Substances Included Synonyms

Therapeutic Toxic Class

A)

Specific Substances

1) Desiccated thyroid (Synonym)
2) Levothyroxine (Synonym)
3) L-thyroxine (Synonym)
4) T4 (Synonym)
5) Liothyronine (Synonym)
6) T3 (Synonym)
7) Liotrix (Synonym)
8) Thyroglobulin (Synonym)
9) Thyroid Stimulating Hormone, Recombinant, Human (TSH) (Synonym)
10) Thyrotropin (Synonym)
11) Thyroxine (Synonym)
12) Triac (Synonym)
13) Triiodothyroacetic acid (Synonym)

1.2.1) MOLECULAR FORMULA
1) LIOTHYRONINE SODIUM: C15H11I3NNaO4

Available Forms Sources

A)

1) Crude thyroid = Desiccated thyroid

a) Desiccated thyroid - 1/4, 1/2, 1, 2, 3, 4, 5 grains
b) Thyroglobin = Proloid(R) = 1/4, 1/2, 1, 1 1/2, 3, 5 grains

2) Levothyroxine (L-thyroxine, sodium) (T4)

a) Cytolen(R) = 0.1 mg
b) Levoid(R) = 0.1, 0.2 mg; 100 mcg/mL injection
c) Synthroid(R) - 0.025, 0.05, 0.1, 0.15, 0.2, 0.3, 0.5 mg; 100 mcg/mL injection

3) Liothyronine (L-triiodothyronine, sodium) (T3)

a) Cytomel(R) = 5, 25 and 50 mcg

4) Liotrix (L-thyroxine/L-thronine 4:1 mix)

a) Euthyroid: 1/2, 1, 2, 3 grain equivalent
b) Thyrolar: 1/4, 1/2, 1, 2, 3 grain equivalent

5) Thyrotropin, or recombinant human thyroid stimulating hormone, is available in the US as Thyrogen(R). It is indicated for thyroid cancer diagnostic/monitoring (Anon, 1994). It is available as a 1.1 mg kit for intramuscular injection.
6) Triax Metabolic Accelerator(R), which contains the active ingredient triiodothyroacetic acid (Triac), is a weight-loss dietary supplement marketed by Syntrax Innovations, Inc. It has been reported by the FDA to be an unapproved new drug causing abnormal thyroid function test results in some users. These users were reporting symptoms of severe diarrhea, fatigue, lethargy or profound weight loss ((Anon, 1999)). Other similar dietary supplements containing tiratricol which have been recalled include: Tricana Metabolic Hormone analogue 1 mg capsules and Tira-Cutz Thyroid Stimulator containing 1 mg per capsule (Anon, 2000).

Overview

Life Support

A)

Clinical Effects

0.2.1)

A) USES: Levothyroxine (T4) and triiodothyronine (liothyronine) (T3) are used for the treatment of hypothyroidism.
B) EPIDEMIOLOGY: Exposure to thyroid products is common, but clinical effects are rare. Most cases of severe toxicity are related to prolonged, repeated exposure (either inadvertent or deliberate abuse). There are a few reports of toxicity in children following large (greater than 10 mg) single ingestions.
C) PHARMACOLOGY: About 40% of T4 is converted to the primarily active T3. Pharmacologic action of T3 is mediated by activation of nuclear thyroid hormone receptors that modulates gene transcription and ultimately protein synthesis. Excessive thyroid hormone exposure is associated with metabolic activation and increased oxygen consumption in peripheral tissues.
D) TOXICOLOGY: T3 upregulates beta adrenergic receptor synthesis, increasing the number of beta receptors in various tissues, and modulates intracellular signaling in myocytes leading to increased catecholamine effects. The net effect is increased catecholamine activity, leading to sympathomimetic clinical manifestations (ie, tachycardia, tremor, anxiety, elevated body temperature, supraventricular tachycardia and other cardiac dysrhythmias, hypertension, altered mental status, and very rarely seizures).
E) WITH THERAPEUTIC USE

1) ADVERSE EFFECTS: Sleeplessness, anxiety, nervousness, tremor, diaphoresis, palpitations, and diarrhea are common side effects from thyroid hormone replacement therapy. CHRONIC EXPOSURE: THYROTOXICOSIS is fairly common after chronic overdose, but is unusual after acute exposure.

F) WITH POISONING/EXPOSURE

1) MILD TO MODERATE TOXICITY: Subtle tremor, anxiety, mild sinus tachycardia and hypertension.
2) SEVERE TOXICITY: Altered mental status including severe agitation, confusion, and rarely CNS depression. Seizures are occasionally reported. Hyperthermia, severe hypertension, cardiac dysrhythmias (most commonly supraventricular tachycardia), and diarrhea may be seen. Be aware of a possibly increased risk of cardiovascular complications in the elderly with underlying cardiac disease. Effects are often delayed several days after the ingestion.
3) CHRONIC: THYROTOXICOSIS is fairly common after chronic overdose, but is unusual after acute exposure.

0.2.3)

A) Tachycardia, hypertension and fever may develop.

0.2.4)

A) Dilated pupils have been noted.

0.2.5)

A) Tachycardia, hypertension, heart failure and circulatory collapse may occur. Cardiac dysrhythmias and angina attacks have occurred, particularly following chronic supratherapeutic doses.

0.2.7)

A) Signs and symptoms of restlessness, insomnia, headache, fever, tremor, dizziness, seizures, and coma may occur.

0.2.8)

A) Vomiting and diarrhea may occur.

0.2.16)

A) WITH POISONING/EXPOSURE

1) Thyrotoxicosis has resulted following massive ingestions of levothyroxine.

0.2.20)

A) Thyroid preparations are excreted into breast milk in low concentrations.

Laboratory Monitoring

A)

B)

C)

Treatment Overview

0.4.2)

A) MANAGEMENT OF MILD TO MODERATE TOXICITY

1) Primarily supportive care; single dose activated charcoal is advised in patients presenting shortly after an ingestion of more than 3 mg.

B) MANAGEMENT OF SEVERE TOXICITY

1) Give activated charcoal if a patient presents early after ingestion of more than 3 mg. In case of seizure, severe agitation, or significant CNS depression, perform orotracheal intubation for airway protection before giving charcoal. Administer benzodiazepines to treat seizures and agitation. Signs of catecholamine excess such as significant hypertension and tachycardia are effectively treated with propranolol 10 to 80 mg orally every 4 to 6 hours. Consider a beta 1 selective agent (ie, esmolol 50 to 200 mcg/kg/min intravenously), or a calcium channel blocker (ie, diltiazem 1 to 3 mg/kg orally every 6 to 8 hours) in patients with a history of asthma. Carefully assess volume status especially in case of severe hyperthermia. In the case of an excessive ingestion of T4 consider dexamethasone (4 mg orally every 8 hours) or propylthiouracil (PTU) (75 to 100 mg orally every 6 to 8 hours) therapy to block conversion of T4 to T3. However, the efficacy of PTU is limited because it mainly inhibits de novo synthesis of T4. Administration of aspirin and NSAIDs for the treatment of hyperthermia is discouraged, because of possible displacement of T3 and T4 from plasma proteins.

C) DECONTAMINATION

1) PREHOSPITAL: Not routinely recommended.
2) HOSPITAL: Administer single-dose activated charcoal after a recent substantial ingestion (more than 3 mg of T4) and if the patient is able to protect the airway. Gastric lavage is not routinely recommended.

D) AIRWAY MANAGEMENT

1) Orotracheal intubation may be needed in patients with signs of severe intoxication (ie, marked CNS depression, seizures, agitation, confusion, and severe hyperthermia).

E) ANTIDOTE

1) There is no antidote for thyroid hormone poisoning.

F) ENHANCED ELIMINATION

1) There is no role for repeat-dose activated charcoal. Hemodialysis is not useful given the large volume of distribution and excessive protein binding.

G) PATIENT DISPOSITION

1) HOME CRITERIA: Children may be managed at home if overdose was inadvertent and dose ingested was less than 0.5 to 2 mg. Toxicity in adults may depend on comorbidities and recommendations are less well based on scientific evidence than for children. Since signs and symptoms of thyroid hormone toxicity are delayed for hours (T3 ingestion) or several days (T4 ingestion), follow-up must be provided for up to 14 days postingestion.
2) OBSERVATION CRITERIA: Any patient who overdosed in a suicide attempt or inadvertently ingested more than 2 to 3 mg should be sent to a health care facility for treatment or evaluation. Elderly patients with cardiovascular comorbidities may require evaluation even after a small ingestion. Outpatient follow-up for the next 14 days should be ensured for patients who do not require admission, as signs and symptoms may be delayed.
3) ADMISSION CRITERIA: Patients with dysrhythmias (more than mild tachycardia), severe agitation, seizures, or significant hyperthermia should be admitted.
4) CONSULT CRITERIA: Consult a poison center or medical toxicologist for assistance in decision making whether or not admission is advisable, managing patients with severe toxicity, to arrange follow-up calls, or in whom the diagnosis is not clear.

H) PHARMACOKINETICS

1) Bioavailability of T3 and T4 is approximately 48% to 90%. T4 and T3 are high (greater than 99.5%) protein-bound. Volume of distribution is about 8 to 10 L/kg. About 40% of T4 is converted to active T3 and 40% to inactive reverse T3 (rT3) in the liver. Remaining T4 undergoes hepatic glucuronidation and secretion into the bile. The elimination half-life of T4 is 6 to 8 days. In hypothyroidism half-life may be prolonged to 9 to 10 days, whereas in hyperthyroidism half-life is shortened to 3 to 4 days. The half-life of T3 is about 24 hours, however, apparent half-life of T3 can be prolonged to several days after a substantial ingestion of T4.

