Hyperthyroidism, Thyroid Storm, and Graves Disease Treatment & Management
- Author: Erik D Schraga, MD; Chief Editor: Rick Kulkarni, MD more...
Emergency Department Care
- Do not delay treatment once thyroid storm is suspected.
- Patients with severe thyrotoxicosis must be placed on a cardiac monitor. The patient should be intubated if profoundly altered. Supplemental oxygen may be required. Aggressive fluid resuscitation may be indicated.
- Fevers are treated with cooling measures and antipyretics. However, aspirin should be avoided to prevent decreased protein binding and subsequent increases in free T3 and T4 levels. Only in the setting of subacute thyroiditis is aspirin indicated.
- Aggressive hydration of up to 3-5 L/d of crystalloid compensates for potentially profound GI and insensible losses.
- Appropriate electrolyte replacement should be directed by laboratory values.
- Atrial fibrillation due to thyroid storm may be refractory to rate control, and conversion to sinus rhythm may be impossible until after antithyroid therapy has been initiated.
- Intravenous glucocorticoids are indicated if adrenal insufficiency is suspected. Large doses of dexamethasone (2 mg q6h) inhibit hormone production and decrease peripheral conversion from T4 to T3.
- Antithyroid medications such as propylthiouracil (PTU) and methimazole (MMI) oppose synthesis of T4 by inhibiting the organification of tyrosine residues.
- PTU also inhibits the conversion of T4 to active T3, although this effect is minimal and not usually clinically significant.
- Clinical effects may be seen as soon as 1 hour after administration. Both agents are administered orally or via a nasogastric tube.
- PTU and MMI inhibit the synthesis of new thyroid hormone but are ineffective in blocking the release of preformed thyroid hormone. Iodide administration serves this purpose well; however, it should be delayed until 1 hour after the loading dose of antithyroid medication to prevent the utilization of iodine in the synthesis of new thyroid hormone. Lithium may be used as an alternative in those with iodine allergy.
- Antithyroid medications appear to also have an immunosuppressive effect, evidenced by decreased serum concentrations of antithyrotropin-receptor antibodies.
- Primary antithyroid treatment (as an alternative to surgery) is often suggested for Graves disease, as remission after cessation of medical management is possible. In those with toxic multinodular goiters and solitary autonomous nodules, first-line treatment with antithyroid drugs is not recommended since spontaneous remission is rare.
- 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.[2]
- 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.
- Beta-adrenergic blocking agents are the mainstays of symptomatic therapy for thyrotoxicosis. Propranolol has been used with the greatest success due to the additional benefit of inhibition of peripheral conversion of T4 to T3.
- Charcoal hemoperfusion has been shown to be effective in treatment of iatrogenic or intentional ingestion of excessive doses of levothyroxine.[3]
Consultations
- An intensivist should be consulted for admission to an ICU when thyroid storm is the presumptive diagnosis.
- An endocrinologist or internist may be helpful in confirming the diagnosis and in assisting in patient management.
Williamson S, Greene SA. Incidence of thyrotoxicosis in childhood: a national population based study in the UK and Ireland. Clin Endocrinol (Oxf). Mar 2010;72(3):358-63. [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.
Kreisner E, Lutzky M, Gross JL. Charcoal hemoperfusion in the treatment of levothyroxine intoxication. Thyroid. Feb 2010;20(2):209-12. [Medline].
Chong HW, See KC, Phua J. Thyroid storm with multiorgan failure. Thyroid. Mar 2010;20(3):333-6. [Medline].
Basaria S, Cooper DS. Amiodarone and the thyroid. Am J Med. Jul 2005;118(7):706-14. [Medline].
Braverman LE, Utiger RD. Werner and Ingbar's The Thyroid: A Fundamental and Clinical Text. 7th ed. 1996.
Burch HB, Wartofsky L. Life-threatening thyrotoxicosis. Thyroid storm. Endocrinol Metab Clin North Am. Jun 1993;22(2):263-77. [Medline].
