What are the side effects of liothyronine (triiodothyronine, T3)?

Side Effects of Liothyronine

Liothyronine is generally safe when properly dosed, but adverse effects primarily occur from therapeutic overdosage causing iatrogenic hyperthyroidism, with rare allergic reactions reported. 1

Common Side Effects from Therapeutic Overdosage

The most frequent adverse effects of liothyronine result from excessive dosing that induces hyperthyroidism, including 1:

• Cardiovascular effects: Tachycardia, arrhythmias, angina pectoris, and potential induction or aggravation of congestive heart failure 1
• Neurological symptoms: Headache, irritability, nervousness 1
• Metabolic effects: Sweating, increased bowel motility 1
• Reproductive effects: Menstrual irregularities 1

Severe Adverse Effects from Overdosage

Massive overdosage can result in thyroid storm, a life-threatening condition that may be fatal even in previously healthy individuals. 2, 3

• A case report documented lethal thyroid storm in a 29-year-old euthyroid male (BMI 32) without cardiac disease who consumed uncontrolled liothyronine for weight loss, resulting in multiple areas of focal myocardial necrosis and acute heart failure 3
• Another case involved a 33-year-old obese man (BMI 40) who developed severe thyrotoxicosis with wide complex tachycardia and chest pain after consuming 135 µg liothyronine tablets for five days, requiring intensive care and resulting in borderline left ventricular dysfunction 2
• Shock may develop in severe cases 1

Cardiovascular Risks with Chronic Supraphysiological Dosing

When liothyronine is used at suppressive doses (slightly supraphysiological), potential cardiovascular changes include 4:

• Shortening of systolic time intervals 4
• Increased frequency of atrial premature beats 4
• Possible left ventricular hypertrophy 4

Bone-Related Adverse Effects

Chronic supraphysiological dosing may cause 4:

• Reduced bone density and bone mass 4

Rare Allergic Reactions

• In rare instances, allergic skin reactions have been reported with liothyronine 1

Long-Term Safety Data from Observational Studies

A large 17-year observational study (n=34,355) found reassuring safety data for regulated liothyronine use. 5

Compared to levothyroxine-only users, liothyronine users showed 5:

• No increased risk of cardiovascular disease (HR 1.04; 95% CI 0.70-1.54) 5
• No increased risk of atrial fibrillation (HR 0.91; 95% CI 0.47-1.75) 5
• No increased risk of fractures (HR 0.79; 95% CI 0.49-1.27) 5
• Increased risk of new antipsychotic medication prescriptions (HR 2.26; 95% CI 1.64-3.11), proportional to number of liothyronine prescriptions 5
• Non-significant trend toward increased breast cancer and antidepressant use 5

Meta-Analysis Safety Findings

A comprehensive meta-analysis of 52 studies (n=630,254) demonstrated that regulated liothyronine use is not associated with increased risk of death or serious adverse outcomes. 6

Key findings include 6:

• Similar adverse event risk for combination therapy (liothyronine + levothyroxine) versus levothyroxine monotherapy in RCTs (RR 1.22; 95% CI 0.66-2.25) 6
• No increased risk of atrial fibrillation (RR 1.10; 95% CI 0.74-1.63) 6
• No increased risk of heart failure (RR 1.54; 95% CI 0.95-2.47) 6
• No increased risk of strokes (RR 0.86; 95% CI 0.11-6.75) 6
• Reduced mortality risk observed (RR 0.70; 95% CI 0.62-0.78) 6
• Liothyronine-related adverse events were only reported with unregulated use or pharmacy compounding errors 6

Critical Pitfalls to Avoid

• Never use unregulated or over-the-counter liothyronine products, as documented cases of severe toxicity and death have occurred with uncontrolled consumption 2, 3
• Avoid supraphysiological dosing by carefully monitoring serum free T3 and TSH levels and adjusting dosage accordingly 4
• The risk of adverse effects can be minimized through proper dose titration and regular monitoring 4
• Liothyronine has a shorter half-life than levothyroxine, making it more prone to causing acute toxicity if overdosed 2, 3

Treatment of Overdosage

If signs of overdosage appear 1:

• Reduce dosage or temporarily discontinue therapy 1
• Treatment may be reinstituted at a lower dosage 1
• For acute massive overdosage, treatment is symptomatic and supportive, including oxygen administration, ventilation maintenance, and cardiac glycosides if heart failure develops 1
• Propranolol is advantageous for treating increased sympathetic activity: 1-3 mg IV over 10 minutes or 80-160 mg/day orally when no contraindications exist 1
• Cholestyramine may be used to reduce absorption 2