Thyroxine toxicity

Thyroxine overdose rarely causes hyperthyroidism, if it does, symptoms are usually mild and can be managed as an outpatient.

Toxic Mechanism:

Thyroxine (T4) is converted to triiodothyronine (T3) in the liver and kidney, it then enters the nucleus to exert is metabolic effects.

Toxicokinetics: 

• Oral bioavailability is 80%
• Peak absorption at 2 hours
• Hormonal effects are not apparent for 1 – 3 weeks
• It is extensively distributed and bound to protein
• Elimination half life is 6 – 7 days in therapeutic dosing and is shortened in overdose to 3 days.

Resuscitation:

• Rarely required

Risk Assessment

• Symptoms are not expected unless >10mg of thyroxine is ingested
• Most remain asymptomatic or experience some mild hyperthyroid symptoms 2 – 7 days later (fever, agitation, sweating, tachycardia, hypertension, headache, diarrhoea and vomiting)
• Those with cardiovascular disease or increased age are at increased risk
• Severe toxicity is more likely to occur with chronic hormone abuse. Symptoms include angina, myocardial infarction, myocarditis, ventricular and atrial dysrhythmias, LVH, thyrotoxicosis and thyroid storm.
• Children: Up to 5 mg is associated with minimal symptoms. Severe thyrotoxicosis has not been reported after unintentional paediatric ingestion.

Supportive Care

• Beta-blockers can control the symptoms of thyroid excess. If there are no contraindications administer 10 – 40 mg (0.2 – 0.5 mg/kg in children) every 6 hours.
• Calcium channel blockers can be used as an alternative. Administer diltiazem 60 – 180 mg (1 – 3mg/kg in children – except in children <1yrs of age) every 8 hours.

Investigations

• Screening: 12 lead ECG, BSL, Paracetamol level
• Specific: 
  • Thyroid function tests can be done which will show elevated levels but unfortunately does not help with ongoing management because treatment is dependent on the clinical symptoms.

Decontamination:

• Activated charcoal 50 grams (1 g/kg in children) can be given within 1 hours of patients who have ingested >10 mg (5 mg in children).
• AC is not indicated in unintentional ingestion by children .

Enhanced Elimination

• Not clinically useful

Antidotes

• None available

Disposition

• Children who have ingested <5mg can be observed at home
• Most adults can be medically cleared with advice regarding hyperthyroid symptoms to represent with or seek advice from their GP. This usually involves a 1 week course of beta blockers if the patient is symptomatic. If the patient was on thyroxine this should be stopped for 1 week and can then be re-started.

References and Additional Resources:

Additional Resources:

• Tox conundrum 019 – Thyroxine overdose
• CCC – Thyroid storm

References:

• Lewander WJ et al. Acute thyroxine ingestion in pediatric patients. Pediatrics 1989; 84:262-265.
• Litovitz TL, White JD. Levothyroxine ingestions in children: An analysis of 78 cases. American Journal of Emergency Medicine 1985; 3:297-300.
• Shilo L, Kovatz S, Hadari R et al.  Massive thyroid hormone overdose: Clinical manifestations and management.  Israeli Medical Association Journal 2002; 4:298-289.
• Tunget CL et al. Raising the decontamination level for thyroid hormone ingestions. American Journal of Emergency Medicine 1995; 13:9-13.