I) TOXICOKINETICS

1) In mild to moderate overdose, elimination kinetics seems to be unchanged. However, in very large overdoses of T4, apparent half-life of T3, the mainly active compound, is prolonged to several days.

J) DIFFERENTIAL DIAGNOSIS

1) Consider thyroid storm, sympathomimetic or serotonergic poisoning in case of severe hypertension, tachycardia, and hyperthermia. In case of severe, CNS depression, agitation, confusion, and seizures, rule-out intracerebral pathologies. It is rare to observe significant CNS toxicity in thyroid hormone poisoning, especially early in the course.

Range Of Toxicity

A)

B)

C)

D)

Clinical Effects

Summary Of Exposure

A)

B)

C)

D)

E)

1) ADVERSE EFFECTS: Sleeplessness, anxiety, nervousness, tremor, diaphoresis, palpitations, and diarrhea are common side effects from thyroid hormone replacement therapy. CHRONIC EXPOSURE: THYROTOXICOSIS is fairly common after chronic overdose, but is unusual after acute exposure.

F)

1) MILD TO MODERATE TOXICITY: Subtle tremor, anxiety, mild sinus tachycardia and hypertension.
2) SEVERE TOXICITY: Altered mental status including severe agitation, confusion, and rarely CNS depression. Seizures are occasionally reported. Hyperthermia, severe hypertension, cardiac dysrhythmias (most commonly supraventricular tachycardia), and diarrhea may be seen. Be aware of a possibly increased risk of cardiovascular complications in the elderly with underlying cardiac disease. Effects are often delayed several days after the ingestion.
3) CHRONIC: THYROTOXICOSIS is fairly common after chronic overdose, but is unusual after acute exposure.

Vital Signs

3.3.1)

A) Tachycardia, hypertension and fever may develop.

3.3.3)

A) WITH POISONING/EXPOSURE

1) FEVER has been reported following acute overdose (Sola et al, 2002; Jonare et al, 2001; Brown et al, 1998; Tunget et al, 1995; Berkner et al, 1991; Funderburk & Spaulding, 1970) and may be a common effect due to adrenergic stimulation.
2) A fever of 40 degrees C was reported in a patient 9 days after being prescribed 25 mcg of triiodothyronine every 8 hours. A serum triiodothyronine level, measured by chemoluminescent immunoassay 11 hours after ingestion of the last capsule, was 575.2 nmol/L. It is believed that the patient may have received capsules containing 5 mg of triiodothyronine, a dose that was 200 times higher than was prescribed by her physician (Botella de Maglia et al, 2003).

3.3.4)

A) WITH POISONING/EXPOSURE

1) HYPERTENSION: Mild hypertension may occur due to adrenergic discharge resulting in hyperthyroidism (Willgerodt et al, 2003; Berkner et al, 1991).

3.3.5)

A) WITH POISONING/EXPOSURE

1) TACHYCARDIA is a frequent occurrence as a result of adrenergic stimulation (Ohye et al, 2005; Botella de Maglia et al, 2003; Willgerodt et al, 2003; Sola et al, 2002; Hack et al, 1999; Brown et al, 1998; Tunget et al, 1995; Berkner et al, 1991; Singh & Winterborn, 1991; Lehrner & Weir, 1984; Gerard et al, 1972).

Heent

3.4.1)

A) Dilated pupils have been noted.

3.4.3)

A) MYDRIASIS has been reported (Hack et al, 1999) (Levy & Gilger, 1957).

Cardiovascular

3.5.1)

A) Tachycardia, hypertension, heart failure and circulatory collapse may occur. Cardiac dysrhythmias and angina attacks have occurred, particularly following chronic supratherapeutic doses.

3.5.2)

A) CARDIOVASCULAR FINDING

1) WITH POISONING/EXPOSURE

a) LARGE OVERDOSE: A large overdose (eg, 800 grains of desiccated thyroid consumed over several days) may produce cardiovascular effects and other sequelae (pneumonia, bleeding, murmurs, hypokalemic alkalosis and coma) for weeks after the exposure (Schottstaedt & Smoller, 1966).

1) Clinical signs of toxicity, including signs of adrenergic stimulation, such as agitation, sweating, tachycardia, hypertension, diarrhea, vomiting, and cardiovascular collapse, may occur as a result of high output failure.

B) MYOCARDITIS

1) WITH POISONING/EXPOSURE

a) CHRONIC: Thyroid compounds may induce myocarditis in chronic overdoses and can be associated with sudden death in the presence of coronary artery disease.

C) MYOCARDIAL INFARCTION

1) WITH THERAPEUTIC USE

a) Myocardial infarction due to coronary spasm has been reported after therapeutic (50 mcg/day) doses (Hiasa et al, 1989). Myocardial infarction is more likely to occur following chronic supratherapeutic doses.

2) WITH POISONING/EXPOSURE

a) A small infarction associated with left ventricular ischemia and cardiogenic shock was reported in a woman with normal coronary arteries and no coronary artery spasm after ingesting 260 mg/day of desiccated thyroid for 6 months. Ischemic changes were reversible after discontinuation (Bergeron et al, 1988).

D) CONDUCTION DISORDER OF THE HEART

1) Angina and ventricular dysrhythmias have been reported (Binimelis et al, 1987; Bhasin et al, 1981). T-3 is more likely to cause angina than T-4 (Refetoff, 1975). Isolated ventricular extrasystoles were reported in a 3.5-year-old after ingestion of 10 mg levothyroxine (Jonare et al, 2001).
2) ATRIAL FIBRILLATION

a) In a case of accidental overdose of triiodothyronine (400 mg over an 8-day period), a 44-year-old woman developed paroxysmal atrial fibrillation episodes with alternate sinus tachycardia and frequent ventricular extrasystoles. The atrial fibrillation resolved with no antidysrhythmic treatment (Sola et al, 2002).
b) Atrial fibrillation may occur as a result of prolonged adrenergic discharge, particularly following chronic supratherapeutic doses (Seger, 1994).

3) TACHYCARDIA

a) Tachycardia is another frequent occurrence, a result of adrenergic stimulation (Ohye et al, 2005; Botella de Maglia et al, 2003; Willgerodt et al, 2003; Sola et al, 2002; Jonare et al, 2001; Hack et al, 1999; Brown et al, 1998; Tunget et al, 1995; Berkner et al, 1991; Singh & Winterborn, 1991; Lehrner & Weir, 1984; Gerard et al, 1972). Profound tachycardia may be resistant to therapy (Hack et al, 1999).
b) Biondi et al (1993) studied cardiac effects of therapeutic levothyroxine dosing in a group of 20 patients as compared to a control group. Heart rates and atrial premature beats were significantly increased in the T-4 group as compared to controls. No significant differences were reported in the number of ventricular dysrhythmias.
c) CASE REPORT: Following a massive (unknown quantity) ingestion of levothyroxine, a 2.5-year-old boy progressively, over one day, developed increased pulse rate (90/min at 3 hr postingestion to 140/min 22 hr later). Within 24 hr of starting iopanic acid, the boy's heart rate significantly decreased (Brown et al, 1998).
d) CASE REPORT: Following a massive accidental triiodothyronine overdose of 400 mg over an 8-day period, a 44-year-old woman presented to the ED with pulse rate of 170 bpm but with normal blood pressure. She recovered after symptomatic care (Sola et al, 2002).
e) CASE REPORT: A 44-year-old woman developed palpitations with a heart rate of 100 bpm and anxiety after ingesting 84 thyroxine tablets (100 mcg each; total dose 8.4 mg) and 20 alprazolam tablets (125 mcg each; total dose 2.5 mg). Plasma T4 and free T3 levels, obtained 3 days postingestion, were greater than 100 pmol/L (normal range 12 to 22 pmol/L) and 48.4 pmol/L (normal range 2.8 to 7.1 pmol/L), respectively. On day 5, she was stable and discharged to home; she was lost to follow-up (Lo et al, 2004).

E) HYPERTENSIVE EPISODE

1) WITH POISONING/EXPOSURE

a) Mild hypertension has been reported (Willgerodt et al, 2003; Berkner et al, 1991), but has not been crucial in acute thyroid poisonings. Hypertension is a clinical effect which may result from hyperthyroidism due to adrenergic discharge. Berkner et al (1991) found thyroid hormone levels to correlate with systolic blood pressure in 2 children following an acute ingestion of L-thyroxine (Berkner et al, 1991).

F) HYPOTENSIVE EPISODE

1) WITH THERAPEUTIC USE

a) High output failure may lead to circulatory collapse from prolonged stimulation, an effect of adrenergic discharge. This is more likely to occur following chronic supratherapeutic doses. (Seger, 1994).

2) WITH POISONING/EXPOSURE

a) CASE REPORT: A 2.5-year-old boy had an initial T4 serum concentration of 1525 nmol/L (118.5 mcg/dL) upon admission along with progressive increases in blood pressure (initial, 70/46 mmHg and 124/64 mmHg 22 hr later). Therapy with propylthiouracil, propranolol and iopanoic acid resulted in normalization of blood pressure over several days (Brown et al, 1998a).

G) RIGHT HEART FAILURE

1) WITH THERAPEUTIC USE

a) CONGESTIVE HEART FAILURE with cardiomegaly and pulmonary edema is reported in a 35-year-old overweight male who had consumed supratherapeutic amounts of levothyroxine over several months. Atrial fibrillation and tachycardia were evident during ECG monitoring. Levothyroxine-induced thyrotoxicosis was diagnosed (Somberg et al, 1992).

H) CARDIOMEGALY

1) WITH THERAPEUTIC USE

a) VENTRICULAR HYPERTROPHY: Left ventricular mass index was significantly increased in patients on chronic therapeutic doses of levothyroxine as compared to a control group (Biondi et al, 1993).

