What is Graves' disease?

Graves' disease is the most common cause of hyperthyroidism — an autoimmune condition in which TRAb (TSH receptor antibodies) continuously stimulate the thyroid to produce excess hormone. Affects predominantly women (10:1 F:M), ages 20-60. Features: hyperthyroidism (weight loss, palpitations, heat intolerance, tremor, anxiety, diarrhoea); diffuse smooth goitre; Graves' ophthalmopathy (proptosis, periorbital swelling, diplopia — 25-30%); rare pretibial myxoedema.

What is the most dangerous side effect of carbimazole?

Agranulocytosis — severe neutropenia from bone marrow suppression, affecting 0.2-0.5% of patients, typically in the first 3 months. Without adequate neutrophils, life-threatening bacterial infection can develop within hours. MANDATORY patient education: if fever (>38°C) or sore throat develops while taking carbimazole — STOP IMMEDIATELY and attend hospital for an FBC. Never switch to PTU if agranulocytosis occurs (50% cross-reactivity). Recovery after drug cessation (with G-CSF support if needed).

How is Graves' disease treated?

Three options: (1) ATDs (carbimazole/methimazole) 12-18 months — only option offering remission; approximately 50% relapse after stopping; reversible; best for first-time treatment. (2) Radioiodine — single oral dose; definitive; causes hypothyroidism (then lifelong levothyroxine); safe; avoid in pregnancy, breastfeeding, significant ophthalmopathy. (3) Total thyroidectomy — immediately curative; preferred for large goitre, compressive symptoms, suspected cancer, significant TED; small risks (1-2%) of hypoparathyroidism and RLN injury.

What is Graves ophthalmopathy?

Orbital autoimmune inflammation in 25-30% of Graves' patients — driven by IGF-1R activation on orbital fibroblasts causing expansion of orbital fat and extraocular muscles. Manifestations: proptosis; periorbital swelling; lid retraction; diplopia (extraocular muscle restriction); corneal exposure; optic nerve compression (sight-threatening). Follows a different course from thyroid disease. Treatment: mild — lubricants, UV protection; active moderate-severe — IV methylprednisolone pulses; teprotumumab (FDA 2020) dramatically reduces proptosis and diplopia; orbital decompression for sight-threatening.

How does GMJ News cover Graves' disease?

GMJ News covers TRAb mechanism, carbimazole agranulocytosis warning (mandatory counselling), three treatment options, Graves ophthalmopathy and CAS staging, teprotumumab 2020 approval, radioiodine precautions, thyroid storm (Burch-Wartofsky), PTU in pregnancy first trimester, neonatal Graves' monitoring, and autoimmune associations.

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Graves Disease

GMJ News knowledge hub · last reviewed August 2026 · Georgian Medical Journal

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Graves’ disease — an autoimmune thyroid condition in which TSH receptor antibodies (TRAb) act as continuous TSH agonists, driving uncontrolled thyroid hormone production and causing the most common form of hyperthyroidism (approximately 80-90% of cases in HICs) — presents with the classic hyperthyroidism syndrome (weight loss, palpitations, heat intolerance, tremor, anxiety) plus Graves-specific features: diffuse smooth goitre, Graves ophthalmopathy (proptosis, periorbital oedema, diplopia — affecting approximately 25-30%) and rare pretibial myxoedema (WHO). Three treatment options exist — each with distinct advantages: antithyroid drugs (carbimazole/methimazole for 12-18 months — the only option offering remission chance, but approximately 50% relapse rate; agranulocytosis is the most dangerous side effect — any fever or sore throat requires urgent blood count); radioiodine (131I — definitive, safe, but causes hypothyroidism intentionally and may worsen ophthalmopathy); and total thyroidectomy (immediate, preferred for large goitres or significant eye disease).

Key messages

TRAb — the driving autoantibody; pathognomonic for Graves'

TSH receptor antibodies (TRAb) act as TSH agonists — continuously stimulating thyroid hormone production independently of the normal feedback loop. TRAb measurement is essential: confirms Graves' diagnosis; predicts relapse risk (persistently elevated TRAb at end of ATD course predicts relapse); monitors neonatal Graves' risk in pregnancy.

CRITICAL SAFETY WARNING: Carbimazole/methimazole agranulocytosis

Agranulocytosis (severe neutropenia) affects approximately 0.2-0.5% of patients on carbimazole or methimazole — typically within the first 3 months. EVERY patient must receive this warning at drug initiation: if fever or sore throat develops, STOP the drug IMMEDIATELY and attend hospital for an urgent blood count. Agranulocytosis is life-threatening but recoverable if caught early. Do not switch to PTU if agranulocytosis occurs — approximately 50% cross-reactivity.

Three treatment options: ATDs, radioiodine, surgery

Antithyroid drugs (carbimazole/methimazole): 12-18 months; only option offering potential remission (~50% relapse after stopping); reversible. Radioiodine (131-I): definitive; causes intentional hypothyroidism; avoid in pregnancy/significant ophthalmopathy. Total thyroidectomy: immediate definitive; preferred for large goitre, compressive symptoms, suspected cancer, significant ophthalmopathy, patient preference.

