++
Based on the existing literature, conservative management is adequate in most cases of acute unintentional thyroxine ingestions in both adults and children. Most children with acute overdose are managed with home observation and follow-up appointments. In cases where the acute thyroxine dose is estimated to be greater than 4000 µg, patient follow-up by regular telephone contact for 10 days is suggested.27 Historically, most children with unintentional ingestions have been treated with GI decontamination with activated charcoal and/or syrup of ipecac, or by gastric lavage,27,45,56,58,66,63 but these procedures (especially emesis and lavage) are probably unnecessary. Based on two large series of unintentional exposures in children in which no toxicity was observed in the vast majority of cases, clinically significant toxicity is not expected with estimated ingestions less than 4000 µg.27,107 Because children almost uniformly develop no more than minor symptoms, activated charcoal administration should be considered only if the ingestion is greater than 5000 µg of thyroxine. Aspiration risks are minimal in awake, alert children who are able to protect their airways and take activated charcoal orally, without nasogastric tube placement.58,105 By extension, adults with acute ingestions greater than 5000 µg of thyroxine also should be treated with activated charcoal. Except in early presentations with massive thyroxine ingestions (>10,000–50,000 µg) in suicidal adults or ingestions of preparations containing large amounts of T3, gastric emptying procedures such as orogastric lavage are unwarranted.8,32 Similarly, patients with massive ingestions (>10,000–50,000 µg) or ingestion of T3-containing products should be admitted for observation in anticipation of developing significant symptoms.8,32,56,61
++
Treatment should be based on the development of toxicity and should include rehydration, airway protection, and control of sympathomimetic symptoms, mental status alterations, and hyperpyrexia. β-Adrenergic antagonism with propranolol has been used for sympathomimetic symptoms in numerous cases.24,45,56,66,77,100 Empiric treatment with β-adrenergic antagonists is not recommended. Treatment is only indicated for clinically significant tachycardia, dysrhythmias, and other signs and symptoms of catecholaminelike excess.24
++
If sedation is required, parenteral benzodiazepines and barbiturates are recommended. Rapid-acting benzodiazepines, such as midazolam, or diazepam should be used to control severely agitated or symptomatic patients. Phenobarbital should be considered as an additional treatment in intubated patients or as an adjunct in patients requiring sedation because it offers the added theoretical benefit of inducing enhanced hepatic elimination of thyroxine (Table 56–2). Because of the general risks of sedation and the lack of evidence regarding the clinical use of enhanced hepatic elimination from phenobarbital, sedation with phenobarbital for the sole purpose of enhanced elimination is not indicated. Sedation with antipsychotics such as haloperidol and droperidol should be avoided because their significant anticholinergic properties can exacerbate thyrotoxic symptoms. In addition, the tendency for this class of drugs to prolong the QT interval and predispose to malignant dysrhythmias is of concern in the already catecholaminergic patient. Antipsychotics should be reserved for medically stable patients with psychiatric behavioral disturbances.
+++
Catecholaminelike Excess andCardiovascular Symptoms
++
The principal therapeutic role of β-adrenergic antagonists in hyperthyroidism is for their sympatholytic effects.76 In addition, propranolol inhibits 5′-deiodinase, thereby decreasing peripheral conversion of T4 to T3 (Table 56–2). The clinical significance of decreased peripheral conversion in the setting of overdose is unknown. Propranolol is the most frequently used β-adrenergic antagonist in thyrotoxic patients,27,45,56,66,77,100 and should be used parenterally when signs and symptoms are severe or when rapid control of heart rate is required. Starting doses of 1 to 2 mg IV propranolol every 10 to 15 minutes are recommended. Higher doses have been reported in massive thyroxine overdose, where a patient received 23 mg propranolol IV over one hour on initial presentation, then required an average of 30 mg/day IV for 5 more days.32 Oral propranolol can be used for persistent symptoms in patients who are both hemodynamically and medically stable and are not acutely agitated. High oral doses in the range of 20 to 120 mg every 6 hours may be required. Other β-adrenergic antagonists, such as atenolol, nadolol, metoprolol, and esmolol, can be used for symptoms of adrenergic excess, but these may not inhibit the peripheral conversion of T4 to T3. Continuous electrocardiographic and hemodynamic monitoring are indicated when parenteral β-adrenergic antagonists are used or when patients require hospitalization.
