Levothyroxine intoxication

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The course of thyroxine intoxication in mokopuna (children) tends to be mild but severe intoxication can be life threatening

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Starship clinical guidelines

Background

  • Thyroid hormones circulate as T3 and T4. T3 is approximately 4 times as potent as T4.

  • Thyroglobulin is the main carrier for circulating T4 and T3 in humans. In target tissues, T4 is converted to T3 and reverse T3 (rT3), which is devoid of biologic activity.

  • Synthetic thyroid hormones are one of the most commonly prescribed drugs:

    • Levothyroxine (thyroxine sodium; tetraiodothyronine sodium; T4) is fully subsidized and comes in different strengths and forms (25, 50 and 100 mcg tablets; 15 and 25 mcg/mL solution).

    • Liothyronine (triiodothyronine, T3) is not an approved medicine in New Zealand.

  • Following oral intake, Tmax of levothyroxine is reached at 5-6 hours. Elimination half-life (T1/2) is 7 days for T4 and 0.8 day for T31. Following intoxication, T4 T1/2 is shorter (2.8 days) and T1/2 for T3 is longer (6 days)2.

Assessment

History

  • How much L-thyroxine was ingested? (strength of the tablet and number of missing tablets)

  • How many hours between intoxication and presentation at the emergency department?

  • Ask for concomitant ingestion of other medicines that could affect clinical course.

Signs and symptoms

  • Does the patient present with signs and symptoms of L-thyroxine intoxication? (Signs and symptoms after thyroid hormone ingestion can be delayed by up to 24-48 hours after ingestion).

    More common
    Nervousness, restlessness, irritability
    Insomnia, unable to go to sleep
    Tremors
    Blood pressure elevation
    Hyperthermia
    Tachycardia
    Loose stools
    Less common
    Dysrhythmias
    Hypotension
    Cardiac failure
    Altered mental status
    Seizures
    Multi-organ failure

Investigations

  • Plasma/serum free T4 and free T3 (If free T4 > 100 pmol/L, call the laboratory and ask for a total T4 (TT4) with dilution).

  • Plasma/serum TSH.

  • (reverse T3 determination is not commonly available and is not useful).

Management

  • The course of thyroxine intoxication in children tends to be mild but severe intoxication can be life threatening1,2,3. Mokopuna (children) can have mild4 or severe5 symptoms even following massive L-thyroxine ingestion.

  • L-thyroxine is readily absorbed. Free T4 and free T3 concentrations rise 1-2 hours following ingestion.

  • There is a poor correlation between free T3 and free T4 concentrations, the amount of levothyroxine ingested and the severity of signs and symptoms of intoxication.

  • There is no definite recommendation for the threshold of management. Hartman et al1 suggested that mokopuna (children) who ingested > 0.1 mg levothyroxine/kg, with a short interval since ingestion, symptomatic at presentation and/or with a free T4 > 100 pmol/l be managed in hospital with cardiac monitoring and serial thyroid function tests.

    If dose of levothyroxine ingested is < 0.1 mg/kg
    Consider activated charcoal 1 g/kg if levothyroxine ingestion took place < 6-9 hours
    Reassurance
    Inform whānau (family/families) of the clinical signs of levothyroxine intoxication
    Patient to be observed by whānau for 10-14 days with repeat thyroid function tests after 3 days
    If dose of levothyroxine ingested is > 0.1 mg/kg (to be adapted individually as many patients who take > 0.1 mg/kg will have no or minimal symptoms)
    Activated charcoal 1g/kg (repeat dose is not necessary) if levothyroxine ingestion took place < 6-9 hours
    Propranolol 2mg/kg/day given QID (range: 0.5 - 4 mg/kg/day)
    IV line if necessary
    Cardiac monitoring and observation for an initial 24 to 48 hours with further monitoring based on clinical course
    Thereafter, patient to be observed by whānau (family/families) for 10-14 days

Note:

  • Thyroid storm is a rare but potentially life-threatening complication. It should be considered when there is multi-organ involvement, especially when there is GI (diarrhoea, vomiting or abdominal pain), CNS (marked agitation, delirium, coma or seizures), and unexplained pyrexia >38 C. Scoring systems are available and useful as a guide but are not validated in mokopuna (children)6. If there is concern about multiorgan involvement a paediatric endocrinologist should be consulted.

  • Propranolol decreases the symptoms of hyperthyroidism and promotes the conversion of T4 into inactive reverse T3.

  • The following medicines/approaches have not conclusively been shown to be useful: corticosteroids, ipodate, plasmapheresis, dialysis, methimazole, propylthiouracil (PTU), iodine.

 

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