Respiratory

3.6.2)

A) ACUTE LUNG INJURY

1) WITH POISONING/EXPOSURE

a) Pulmonary edema, presenting as sudden dyspnea several days after overdose, requiring endotracheal intubation, has been reported after triiodothyronine overdose (Sola et al, 2002).

Neurologic

3.7.1)

A) Signs and symptoms of restlessness, insomnia, headache, fever, tremor, dizziness, seizures, and coma may occur.

3.7.2)

A) PSYCHOMOTOR AGITATION

1) WITH POISONING/EXPOSURE

a) Agitation, delirium, and fine tremor, with profuse sweating (Ohye et al, 2005; Botella de Maglia et al, 2003; Hack et al, 1999; Brown et al, 1998; Pearl & Chambers, 1977; Gerard et al, 1972) may occur over 1 to 5 days and may be expected after large overdoses.
b) A case series of 92 pediatric patients reports hyperactivity in 4 children and irritability and insomnia in 2 others. Doses ranged between 0.1 and 3.75 mg of levothyroxine (Tunget et al, 1995).

B) HEADACHE

1) Headache has been reported (Ohye et al, 2005; von Hofe & Young, 1977).

C) SEIZURE

1) WITH POISONING/EXPOSURE

a) Seizures may occur following an acute massive overdose.
b) ADULT

1) Seizure was reported in a 44-year-old woman after accidental overdose of 400 mg triiodothyronine over an 8-day period (Sola et al, 2002).

c) PEDIATRIC

1) A 3.5-year-old boy was presumed to have ingested up to 41 88-mcg levothyroxine tablets and was in good health until he developed a 5 to 10 minute tonic-clonic seizure 3 days after exposure. Thyroid function studies included a total thyroxine (T4) greater than 24.0 mcg/dL (reference range 4.7 to 11.1 mcg/dL), free T4 of 5.5 ng/dL (reference range 0.6 to 2.0 ng/dL) and a thyroid-stimulating hormone level of 0.26 mU/L (reference range: 0.49 to 4.67 mU/L); total triiodothyronine levels were not tested. No further seizures occurred and the patient was discharged to home. Follow-up over 10-months was normal with appropriate development (Tsutaoka et al, 2005).
2) Seizures were reported 7 days after ingestion of up to 180 of the 0.1 mg tablets of levothyroxine (Synthroid(R)) in a 30-month-old boy (Kulig et al, 1985).

D) COMA

1) WITH POISONING/EXPOSURE

a) Grade II to III coma was reported in 5 adults who ingested 70 to 1200 mg of levothyroxine over 2 to 12 days. Coma developed within 7 to 10 days of ingestion (Binimelis et al, 1987).

E) PSYCHOTIC DISORDER

1) WITH POISONING/EXPOSURE

a) Acute psychosis has been reported to occur following overdoses (Seger, 1994). Following a case of accidental overdose of 400 mg triiodothyronine over an 8-day period, a 44-year-old woman developed confusion, disorientation, behavior disorder, visual hallucinations, delirium and aggressiveness (Sola et al, 2002).

Gastrointestinal

3.8.1)

A) Vomiting and diarrhea may occur.

3.8.2)

A) GASTRITIS

1) WITH POISONING/EXPOSURE

a) Vomiting and diarrhea have been reported (Sola et al, 2002; Hack et al, 1999; Tunget et al, 1995; Funderburk & Spaulding, 1970) and may be an expected adrenergic response.
b) CASE REPORT: Nausea, vomiting, and abdominal pain occurred in a patient approximately 9 days after being prescribed 25 mcg of triiodothyronine every 8 hours. During the following 10 days, the patient also experienced constipation progressing to diarrhea. A serum total triiodothyronine level, measured by chemoluminescent immunoassay 11 hours after ingestion of the last capsule, was 575.2 nmol/L. It is believed that the patient may have received capsules containing 5 mg of triiodothyronine, a dose that was approximately 200 times higher than was prescribed (Botella de Maglia et al, 2003).

Hepatic

3.9.3)

A) ANIMAL STUDIES

1) SGPT INCREASED

a) Serum alanine transferase levels were elevated to 345 U/L (normal, 10-38 U/L) 6 days after a dog ingested up to 10.12 mg/kg levothyroxine (Hansen et al, 1992).

Dermatologic

3.14.2)

A) FLUSHING

1) Flushing has been reported (Funderburk & Spaulding, 1970; Tunget et al, 1995).

B) GENERALIZED EXFOLIATIVE DERMATITIS

1) WITH POISONING/EXPOSURE

a) Intense laminar desquamation of the soles and palms developed 17 to 37 days after accidental ingestion of 70 to 1200 mg of levothyroxine for 3 to 12 days (Binimelis et al, 1987).

C) ERUPTION

1) Rash was reported in 2 pediatric patients following ingestions of up to 1.5 mg of thyroid hormone (Tunget et al, 1995).

D) EXCESSIVE SWEATING

1) WITH POISONING/EXPOSURE

a) Diaphoresis may occur as a clinical sign of thyrotoxicosis or hyperthyroidism following an overdose. Sweating may be profuse (Hack et al, 1999; Seger, 1994).

Musculoskeletal

3.15.2)

A) TOXIC MYOPATHY

1) Myopathy, characterized by severe and progressive weakness, has been reported. Rhabdomyolysis with a CPK of 965 IU/L, was reported in one case of T3 overdose; a complication of distal predominant myopathy requiring rehabilitation occurred (Sola et al, 2002).

Endocrine

3.16.1)

A) WITH POISONING/EXPOSURE

1) Thyrotoxicosis has resulted following massive ingestions of levothyroxine.

3.16.2)

A) INCREASED THYROXINE LEVEL

1) WITH POISONING/EXPOSURE

a) Massive acute levothyroxine (T4) and triiodothyronine (T3) ingestions have resulted in thyrotoxicosis (Sola et al, 2002; Hack et al, 1999). Thyrotoxicosis is fairly common after chronic overdoses of T3 and T4, but is generally unusual following acute ingestions.
b) CASE REPORT: A 34-year-old male developed severe delayed toxicity, including profound thyrotoxicosis with tachycardia, fever, vomiting, hyperreflexia, agitation, insomnia, and a 20 kg weight loss over 15 days after a suicidal ingestion of 720 mg veterinary T4. Free T4 serum levels ranged from greater than 13 mcg/dL on day 6 to 1.3 mcg/dL on day 21. Treatment consisted of activated charcoal, haloperidol, phenobarbital, propranolol, diazepam, and rehydration. Approximately 32 days after the ingestion the patient was reported to be clinically euthyroid (Hack et al, 1999).
c) CASE REPORT: A 44-year-old woman developed palpitations with a heart rate of 100 bpm and anxiety after ingesting 84 thyroxine tablets (100 mcg each; total dose 8.4 mg) and 20 alprazolam tablets (125 mcg each; total dose 2.5 mg). Plasma T4 and free T3 levels, obtained 3 days postingestion, were greater than 100 pmol/L (normal range 12 to 22 pmol/L) and 48.4 pmol/L (normal range 2.8 to 7.1 pmol/L), respectively (Lo et al, 2004).
d) A series of 12 patients who developed signs and symptoms of hyperthyroidism (ie, headache, tachycardia, tremors, thirst, and irregular menstruation) after chronically ingesting 2 different kinds of herbal supplements for weight loss has been reported. All had depressed thyrotropin concentrations and increased free T4 concentrations (Ohye et al, 2005).

1) One of the involved products was Ever Youth, an herbal supplement claiming to contain only the natural food products of radish, lotus leaf, chrysanthemum, hawthorn, senna tea, Chinese matrimony vine, and seaweed. Laboratory analysis of the supplement showed T3 and T4 contents of 1.1 mcg/capsule and 4.5 mcg/capsule, respectively (Ohye et al, 2005).
2) The other product was Dream Shape, an herbal supplement claiming to contain only the natural food products of hydrangea vine, maltose, chrysanthemum, Chinese matrimony vine, saccharose, and seaweed. Laboratory analysis of the supplement showed a T3 content of 0.97 mcg/capsule and a T4 content of 3.4 mcg/capsule(Ohye et al, 2005).

B) FINDING OF THYROID FUNCTION

1) WITH POISONING/EXPOSURE

a) DIETARY SUPPLEMENT: Abnormal thyroid function tests, associated with severe diarrhea, fatigue, lethargy or profound weight loss, has been reported in some patients following the use of a dietary supplement product (Triax Metabolic Accelerator) containing the active ingredient, triiodothyroacetic acid. The FDA has issued a warning of possible heart trouble due to this product ((Anon, 1999)).

Reproductive

3.20.1)

A) Thyroid preparations are excreted into breast milk in low concentrations.

3.20.3)

A) PREGNANCY CATEGORY

DEXTROTHYROXINE	C
LEVOTHYROXINE	A
LIOTHYRONINE	A
LIOTRIX	A
THYROGLOBULIN	A
THYROID	A
THYROTROPIN	C
Reference: Briggs et al, 1998

3.20.4)

A) BREAST MILK

1) Thyroid preparations are excreted into breast milk in low concentrations (Briggs et al, 1998).

Laboratory Monitoring

Monitoring Parameters Levels

4.1.1)

A) Monitor vital signs and mental status.
B) Free T4 (fT4) and total T3 blood concentrations help to ascertain diagnosis, but they are not strongly correlated to clinical findings or prognosis, and are not beneficial in guiding therapy. Therefore, serial measurements of thyroid hormone concentrations are generally unnecessary.
C) Obtain an ECG and institute continuous cardiac monitoring in patients with symptoms and signs of cardiac toxicity.

