📋 Key Information Summary
- Hyperthyroidism management requires aetiological diagnosis; Graves' disease, toxic multinodular goitre, and toxic adenoma are most common in Australia.
- First-line antithyroid drug (ATD) for most non-pregnant adults is carbimazole (Mycril®); propylthiouracil (PTU) reserved for first trimester pregnancy, thyroid storm, or carbimazole intolerance.
- Carbimazole initial dose 15–40 mg/day, titrated to lowest维持 dose maintaining euthyroidism; typical course 12–18 months for Graves' disease.
- Major ATD risk is agranulocytosis (~0.2–0.5%); patients must be counselled to stop drug and seek urgent FBC if febrile illness or sore throat develops.
- Radioiodine (I-131) is definitive therapy for Graves' disease and toxic nodular disease; contraindicated in pregnancy and breastfeeding.
- Post-radioiodine hypothyroidism is expected (≥50% at 10 years); requires lifelong levothyroxine monitoring and replacement.
- Total thyroidectomy indicated for large goitre with compressive symptoms, suspected malignancy, or failed/contraindicated medical/radioiodine therapy.
- Pregnancy: PTU in first trimester, switch to carbimazole in second/third trimester; aim for free T4 at or just above upper normal limit.
- Paediatric Graves': ATDs are first-line; surgery if ATD failure/toxicity; radioiodine generally avoided in children <10 years.
- Thyroid storm is a medical emergency with high mortality; requires ICU admission, beta-blockade, high-dose PTU, iodine, and corticosteroids.
- Monitor thyroid function every 4–6 weeks during ATD titration, then every 3–6 months once stable.
- Aboriginal and Torres Strait Islander peoples have higher prevalence of thyroid disease and may face barriers to specialist access; culturally safe care and long-term follow-up are essential.
🎧 Audio Brief
Introduction & Australian Epidemiology
Hyperthyroidism, or thyrotoxicosis, is a clinical state resulting from excess circulating thyroid hormones. Management is guided by the underlying aetiology, severity, patient age, comorbidities, and reproductive plans. In Australia, the most common causes are Graves' disease (an autoimmune condition), toxic multinodular goitre, and toxic adenoma.
Australian epidemiological data indicate a prevalence of hyperthyroidism of approximately 1–2%, with a female-to-male ratio of 5–10:1. Graves' disease is the predominant cause in younger adults, while toxic nodular disease increases in prevalence with age. Access to care, particularly endocrinology and nuclear medicine services, varies significantly between metropolitan and regional/remote areas.
The three definitive treatment modalities are antithyroid drugs (ATDs), radioactive iodine (RAI) therapy, and thyroidectomy. The choice is individualised, considering efficacy, side-effect profiles, patient preference, and long-term outcomes.
Pathophysiology
Thyroid hormone synthesis and release are regulated by the hypothalamic-pituitary-thyroid (HPT) axis. Hyperthyroidism arises from autonomous thyroid hormone production, independent of TSH stimulation.
Key Aetiologies:
- Graves' disease: TSH-receptor stimulating antibodies (TRAb) cause diffuse thyroid stimulation and hormone overproduction. It is associated with extrathyroidal manifestations like ophthalmopathy.
- Toxic multinodular goitre: Somatic mutations lead to autonomously functioning nodules, more common in iodine-deficient regions and the elderly.
- Toxic adenoma: A single autonomously functioning benign adenoma.
- Thyroiditis: Destructive processes (e.g., subacute, postpartum) cause release of preformed hormone, typically resulting in transient thyrotoxicosis.
- Drug-induced: Amiodarone-induced thyrotoxicosis (AIT) has two types: Type 1 (excess synthesis) and Type 2 (destructive thyroiditis).
Clinical Presentation & Diagnostic Criteria
Presentation ranges from asymptomatic biochemical abnormality to life-threatening thyroid storm.
