Major therapeutic use of thyroxine is as hormone replacement therapy for hypothyroidism and cretinism. Natural (desiccated thyroid and thyroglobulin) thyroid hormone is available to treat hypothyroid disease states and thyroid cancer. Synthetic prepa-rations of thyroid hormone include Levothyroxine sodium (T4) and Liothyronine sodium (T3). Liotrix is a mixture of thyroxine and tri-iodothyronine (4 parts T4 to 1 part T3). Thyrotropin, or recombinant human thyroid stimulating hormone, is avail-able in the US as Thyrogen®. It is indicated for thyroid cancer diagnostic/monitoring.
Both hormones (T3 and T4) are metabolised primarily by deiodination with only 20% of the hormone excreted in the faeces intact or conjugated. Approximately 40% of T4 is converted in peripheral tissues to T3.
Adverse effects include exacerbation of angina, arrhyth-mias, and provocation of myocardial infarction. Tremor, sweating, headache, flushing, tachycardia, and palpitations have been reported. Loss of weight is common.
Toxicity following massive overdosage may occur within 12 to 24 hours if a tri-iodothyronine (T3) containing product has been ingested. Acute ingestions of levothyroxine result in only mild symptoms, usually days after ingestion. Adults rarely experience symptoms with one -time ingestions of at least 6 grains desiccated thyroid (usual adult dose is 1.5 to 2.5 grains/ day), or 3 mg of levothyroxine. Similar amounts are probably required to produce symptoms in young children. Fatalities are extremely unlikely with acute thyroid hormone overdose.
The following signs and symptoms have occurred in overdose cases: vomiting, diarrhoea, abdominal pain, fever, tachycardia, palpitations, hypertension, increased sweating, congestive heart failure, and cardiac arrhythmias. Pulmonary oedema, presenting as sudden dyspnoea several days after overdose, requiring endotracheal intubation, has been reported after tri-iodothyronine overdose. Headache, confusion, agitation, mydriasis, and tremor are common. Psychosis has been reported. Seizures may occur following massive acute overdoses.
Symptoms may be delayed up to 10 to 15 days, and hence keeping the patient under observation is important. Mild hypertension may occur due to adrenergic discharge resulting in hyperthyroidism. Angina and ventricular dysrhythmias have been reported. T3 is more likely to cause angina than T4.
Chronic intake causes weight loss, myocarditis, angina, and ventricular arrhythmias. Thyrotoxicosis is fairly common after chronic overdoses of T3 and T4, but is generally unusual following acute ingestions. Thyroid compounds may induce myocarditis in chronic overdoses and can be associated with sudden death in the presence of coronary artery disease.
· It is advisable to monitor patients through follow-up tele- phone calls for 5 days at home if initially asymptomatic or minimal symptoms, due to the prolonged onset of action of levothyroxine. Levels of T3, T4 and protein-bound iodine (PBI) may be markedly elevated both with and without clinical signs of toxicity; these values are virtually no help in treatment or prognosis of the overdose. Gastric decontamination is probably not warranted in most cases. However, consider administration of activated charcoal after a potentially toxic ingestion. Propranolol may be administered (1 mg/dose IV, administered no faster than 1 mg/min, repeated every 5 minutes up to a maximum of 5 mg) to treat the adrenergic findings associated with hyper- thyroidism. Alternatives to propranolol include labetalol or sotalol.
· Institute continuous cardiac monitoring and obtain an ECG in patients with moderate or severe symptoms.
· Prednisolone and propranolol to block the peripheral effects of thyroxine.
· Cholestyramine (4 grams orally every 6 to 8 hours) to block the enterohepatic circulation of thyroid hormone.
· Propylthiouracil (vide infra) to block endogenous thyroxine production.
· Sodium ipodate and iopanoic acid have been advocated as effective and safe alternatives for the treatment of hyper- thyroidism.
· Charcoal haemoperfusion or plasmapheresis to enhance elimination. Diuresis and haemodialysis are ineffective due to high protein binding.