4.1.2)

A) TOXICITY

1) Correlation of laboratory results with symptoms is poor. High levels of T3 or T4 do NOT necessarily predict toxicity (Nystrom et al, 1980; Golightly et al, 1987; Tenenbein & Dean, 1986).
2) Based on a single case, a high T4 radioimmunoassay on day 1 of an ingestion might be a good prognosticator of subsequent thyrotoxicosis. However, this has not been confirmed in other cases (von Hofe & Young, 1977).
3) Thyrotoxicosis has been reported with normal T3 levels (Ogbuawa & Johnson, 1980). A patient was asymptomatic with a PBI level of 89 mcg per 100 mL at 14 hours and 47 mcg per 100 mL at 44 hours (Funderburk & Spaulding, 1970).

B) ENDOCRINE

1) NORMAL THYROID LEVELS (von Hofe & Young, 1977):

1) T3U = Triiodothyronine resin uptake, 25% to 35%
2) T4 (RIA) = Serum thyroxine concentration determined by radio immunoassay, 4.5 to 11.5 mcg per 100 mL
3) T3 (RIA) = Serum triiodothyronine concentration determined by radio immunoassay, 80 to 250 ng per 100 mL
4) TSH = Thyrotropin measured by radio immunoassay, less than 6 microunits/mL

4.1.4)

A) OTHER

1) MONITORING

a) Institute continuous cardiac monitoring and obtain an ECG in patients with moderate or severe symptoms.

Treatment

Life Support

A)

Patient Disposition

6.3.1)

6.3.1.1) ADMISSION CRITERIA/ORAL

A) Patients with dysrhythmias (more than mild tachycardia), severe agitation, seizures, or significant hyperthermia should be admitted.

6.3.1.2) HOME CRITERIA/ORAL

A) Children may be managed at home if overdose was inadvertent and dose ingested was less than 0.5 to 2 mg. Toxicity in adults may depend on comorbidities and recommendations are less well based on scientific evidence than for children. Since signs and symptoms of thyroid hormone toxicity are delayed for hours (T3 ingestion) or several days (T4 ingestion), follow-up must be provided for up to 14 days postingestion.
B) Children who ingest less than 0.5 mg of levothyroxine do not require referral to a health care facility or decontamination (Litovitz & White, 1985).
C) Other authors suggest that children who ingest less than 5 mg of levothyroxine can be managed at home without decontamination (Tunget et al, 1995).
D) Children who ingest more than 4 mg of levothyroxine should receive daily telephone follow-up and referral to a health care facility if symptoms develop (Willgerodt et al, 2003; Golightly et al, 1987).

6.3.1.3) CONSULT CRITERIA/ORAL

A) Consult a poison center or medical toxicologist for assistance in decision making whether or not admission is advisable, managing patients with severe toxicity, to arrange follow-up calls, or in whom the diagnosis is not clear.

6.3.1.5) OBSERVATION CRITERIA/ORAL

A) Any patient who overdosed in a suicide attempt or inadvertently ingested more than 2 to 3 mg should be sent to a health care facility for treatment or evaluation. Elderly patients with cardiovascular comorbidities may require evaluation even after a small ingestion. Outpatient follow-up for the next 14 days should be ensured for patients who do not require admission, as signs and symptoms may be delayed.

Monitoring

A)

B)

C)

Oral Exposure

6.5.1)

A) Prehospital gastrointestinal decontamination is not routinely recommended.
B) Gastric decontamination is probably not warranted in ingestions of less than or equal to 2 mg of levothyroxine (Tenenbein & Dean, 1986). Tunget et al (1995) suggested decontamination in pediatric patients who ingest 5 mg or greater of levothyroxine based on a study of 92 pediatric patients with acute thyroid hormone ingestions (Tunget et al, 1995).
C) Complications from ingestions of less than 5 mg have been mild, and less severe than side effects of gastrointestinal decontamination.

6.5.2)

A) ACTIVATED CHARCOAL

1) Gastric decontamination is probably not warranted in ingestions of less than or equal to 2 mg of levothyroxine. Some clinicians suggest no decontamination to be necessary for ingestions less than 5 mg levothyroxine.
2) CHARCOAL ADMINISTRATION

a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.

3) CHARCOAL DOSE

a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).

1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).

b) ADVERSE EFFECTS/CONTRAINDICATIONS

1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).

6.5.3)

A) MONITORING OF PATIENT

1) Monitor vital signs and mental status.
2) Free T4 (fT4) and total T3 blood concentrations help to ascertain diagnosis, but are not strongly correlated to clinical findings or prognosis, and are not beneficial in guiding therapy. Therefore, serial measurements of thyroid hormone concentrations are generally unnecessary.
3) Obtain an ECG and institute continuous cardiac monitoring in patients with symptoms and signs of cardiac toxicity.

B) BETA-ADRENERGIC BLOCKER

1) PROPRANOLOL

a) Propranolol may be administered to treat the adrenergic findings associated with hyperthyroidism. Alternatives to propranolol include labetalol or sotalol.
b) PROPRANOLOL/ADULT DOSE

1) INTRAVENOUS: 0.5 mg to 1 mg per dose IV over 1 minute. May repeat dose up to a total of 0.1 mg/kg, if needed (Neumar et al, 2010). A second dose may be repeated in 2 minutes, if necessary; however, any additional drug administration should be given at least 4 hours later (Prod Info propranolol HCl IV injection, 2008).
2) The maximum dose is 3 mg; the rate should not exceed 1 mg/min (Prod Info propranolol HCl IV injection, 2008).

c) PROPRANOLOL/PEDIATRIC DOSE

1) INTRAVENOUS: 0.01 to 0.15 mg/kg IV every 6 to 8 hours (Luedtke et al, 1997).

d) MONITORING

1) The drug should be administered with cardiac monitoring or central venous pressure monitoring. Monitor for bradycardia, hypotension and congestive heart failure (Prod Info propranolol HCl IV injection, 2008).

2) BISOPROLOL

a) Eleven patients with cardiac symptoms of adrenergic overactivity from therapeutic levothyroxine were treated with bisoprolol, 2.5 to 5 mg daily, in conjunction with levothyroxine. Left ventricular mass index normalized and indices of left ventricular systolic function were reduced after 6 months of therapy (Biondi et al, 1994).

C) IPODATE

1) SODIUM IPODATE

a) Additional clinical studies are needed to determine the safety and efficacy of sodium ipodate or iopanoic acid for the treatment of symptoms associated with L-thyroxine overdose.
b) CAUTIONS: Sodium ipodate (Oragrafin(R)) or iopanoic acid (Telepaque(R)) should not be given to patients who are hypersensitive to iodine compounds.
c) Massive ingestion of L-thyroxine is associated with minimal morbidity in reported cases (Litovitz & White, 1985; Gorman et al, 1988; Golightly et al, 1987; Lewander et al, 1989).
d) EFFICACY: Sodium ipodate is advocated as an effective and safe alternative for the treatment of hyperthyroidism (Robuschi et al, 1986) (Wu et al, 1982) (Wu et al, 1978a; Roti et al, 1985; Wu et al, 1978; Sharp et al, 1981; Shen et al, 1985; Karpman et al, 1987).
e) MECHANISM: Sodium ipodate or iopanoic acid inhibits peripheral conversion of T4 to T3. T4 is shunted to reverse triiodothyroxine. Onset of action of sodium ipodate is 6 hours with a duration of action of 36 to 48 hours (Berkner et al, 1991).
f) CASE REPORT: Sodium ipodate 3 g/1.7 m(2) was administered to a 2.5-year-old and a 3-year-old in response to tachycardia, hypertension, and fever 10 hours following an acute ingestion of 14 mg of L-thyroxine. A second dose of sodium ipodate was given 82 hours postingestion for recurrence of tachycardia, hypertension, and fever (Berkner et al, 1991).
g) CASE REPORT: Lopanoic acid (Telepaque(R)) 125 mg daily was added to a therapy regimen of propylthiouracil (PTU) 25 mg 3 times daily and propranolol 15 mg every 6 hours in a 2.5 year-old boy following a symptomatic overdose of levothyroxine. Within 24 hours of iopanoic acid dosing, his heart rate and agitation decreased. Iopanoic acid was discontinued on the sixth day after the ingestion. PTU was stopped on the third day, and the propranolol dosage was tapered downwards and stopped on the seventh day (Brown et al, 1998).

D) SEIZURE

1) SUMMARY

a) Attempt initial control with a benzodiazepine (eg, diazepam, lorazepam). If seizures persist or recur, administer phenobarbital or propofol.
b) Monitor for respiratory depression, hypotension, and dysrhythmias. Endotracheal intubation should be performed in patients with persistent seizures.
c) Evaluate for hypoxia, electrolyte disturbances, and hypoglycemia (or, if immediate bedside glucose testing is not available, treat with intravenous dextrose).

2) DIAZEPAM

a) ADULT DOSE: Initially 5 to 10 mg IV, OR 0.15 mg/kg IV up to 10 mg per dose up to a rate of 5 mg/minute; may be repeated every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
b) PEDIATRIC DOSE: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
c) Monitor for hypotension, respiratory depression, and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after repeated doses of diazepam .