Typical Symptoms & Signs:
| System | Symptoms | Signs |
|---|---|---|
| Constitutional | Heat intolerance, weight loss despite increased appetite, fatigue | Warm moist skin, fine tremor |
| Cardiovascular | Palpitations, dyspnoea on exertion | Tachycardia, atrial fibrillation, systolic hypertension, high-output cardiac failure |
| Neuropsychiatric | Anxiety, irritability, insomnia | Hyperreflexia, lid lag |
| Musculoskeletal | Proximal myopathy | Muscle weakness |
| Reproductive | Oligomenorrhoea, gynaecomastia | |
| Graves'-specific | Eye irritation, diplopia | Proptosis, lid retraction, pretibial myxoedema, thyroid acropachy |
Diagnostic Criteria:
Diagnosis is biochemical:
- Primary hyperthyroidism: Suppressed TSH (<0.1 mIU/L) with elevated free T4 (fT4) and/or free T3 (fT3).
- Subclinical hyperthyroidism: Suppressed TSH with normal fT4 and fT3.
- Aetiological diagnosis: TSH-receptor antibodies (TRAb) for Graves', uptake scan (RAIU) for nodular disease vs. thyroiditis.
Investigations
Initial and aetiological investigations are essential for guiding therapy.
Essential
Thyroid Function Tests (TSH, fT4, fT3)
MBS Item 66716. Confirms diagnosis and monitors treatment.
Essential
TSH-receptor antibodies (TRAb)
MBS Item 66836. High sensitivity/specificity for Graves' disease. Avoids unnecessary radioiodine exposure if thyroiditis suspected.
Available
Radioactive Iodine Uptake (RAIU) Scan
MBS Item 61306. Differentiates high-uptake (Graves', toxic nodule) from low-uptake (thyroiditis) causes. Requires access to nuclear medicine.
Available
Thyroid Ultrasound with Doppler
MBS Item 55039. Assesses gland size, nodularity, vascularity (increased in Graves').
Available
Full Blood Count (FBC)
Baseline before ATDs to monitor for agranulocytosis.
Available
Liver Function Tests (LFTs)
Baseline before ATDs; can be abnormal in thyrotoxicosis and with drug hepatotoxicity.
Risk Stratification & Severity Scoring
Severity is assessed clinically and biochemically to determine urgency of treatment.
Mild
Subclinical or Mild Overt
Weight loss <5%, heart rate <100 bpm, no AF, mild tremor.
Setting: Outpatient management
Moderate
Moderate Overt
Weight loss 5–10%, heart rate 100–120 bpm, prominent symptoms.
Setting: Outpatient, urgent initiation of therapy
Severe
Severe Overt / Thyroid Storm
Weight loss >10%, heart rate >120 bpm, AF, heart failure, agitation, delirium. Burch-Wartofsky score ≥45.
Setting: Hospital/ICU admission
Thyroid Storm: Medical emergency. Mortality 10–30%. Requires immediate hospitalisation, aggressive beta-blockade, high-dose PTU, inorganic iodine, corticosteroids, and supportive care in ICU.
Management Overview
Treatment goals are to restore euthyroidism, manage symptoms, and select definitive therapy to prevent recurrence.
General Measures:
- Beta-blockers: Propranolol 20–40 mg PO 6–8 hourly (or long-acting 80–160 mg daily) for symptom control of adrenergic symptoms (palpitations, tremor, anxiety).
- Avoid iodine-rich contrast media and medications (e.g., amiodarone) where possible.
- Patient education on disease course, medication adherence, and warning signs of agranulocytosis and thyroid storm.
Antithyroid Drugs (Carbimazole/PTU)
Mechanism & Choice
ATDs inhibit thyroid hormone synthesis by blocking thyroid peroxidase. Carbimazole (converted to methimazole) is preferred due to once-daily dosing and lower hepatotoxicity risk. PTU has additional peripheral T4-to-T3 conversion inhibition.
Carbimazole
Mycril® · Neomercazole® · Thiamazole
Adult dose
Initial: 15–40 mg PO daily (divided or single dose). Maintenance: 5–15 mg daily.
Paediatric dose
0.5–1.0 mg/kg/day (initial), 0.2–0.5 mg/kg/day (maintenance).
Duration
12–18 months for Graves' disease. 6–12 months for toxic nodular disease before definitive therapy.
