Hyperosmolar state

Introduction

Hyperthyroidism is a clinical syndrome resulting from excessive thyroid hormone production and/or release. It affects approximately 1-2% of Australians, with a higher prevalence in women (5-10:1 female to male ratio) and peak incidence between 20-50 years of age. The condition presents significant morbidity if untreated and requires prompt recognition and appropriate management.

ℹ️

Clinical Definition: Biochemical hyperthyroidism is defined as suppressed TSH (<0.1 mIU/L) with elevated free T4 and/or free T3. Clinical hyperthyroidism includes both biochemical abnormalities and symptomatic disease.

Common Causes in Australia

Cause	Frequency	Key Features
Graves' disease	70-80%	Diffuse goitre, ophthalmopathy, TSI positive
Toxic multinodular goitre	15-20%	Elderly patients, nodular goitre, normal eyes
Toxic adenoma	3-5%	Single hot nodule, suppressed surrounding tissue
Thyroiditis	2-5%	Transient, painful (subacute) or painless (postpartum)
Iodine-induced	1-2%	Medication history, contrast exposure

Clinical Spectrum

Subclinical

Subclinical Hyperthyroidism

Suppressed TSH with normal T4/T3. May be asymptomatic or have subtle symptoms. Risk of progression and cardiac effects in elderly.

Outpatient management

Overt

Overt Hyperthyroidism

Suppressed TSH with elevated T4/T3. Classic symptoms present. Requires definitive treatment to prevent complications.

Outpatient ± urgent referral

Crisis

Thyroid Storm

Life-threatening emergency. Hyperthermia, altered consciousness, cardiovascular instability. Mortality 10-30% if untreated.

Emergency admission

⚠️

High-Risk Populations: Elderly patients may present with apathetic hyperthyroidism (minimal symptoms but increased cardiac risk). Pregnant women require urgent endocrinology referral due to maternal and fetal complications.

Guideline Scope

This guideline covers the diagnosis, investigation, and management of hyperthyroidism in Australian healthcare settings, with specific considerations for:

Primary care assessment and initial management
Emergency presentation and thyroid storm
Special populations (pregnancy, elderly, children)
Aboriginal and Torres Strait Islander health considerations
Referral pathways and follow-up protocols

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Treatment Goals: Restore euthyroid state, prevent complications, address underlying cause, and optimise quality of life with consideration of patient preferences and comorbidities.

Clinical Presentation

Mild

Subclinical Hyperthyroidism

TSH suppressed, normal T3/T4. Often asymptomatic or subtle symptoms.

Outpatient management

Moderate

Overt Hyperthyroidism

Classic symptoms present. TSH suppressed, elevated T3/T4. Functional impairment.

Outpatient management

Severe

Thyroid Storm

Life-threatening. Hyperpyrexia, altered mental state, cardiovascular instability.

Emergency admission required

Cardinal Symptoms

Sympathetic Symptoms

Palpitations, tachycardia
Tremor (fine, distal)
Anxiety, restlessness
Heat intolerance
Excessive sweating
Hyperdefecation

Metabolic Symptoms

Weight loss with increased appetite
Fatigue, weakness
Muscle weakness (proximal)
Insomnia
Menstrual irregularity
Hair loss

Physical Examination Findings

System	Clinical Signs	Specific Features
Cardiovascular	Tachycardia, systolic hypertension, atrial fibrillation	Wide pulse pressure, systolic flow murmur
Thyroid gland	Goitre, bruit, tenderness	Graves': diffuse enlargement, bruit. Toxic nodule: palpable nodule
Neurological	Fine tremor, hyperreflexia, proximal weakness	Periodic paralysis (especially Asian males)
Skin/Hair	Warm, moist skin, hair thinning	Graves': pretibial myxoedema (rare)
Eyes	Lid retraction, stare	Graves' ophthalmopathy: proptosis, diplopia, periorbital oedema

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Thyroid Storm Features: Hyperpyrexia (>38.5°C), altered mental state, cardiovascular instability (heart failure, arrhythmias), gastrointestinal symptoms (nausea, vomiting, diarrhoea), precipitated by infection, surgery, or medication non-compliance.