3) NO INTRAVENOUS ACCESS

a) DIAZEPAM may be given rectally or intramuscularly (Manno, 2003). RECTAL DOSE: CHILD: Greater than 12 years: 0.2 mg/kg; 6 to 11 years: 0.3 mg/kg; 2 to 5 years: 0.5 mg/kg (Brophy et al, 2012).
b) MIDAZOLAM has been used intramuscularly and intranasally, particularly in children when intravenous access has not been established. ADULT DOSE: 0.2 mg/kg IM, up to a maximum dose of 10 mg (Brophy et al, 2012). PEDIATRIC DOSE: INTRAMUSCULAR: 0.2 mg/kg IM, up to a maximum dose of 7 mg (Chamberlain et al, 1997) OR 10 mg IM (weight greater than 40 kg); 5 mg IM (weight 13 to 40 kg); INTRANASAL: 0.2 to 0.5 mg/kg up to a maximum of 10 mg/dose (Loddenkemper & Goodkin, 2011; Brophy et al, 2012). BUCCAL midazolam, 10 mg, has been used in adolescents and older children (5-years-old or more) to control seizures when intravenous access was not established (Scott et al, 1999).

4) LORAZEPAM

a) MAXIMUM RATE: The rate of intravenous administration of lorazepam should not exceed 2 mg/min (Brophy et al, 2012; Prod Info lorazepam IM, IV injection, 2008).
b) ADULT DOSE: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist (Manno, 2003; Brophy et al, 2012).
c) PEDIATRIC DOSE: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008; Sreenath et al, 2009; Chin et al, 2008).

5) PHENOBARBITAL

a) ADULT LOADING DOSE: 20 mg/kg IV at an infusion rate of 50 to 100 mg/minute IV. An additional 5 to 10 mg/kg dose may be given 10 minutes after loading infusion if seizures persist or recur (Brophy et al, 2012).
b) Patients receiving high doses will require endotracheal intubation and may require vasopressor support (Brophy et al, 2012).
c) PEDIATRIC LOADING DOSE: 20 mg/kg may be given as single or divided application (2 mg/kg/minute in children weighing less than 40 kg up to 100 mg/min in children weighing greater than 40 kg). A plasma concentration of about 20 mg/L will be achieved by this dose (Loddenkemper & Goodkin, 2011).
d) REPEAT PEDIATRIC DOSE: Repeat doses of 5 to 20 mg/kg may be given every 15 to 20 minutes if seizures persist, with cardiorespiratory monitoring (Loddenkemper & Goodkin, 2011).
e) MONITOR: For hypotension, respiratory depression, and the need for endotracheal intubation (Loddenkemper & Goodkin, 2011; Manno, 2003).
f) SERUM CONCENTRATION MONITORING: Monitor serum concentrations over the next 12 to 24 hours. Therapeutic serum concentrations of phenobarbital range from 10 to 40 mcg/mL, although the optimal plasma concentration for some individuals may vary outside this range (Hvidberg & Dam, 1976; Choonara & Rane, 1990; AMA Department of Drugs, 1992).

6) OTHER AGENTS

a) If seizures persist after phenobarbital, propofol or pentobarbital infusion, or neuromuscular paralysis with general anesthesia (isoflurane) and continuous EEG monitoring should be considered (Manno, 2003). Other anticonvulsants can be considered (eg, valproate sodium, levetiracetam, lacosamide, topiramate) if seizures persist or recur; however, there is very little data regarding their use in toxin induced seizures, controlled trials are not available to define the optimal dosage ranges for these agents in status epilepticus (Brophy et al, 2012):

1) VALPROATE SODIUM: ADULT DOSE: An initial dose of 20 to 40 mg/kg IV, at a rate of 3 to 6 mg/kg/minute; may give an additional dose of 20 mg/kg 10 minutes after loading infusion. PEDIATRIC DOSE: 1.5 to 3 mg/kg/minute (Brophy et al, 2012).
2) LEVETIRACETAM: ADULT DOSE: 1000 to 3000 mg IV, at a rate of 2 to 5 mg/kg/min IV. PEDIATRIC DOSE: 20 to 60 mg/kg IV (Brophy et al, 2012; Loddenkemper & Goodkin, 2011).
3) LACOSAMIDE: ADULT DOSE: 200 to 400 mg IV; 200 mg IV over 15 minutes (Brophy et al, 2012). PEDIATRIC DOSE: In one study, median starting doses of 1.3 mg/kg/day and maintenance doses of 4.7 mg/kg/day were used in children 8 years and older (Loddenkemper & Goodkin, 2011).
4) TOPIRAMATE: ADULT DOSE: 200 to 400 mg nasogastric/orally OR 300 to 1600 mg/day orally divided in 2 to 4 times daily (Brophy et al, 2012).

Enhanced Elimination

A)

1) Enhanced elimination is generally not necessary after acute exposure, even if massive. Symptomatic treatment is suggested to alleviate symptoms. It is common that several days after the exposure, T3 and T4 levels are still elevated, even though the patient is asymptomatic (Jonare et al, 2001).

B)

1) Diuresis and hemodialysis are ineffective due to high protein binding.

C)

1) Exchange transfusion may be effective, but only limited data are available.

a) This was tried in one case by Gerard et al (1972). One of two sisters was treated with exchange transfusion, the other was not. The untreated sibling maintained a T-4 of 11 to 12 mcg/100 mL for 34 hours.
b) The treated child had levels of T-4 reduced from 20 mcg/100 mL to 11.6 mcg/100 mL and a T-3RU from 41% to 33% (12 hours and 348 mL of blood were used).

D)

1) Both plasmapheresis charcoal plasma perfusion and charcoal hemoperfusion appeared to be effective in removing levothyroxine (Candrina et al, 1989).
2) CASE REPORT: A 3-year-old child was treated with 3 courses of hemoperfusion after ingesting a maximum of 80 tablets of 0.15 mg levothyroxine. Hemoperfusion did not decrease serum levels of T3 or T4 (Lehrner & Weir, 1984).
3) In a case of massive triiodothyronine (T3) overdose (400 mg), hemoperfusion failed to significantly accelerate the decay of blood levels of free T3. A total of 16 hemoperfusions were performed over 2 weeks. The amount of T3 extracted in the cartridges was not measured. Serum concentrations of free T3 appeared to decrease, because of elapsed time as opposed to the repeated hemoperfusions (Sola et al, 2002).

E)

1) Binimelis et al (1987) reported a series of 6 massive overdoses of 70 to 1200 mg over an interval of 2 to 12 days. Plasmapheresis increased elimination of T4 by 30 fold, while hemoperfusion increased the elimination 5-fold.
2) Plasmapheresis was not effective in a case of acute thyroxine (T4) overdose (6 mg) in a 16-year-old female. Two liters of 5% human serum albumin were used as the replacement fluid in the plasmapheresis procedure. Total and free T4 concentrations were reduced during the procedure, but quickly rose to pre-plasmapheresis values after discontinuation of the procedure. An estimated 0.32 mg of T4 was eliminated, which was only 5% of the total dose ingested. A second plasmapheresis was performed, with removal of only 0.2 mg of T4. No significant pharmacokinetic or clinical benefit was seen in this case (Henderson et al, 1994).

F)

1) Thyroid hormone elimination appears to be enhanced by the serial administration of cholestyramine, 4 g orally every 6 to 8 hours. In thyrotoxic states, the enterohepatic circulation of thyroid hormones is increased. In one case, the thyroid hormone level declined to normal values following 6 days of cholestyramine therapy (de Luis et al, 2002).

Abstracts

Case Reports

A)

1) LIOTHYRONINE (T3)

a) A 30-year-old woman took 80 liothyronine 20 mcg tablets together with brompheniramine 480 mg and clomipramine 200 mg. The patient developed tachycardia (110 bpm) and diaphoresis which disappeared over the next 12 hours. Over the next week this patient experienced profound metabolic changes in T3, T4 and TSH because of the initial imbalance in the T3 levels. The short transitory clinical effects were explained by a rapid elimination of T3 from the serum. The patient recovered fully. In general, because of the rapid clearance of T3, ingestion of doses of liothyronine 50 times normal present little or no danger (Dahlberg, 1979).

2) LEVOTHYROXINE (T4)

a) PEDIATRIC ACUTE INGESTIONS: Acute ingestions of levothyroxine have resulted in only mild symptoms (ie, tachycardia, hyperactivity, fever, vomiting, diarrhea, diaphoresis, or flushing), and seizures usually days after ingestion (Gorman et al, 1988).

1) Symptoms were only seen in 3 children with T4 levels of 75 mcg/dL or greater in a small series (Lewander et al, 1989). Significant elevations resulted in only minor symptoms.
2) Symptoms, even after large ingestions and an elevated T4, are often delayed for days.
3) Fever is usually an early effect (within 12 to 24 hours) while tachycardia, and hyperactivity may be delayed for 2 to 11 days.

b) TODDLER: A 30-month-old boy developed seizures 7 days after ingestion of up to 180 tablets of 0.1 mg levothyroxine. During hospitalization, the child developed tachycardia but no other symptoms, and was discharged 6 days after exposure. The day after discharge, the child developed grand mal seizure activity lasting 2 minutes associated with postictal lethargy. He was readmitted to the hospital where a second grand mal seizure occurred. The child was treated with 60 mg phenobarbital IM followed by 30 mg orally, twice daily, in addition to propranolol 10 mg orally, twice daily. This resulted in improvement in symptoms of hyperthyroidism observed in admission (ie, tremors, irritability, tachycardia, diaphoresis, diarrhea). No further seizure activity was observed. In this patient, serum T4 levels were 117 mcg/dL, which decreased to 45 mcg/dL upon discharge. At the time of readmission, the T4 level was 38 mcg/dL (Kulig et al, 1985).
c) TODDLER: Ingestion of 12 mg of levothyroxine by a child weighing 8.6 kg resulted in tachycardia (160 bpm) and irritability 4 days postingestion. Diaphoresis, several loose stools, and mild fever were also present. Propranolol therapy of up to 10 mg/kg/day was administered without apparent effect (Gorman et al, 1988).
d) TODDLER: A 29-month-old girl ingested 18 mg of levothyroxine by history. An admission T4 level, obtained 27 hours postingestion, was 282 mcg/dL. A single dose of activated charcoal was given. Irritability and mild tachycardia (pulse 120 to 160 bpm) were the only signs present over the next 3 days. On the fourth day she developed increasing tachycardia (pulse 165 bpm), vomiting, and mild tremor. Propranolol was given (5 mg every 6 hours) for 12 days postingestion, resulting in improvement in tremor and tachycardia. No additional therapy was required (Mandel et al, 1989).

