Thyroid Hormone Toxicity Medication
- Author: Lisandro Irizarry, MD, MPH, FACEP; Chief Editor: Asim Tarabar, MD more...
The goals of pharmacotherapy are to reduce morbidity and prevent complications.
Empirically used to minimize systemic absorption of the toxin. May only benefit if administered within 1-2 h of ingestion.
Emergency treatment in poisoning caused by drugs and chemicals. Network of pores present in activated charcoal adsorbs 100-1000 mg of drug per gram of charcoal. Does not dissolve in water.
Most useful if used within 4 h of ingestion. Repeated doses may be used, particularly with ingestions of sustained-released agents. May repeat dose q4h at 0.5 g/kg. Alternate with and without cathartic, if used.
Beta-blockers are administered to counteract the increase in adrenergic activity and treat serious tachyarrhythmias.
Noncardioselective beta-blocker, widely available. DOC in treating cardiac arrhythmias resulting from hyperthyroidism. Controls cardiac and psychomotor manifestations within minutes.
Important added benefit is the inhibition of peripheral conversion of T4 to T3.
A short-acting IV cardioselective beta-adrenergic blocker with no membrane depressant activity. Intravenous agent with half-life of 8 min, which allows for titration to effect and quick discontinuation prn.
Thyroid agents are administered to prevent peripheral conversion of T4 to T3.
The US Food and Drug Administration (FDA) had added a boxed warning, the strongest warning issued by the FDA, to the prescribing information for propylthiouracil. The boxed warning emphasizes the risk for severe liver injury and acute liver failure, some of which have been fatal. The boxed warning also states that propylthiouracil should be reserved for use in those who cannot tolerate other treatments such as methimazole, radioactive iodine, or surgery.
The decision to include a boxed warning was based on the FDA's review of postmarketing safety reports and meetings held with the American Thyroid Association, the National Institute of Child Health and Human Development, and the pediatric endocrine clinical community.
The FDA has identified 32 cases (22 adult and 10 pediatric) of serious liver injury associated with propylthiouracil (PTU). Of the adults, 12 deaths and 5 liver transplants occurred, and among the pediatric patients, 1 death and 6 liver transplants occurred. PTU is indicated for hyperthyroidism due to Graves disease. These reports suggest an increased risk for liver toxicity with PTU compared with methimazole. Serious liver injury has been identified with methimazole in 5 cases (3 resulting in death).
PTU is considered as a second-line drug therapy, except in patients who are allergic or intolerant to methimazole, or for women who are in the first trimester of pregnancy. Rare cases of embryopathy, including aplasia cutis, have been reported with methimazole during pregnancy. The FDA recommends the following criteria be considered for prescribing PTU.
For more information, see the FDA Safety Alert.
- Reserve PTU use during first trimester of pregnancy, or in patients who are allergic to or intolerant of methimazole.
- Closely monitor PTU therapy for signs and symptoms of liver injury, especially during the first 6 months after initiation of therapy.
- For suspected liver injury, promptly discontinue PTU therapy and evaluate for evidence of liver injury and provide supportive care.
- PTU should not be used in pediatric patients unless the patient is allergic to or intolerant of methimazole, and no other treatment options are available.
- Counsel patients to promptly contact their health care provider for the following signs or symptoms: fatigue, weakness, vague abdominal pain, loss of appetite, itching, easy bruising, or yellowing of the eyes or skin.
Derivative of thiourea that inhibits organification of iodine by thyroid gland. Blocks oxidation of iodine in thyroid gland, thereby, inhibiting thyroid hormone synthesis; inhibits T4 to T3 conversion.
Bile acid sequestrants
These agents used to be utilized to bind thyroid hormone agents, which undergo enterohepatic recycling and reabsorption. There is no current strong recommendation supporting use of cholestyramine.
Forms a nonabsorbable complex with bile acids in the intestine, which, in turn, inhibits enterohepatic reuptake of intestinal bile salts.
Used to treat hyperthermia.
Inhibits action of endogenous pyrogens on heat-regulating centers; reduces fever by a direct action on the hypothalamic heat-regulating centers, which, in turn, increase the dissipation of body heat via sweating and vasodilation.
Used when adrenal crisis suspected.
Can be used to treat the potential adrenal insufficiency occurring secondary to the hypermetabolic hyperthyroid state.
DOC because of mineralocorticoid activity and glucocorticoid effects.
Used as empiric treatment of shock in suspected adrenal crisis or insufficiency until serum cortisol levels are drawn.
Adverse effects are hyperglycemia, hypertension, weight loss, GI bleeding or perforation synthesis, cerebral palsy, adrenal suppression, and death. Most of the adverse effects of corticosteroids are dose-dependent or duration-dependent.
Readily absorbed via the GI tract and metabolized in the liver. Inactive metabolites are excreted via the kidneys. Lacks salt-retaining property of hydrocortisone.
Patients can be switched from an IV to PO regimen in a 1:1 ratio.
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). 2009 Dec. 47(10):911-1084. [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. Available at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm164162.htm. Accessed: June 3, 2009.
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].