Cause-Specific Presentations

1

Graves' Disease (80%)

Diffuse goitre, eye signs, pretibial myxoedema. Often young women. Family history of autoimmune disease.

2

Toxic Multinodular Goitre

Older patients, irregular goitre, no eye signs. Gradual onset. May present with isolated atrial fibrillation.

3

Toxic Adenoma

Single palpable nodule, younger patients. No goitre or eye signs.

4

Thyroiditis

Painful thyroid (subacute), recent pregnancy (postpartum), or drug-induced. Transient hyperthyroidism.

⚠️

Apathetic Hyperthyroidism in Elderly: May present with weight loss, depression, atrial fibrillation, and heart failure rather than classic hyperadrenergic symptoms. High index of suspicion required.

Red Flag Symptoms

Sudden onset severe symptoms
Fever with altered mental state
Cardiovascular compromise
Severe eye symptoms (visual disturbance, severe pain)
Compressive symptoms (stridor, dysphagia)
Periodic paralysis

ℹ️

Clinical Pearl: Hyperthyroidism can unmask or worsen underlying conditions including coronary artery disease, heart failure, and osteoporosis. Consider cardiac assessment in older patients or those with risk factors.

Investigations

ℹ️

Key Principle: TSH is the most sensitive screening test. If TSH is suppressed, measure free T4 and free T3 to confirm hyperthyroidism and assess severity.

Initial Laboratory Investigations

Essential

Thyroid Stimulating Hormone (TSH)

Most sensitive initial test. TSH <0.1 mIU/L suggests hyperthyroidism. Normal TSH excludes primary hyperthyroidism.
Essential

Free Thyroxine (fT4)

If TSH suppressed. Normal range 9-24 pmol/L. Elevated confirms hyperthyroidism.
Essential

Free Triiodothyronine (fT3)

If TSH suppressed. Normal range 3.5-6.5 pmol/L. May be elevated when fT4 normal (T3 toxicosis).
First Line

Full Blood Count

Check for anaemia, neutropenia. Baseline before antithyroid drugs.
First Line

Liver Function Tests

Baseline ALT, bilirubin. Hyperthyroidism can cause elevated enzymes. Monitor during treatment.
First Line

Electrolytes, Urea, Creatinine

Check for hypokalaemia, assess renal function before radioiodine therapy.

Aetiology-Specific Investigations

Second Line

TSH Receptor Antibodies (TRAb)

Confirms Graves' disease. Positive in >95% of Graves' patients. Useful for predicting remission and guiding treatment duration.
Second Line

Thyroid Peroxidase Antibodies (TPOAb)

May be positive in Graves' disease or Hashimoto's thyroiditis. Less specific than TRAb for Graves'.
Specialist

Technetium-99m Thyroid Scan

Differentiates Graves' (diffuse uptake) from toxic nodular disease (patchy uptake) or thyroiditis (low uptake).
Specialist

Radioiodine Uptake Study

24-hour uptake. High in Graves'/toxic nodules, low in thyroiditis. Required before radioiodine treatment planning.
Available

Thyroid Ultrasound

Assess gland size, nodules, blood flow. Doppler shows increased vascularity in Graves' disease.

⚠️

Thyroid Storm Investigation: If suspected, add arterial blood gas, blood glucose, cortisol, cardiac enzymes, and ECG. Consider blood cultures if febrile.

Interpretation Patterns

Pattern	TSH	fT4	fT3	Clinical Significance
Overt Hyperthyroidism	↓↓ (<0.1)	↑	↑	Classical hyperthyroidism requiring treatment
T3 Toxicosis	↓↓ (<0.1)	Normal	↑	Early or mild hyperthyroidism, toxic nodules
Subclinical	↓ (0.1-0.4)	Normal	Normal	Mild disease, monitor or treat if symptomatic
Central Hyperthyroidism	↑ or Normal	↑	↑	TSH-secreting adenoma (rare)

Monitoring During Treatment

Baseline

TSH, fT4, fT3, FBC, LFTs, U&E

2-4 weeks

TSH, fT4, fT3 (earlier if severe). FBC if on antithyroid drugs

6-8 weeks

TSH, fT4, fT3. FBC, LFTs if on antithyroid drugs

3-6 monthly

TSH, fT4 when stable. TRAb annually in Graves' to assess remission likelihood

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Drug Monitoring Alert: Check FBC and LFTs within 2 weeks of starting carbimazole or propylthiouracil. Stop drug immediately if neutrophil count <1.0 × 10⁹/L or ALT >3× upper limit normal.