Range Of Toxicity

Summary

A)

B)

C)

D)

Therapeutic Dose

7.2.1)

A) THYROID (ARMOUR(R))

1) HYPOTHYROIDISM: INITIAL DOSE: 30 mg/day orally, with increases of 15 mg every 2 to 3 weeks as indicated. In patients with longstanding myxedema a starting dose of 15 mg/day is recommended. Most patients require 60 to 120 mg/day (Prod Info Armour(R) Thyroid oral tablets, 2012).

B) LEVOTHYROXINE

1) AVERAGE FULL REPLACEMENT DOSE: 1.7 mcg/kg/day (eg, 100 to 125 mcg/day for a 70 kg adult) orally in a single daily dose for hypothyroidism (Prod Info TIROSINT oral capsules, 2012; Prod Info SYNTHROID(R) oral tablets, 2008).
2) MAINTENANCE: Individualized based on clinical response and serum TSH levels; doses greater than 200 mcg/day are seldom required; 300 mcg/day or greater may indicate inadequate response (Prod Info TIROSINT oral capsules, 2012; Prod Info SYNTHROID(R) oral tablets, 2008).
3) SEVERE: Severe hypothyroidism, initial 12.5 to 25 mcg/day orally with increases of 25 mcg/day every 2 to 4 weeks based on serum TSH levels (Prod Info SYNTHROID(R) oral tablets, 2008)
4) AGE GREATER THAN 50 YEARS: INITIAL DOSE: 12.5 to 50 mcg/day orally with tapered increments at 6 to 8 week intervals (Prod Info TIROSINT oral capsules, 2012; Prod Info SYNTHROID(R) oral tablets, 2008).
5) AGE LESS THAN 50 YEARS WITH UNDERLYING CARDIAC DISEASE: INITIAL DOSE: 12.5 to 50 mcg/day orally with tapered increments at 6 to 8 week intervals (Prod Info TIROSINT oral capsules, 2012; Prod Info SYNTHROID(R) oral tablets, 2008).
6) PARENTERAL: (IM, IV): INITIAL DOSE: One-half the previously established oral dose (Prod Info levothyroxine sodium for injection, 2003).
7) PARENTERAL: (IM, IV): MAINTENANCE DOSE: Individualized based on clinical response and serum thyroid and TSH levels; 50 to 100 mcg IV or IM (Prod Info levothyroxine sodium for injection, 2003).

C) LIOTHYRONINE

1) MILD HYPOTHYROIDISM: INITIAL DOSE: 25 mcg orally once daily; increase by 12.5 to 25 mcg/day every 1 to 2 weeks; usual maintenance, 25 to 75 mcg/day (Prod Info CYTOMEL(R) oral tablets, 2004).
2) MYXEDEMA: INITIAL DOSE: 5 mcg orally once daily; increase by 5 to 10 mcg daily every 1 to 2 weeks; when 25 mcg is reached, may increase by 5 to 25 mcg every 1 to 2 weeks; usual maintenance 50 to 100 mcg/day (Prod Info CYTOMEL(R) oral tablets, 2004).
3) SIMPLE (NON-TOXIC) GOITER: INITIAL DOSE: 5 mcg orally once daily; increase by 5 to 10 mcg/day every 1 to 2 weeks; when 25 mcg/day is reached, may increase by 12.5 to 25 mcg every 1 to 2 weeks; usual maintenance, 75 mcg/day (Prod Info CYTOMEL(R) oral tablets, 2004).
4) CONGENITAL HYPOTHYROIDISM: INITIAL DOSE: 5 mcg orally once daily; increase by 5 mcg every 3 to 4 days (Prod Info CYTOMEL(R) oral tablets, 2004).

D) THYROTROPIN

1) MALIGNANT TUMOR OF THYROID GLAND: The recommended dose is 0.9 mg IM followed by a second dose 24 hours later for a total of 2 doses (Prod Info THYROGEN(R) intramuscular injection, 2014).

7.2.2)

A) SPECIFIC SUBSTANCE

1) LEVOTHYROXINE

a) The following guidelines are for pediatric hypothyroidism. The dose should be adjusted based on clinical response and laboratory parameters(Prod Info TIROSINT oral capsules, 2012; Prod Info SYNTHROID(R) oral tablets, 2008):

1) 0 to 3 months: 10 to 15 mcg/kg/day orally*
2) 3 to 6 months: 8 to 10 mcg/kg/day orally*
3) 6 to 12 months: 6 to 8 mcg/kg/day orally*
4) 1 to 5 years: 5 to 6 mcg/kg/day orally*
5) 6 to 12 years: 4 to 5 mcg/kg/day orally
6) Over 12 years, growth and puberty incomplete: 2 to 3 mcg/kg/day orally
7) Growth and puberty complete: 1.7 mcg/kg/day orally

1) *Note: Dosing specific for Sythroid(R) oral tablets only (Prod Info SYNTHROID(R) oral tablets, 2008).

b) CHRONIC or SEVERE: In children with chronic or severe hypothyroidism, a lower initial dose of 25 mcg/day orally with increases of 25 mcg every 2 to 4 weeks until the desired effect is achieved (Prod Info TIROSINT oral capsules, 2012).

2) LIVOTHYRONINE

a) MILD HYPOTHYROIDISM: INITIAL DOSE: 5 mcg orally once daily; increase by 5 mcg/day every 1 to 2 weeks until satisfactory response (Prod Info CYTOMEL(R) oral tablets, 2004); usual maintenance, 15 to 20 mcg/day (Shirkey, 1980).
b) MYXEDEMA: INITIAL DOSE: 5 mcg orally once daily and increased by 5 mcg increments every 1 to 2 weeks (Prod Info CYTOMEL(R) oral tablets, 2004).
c) SIMPLE (NON-TOXIC) GOITER: INITIAL DOSE: 5 mcg orally once daily; increase by 5 mcg/day every 1 to 2 weeks according to patient response (Prod Info CYTOMEL(R) oral tablets, 2004).
d) CONGENITAL HYPOTHYROIDISM: Treatment should be started immediately upon diagnosis and maintained for life, unless there is evidence of transient hypothyroidism. Therapy may be interrupted for 2 to 8 weeks after the age of 3 years to evaluate and reassess the condition. Cessation of therapy would be indicated in patients who have maintained a normal TSH for 2 to 8 weeks (Prod Info CYTOMEL(R) oral tablets, 2004).

1) INITIAL DOSE: 5 mcg orally once daily; increase by 5 mcg every 3 to 4 days as needed; typical maintenance dose at a few months of age, 20 mcg/day; at 1 year, 50 mcg/day; above 3 years, full adult dosage may be necessary (Prod Info CYTOMEL(R) oral tablets, 2004).

3) THYROID (ARMOUR(R))

a) CONGENITAL HYPOTHYROIDISM

1) The following is the recommended dosage for congenital hypothyroidism for pediatric patients (Prod Info Armour(R) Thyroid oral tablets, 2012):

1) 0 to 6 months: 15 to 30 mg/day (4.8 to 6 mg/kg/day) orally
2) 6 to 12 months: 30 to 45 mg/day (3.6 to 4.8 mg/kg/day) orally
3) 1 to 5 years: 45 to 60 mg/day (3 to 3.6 mg/kg/day) orally
4) 6 to 12 years: 60 to 90 mg/day (2.4 to 3 mg/kg/day) orally
5) Over 12 years: Over 90 mg/day (1.2 to 1.8 mg/kg/day) orally

4) THYROTROPIN

a) MALIGNANT TUMOR OF THYROID GLAND

1) The safety and efficacy of thyrotropin alfa has not been established in pediatric patients (Prod Info THYROGEN(R) intramuscular injection, 2014).

Minimum Lethal Exposure

A)

1) Fatalities are extremely unlikely with acute thyroid hormone overdose. In 616 cases reported to the AAPCC in 1984, no deaths were noted.
2) Clinical thyrotoxicosis and death have occurred following repeated ingestions of large amounts over several days to years (Bhasin et al, 1981; Schottstaedt & Smoller, 1966).

Maximum Tolerated Exposure

A)

1) DESICCATED THYROID

a) ADULT

1) Adults rarely experience symptoms with one-time ingestions of at least 6 grains desiccated thyroid (Wenzel & Meinhold, 1974; LeBoff et al, 1982; Jacobziner & Raybin, 1958).

b) PEDIATRIC

1) In 3 children ingesting 30 to 50 grains of desiccated thyroid, similar mild symptoms were seen (Golightly et al, 1987).
2) In preschool children, 10 to 40 grains of desiccated thyroid have resulted in tachycardia, fever and diarrhea (Jahr, 1936) (Gerard et al, 1972; Jacobziner & Raybin, 1958).
3) A 3-year-old boy developed tachycardia after ingesting 10 grains of desiccated thyroid.
4) Two children together ingested 29 grains of desiccated thyroid and both developed tachycardia and fever (Gerard et al, 1972).
5) 50 grains of desiccated thyroid produced symptoms of hyperactivity, irritability, tachycardia and fever in a 15-month-old (Levy & Gilger, 1957).

