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Toxicity, Thyroid Hormone

Author: Lisandro Irizarry, MD, MPH, FAAEM, Chair, Department of Emergency Medicine, Brooklyn Hospital Center; Assistant Professor, Department of Emergency Medicine, Weill Cornell School of Medicine
Coauthor(s): Nadine A Youssef, MD, Assistant Professor of Emergency Medicine, Tufts University, Department of Emergency Medicine; Anton A Wray, MD, FACEP,, Clinical Assistant Professor of Emergency Medicine, Weill Cornell Medical College; Attending Physician, Department of Emergency Medicine, Brooklyn Hospital Center
Contributor Information and Disclosures

Updated: Jan 5, 2010

Introduction

Background

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.

Pathophysiology

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 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.

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, 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.

Frequency

United States

According to the Annual Report of the American Association of Poison Control Centers’ National Poison Data System, in 2008, 13,005 exposures to thyroid hormone preparations were documented; of the total listed, 9,006 were single substance exposures. The breakdown by age for single substance exposures is as follows; 5,026 were associated with children younger than 6 years; 554 were associated with persons aged 6-19 years; and 2,957 were associated with those aged older than 19 years. Overall, 3 major adverse outcomes and no deaths were reported.2

Race

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

Sex

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

Age

Inadvertent excessive thyroid hormone ingestion occurs primarily in pediatric patients.

Clinical

History

Access to thyroid hormone, especially in pediatric or unknown ingestions, is important. 

Physical

Focus the physical examination on findings consistent with symptoms of increased adrenergic activity and on the following signs:

  • Acute
    • Abdominal pain
    • Nausea or vomiting
    • Diarrhea
    • Increased appetite
    • Insomnia
    • Anxiousness
    • Agitation
    • Tremor
    • Seizures
    • Weakness
    • Diaphoresis
    • Tachycardia
    • Palpitations
    • Hypertension or hypotension
    • Hyperpyrexia/heat intolerance
    • Confusion
    • Psychosis
    • Hypoglycemia
    • Skin flushing
    • Transient systolic ejection murmurs
    • Pulmonary edema
    • Adrenal insufficiency
  • Chronic
    • Weight loss
    • Menstrual irregularities
    • Supraventricular tachycardia (SVT)
    • High-output left ventricular failure
    • Hypotension
    • Hemiparesis
    • Delirium
    • Coma
    • Pneumonia
    • Sepsis
    • Hyperthermia
    • Acute renal failure
    • Myopathy
    • Palmar and plantar desquamation
    • Premature epiphyseal closure in children
    • Craniosynostosis (infants)

Causes

Long-term abuse of thyroid supplements has been reported in obese patients as a method of weight control.

More on Toxicity, Thyroid Hormone

Overview: Toxicity, Thyroid Hormone
Differential Diagnoses & Workup: Toxicity, Thyroid Hormone
Treatment & Medication: Toxicity, Thyroid Hormone
Follow-up: Toxicity, Thyroid Hormone
References
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References

  1. Yamada M, Mori M. Mechanisms related to the pathophysiology and management of central hypothyroidism. Nat Clin Pract Endocrinol Metab. Dec 2008;4(12):683-94. [Medline]. [Full Text].

  2. Bronstein AC, Spyker DA, Cantilena LR Jr, Green JL, Rumack BH, Giffin SL. 2008 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 26th Annual Report. Clin Toxicol (Phila). Dec 2009;47(10):911-1084. [Medline]. [Full Text].

  3. Litovitz TL, White JD. Levothyroxine ingestions in children: an analysis of 78 cases. Am J Emerg Med. Jul 1985;3(4):297-300. [Medline].

  4. Golightly LK, Smolinske SC, Kulig KW, Wruk KM, Gelman CJ, Rumack BH. Clinical effects of accidental levothyroxine ingestion in children. Am J Dis Child. Sep 1987;141(9):1025-7. [Medline].

  5. FDA MedWatch Safety Alerts for Human Medical Products. Propylthiouracil (PTU). US Food and Drug Administration. Available at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm164162.htm. Accessed June 3, 2009.

  6. Bauer LA. Simulations of Levothyroxine Bioavailability Using a Single-Dose Study Protocol. Am J Ther. Jun 1995;2(6):414-416. [Medline].

  7. Berkner PD, Starkman H, Person N. Acute L-thyroxine overdose; therapy with sodium ipodate: evaluation of clinical and physiologic parameters. J Emerg Med. May-Jun 1991;9(3):129-31. [Medline].

  8. Bosse GM, Matyunas NJ. Delayed toxidromes. J Emerg Med. Jul-Aug 1999;17(4):679-90. [Medline].

  9. Lehrner LM, Weir MR. Acute ingestions of thyroid hormones. Pediatrics. Mar 1984;73(3):313-7. [Medline].

  10. 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. Aug 12 1982;307(7):410-2. [Medline].

  11. Seger D. Endocrine principles. In: Goldfrank L, ed. Goldfrank's Toxicologic Emergencies. 5th ed. New York, NY: McGraw-Hill; 1994:338-90.

  12. Singh GK, Winterborn MH. Massive overdose with thyroxine,--toxicity and treatment. Eur J Pediatr. Jan 1991;150(3):217. [Medline].

  13. Tunget CL, Clark RF, Turchen SG, Manoguerra AS. Raising the decontamination level for thyroid hormone ingestions. Am J Emerg Med. Jan 1995;13(1):9-13. [Medline].

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Further Reading

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Keywords

thyroid hormone toxicity, tyrosine, thyroxine, T4, triiodothyronine, T3, thyroid-stimulating hormone, thyrotropin-releasing hormone, levothyroxine, LT4, thyroid hormone overdose, thyroid hormone, thyroid hormone poisoning, thyroid hormone exposure, thyroid hormone ingestion, hypothyroidism, hyperthyroidism

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Contributor Information and Disclosures

Author

Lisandro Irizarry, MD, MPH, FAAEM, Chair, Department of Emergency Medicine, Brooklyn Hospital Center; Assistant Professor, Department of Emergency Medicine, Weill Cornell School of Medicine
Lisandro Irizarry, MD, MPH, FAAEM is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American College of Medical Toxicology, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Coauthor(s)

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, Emergency Medicine Residents Association, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Anton A Wray, MD, FACEP,, Clinical Assistant Professor of Emergency Medicine, Weill Cornell Medical College; Attending Physician, Department of Emergency Medicine, Brooklyn Hospital Center
Anton A Wray, MD, FACEP, is a member of the following medical societies: American College of Emergency Physicians and American Medical Association
Disclosure: Nothing to disclose.

Medical Editor

Jeffrey Glenn Bowman, MD, MS, Consulting Staff, Highfield MRI, Columbus, Ohio
Disclosure: Nothing to disclose.

Pharmacy Editor

John T VanDeVoort, PharmD, Regional Director of Pharmacy, Sacred Heart & 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.

Managing Editor

Fred Harchelroad, MD, FACMT, FAAEM, FACEP, Chair, Department of Emergency Medicine, Director of Medical Toxicology - Allegheny General Hospital, Associate Professor, Department of Emergency Medicine, Drexel University College of Medicine
Disclosure: Nothing to disclose.

CME Editor

John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center
John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Chief Editor

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.

 
 
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