Canaris GJ, Manowitz NR, Mayor G, Ridgway EC. The Colorado thyroid disease prevalence study. Arch Intern Med. Feb 28 2000;160(4):526-34. [Medline].
Cappola AR, Fried LP, Arnold AM, et al. Thyroid status, cardiovascular risk, and mortality in older adults. JAMA. Mar 1 2006;295(9):1033-41. [Medline].
Carlson HE. Gynecomastia. N Engl J Med. Oct 2 1980;303(14):795-9. [Medline].
Cooper DS. Antithyroid drugs. N Engl J Med. Mar 2005;352(9):905-17. [Medline].
Fisher JN. Management of thyrotoxicosis. South Med J. May 2002;95(5):493-505. [Medline].
Gharib H. Changing concepts in the diagnosis and management of thyroid nodules. Endocrinol Metab Clin North Am. Dec 1997;26(4):777-800. [Medline].
Glauser J, Strange GR. Hypothyroidism and hyperthyroidism in the elderly. Emerg Med Rep. 2002;1(2):1-12.
Hollowell JG, Staehling NW, Flanders WD, et al. Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab. Feb 2002;87(2):489-99. [Medline].
Kudrjavcev T. Neurologic complications of thyroid dysfunction. Adv Neurol. 1978;19:619-36. [Medline].
McKeown NJ, Tews MC, Gossain VV, Shah SM. Hyperthyroidism. Emerg Med Clin North Am. Aug 2005;23(3):669-85, viii. [Medline].
Pimentel L, Hansen KN. Thyroid disease in the emergency department: a clinical and laboratory review. J Emerg Med. Feb 2005;28(2):201-9. [Medline].
Ragland E, Urbanic RC. Thyroid emergencies. In: Harwood-Nuss Al, Linden CH, eds. The Clinical Practice of Emergency Medicine. 2nd ed. Lippincott Williams & Wilkins; 1996:736-41.
Ragland G. Thyroid storm. In: Emergency Medicine: A Comprehensive Study Guide. 4th ed. New York, NY: McGraw-Hill; 1996:736-9.
Ringel MD. Management of hypothyroidism and hyperthyroidism in the intensive care unit. Crit Care Clin. Jan 2001;17(1):59-74. [Medline].
Rozien MF. Anesthetic implications of concurrent diseases. In: Anesthesia. Churchill Livingstone; 1994:926-8.
Rozien MF, Fleisher LA. Essence of Anesthesia Practice. WB Saunders Co; 1997:177.
Scott SK. Thyroid disorders. In: Markovchick VJ, Pons PT, Wolfe RE, eds. Emergency Medicine Secrets. Hanley and Belfus; 1993:178-82.
Sniezek JC, Francis TB. Inflammatory thyroid disorders. Otolaryngol Clin North Am. Feb 2003;36(1):55-71. [Medline].
Streetman DD, Khanderia U. Diagnosis and treatment of Graves disease. Ann Pharmacother. Jul-Aug 2003;37(7-8):1100-9. [Medline].
Tietgens ST, Leinung MC. Thyroid storm. Med Clin North Am. Jan 1995;79(1):169-84. [Medline].
Waldstein SS, Slodki SJ, Kaganiec GL. A clinical study of thyroid storm. Ann Intern Med. 1960;52:626-42.
Warofsky L, Ingbar SH. Diseases of the thyroid. In: Wilson JD, Brunwald E, et al, eds. Harrison's Principles of Internal Medicine. McGraw-Hill; 1991:1692-1712.
Weetman AP. Graves' disease. N Engl J Med. Oct 26 2000;343(17):1236-48. [Medline].
Wogan JM. Endocrine disorders. In: Rosen P, Barkin RM, et al, eds. Emergency Medicine: Concepts and Clinical Practice. Mosby-Year Book; 1992:2242-59.