2) LEVOTHYROXINE

a) ADULT

1) Massive accidental ingestion of 70 to 1200 mg over 2 to 12 days resulted in coma in 5 patients and stupor in one (Binimelis et al, 1987).
2) A massive ingestion of 720 mg levothyroxine resulted in profound thyrotoxicosis over 12 days, with symptoms of tachycardia, vomiting, fever, agitation, insomnia, hyperreflexia, and tremulousness (Hack et al, 1999).
3) Following a suicidal ingestion of 5 mg levothyroxine, a 26-year-old female developed only distal tremor and sweating, which appeared one day postingestion (de Luis et al, 2002).
4) CASE REPORT - A 44-year-old woman developed palpitations with a heart rate of 100 bpm and anxiety after ingesting 84 thyroxine tablets (100 mcg each; total dose 8.4 mg) and 20 alprazolam tablets (125 mcg each; total dose 2.5 mg). Plasma T4 and free T3 levels, obtained 3 days postingestion, were greater than 100 pmol/L (normal range 12 to 22 pmol/L) and 48.4 pmol/L (normal range 2.8 to 7.1 pmol/L), respectively. On day 5, she was stable and discharged to home; she was lost to follow-up (Lo et al, 2004).

b) PEDIATRIC

1) CASE SERIES

a) In a case series of 78 accidental ingestions in children, symptoms developed in 4 (5%) cases and consisted of fever, tachycardia, lethargy, vomiting and diarrhea. Treatment was not required. No child ingesting less than 1.5 mg developed symptoms (Litovitz & White, 1985).
b) In 41 children aged 1 to 5 years, ingestion of up to 4.5 mg of levothyroxine produced only mild symptoms and did not require treatment (Golightly et al, 1987).
c) In 9 children aged 2 to 15 years, ingestion of 1.8 to 30 mg of levothyroxine resulted only in mild symptoms that did not require treatment (Tenenbein & Dean, 1986).
d) In a case series of 114 pediatric patients, doses up to 4.33 mg were well tolerated with no decontamination. Ten of the 114 patients developed only minor symptoms (Tunget et al, 1993).
e) Tachycardia, fever, and diarrhea have occurred following ingestion of 4 to 12 mg of levothyroxine in children (Lehrner & Weir, 1984) (Funderbunk & Spaulding, 1970) (Nystrom et al, 1980; Gorman et al, 1988).
f) In a series of 15 pediatric ingestions, symptoms developed in 3 children who ingested 4 mg, 8.8 mg, and an unknown amount. No symptoms were seen in 12 children who ingested 1.5 to 7.5 mg (Lewander et al, 1989).

2) CASE REPORTS

a) A presumed ingestion of up to 41 88-mcg levothyroxine tablets resulted in a tonic-clonic seizure of 5 to 10 minutes duration 3 days after exposure in a 3.5 year-old boy. No other symptoms occurred; development was normal 10 months after exposure (Tsutaoka et al, 2005).
b) Ingestion of as much as 18 mg of levothyroxine produced clinical hyperthyroidism and seizures 8 days after the overdose in a 30-month-old boy (Kulig et al, 1985).
c) Ingestion of as much as 18 mg by a 29-month-old girl resulted in mild tachycardia, vomiting, and mild tremor, which were controlled with propranolol (Mandel et al, 1989).
d) Tachycardia (118 beats/minute) was the only sign of hyperthyroidism observed in a 3-year-old girl following an ingestion of 9.7 mg of thyroxine (Singh & Winterborn, 1991).

3) TRIIODOTHYRONINE

a) ADULT

1) Following an accidental massive ingestion of triiodothyronine (400 mg over an 8-day period), a 44-year-old woman presented to the ED with psychotic symptoms, vomiting and seizure. Her heart rate was 170 beats per minute with a temperature of 41 degrees C. Laboratory findings included a CPK of 965 International Units/L. The patient was started on a beta-blocker along with hemoperfusion. The patient improved over a 2-week course (Sola et al, 2002).

Serum Plasma Blood Concentrations

7.5.2)

A) TOXIC CONCENTRATION LEVELS

1) GENERAL

a) Correlation of Laboratory Values and Clinical Symptoms:

1) Correlation is poor
2) High levels of T3 or T4 do NOT necessarily correlate to toxicity (Nystrom et al, 1980; Golightly et al, 1987)

b) T4: Peak T4 levels were achieved in less than 12 hours in 71% of children with levothyroxine overdose (Lewander et al, 1989).
c) CASE REPORTS

1) PEDIATRIC

a) A child who ingested 12 mg of levothyroxine had a peak T4 level of 180 mcg/dL (normal 4 to 11) on admission, and a peak T3 of 1031 mcg/dL (normal 92 to 270) on the second day (Gorman et al, 1988).
b) Nine children, aged 2 to 15 years, ingested 1.8 to 30 mg of levothyroxine producing T4 levels to 19.9 to 84.7 mcg/dL and T3 levels of 113 to 742 ng/dL (Tenenbein & Dean, 1986).
c) MILD TOXICITY: Initial T4 levels of 74, 115, and 118 mcg/dL were associated with mild toxicity (ie, fever, tachycardia, agitation) in 3 children. In 12 children with levels of 16 to 57.5 mcg/dL, no symptoms developed (Lewander et al, 1989).
d) TODDLER: Ingestion of 18 mg by a 29-month-old child produced a T4 level, at 27 hours postingestion, of 282 mcg/dL. The T3 level peaked at 1837 ng/dL. Neither T3 nor T4 levels correlated with severity of symptoms (Mandel et al, 1989).
e) TODDLER: Four hours after ingesting a total levothyroxine dose of 4 mg, a 2-year-old child had a peak T3 level of 550 ng/dL and a peak T4 level of 38 mcg/dL (Lehrner & Weir, 1984).
f) Following ingestion of an unknown quantity of levothyroxine, serum T4 concentration was reported to be 1525 nmol/L (118.5 mcg/dL) in a 2-year-old boy several hours after the ingestion. The child was symptomatic with increasing pulse, blood pressure and agitation (Brown et al, 1998).
g) A 3-year-old child who ingested 80 tablets of 0.15 mg levothyroxine (a total dose of 12 mg) had a peak T4 level of 35 mcg/dL 22 hours after ingestion and a peak T3 level of 227 ng/dL 2 hours after ingestion (Lehrner & Weir, 1984).
h) Two to 6 hours after a series of 30 children ingested T4 in amounts ranging from 80 to 9500 mcg and T3 in amounts ranging from 20 to 630 mcg, T4 serum levels and T3 serum levels were from 91.3 to 1219 nmol/L and 2.6 to 49.2 nmol/L, respectively (Willgerodt et al, 2003).

2) ADULT

a) Free levothyroxine (T4) serum levels ranged from greater than 13 mcg/dL on day 6 to 1.3 mcg/dL on day 21 following an ingestion of 720 mg of veterinary levothyroxine in a 34-year-old male (Hack et al, 1999).
b) Serum free triiodothyronine (T3) levels of 4789 picomoles/liter (normal, 3.5 to 6.5 picomoles/liter) were reported following an accidental overdose of 400 mg triiodothyronine over an 8-day period in a 44-year-old woman (Sola et al, 2002).
c) A patient, prescribed 25 mcg of triiodothyronine (T3) every 8 hours, had a serum triiodothyronine level of 575.2 nmol/L that was measured 11 hours after the last capsule was taken. It is believed that the patient may have actually received capsules containing 5 mg of triiodothyronine, a dose 200 times higher than was prescribed by the physician (Botella de Maglia et al, 2003).

Pharmacology Toxicology

Pharmacologic Mechanism

A)

B)

C)

Toxicologic Mechanism

A)

Physicochemical

Molecular Weight

A)

Animal Toxicology

Clinical Effects

11.1.3)

A) According to the National Animal Poison Control Center, the clinical signs of thyroid hormone toxicosis for dogs include vomiting, diarrhea, hyperactivity, lethargy, tachycardia, tachypnea, dyspnea, and abnormal pupillary light reflexes. Elderly dogs or those with cardiac disease may be at higher risk following levothyroxine overdose and extended monitoring for several weeks may be required (Hansen et al, 1992).
B) Three episodes of vomiting (1 spontaneous, 2 induced), bilateral hippus, and slight bradycardia (92 beats/minute) developed following the ingestion of up to 170 mg of levothyroxine in a 6-year-old, 16.8-kg, male, Keeshond over the preceding 3 to 9 hours. Treatment was initiated following admission and an uneventful recovery occurred (Hansen et al, 1992).

1) Significant elevations in serum T4 levels (4901 nmol/L) peaked on day 1 and alanine transaminase (345 Unit/L) peaked on day 6. Serum T4 levels returned to normal by day 36.

11.1.6)

A) According to the National Animal Poison Control Center, the clinical signs of thyroid hormone toxicosis for cats include vomiting, diarrhea, hyperactivity, lethargy, tachycardia, tachypnea, dyspnea, and abnormal pupillary light reflexes (Hansen et al, 1992).

Treatment

11.2.1)

A) GENERAL TREATMENT

1) Begin treatment immediately.
2) Keep animal warm and do not handle unnecessarily.
3) Sample vomitus, blood, urine, and feces for analysis.
4) Remove the patient and other animals from the source of contamination.
5) Treatment should always be done on the advice and with the consultation of a veterinarian. Additional information regarding treatment of poisoned animals may be obtained from a Board Certified (ABVT) Veterinary Toxicologist (check with nearest veterinary school or veterinary diagnostic laboratory) or the National Animal Poison Control Center.
6) ANIMAL POISON CONTROL CENTERS

a) ASPCA Animal Poison Control Center, An Allied Agency of the University of Illinois, 1717 S. Philo Rd, Suite 36, Urbana, IL 61802, website www.aspca.org/apcc
b) It is an emergency telephone service which provides toxicology information to veterinarians, animal owners, universities, extension personnel and poison center staff for a fee. A veterinary toxicologist is available for consultation.
c) The following 24-hour phone number is available: (888) 426-4435. A fee may apply. Please inquire with the poison center. The agency will make follow-up calls as needed in critical cases at no extra charge.

