Thyroid Hormone Toxicity

Pharmacokinetics

Oral absorption of thyroid hormone can be erratic (T4 up to 80%; T3 up to 95%) and decreases with age. The time for peak serum levels is 2-4 hours. The onset of action for oral administration is 3-5 days; it is 6-8 hours for intravenous (IV) administration. Thyroid hormone is more than 99% protein-bound, and it is hepatically metabolized to triiodothyronine (the active form). Half-life elimination varies from 6-7 days for euthyroid, 9-10 days for hypothyroid, and 3-4 days for hyperthyroid states. It is excreted in both urine and feces at a rate that decreases with age.

Mechanism

Levothyroxine's delayed onset of toxicity is thought to be secondary to the delay in conversion of T4 to T3 and the distribution of T3 into tissues. As a result, symptoms may be delayed. If the ingested preparation contains T3, clinical symptoms may begin within 24 hours of ingestion. Mixtures of T4 and T3 can have immediate and delayed clinical effects. Thus, symptoms can occur anywhere from 6 hours to 11 days after ingestion.

The mechanism of toxicity involves stimulation of the cardiovascular, GI, and neurologic systems through presumed activation of the adrenergic system. Although the exact mechanism of action is unknown, the metabolic effects of thyroid hormone are thought to be mediated by the control of DNA transcription and protein synthesis. Thyroid hormone is integral to the regulation of normal metabolism, growth, and development. It promotes gluconeogenesis, controls the mobilization and utilization of glycogen stores, increases the basal metabolic rate, and increases protein synthesis at a cellular level.

Etiology

The abuse of thyroid hormone has been reported in patients as a method of weight reduction, with many over-the-counter thyroid supplements containing clinically relevant levels of T3 and T4, sometimes even exceeding doses of levothyroxine prescribed for hypothyroidism. It is important to recognize the potential for unintended ingestions of thyroid hormone from over-the-counter weight loss supplements with unknown ingredients in addition to intentional abuse of thyroid supplements. ^[2]

Thyroid hormone abuse commonly takes the form of factitious thyrotoxicosis; often manifests in association with a psychiatric condition, in many cases one linked to an eating disorder; and can be aimed at obtaining medical attention in the setting of factitious disorder (formerly, Munchausen syndrome). Therefore, “endocrinologists should always consider this diagnosis whenever suspicion is raised by the patient's behavior in consultation” and signs suggesting other sources of hyperthyroidism or thyrotoxicosis are absent. ^[3]

United States statistics

According to the 2023 Annual Report of the National Poison Data System (NPDS) from America’s Poison Centers: 41st Annual Report, in 2023 there were 13,690 mentions of exposures to thyroid preparations, including synthetics and extracts. Of the total listed, 9150 were single substance exposures. The breakdown by known age for single substance exposures was as follows: 3432 were associated with children aged 5 years or younger, 294 were associated with persons aged 6-12 years, 251 were associated with those aged 13-19 years, and 4509 were associated with individuals aged 20 years or older. Overall, 182 minor adverse outcomes, 47 moderate adverse outcomes, four major adverse outcomes, and no deaths were reported. ^[4]

International statistics

In a study by Ergul et al conducted in Turkey, the incidence of acute levothyroxine ingestion in children was 0.07-1.2% per year. No serious complications or deaths were reported. ^[5]

Race-, sex-, and age-related demographics

No scientific data demonstrate that outcomes following a toxic thyroid hormone ingestion are based on race.

No scientific data demonstrate that outcomes following a toxic thyroid hormone ingestion are based on sex.

Inadvertent excessive thyroid hormone ingestion occurs primarily in pediatric patients.

Significant toxicity with acute ingestions is rare. Serious toxicity is more commonly observed with chronic ingestions of large amounts of T4 than with other thyroid hormone ingestions. 

For patient education resources, see Drug Overdose, Poisoning, and Anatomy of the Endocrine System, as well as Activated Charcoal, Poison Proofing Your Home, and Thyroid Problems.