Hyperthyroidism, Thyroid Storm, and Graves Disease
- Author: Erik D Schraga, MD; Chief Editor: Rick Kulkarni, MD more...
Background
Hyperthyroidism, thyroid storm, and Graves disease are conditions of excess thyroid hormone. The elevated level of thyroid hormones can result in clinical manifestations ranging from mild to severely toxic with resultant morbidity and mortality for affected patients.
Hyperthyroidism
Hyperthyroidism presents as a constellation of symptoms due to elevated levels of circulating thyroid hormones. Because of the many actions of thyroid hormone on various organ systems in the body, the spectrum of clinical signs produced by the condition is broad. The presenting symptoms can be subtle and nonspecific, making hyperthyroidism difficult to diagnose in its early stages without the aid of laboratory data.
The term hyperthyroidism refers to inappropriately elevated thyroid function. Though often used interchangeably, the term thyrotoxicosis, which is an excessive amount of circulating thyroid hormone, is not synonymous with hyperthyroidism. Increased levels of hormone can occur despite normal thyroid function, such as in instances of inappropriate exogenous thyroid hormone or excessive release of stored hormone from an inflamed thyroid gland.
Graves disease
Graves disease (diffuse toxic goiter), the most common form of overt hyperthyroidism, is an autoimmune condition in which autoantibodies are directed against the thyroid-stimulating hormone (TSH) receptor. As a result, the thyroid gland is inappropriately stimulated with ensuing gland enlargement and increase of thyroid hormone production. Risk factors for Graves disease include family history of hyperthyroidism or various other autoimmune disorders, high iodine intake, stress, use of sex steroids, and smoking. The disease is classically characterized by the triad of goiter, exophthalmos, and pretibial myxedema.
Thyroid storm
Thyroid storm is a rare and potentially fatal complication of hyperthyroidism. It typically occurs in patients with untreated or partially treated thyrotoxicosis who experience a precipitating event such as surgery, infection, or trauma. Thyroid storm must be recognized and treated on clinical grounds alone, as laboratory confirmation often cannot be obtained in a timely manner. Patients typically appear markedly hypermetabolic with high fevers, tachycardia, nausea and vomiting, tremulousness, agitation, and psychosis. Late in the progression of disease, patients may become stuporous or comatose with hypotension.
For more information, see Medscape's Thyroid Disease Resource Center.
Pathophysiology
In healthy patients, the hypothalamus produces thyrotropin-releasing hormone (TRH), which stimulates the anterior pituitary gland to secrete thyroid-stimulating hormone (TSH); this in turn triggers the thyroid gland to release thyroid hormone.
Thyroid hormone concentration is regulated by negative feedback by circulating free hormone primarily on the anterior pituitary gland and to a lesser extent on the hypothalamus. The secretion of TRH is also partially regulated by higher cortical centers.
The thyroid gland produces the prohormone thyroxine (T4), which is deiodinated primarily by the liver and kidneys to its active form, triiodothyronine (T3). The thyroid gland also produces a small amount of T3 directly. T4 and T3 exist in 2 forms: a free, unbound portion that is biologically active and a portion that is protein bound to thyroid-binding globulin (TBG). Despite consisting of less than 0.5% of total circulating hormone, free or unbound T4 and T3 levels best correlate with the patient's clinical status.
Epidemiology
Frequency
United States
The overall incidence of hyperthyroidism is estimated between 0.05% and 1.3%, with the majority consisting of subclinical disease. A population-based study in the United Kingdom and Ireland found an incidence of 0.9 cases per 100,000 children younger than 15 years, showing that the disease incidence increases with age.[1] The prevalence of hyperthyroidism is approximately 5-10 times less than hypothyroidism.
Thyroid storm is a rare disorder. Approximately 1-2% of patients with hyperthyroidism progress to thyroid storm.
Mortality/Morbidity
- Thyroid storm, if unrecognized and untreated, is often fatal.
- Adult mortality rate from thyroid storm is approximately 10-20%, but it has been reported to be as high as 75% in hospitalized populations. Underlying precipitating illness may contribute to high mortality.
Race
- White and Hispanic populations in the United States have a slightly higher prevalence of hyperthyroidism in comparison with black populations.
Sex
- A slight predominance of hyperthyroidism exists among females.
Age
- Thyroid storm may occur at any age but is most common in those in their third through sixth decades of life.
- Graves disease predominantly affects those aged 20-40 years.
- The prevalence of toxic multinodular goiter increases with age and becomes the primary cause of hyperthyroidism in elderly persons.
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.
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