7) Due to lack of reports of large animal intoxication with this substance, the following sections address small animals (dogs and cats) only. In the case of a poisoning involving large animals, consult a veterinary poison control center.

11.2.2)

A) GENERAL

1) MAINTAIN VITAL FUNCTIONS: Secure airway, supply oxygen, and begin supportive fluid therapy if necessary.

11.2.4)

A) GASTRIC DECONTAMINATION

1) DOG

a) SUMMARY

1) According to the National Animal Poison Control Center, overdoses of levothyroxine in asymptomatic dogs should be managed by the induction of emesis, followed by activated charcoal 1 to 2 g/kg orally and a saline cathartic (magnesium sulfate or sodium sulfate 250 mg/kg orally). Repeated administration of activated charcoal (0.5 to 1 g/kg every 4 to 8 hours) may be useful. A one-time, additional dose of a saline cathartic to be administered at one-half the original dose can be administered with the second dose of activated charcoal (Hansen et al, 1992).

b) EMESIS AND LAVAGE

1) If within 2 hours of exposure, induce emesis with 1 to 2 milliliters/kilogram syrup of ipecac per os. Dogs may vomit more readily with 1 tablet (6 milligrams) apomorphine diluted in 3 to 5 milliliters water and instilled into the conjunctival sac or per os.
2) Dogs may also be given apomorphine intravenously at 40 micrograms/kilogram, although this route may not be as effective. Do not use an emetic if the animal is hypoxic.
3) In the absence of a gag reflex or if vomiting cannot be induced, place a cuffed endotracheal tube and begin gastric lavage. Pass large bore stomach tube and instill 5 to 10 milliliters/kilogram water or lavage solution, then aspirate. Repeat 10 times (Kirk, 1986).

c) ACTIVATED CHARCOAL

1) Administer activated charcoal. Dose: 2 grams/kilogram per os or via stomach tube. Avoid aspiration by proper restraint, careful technique, and if necessary tracheal intubation.
2) Constipation, which should be avoided, may result from repeated administration of activated charcoal. The significance of following T3 and T4 levels is unknown. Elderly dogs or those with cardiac disease may be at higher risk following levothyroxine overdose and may require monitoring for several weeks (Hansen et al, 1992).

d) CATHARTIC

1) Administer a dose of a saline cathartic such as magnesium or sodium sulfate (sodium sulfate dose is 1 gram/kilogram). If access to these agents is limited, give 5 to 15 milliliters magnesium oxide (Milk of Magnesia) per os for dilution.

11.2.5)

A) GENERAL TREATMENT

1) MAINTAIN VITAL FUNCTIONS - as necessary.
2) PROPRANOLOL

a) Propranolol is dosed in dogs at 0.04 to 0.15 milligrams/kilogram intravenously over 1 to 2 minutes three times daily. In cats, use propranolol instead of lidocaine; dose at 0.25 milligram diluted in 1 milliliter saline and give 0.2 milliliter boluses intravenously to effect. Monitor for hypotension and decrease in cardiac output.

1) SEVERE ARRHYTHMIAS necessitate constant ECG monitoring. Administer propranolol 0.5 to 1 milligram/kilogram intravenously or intramuscularly as needed to control arrythmias.

3) OBSERVE OVERNIGHT

a) Keep animal overnight and re-evaluate the next day.

4) MONITORING

a) Monitor body temperature and correct for abnormalities.

5) FOLLOW UP

a) Instruct the owner to return for a follow up appointment at which physical examination and appropriate laboratory tests will be repeated.

Continuing Care

11.4.1)

11.4.1.2) DECONTAMINATION/TREATMENT

A) GENERAL TREATMENT

1) Begin treatment immediately.
2) Keep animal warm and do not handle unnecessarily.
3) Sample vomitus, blood, urine, and feces for analysis.
4) Remove the patient and other animals from the source of contamination.
5) Treatment should always be done on the advice and with the consultation of a veterinarian. Additional information regarding treatment of poisoned animals may be obtained from a Board Certified (ABVT) Veterinary Toxicologist (check with nearest veterinary school or veterinary diagnostic laboratory) or the National Animal Poison Control Center.
6) ANIMAL POISON CONTROL CENTERS

a) ASPCA Animal Poison Control Center, An Allied Agency of the University of Illinois, 1717 S. Philo Rd, Suite 36, Urbana, IL 61802, website www.aspca.org/apcc
b) It is an emergency telephone service which provides toxicology information to veterinarians, animal owners, universities, extension personnel and poison center staff for a fee. A veterinary toxicologist is available for consultation.
c) The following 24-hour phone number is available: (888) 426-4435. A fee may apply. Please inquire with the poison center. The agency will make follow-up calls as needed in critical cases at no extra charge.

7) Due to lack of reports of large animal intoxication with this substance, the following sections address small animals (dogs and cats) only. In the case of a poisoning involving large animals, consult a veterinary poison control center.

11.4.2)

11.4.2.2) GASTRIC DECONTAMINATION

A) GASTRIC DECONTAMINATION

1) DOG

a) SUMMARY

1) According to the National Animal Poison Control Center, overdoses of levothyroxine in asymptomatic dogs should be managed by the induction of emesis, followed by activated charcoal 1 to 2 g/kg orally and a saline cathartic (magnesium sulfate or sodium sulfate 250 mg/kg orally). Repeated administration of activated charcoal (0.5 to 1 g/kg every 4 to 8 hours) may be useful. A one-time, additional dose of a saline cathartic to be administered at one-half the original dose can be administered with the second dose of activated charcoal (Hansen et al, 1992).

b) EMESIS AND LAVAGE

1) If within 2 hours of exposure, induce emesis with 1 to 2 milliliters/kilogram syrup of ipecac per os. Dogs may vomit more readily with 1 tablet (6 milligrams) apomorphine diluted in 3 to 5 milliliters water and instilled into the conjunctival sac or per os.
2) Dogs may also be given apomorphine intravenously at 40 micrograms/kilogram, although this route may not be as effective. Do not use an emetic if the animal is hypoxic.
3) In the absence of a gag reflex or if vomiting cannot be induced, place a cuffed endotracheal tube and begin gastric lavage. Pass large bore stomach tube and instill 5 to 10 milliliters/kilogram water or lavage solution, then aspirate. Repeat 10 times (Kirk, 1986).

c) ACTIVATED CHARCOAL

1) Administer activated charcoal. Dose: 2 grams/kilogram per os or via stomach tube. Avoid aspiration by proper restraint, careful technique, and if necessary tracheal intubation.
2) Constipation, which should be avoided, may result from repeated administration of activated charcoal. The significance of following T3 and T4 levels is unknown. Elderly dogs or those with cardiac disease may be at higher risk following levothyroxine overdose and may require monitoring for several weeks (Hansen et al, 1992).

d) CATHARTIC

1) Administer a dose of a saline cathartic such as magnesium or sodium sulfate (sodium sulfate dose is 1 gram/kilogram). If access to these agents is limited, give 5 to 15 milliliters magnesium oxide (Milk of Magnesia) per os for dilution.

11.4.3)

11.4.3.5) SUPPORTIVE CARE

A) GENERAL

1) Ongoing treatment is symptomatic and supportive.

11.4.3.6) OTHER

A) OTHER

1) DOG

a) CASE REPORT - A 6-year-old, 16.8-kg, male, Keeshond ingested up to 170 mg of levothyroxine over the preceding 3 to 9 hours. Spontaneous vomiting and 2 additional episodes that were induced by hydrogen peroxide produced a pink vomitus, similar to the color of the tablets. Upon admission, the dog was alert, demonstrated bilateral hippus and slight bradycardia (92 beats/minute) (Hansen et al, 1992).

1) Management included the administration of activated charcoal 23.3 grams orally and magnesium sulfate 125 mg/kg diluted in water as a cathartic. Hospitalization for observation was recommended, but was declined.
2) On day 1, the peak serum T4 level was 4901 nmol/L and follow-up on day 3 revealed a slight elevation of serum T3 (5.3 nmol/L); both elevations declined and were normal by day 36 and day 5, respectively. Serum alanine transaminase peaked on day 6 (345 Unit/L). Heart rate was normal on subsequent visits and other serum biochemical parameters, the CBC, and pupils were normal on day 3, 6, 9, and 15. The patient made an uneventful recovery.

Kinetics

11.5.1)

A) DOG

1) In dogs, 10 to 50% of an orally administered dose of levothyroxine is absorbed (Hansen et al, 1992).

11.5.2)

A) SPECIFIC TOXIN

1) The liver and kidneys quickly equilibrate thyroid hormones with plasma and may act as buffers in metabolizing, eliminating, and concentrating these hormones (Hansen et al, 1992).

11.5.3)

A) SPECIFIC TOXIN

1) Various routes of metabolism of levothyroxine exist including deiodination of T4 to T3 and production of inactive reverse T3. Approximately 45% of T4 and 70% of T3 are metabolized by deiodination. Levothyroxine and T3 are conjugated in the liver, primarily by glucuronidation, and excreted in the bile. Less than 15% of T4 that is enterohepatically circulated is reabsorbed in dogs (Hansen et al, 1992).

11.5.4)

A) DOG

1) In healthy dogs, levothyroxine is eliminated in a triphasic fashion. The half-life of the initial phase is undetermined, but is estimated at several minutes, compared to 10.3 hours and 5.6 days for the second and the terminal phase, respectively (Hansen et al, 1992).

References

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THYROID

Classification | Detailed evidence-based information

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General Bibliography