using TSH alone for early carbimazole titration while it remains suppressed.
03
Continuing carbimazole through fever and sore throat without urgent blood count.
04
Offering radioiodine without asking about active eye disease, smoking and pregnancy plans.
05
Assuming a normal thyroid profile excludes active orbital inflammation.
06
Using systemic glucocorticoids for eye disease without a specialist cumulative-dose and safety protocol.
07
Stopping antithyroid treatment abruptly in pregnancy without immediate expert advice.