Renal adjustment
No adjustment required. Monitor closely in severe impairment.
Hepatic adjustment
Use with caution; monitor LFTs. Avoid in severe liver disease.
PBS status
✔ PBS General Benefit
Propylthiouracil (PTU)
Propylthiouracil · PTU
Adult dose
Initial: 200–400 mg PO daily in divided doses (8 hourly). Maintenance: 50–150 mg daily.
Paediatric dose
5–7 mg/kg/day (initial) in divided doses.
Key indication
First trimester pregnancy. Thyroid storm (high dose).
PBS status
✔ PBS General Benefit
Regimen Strategies
- Titration regimen: Start high, taper to lowest维持 dose. Most common in Australia.
- Block-and-replace: High-dose ATD + levothyroxine. Used for rapid control or unstable thyrotoxicosis. Not for routine Graves' disease.
Critical Safety Alert - Agranulocytosis: Occurs in 0.2–0.5% of patients on ATDs, usually within first 3 months. All patients must be instructed to stop ATD immediately and seek an urgent full blood count (FBC) if they develop fever, sore throat, mouth ulcers, or any sign of infection. This is a potentially fatal adverse effect.
Radioiodine Therapy (I-131)
Radioiodine (I-131) is a safe, effective, and commonly used definitive therapy for Graves' disease and toxic nodular goitre in Australia.
Indications & Contraindications
Indications
- Relapse after ATD therapy.
- ATD intolerance or non-adherence.
- Toxic multinodular goitre or toxic adenoma.
- Patient preference for definitive therapy.
Contraindications
- Pregnancy (absolute).
- Breastfeeding.
- Severe active Graves' ophthalmopathy (may exacerbate).
- Inability to comply with radiation safety precautions.
Procedure & Outcomes
- Pre-treatment: Discontinue ATDs (carbimazole 5–7 days, PTU 1–2 weeks) before therapy. Low-iodine diet may be advised.
- Dosing: Fixed dose (e.g., 400–600 MBq for Graves') or calculated based on gland size/uptake. Administered orally as a capsule.
- Post-therapy: Radiation safety precautions for 2–4 weeks (avoid prolonged close contact with children/pregnant women).
- Outcome: Hypothyroidism is the goal (≥50% at 1 year for Graves'). Requires lifelong levothyroxine replacement and monitoring.
Thyroidectomy
Surgery offers rapid, definitive treatment but carries operative risks. Performed by a high-volume endocrine surgeon for optimal outcomes.
Indications
- Large goitre with compressive symptoms (dysphagia, dyspnoea).
- Coexisting thyroid malignancy or suspicious nodule.
- Severe ophthalmopathy (preferred over radioiodine).
- Patient preference, especially in women planning future pregnancy.
- Failed or contraindicated ATD and radioiodine therapy.
Pre-operative, Operative & Post-operative Care
1
Pre-operative Optimisation
Render patient euthyroid with ATDs. Consider Lugol's iodine (SSKI) 7–10 days pre-op to reduce vascularity.
2
Surgery
Total or near-total thyroidectomy is standard for Graves'. Performed under general anaesthesia.
3
Immediate Complications
Bleeding/haematoma, recurrent laryngeal nerve injury (hoarseness), hypoparathyroidism (hypocalcaemia).
4
Long-term Management
Lifelong levothyroxine replacement. Monitor calcium and PTH if hypoparathyroidism suspected.
Special Circumstances (Pregnancy, Children)
Pregnancy
Management aims to control hyperthyroidism with minimal fetal exposure. Untreated hyperthyroidism increases risk of pre-eclampsia, preterm birth, and low birth weight.
- First trimester: PTU is first-line due to rare but serious carbimazole-associated fetal malformations (aplasia cutis, choanal atresia).
- Second & third trimester: Switch to carbimazole due to PTU-associated hepatotoxicity risk.
- Dosing: Use lowest possible维持 dose. Target fT4 at or just above the upper limit of normal.
- Monitoring: TFTs every 4 weeks. TRAb cross placenta; check at 18–22 weeks if high risk (previous surgery/RAI) to predict neonatal thyrotoxicosis.
