Levothyroxine (T4) Overdose: Signs and Why It Is Dangerous

Levothyroxine is considered an “ordinary tablet” that millions of people take for years. But an excess of thyroid hormone is thyrotoxicosis, with risks for the heart, brain and bones. The editorial team explains how to recognize an overdose and why it is dangerous.

Two types of overdose: acute and chronic

When people talk about a levothyroxine overdose, they mean two different situations. The first is acute poisoning, when a person takes a large number of tablets at once: accidentally (most often these are children who found an adult’s medicine) or deliberately. The second is chronic excess, when the hormone is taken for weeks and months at a dose exceeding the body’s need.

The chronic variant occurs much more often. It arises from too high a prescribed dose, an error in intake, an interaction with other medications, and also from self-administration of the hormone for weight loss or “speeding up the metabolism.” In the medical literature such a condition is called exogenous, or iatrogenic, thyrotoxicosis.

Both scenarios have one thing in common: the body receives more thyroid hormone than it can safely use. The consequences affect the heart, nervous system, muscles and bones.

In the US the instructions for levothyroxine contain a boxed warning: large doses, especially in combination with sympathomimetics, can cause serious or even life-threatening manifestations of toxicity. Therefore an overdose of the hormone is not a “mild side effect” but a condition that requires medical assessment.

Why symptoms may appear with a delay

Levothyroxine is a prohormone. To act, it must be converted in the tissues into the active triiodothyronine (T3) with the participation of deiodinase enzymes. In addition, T4 has a long half-life — about a week. Because of this, after acute intake of a large dose, symptoms may appear not immediately but after hours and even several days.

Toxicology manuals, in particular Goldfrank’s Toxicologic Emergencies, draw attention precisely to this feature. A person may feel normal on the first day, and this creates a false sense of safety. Therefore after a significant overdose doctors recommend observation and reassessment of the condition, even if there are no complaints at first.

In chronic excess the picture develops gradually. A person may for weeks explain palpitations by “coffee,” insomnia by “stress,” and weight loss by “dieting,” until more pronounced manifestations appear.

For liothyronine (T3) everything happens faster: the effect sets in within hours but also passes more quickly. This is one of the reasons why an overdose of T4 and T3 is assessed differently.

Signs of overdose

The symptoms of levothyroxine excess correspond to the picture of thyrotoxicosis. They can be grouped by body systems to make it easier to recognize the dangerous signals.

Older people and patients with heart disease must be especially attentive. In them an excess of the hormone may manifest not as classic “agitation” but predominantly as cardiac symptoms — atrial fibrillation or decompensation of heart failure.

In children, accidental swallowing of levothyroxine tablets in most cases proceeds relatively mildly, but this is no reason for self-treatment: only a doctor or a poison control center can assess the risk.

In the laboratory, chronic exogenous thyrotoxicosis has a recognizable picture: suppressed TSH, elevated free hormones and a low level of thyroglobulin. The latter helps doctors distinguish intake of hormones from outside from diseases of the gland itself.

Why it is dangerous

The most formidable complication of an excess of thyroid hormones is thyroid storm. This is a rare but life-threatening condition with high fever, pronounced tachycardia, impaired consciousness and multiple organ failure. According to the review by Burch and Wartofsky, mortality in thyroid storm remains significant even with intensive treatment.

The second group of risks is cardiac. Thyroid hormones increase the rate and force of heart contractions and the myocardium’s need for oxygen. In a person with hidden ischemic heart disease this can provoke angina or a heart attack, and at any age — atrial fibrillation with a risk of stroke.

The third group is the long-term consequences of chronic excess. The study by Flynn and colleagues showed that in patients on long-term therapy with suppressed TSH, cardiovascular events and fractures occurred more often. Bone mass is lost gradually and imperceptibly.

• The combination of thyroid hormones with stimulants (ephedrine, caffeine in large doses, clenbuterol) increases the load on the heart.
• Heat, dehydration and intense training worsen thermoregulation against the background of thyrotoxicosis.
• Hidden intake of the hormone complicates diagnosis: the doctor may search for a disease of the gland that does not exist.

We emphasize separately the psyche. Thyrotoxicosis can cause pronounced anxiety, panic attacks, sleep disturbances, and in severe cases — psychotic manifestations. A person in such a state is not always able to adequately assess what is happening to them, so an important role is played by loved ones who notice changes in behavior.

What to do if an overdose is suspected

With acute intake of a large number of tablets, especially by a child, it is necessary to contact the emergency service or a poison control center, even if there are no symptoms yet. It is advisable to take the medicine packaging with you, so that doctors know the dosage and the approximate number of tablets taken.

Treatment of an overdose is carried out only by medical professionals. The guidelines of the American Thyroid Association (2016) on thyrotoxicosis describe the general approaches: control of the heart rhythm, cooling, support of circulation, and in a severe condition — intensive care. Specific drugs and doses are chosen by a doctor taking the patient’s condition into account.

Immediate help is also needed if chest pain, pronounced shortness of breath, fainting, an irregular heartbeat, high fever or confusion appear in a person taking thyroid hormones.

In chronic excess, when the symptoms are moderate, the first step is a visit to an endocrinologist and tests. It is not advisable to sharply change the dose of a prescribed drug on your own: the adjustment should be determined by a doctor who sees the full picture.

Editorial conclusions

A levothyroxine overdose can be acute and chronic. Because of the slow conversion of T4 into T3, the symptoms of acute poisoning may appear with a delay, which creates a deceptive sense of safety.

The main threats are cardiac arrhythmias, ischemia, thyroid storm and long-term loss of bone mass.

The use of levothyroxine for weight loss is directly prohibited by official warnings and has no evidence-based basis.

Also read on the blog: interactions of levothyroxine with other drugs, tests during its medical use and ephedrine overdose.

References

1. U.S. Food and Drug Administration. Synthroid (levothyroxine sodium) tablets: prescribing information. Silver Spring (MD): FDA.
2. Ross DS, Burch HB, Cooper DS, et al. 2016 American Thyroid Association guidelines for diagnosis and management of hyperthyroidism and other causes of thyrotoxicosis. Thyroid. 2016;26(10):1343–1421.
3. Burch HB, Wartofsky L. Life-threatening thyrotoxicosis: thyroid storm. Endocrinol Metab Clin North Am. 1993;22(2):263–277.
4. Nelson LS, Howland MA, Lewin NA, et al. (eds). Goldfrank's Toxicologic Emergencies. 11th ed. New York: McGraw-Hill; 2019.
5. Flynn RW, Bonellie SR, Jung RT, et al. Serum thyroid-stimulating hormone concentration and morbidity from cardiovascular disease and fractures in patients on long-term thyroxine therapy. J Clin Endocrinol Metab. 2010;95(1):186–193.
6. Biondi B, Cooper DS. The clinical significance of subclinical thyroid dysfunction. Endocr Rev. 2008;29(1):76–131.
7. Jonklaas J, Bianco AC, Bauer AJ, et al. Guidelines for the treatment of hypothyroidism: prepared by the American Thyroid Association task force on thyroid hormone replacement. Thyroid. 2014;24(12):1670–1751.