Thyroid Hormone Toxicity
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Iodine is absorbed from the GI tract and is transferred to the thyroid gland where oxidization and incorporation into tyrosyl residues of thyroglobulin occurs. Tyrosine is further oxidized to form monoiodotyrosine (MIT) and diiodotyrosine (DIT). The combination of 2 molecules of DIT forms thyroxine (T4). Triiodothyronine (T3) is made by the combination of MIT and DIT and by the monodeiodination of T4 in the periphery.
T3 is 4 times more active than the more abundant T4. The half-life of T4 is 5-7 days; the half-life of T3 is only 1 day. Approximately 99% of the circulating thyroid hormone is bound to plasma protein and is metabolized primarily by the liver.
Levels of thyroid hormones in the serum are tightly regulated by the hypothalamic-pituitary-thyroid axis. Thyroid-releasing hormone (TRH) is secreted by the hypothalamus, and stimulates the release of thyroid-stimulating hormone (TSH) from the pituitary gland. Mature TSH reaches the thyroid gland and stimulates thyroid hormone production and release. The main hormone secreted from the thyroid gland is T4, which is converted to T3 by deiodinase in the peripheral organs. Secreted thyroid hormone reaches the hypothalamus and the pituitary, where it inhibits production and secretion of TRH and TSH, thereby establishing the hypothalamic-pituitary-thyroid axis. [1]
The most common thyroid hormone used clinically is levothyroxine (LT4), which is available in intravenously and orally administered forms to treat hypothyroidism and myxedema coma. Usual dosage ranges from 25-500 mcg/d. The higher doses can be used intravenously to treat myxedema coma.
For related information, see Medscape’s Hypothyroidism Resource Center.
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 and 6-8 hours for 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, and this also decreases with age.
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, developing anyway from 6 hours to 11 days after ingestion. 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.
Mechanism of toxicity involves stimulation of the cardiovascular (CV), 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.
United States
According to the Annual Report of the American Association of Poison Control Centers’ National Poison Data System, in 2014, 13,623 exposures to thyroid hormone preparations were documented; of the total listed, 9,301 were single substance exposures. The breakdown by age for single substance exposures is as follows; 4,444 were associated with children younger than 5 years; 427 were associated with persons aged 6-12 years; 295 were associated with those aged 13-19 years; and 3,597 were associated with those greater than 20 years old. Overall, 53 moderate adverse outcomes, 3 major adverse outcomes and no deaths were reported. [2]
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.
Yamada M, Mori M. Mechanisms related to the pathophysiology and management of central hypothyroidism. Nat Clin Pract Endocrinol Metab. 2008 Dec. 4(12):683-94. [Medline]. [Full Text].
Mowry JB, Spyker DA, Brooks DE, McMillan N, Schauben JL. 2014 Annual Report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 32nd Annual Report. Clin Toxicol. 2015 Dec. 53(10):962-1146. [Medline]. [Full Text].
Litovitz TL, White JD. Levothyroxine ingestions in children: an analysis of 78 cases. Am J Emerg Med. 1985 Jul. 3(4):297-300. [Medline].
Golightly LK, Smolinske SC, Kulig KW, Wruk KM, Gelman CJ, Rumack BH. Clinical effects of accidental levothyroxine ingestion in children. Am J Dis Child. 1987 Sep. 141(9):1025-7. [Medline].
FDA MedWatch Safety Alerts for Human Medical Products. Propylthiouracil (PTU). US Food and Drug Administration. Accessed: 2016-02-12.
Bauer LA. Simulations of Levothyroxine Bioavailability Using a Single-Dose Study Protocol. Am J Ther. 1995 Jun. 2(6):414-416. [Medline].
Berkner PD, Starkman H, Person N. Acute L-thyroxine overdose; therapy with sodium ipodate: evaluation of clinical and physiologic parameters. J Emerg Med. 1991 May-Jun. 9(3):129-31. [Medline].
Bosse GM, Matyunas NJ. Delayed toxidromes. J Emerg Med. 1999 Jul-Aug. 17(4):679-90. [Medline].
Lehrner LM, Weir MR. Acute ingestions of thyroid hormones. Pediatrics. 1984 Mar. 73(3):313-7. [Medline].
Mariotti S, Martino E, Cupini C, Lari R, Giani C, Baschieri L, et al. Low serum thyroglobulin as a clue to the diagnosis of thyrotoxicosis factitia. N Engl J Med. 1982 Aug 12. 307(7):410-2. [Medline].
Seger D. Endocrine principles. Goldfrank L, ed. Goldfrank’s Toxicologic Emergencies. 5th ed. New York, NY: McGraw-Hill; 1994. 338-90.
Singh GK, Winterborn MH. Massive overdose with thyroxine,–toxicity and treatment. Eur J Pediatr. 1991 Jan. 150(3):217. [Medline].
Tunget CL, Clark RF, Turchen SG, Manoguerra AS. Raising the decontamination level for thyroid hormone ingestions. Am J Emerg Med. 1995 Jan. 13(1):9-13. [Medline].
Lisandro Irizarry, MD, MPH, FACEP Chair, Department of Emergency Medicine, Wyckoff Heights Medical Center
Lisandro Irizarry, MD, MPH, FACEP is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American College of Medical Toxicology, Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.
Nadine A Youssef, MD Assistant Professor of Emergency Medicine, Tufts University, Department of Emergency Medicine
Nadine A Youssef, MD is a member of the following medical societies: American College of Emergency Physicians, American Medical Association, Society for Academic Emergency Medicine, Emergency Medicine Residents’ Association
Disclosure: Nothing to disclose.
Anton A Wray, MD, FACEP Assistant Professor of Clinical Emergency Medicine, New York Medical College; Program Director Department of Emergency Medicine, Wyckoff Heights Medical Center
Anton A Wray, MD, FACEP is a member of the following medical societies: American College of Emergency Physicians, American Medical Association
Disclosure: Nothing to disclose.
John T VanDeVoort, PharmD Regional Director of Pharmacy, Sacred Heart and St Joseph’s Hospitals
John T VanDeVoort, PharmD is a member of the following medical societies: American Society of Health-System Pharmacists
Disclosure: Nothing to disclose.
Fred Harchelroad, MD, FACMT, FAAEM, FACEP Attending Physician in Emergency Medicine and Medical Toxicology, Excela Health System
Fred Harchelroad, MD, FACMT, FAAEM, FACEP is a member of the following medical societies: American College of Medical Toxicology
Disclosure: Nothing to disclose.
Asim Tarabar, MD Assistant Professor, Director, Medical Toxicology, Department of Emergency Medicine, Yale University School of Medicine; Consulting Staff, Department of Emergency Medicine, Yale-New Haven Hospital
Disclosure: Nothing to disclose.
Jeffrey Glenn Bowman, MD, MS Consulting Staff, Highfield MRI
Disclosure: Nothing to disclose.
Thyroid Hormone Toxicity
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