Levothyroxine is a synthetic form of the thyroid hormone thyroxine (T4), widely prescribed to treat hypothyroidism, a condition where the thyroid gland does not produce enough hormone. The medication replaces the missing hormone, regulating metabolism, energy levels, and body temperature. Acute overdose can lead to drug-induced thyrotoxicosis, which overstresses multiple body systems and demands immediate medical intervention.
Acute Symptoms of Levothyroxine Overdose
The body’s reaction to an acute ingestion of Levothyroxine is characterized by a delayed onset of symptoms, typically taking two to five days to become clinically apparent. This delay occurs because Levothyroxine (T4) is a prohormone with a long half-life of about seven days. It must first be gradually converted into the more biologically active form, triiodothyronine (T3), before the resulting hypermetabolic state manifests symptoms affecting the cardiovascular system.
Patients commonly experience tachycardia (rapid heart rate), palpitations, hypertension, and serious cardiac arrhythmias such as atrial fibrillation. This stimulation places strain on the heart muscle. The central nervous system also becomes stimulated, leading to anxiety, agitation, insomnia, and fine tremors. Severe toxicity can progress to life-threatening complications, including acute psychosis, seizures, or thyroid storm. Other symptoms include fever, excessive sweating, and gastrointestinal distress like diarrhea and vomiting. Due to the potential for a severe, delayed reaction, close monitoring in a controlled medical setting is necessary.
Factors Determining Toxicity and Lethality
Defining a single fatal dose of Levothyroxine is not possible because the outcome of an overdose depends highly on individual patient factors and co-morbidities, not solely the quantity ingested. Many individuals, particularly euthyroid adults and children, have survived acute ingestions exceeding \(5 \text{ mg}\) of T4 with only mild symptoms. Case reports document survival following acute ingestions as high as \(15 \text{ mg}\).
The most significant factor escalating the risk of severe toxicity and death is pre-existing cardiac disease. High levels of thyroid hormone increase heart rate and myocardial contractility, stressing a compromised heart. This stress can precipitate a fatal event, such as a heart attack or severe arrhythmia.
Age also plays a role in vulnerability, with both the elderly and young children being at greater risk for severe outcomes. The elderly are particularly susceptible to cardiovascular complications due to age-related changes in heart function. Furthermore, co-ingestion of other substances, especially those affecting the heart or central nervous system, can worsen the prognosis.
The context of ingestion also influences lethality. Chronic misuse or over-medication over a long period is more likely to lead to serious cardiac remodeling and sudden death than a single, acute overdose. The body attempts to compensate by increasing binding to proteins and conversion to inactive reverse T3. For an acute ingestion, doses exceeding \(5 \text{ mg}\) in adults are considered potentially toxic and require urgent medical evaluation.
Emergency Treatment and Medical Management
Immediate action following a suspected overdose involves contacting emergency medical services or a Poison Control Center to guide initial steps and arrange for hospital transport. Due to the delayed onset of symptoms, treatment is initiated early to prevent severe thyrotoxicosis. If ingestion occurred recently (typically within the first few hours), gastric decontamination may be considered to limit further absorption of the drug.
A common intervention is activated charcoal, which binds to the drug in the stomach and gut, reducing absorption into the bloodstream. Management focuses on supportive care and controlling the hypermetabolic state, especially cardiac effects.
Beta-blockers, most notably Propranolol, are a cornerstone of treatment administered to manage severe cardiovascular symptoms like tachycardia and palpitations. Propranolol is especially useful because it controls heart rate and helps block the peripheral conversion of the less active T4 into the highly potent T3. Other medications may also be used to accelerate the elimination of the drug from the body.
Cholestyramine, a bile acid sequestrant, can be given orally to bind to the Levothyroxine in the intestine, interrupting its enterohepatic recycling and increasing its fecal excretion. In severe cases, glucocorticoids like dexamethasone may be administered to further inhibit the T4 to T3 conversion. Given the drug’s long half-life, patients require hospitalization and continuous cardiac monitoring for at least 48 to 72 hours, even if initially asymptomatic.