Special Populations — Investigation Adjustments

🤰 Pregnancy

TRAb Check if Graves' disease — high levels predict neonatal hyperthyroidism

TFTs Monitor monthly during pregnancy — thyroid function changes rapidly

TSH range Use pregnancy-specific TSH ranges (lower in first trimester)

👴 Elderly

ECG Add ECG and cardiac enzymes — higher risk of atrial fibrillation

Echocardiogram Consider if heart failure suspected

DEXA scan Bone density scan if prolonged subclinical hyperthyroidism

Treatment

⚠️

Thyrotoxic Crisis: Medical emergency requiring immediate IV beta-blockers, high-dose antithyroid drugs, corticosteroids and supportive care. Consider plasmapheresis if severe.

Treatment Approach by Cause

Graves' Disease

First-line: Antithyroid drugs

Carbimazole preferred. Consider radioiodine or surgery for refractory cases.

Outpatient management

Toxic Nodular Goitre

Radioiodine therapy

First-line treatment. Surgery if contraindicated to radioiodine.

Specialist referral

Thyrotoxic Crisis

Emergency management

High-dose antithyroid drugs + beta-blockers + corticosteroids.

Hospital admission

Antithyroid Medications

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Carbimazole

Neo-Mercazole® · First-line antithyroid

Adult Dose Initial: 15-40 mg daily, maintenance: 5-15 mg daily

Paediatric 0.5-1 mg/kg/day divided doses

Route Oral, once daily or divided doses

Duration 12-18 months minimum

PBS Status ✔ PBS General Benefit

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Propylthiouracil (PTU)

PTU · Second-line antithyroid

Adult Dose Initial: 300-600 mg daily, maintenance: 50-150 mg daily

Route Oral, divided 6-8 hourly

Indications First trimester pregnancy, carbimazole intolerance

PBS Status ✔ PBS General Benefit

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Agranulocytosis Risk: Occurs in 0.3% of patients on antithyroid drugs. Advise patients to stop medication and seek urgent medical attention if sore throat, fever, mouth ulcers or other signs of infection develop.

Symptomatic Management

🫀

Propranolol

Inderal® · Beta-blocker for symptom control

Adult Dose 40-160 mg daily divided doses

Route Oral, 2-3 times daily

Contraindications Asthma, COPD, heart block, severe heart failure

PBS Status ✔ PBS General Benefit

🫀

Atenolol

Tenormin® · Alternative beta-blocker

Adult Dose 25-100 mg daily

Route Oral, once daily

Renal Adj. Reduce dose if CrCl <35 mL/min

PBS Status ✔ PBS General Benefit

Definitive Treatment Options

Treatment	Indications	Contraindications	Success Rate
Radioiodine (I-131)	Graves' disease, toxic nodular goitre, age >18 years	Pregnancy, breastfeeding, ophthalmopathy	80-90%
Total thyroidectomy	Large goitre, suspected malignancy, pregnancy planning	High surgical risk, severe comorbidities	95-99%
Antithyroid drugs	Graves' disease, pregnancy, young patients	Previous agranulocytosis, severe hepatotoxicity	50-60%

Treatment Monitoring

1

Baseline Assessment

FBC, LFTs, TFTs before starting antithyroid drugs

2

Initial Monitoring

TFTs at 4-6 weeks, then 3-monthly once stable

3

Safety Monitoring

FBC if infection symptoms. LFTs if clinically indicated

4

Treatment Duration

Minimum 12-18 months for Graves' disease

🤱 Pregnancy

Propylthiouracil (PTU) Preferred in first trimester. Switch to carbimazole in second trimester if possible

Beta-blockers Propranolol safe in pregnancy. Avoid atenolol (growth restriction)