- Definitive therapy: Surgery (if essential) in second trimester. Radioiodine is absolutely contraindicated.
Paediatric Hyperthyroidism
Graves' disease is the most common cause. Management differs from adults.
- First-line: ATD therapy (carbimazole preferred). Dose based on weight. Duration often longer than adults (3–5 years).
- Second-line: Total thyroidectomy if ATD failure, toxicity, or non-adherence. Requires experienced paediatric surgeon.
- Radioiodine: Generally avoided in children <10 years due to theoretical long-term malignancy risk. May be considered in older children after failed ATDs.
- Monitoring: Close supervision of growth, development, and school performance.
Monitoring
Regular monitoring is essential for safety and efficacy across all treatment modalities.
ATD Therapy
Every 4–6 weeks during initial titration. Once euthyroid, every 3–6 months. Check FBC and LFTs at baseline and if symptoms arise. Monitor for relapse after cessation.
Post-Radioiodine
TFTs 4–6 weeks post-treatment, then every 2–3 months in first year, then annually once hypothyroid on stable levothyroxine.
Post-Thyroidectomy
Check calcium 6–12 hours post-op and monitor for symptoms of hypocalcaemia. TFTs 4–6 weeks post-op to guide levothyroxine dose, then annually.
Other Special Populations
Elderly
Higher risk of atrial fibrillation and heart failure.
Lower threshold for RAI. May present with "apathetic thyrotoxicosis". Beta-blockers require caution in heart failure.
Renal Impairment
Carbimazole/PTU do not require dose adjustment.
Monitor fluid status and electrolytes closely, especially with heart failure. Levothyroxine dose may need adjustment.
Hepatic Impairment
PTU-associated hepatitis is a concern.
Carbimazole preferred. Monitor LFTs closely. Thyroid hormones are highly protein-bound; changes in binding proteins occur in liver disease.
Immunocompromised
Higher risk of infection if agranulocytosis occurs.
Low threshold for FBC with any infective symptoms. Consider earlier definitive therapy (surgery/RAI) to avoid prolonged ATD use.
Aboriginal and Torres Strait Islander Health Considerations
Thyroid disorders, including hyperthyroidism, are prevalent in Aboriginal and Torres Strait Islander peoples. Management must be culturally safe and address specific barriers.
📚 References
- 1. Australian Institute of Health and Welfare (AIHW). Thyroid disease in Australia. Cat. no. PHE 249. Canberra: AIHW; 2020.
- 2. The Royal Australian College of General Practitioners (RACGP). Thyroid disease: diagnosis and management. East Melbourne, Vic: RACGP; 2023.
- 3. Ross DS, Burch HB, Cooper DS, et al. 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis. Thyroid. 2016;26(10):1343-1421.
- 4. Kahaly GJ, Bartalena L, Hegedüs L, et al. 2018 European Thyroid Association Guideline for the Management of Graves' Hyperthyroidism. Eur Thyroid J. 2018;7(4):167-186.
- 5. Australian Government Department of Health. PBS Online: Carbimazole, Propylthiouracil. Accessed 2024.
- 6. Endocrine Society of Australia (ESA). Position Statement: Management of Hyperthyroidism in Pregnancy. 2022.
- 7. National Health and Medical Research Council (NHMRC). National Statement on Ethical Conduct in Human Research. Canberra: NHMRC; 2023 (Updated).
- 8. Aboriginal and Torres Strait Islander Health Practice Board of Australia. Cultural safety framework. 2022.
- 9. Burch HB, Wartofsky L. Life-threatening thyrotoxicosis. Thyroid storm. Endocrinol Metab Clin North Am. 1993;22(2):263-277.
- 10. Smith TJ, Hegedüs L. Graves' Disease. N Engl J Med. 2016;375(16):1552-1565.
- 11. Australian Commission on Safety and Quality in Health Care (ACSQHC). Australian Atlas of Healthcare Variation. Sydney: ACSQHC; 2023.
- 12. Stagnaro-Green A, Abalovich M, Alexander E, et al. Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum. Thyroid. 2011;21(10):1081-1125.