++
When nonspecific β-adrenergic antagonists are contraindicated, as in patients with asthma or severe congestive heart failure, β1-selective antagonists (such as atenolol or metoprolol) or calcium channel blockers can be used as an alternative. Among calcium channel blockers, diltiazem is the most studied for the management of thyrotoxicosis.68,88 A double-blind, crossover trial that compared propranolol to diltiazem for thyrotoxic symptoms found that diltiazem was well tolerated and appeared as effective as propranolol.73 Another study successfully used diltiazem as the sole treatment of cardiovascular signs and symptoms in 11 thyrotoxic patients.93 Oral doses of 60 to 120 mg diltiazem three to four times daily or 5 to 10 mg/h parenterally have been used.73,93 A possible explanation for the efficacy of calcium channel blockers in thyrotoxicosis is that thyroid hormone enhances Ca2+ uptake by L-type voltage-gated Ca2+ channels, accelerates Ca2+ entry into the sarcoplasmic reticulum, and increases cellular Ca2+ storage capacity.49,50,74,97 The net effect of these changes is increased inotropy and chronotropy. Calcium channel blockers, particularly diltiazem and verapamil, attenuate these effects. However, the use of parenteral β-adrenergic antagonists in combination with parenteral calcium channel blockers is contraindicated because of the risk for profound hypotension and cardiovascular collapse.79
++
Antipyretics are not recommended for hyperthermia associated with catecholamine excess and thyrotoxic condition. Aspirin, particularly high doses (1.5–3 g/day), should be avoided because it carries a theoretical risk of increased thyrotoxicity from displacement of T3 and T4 from thyroxine-binding globulin (Table 56–2). Note, however, that hyperthermia, especially extreme hyperthermia (> 106°F {> 41°C}), is most likely secondary to psychomotor agitation and excess heat production from the hypermetabolic, catecholaminergic, and thyrotoxic conditions. Extreme hyperthermia should be considered a medical emergency and should be rapidly and aggressively treated with active external cooling with ice baths and with β-adrenergic antagonism, sedation with benzodiazepines and/or barbiturates, and endotracheal intubation with paralysis if necessary (Chap. 30).
++
Bile acid sequestrants, such as cholestyramine and colestipol, and aluminum hydroxide (antacids) and sucralfate bind to exogenous T4 and decrease GI absorption (Table 56–2). Because the evidence supporting their effectiveness is poor, they are not routinely recommended for thyroid hormone overdose.58
++
Oral iodine containing contrast media is known to decrease peripheral conversion of T4 to T3. Doses of 1 to 2.5 mg/kg iodine PO daily are routinely used for thyroid storm (oral drops commonly referred to as saturated solution potassium iodide {KI}). Thioamides, such as propylthiouracil (PTU) and methimazole, and the corticosteroids are thyroid gland inhibitors that are used for treatment of non drug related hyperthyroidism. In addition, thioamides inhibit peripheral conversion of T4 to T3. Evidence from limited case reports suggests poor efficacy of both thioamides and corticosteroids in acute overdose8,25,58 (see Thioamides and Iodides).
++
Although use of antithyroid drugs such as PTU, corticosteroids, and iodine contrast media in thyroxine overdose has theoretical benefits, these xenobiotics are not validated, potentially harmful, and unlikely to offer additional benefit, or be superior to conventional therapy with activated charcoal, β-adrenergic antagonism, and sedation. These treatments are not recommended as adjunctive therapies for treatment of exogenous thyroxine overdose.
+++
Extracorporeal Drug Removal
++
Extracorporeal drug removal procedures, such as plasma exchange or plasmapheresis, exchange transfusion (in children), and charcoal hemoperfusion, have been used in extreme cases of thyroid hormone overdose and thyroid storm.1,8,9,25,39,46,54,58,62,71,75,102,106 Overall, results regarding improvement of clinical condition and plasma clearances of thyroid hormones with these methods are conflicting. The largest series of acute ingestions involved six patients who became critically ill after massive thyroxine ingestions of prescribed capsules containing a 1000-fold concentration excess of thyroxine (dose range, 50,000–125,000 µg/day for 2–12 days). Charcoal hemoperfusion and plasmapheresis were used in all patients. Plasmapheresis was found to be more effective than hemoperfusion in the extraction of thyroxine. The authors suggest this intervention may shorten the duration of thyrotoxicosis. Rebound elevations in plasma concentrations occurred 24 hours later, suggesting redistribution between extravascular and intravascular compartments.8 This redistribution is expected given the large volume of distribution for thyroid hormones (Table 56–1). There may be a role for early plasmapheresis in the exceptional situation of a known massive ingestion of thyroid hormone. Because the outcomes from most ingestions of thyroid hormone will be favorable with good supportive care, sedation, and β-adrenergic antagonism, the risks of plasmapheresis should be evaluated on a case by case basis after consultation with a medical toxicologist.