Radioiodine Absolutely contraindicated in pregnancy and breastfeeding

👶 Paediatrics

Carbimazole 0.5-1 mg/kg/day. Monitor growth and development

Propranolol 1-2 mg/kg/day divided doses for symptom control

Radioiodine Generally avoided in children <18 years

👴 Elderly

Beta-blockers Start low dose. Monitor for heart failure, bradycardia

Radioiodine Often preferred definitive treatment in elderly

Surgery Higher perioperative risk. Careful anaesthetic assessment

🫘 Renal Impairment

Carbimazole No dose adjustment required for renal impairment

Atenolol Reduce dose if CrCl <35 mL/min. Consider propranolol alternative

Radioiodine Use with caution in severe renal impairment — consult nuclear medicine

Special Populations

🤰 Pregnancy & Breastfeeding

Key risks Thyrotoxicosis increases risk of pre-eclampsia, preterm labour, IUGR. TSI can cross placenta causing fetal/neonatal thyrotoxicosis.

TFT monitoring Monitor TSH, free T4 monthly during pregnancy

Preferred treatment Propylthiouracil (1st trimester), then carbimazole from 2nd trimester onwards

👶 Paediatric Populations

Remission Higher remission rates with antithyroid drugs vs adults

Carbimazole 0.5-1 mg/kg/day divided 8-12 hourly. Monitor growth and development.

Propylthiouracil 5-10 mg/kg/day divided 8 hourly. Second-line in paediatrics.

👴 Elderly Patients

AF risk Increased risk of atrial fibrillation and heart failure. May present with apathetic thyrotoxicosis.

Beta-blockers Start low dose, monitor for heart block

Warfarin Enhanced anticoagulation effect — monitor INR closely

🫘 Renal Impairment

Carbimazole No dose adjustment required

Propylthiouracil No dose adjustment required. Monitor for accumulation in severe impairment.

Iodinated contrast Avoid if possible — may precipitate thyroid storm

🫀 Hepatic Impairment

LFT monitoring Baseline LFTs before starting antithyroid drugs. Monitor weekly for first month, then monthly.

Propylthiouracil Higher hepatotoxicity risk — avoid if possible

Carbimazole Preferred agent in hepatic impairment. Discontinue if ALT >3× ULN.

🛡️ Immunocompromised

Agranulocytosis Higher risk of antithyroid drug-induced agranulocytosis. Weekly FBC for first month, then fortnightly for 3 months.

Warning signs Fever, sore throat, mouth ulcers — stop medication immediately and seek urgent review

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Pregnancy Alert: Radioactive iodine is absolutely contraindicated in pregnancy and breastfeeding. Perform pregnancy test before RAI in all women of childbearing age.

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Propylthiouracil

PTU · First-line in pregnancy (1st trimester)

Pregnancy Dose 50-150 mg 8 hourly oral

Paediatric 5-10 mg/kg/day divided 8 hourly

Breastfeeding Compatible — minimal transfer to breast milk

PBS Status ✔ PBS General Benefit

💊

Carbimazole

Neo-Mercazole® · Preferred post 1st trimester

Pregnancy Dose 5-20 mg daily oral (2nd/3rd trimester)

Paediatric 0.5-1 mg/kg/day divided 8-12 hourly

Elderly Start 5 mg daily, titrate slowly

PBS Status ✔ PBS General Benefit

Aboriginal and Torres Strait Islander Health

Access to Specialist Care

Remote communities may have limited endocrinologist access. Utilise telehealth consultations and strengthen primary care management protocols.

Medication Compliance

Cultural preferences for traditional healing may impact adherence. Engage Aboriginal Health Workers and respect cultural practices while ensuring medical safety.

Monitoring Challenges

Regular blood tests may be difficult in remote areas. Coordinate with visiting medical services and use point-of-care testing where available.

Comorbidity Considerations

Higher rates of diabetes and cardiovascular disease. Monitor for drug interactions and coordinate care with existing chronic disease management programs.

ℹ️

Cultural Safety: Some Aboriginal and Torres Strait Islander people may have concerns about radioactive treatments. Provide culturally appropriate education and involve family/community support where appropriate.

Follow-Up & Prevention

📅

Key Monitoring Principle: TSH may remain suppressed for months after achieving clinical euthyroidism. Free T4 and T3 are better early indicators of treatment response.