Graves ophthalmopathy — assess before choosing treatment

Graves ophthalmopathy (TED) affects approximately 25-30%: proptosis, periorbital oedema, diplopia, lid retraction, corneal exposure. Active TED: clinical activity score (CAS) ≥3/7 — treat with IV methylprednisolone. Radioiodine may worsen TED (give prophylactic steroids if mild TED + RAI chosen; avoid RAI with moderate-severe TED). Teprotumumab (anti-IGF-1R, FDA 2020): dramatically reduces proptosis and diplopia in active moderate-severe TED.

PTU for first trimester pregnancy and thyroid storm

PTU is preferred over carbimazole in the first trimester (methimazole embryopathy — choanal atresia, aplasia cutis). Switch back to carbimazole after 16 weeks (PTU hepatotoxicity risk). In thyroid storm: PTU 1000mg loading (blocks T4→T3 conversion) + Lugol's iodine 1 hour later + propranolol + dexamethasone + ICU.

Thyroid storm — the endocrine emergency (Burch-Wartofsky score)

Thyroid storm: life-threatening decompensated thyrotoxicosis — triggered by surgery, infection or contrast in uncontrolled hyperthyroidism. Features: fever >38.5°C; CNS disturbance; AF/tachycardia/heart failure; GI symptoms; jaundice. Burch-Wartofsky score ≥45 = highly likely. Mortality 20-30% even treated. Emergency: PTU → Lugol's iodine (1 hour gap) → propranolol → dexamethasone → ICU.

Key statistics

80-90%

of hyperthyroidism in HICs is Graves' disease

BTA/ETA

0.2-0.5%

risk of agranulocytosis with carbimazole/methimazole — STOP on fever/sore throat

BTA/FDA

~50%

relapse rate after completing 12-18 month antithyroid drug course

BTA/ETA

25-30%

of Graves' patients develop Graves ophthalmopathy

EUGOGO

FDA 2020

teprotumumab (Tepezza) — first approved drug specifically for Graves ophthalmopathy

FDA 2020

10:1

female to male ratio in Graves' disease

BTA/ETA

Graves' disease — three treatment modalities compared

Source: BTA/ETA/ATA. All three are appropriate depending on patient factors, ophthalmopathy and preference.

Glossary of key terms

TRAb (TSH receptor antibodies)
Immunology/EndocrinologyAutoantibodies binding the TSH receptor on thyroid follicular cells — acting as TSH agonists. Cause continuous, feedback-resistant thyroid hormone production. Third-generation immunometric TRAb assay: used to confirm Graves' diagnosis; monitor remission; guide pregnancy surveillance (high TRAb at 30-36 weeks → neonatal Graves' risk).

Carbimazole vs propylthiouracil
PharmacologyBoth block thyroid peroxidase. PTU additionally blocks peripheral T4→T3 conversion (useful in storm). Carbimazole: UK/Europe standard. Methimazole: USA prodrug equivalent. Teratogenicity: methimazole embryopathy (first trimester); PTU hepatotoxicity (prefer after 16 weeks). Titration vs block-replace: equal remission rates, different profiles.

Radioiodine therapy (131-I)
Nuclear medicine131-I taken up via sodium-iodide symporter → beta radiation → thyroid cell destruction → hypothyroidism (intended outcome). Single dose; effect over 2-6 months. Safe — no increased cancer, fertility, or fetal risk (avoid pregnancy 6 months). Contraindications: pregnancy; breastfeeding; planning pregnancy <6 months; significant active ophthalmopathy. Pre-treat to euthyroid with ATDs first (stop ATDs 5-7 days before RAI).

Teprotumumab (Tepezza)
FDA 2020/OphthalmologyAnti-IGF-1R monoclonal antibody — FDA-approved January 2020 for active moderate-severe Graves ophthalmopathy. OPTIC trial: 83% proptosis reduction vs 10% placebo; 70% diplopia improvement. IV every 3 weeks × 8 infusions. Side effects: hyperglycaemia (monitor in diabetes); hearing loss (audiogram). Expensive (~$250,000/course).

Neonatal Graves' disease
Neonatology/EndocrinologyTRAb crosses placenta → fetal/neonatal hyperthyroidism. Risk: persistently elevated maternal TRAb in third trimester. Presentation: delayed 3-5 days (maternal ATDs clear before TRAb effect). Features: tachycardia, irritability, poor feeding, exophthalmos, goitre. Management: fetal heart rate monitoring; thyroid function at birth; carbimazole if needed. Transient — resolves as maternal TRAb clears (6-12 weeks).

Graves' disease in pregnancy
Obstetrics/EndocrinologyTFTs every 4-6 weeks in pregnancy. Target: FT4 in upper-normal range (avoid overtreatment → fetal hypothyroidism). First trimester: PTU preferred (methimazole embryopathy). After 16 weeks: carbimazole (PTU hepatotoxicity). Both ATDs cross placenta — use lowest effective dose. TRAb monitored at 30-36 weeks (predicts neonatal Graves'). Breastfeeding: carbimazole ≤15mg/day is safe.

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