Follow-Up Schedule

2-4 weeks

Initial Response Check

Clinical assessment (heart rate, tremor, weight)
TFTs (TSH, free T4, free T3)
FBC if on antithyroid drugs
Adjust medication dose if needed

6-8 weeks

Treatment Adjustment

TFTs to guide dose titration
FBC for drug monitoring
Consider block-and-replace if on carbimazole

3-6 months

Stabilisation Period

Monthly TFTs until stable
Consider remission in Graves' disease after 12-18 months
Ophthalmology review if eye symptoms

Long-term

Ongoing Management

3-6 monthly TFTs once stable
Annual review if in remission
Monitor for hypothyroidism post-treatment

Monitoring Parameters

Essential

Thyroid Function Tests

TSH, free T4, free T3 — frequency as per timeline above
Essential

Full Blood Count

Monthly while on antithyroid drugs — monitor for agranulocytosis
Available

Liver Function Tests

Baseline and if clinically indicated — carbimazole hepatotoxicity risk
Specialist

TSH Receptor Antibodies

Monitor in pregnancy; assess remission likelihood in Graves' disease
Referral

Thyroid Uptake Scan

Post-partum thyroiditis vs Graves' disease differentiation

Treatment Completion & Remission

1

Assess for Remission

After 12-18 months of antithyroid therapy in Graves' disease, consider gradual withdrawal if TRAb negative and clinically stable

2

Gradual Withdrawal

Reduce carbimazole by 50% every 4-6 weeks while monitoring TFTs closely

3

Post-Treatment Monitoring

TFTs at 6 weeks, 3 months, 6 months, then annually — 50% relapse risk in first year

⚠️

Relapse Risk: Graves' disease relapses in 50-60% of patients within 2 years of stopping antithyroid drugs. Higher risk with: male gender, younger age, large goitre, high TRAb levels.

Long-Term Complications

Complication	Monitoring	Management
Thyroid Eye Disease	Visual symptoms, diplopia, eye pain	Ophthalmology referral, selenium supplementation, smoking cessation
Atrial Fibrillation	ECG, symptoms of palpitations	Anticoagulation as per CHA₂DS₂-VASc, rate/rhythm control
Osteoporosis	DEXA scan if prolonged hyperthyroidism	Calcium/vitamin D supplementation, bisphosphonates if indicated
Post-treatment Hypothyroidism	Regular TFTs post-RAI or surgery	Levothyroxine replacement therapy

Prevention Strategies

Primary Prevention

Adequate iodine intake (but avoid excess)
Smoking cessation (reduces Graves' disease risk)
Stress management
Avoid high-dose iodine supplements

Secondary Prevention

Regular monitoring during high-risk periods
Pregnancy planning and monitoring
Medication adherence education
Early recognition of relapse symptoms

Patient Education & Self-Monitoring

💡

Patient Education Points: Teach patients to recognise symptoms of both hyperthyroidism relapse and hypothyroidism, emphasise medication compliance, and provide written information about when to seek urgent medical care.

Symptom Category	Signs to Watch	Action Required
Hyperthyroid Relapse	Palpitations, tremor, heat intolerance, weight loss	Contact GP within 1-2 days
Drug Side Effects	Sore throat, fever, mouth ulcers, rash	Stop medication, urgent medical review
Eye Symptoms	Double vision, eye pain, swelling, vision changes	Ophthalmology referral within 2 weeks
Hypothyroid Development	Fatigue, cold intolerance, weight gain, depression	TFTs within 1-2 weeks

Aboriginal and Torres Strait Islander Health Considerations

Follow-up Accessibility

Coordinate with Aboriginal Medical Services for culturally appropriate long-term monitoring. Consider telehealth options for remote communities.

Medication Access

Ensure PBS medication access through Section 100 Remote Area Aboriginal Health Services. Provide medication charts in appropriate languages.

Family-Centred Care

Include family members in education about symptom recognition and medication importance. Respect cultural decision-making processes.

📞

Referral Triggers: Refer to endocrinologist for: treatment failure after 6 months, pregnancy planning, recurrent relapses, complicated thyroid eye disease, or consideration for definitive therapy (RAI/surgery).