Diffuse Toxic Goiter (Graves Disease)

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Diffuse Toxic Goiter (Graves Disease)

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Diffuse toxic goiter, first described by the English physician Caleb H. Parry (1755-1822), is also known as Graves disease (after Robert J. Graves) in the English-speaking world and as Basedow disease (after Karl A. von Basedow) in the rest of Europe.

In diffuse toxic goiter, the thyroid gland is diffusely hyperplastic and excessively overproduces thyroid hormone. This results in accelerated metabolism in most body organs. The clinical response and its manifestations are variable in intensity, distribution, and are modified by age, gender, and associated premorbid medical problems. When diffuse toxic goiter is associated with clinical evidence of oculopathy, or rarely with dermopathy/acropachy, the term Graves disease is often applied. Awareness is needed regarding atypical clinical presentations.

The thyroid gland is usually enlarged to a variable degree and is vascular and diffusely affected. This results in a smooth, rubbery-firm consistency, and often a bruit is heard on auscultation. Microscopically, the thyroid follicular cells are hypertrophic and hyperplastic, and they contain little colloid (stored hormone) and show evidence of hypersecretion. Lymphocytes and plasma cells infiltrate into the thyroid gland and may aggregate into lymphoid follicles.

This condition is an autoimmune disorder whereby the thyroid gland is overstimulated by antibodies directed to the thyroid-stimulating hormone (TSH) receptor on the thyroid follicular cells. This antibody stimulates iodine uptake, thyroid hormonogenesis and release, and thyroid gland growth. Although mainly produced within the thyroid gland, these antibodies reach the circulation and can be measured by various assays in most, but not all, cases.

The association with another autoimmune thyroid disease, Hashimoto thyroiditis, and to a lesser degree, with other autoimmune diseases in other endocrine glands and other systems in the same person is high. A strong familial association exists with the same diffuse toxic goiter or the associated disorders, especially Hashimoto thyroiditis. The presence of Hashimoto thyroiditis, which has more of a destructive effect on the thyroid gland, or the presence of another antibody, TSH-receptor blocking antibody, results in a variable natural history of the course of diffuse toxic goiter.

United States

Diffuse toxic goiter is the most common cause of spontaneous hyperthyroidism. A Minnesota study found 0.3 new cases per 1000 per year.

In late childhood, the incidence rate is 3 per 100,000 in girls and 0.5 per 100,000 in boys. Prevalence studies show a rate of 2.7% in women and 0.23% in men.

A marked increase in familial incidence is noted.

International

Prewar Copenhagen found 0.2 new cases per 1000 per year.

British studies found 0.08-0.2 new cases per 1000 per year.

No racial predilection exists.

Diffuse toxic goiter is 7-10 times more common in women than in men. It is often associated with or following pregnancy.

Diffuse toxic goiter can occur in persons of all ages, but it is rare in children younger than 10 years and unusual in elderly persons. The peak incidence is in third and fourth decades of life.

Incidence is increased in postpartum women, when the first presentation of disease often occurs.

The natural history is usually of a benign course, which may vary in intensity of the symptoms and even spontaneously remit. The intensity of the symptoms and effect on quality of life are variable from person to person and are affected by age and gender.

Mortality is rare, but when it occurs, it is due to cardiovascular problems such as heart failure, arrhythmias, or myocardial infarction.

Therapy may be needed for myocardial ischemia, congestive failure, or atrial arrhythmias, which may require anticoagulation.

Debility and infection may occur. Thyroid storm is rare but may be fatal from dehydration, hyperthermia, and organ failure.

Morbidity may result from increased bone turnover and osteoporosis, especially in postmenopausal women, or from atrial fibrillation and its sequelae, such as thromboembolism, especially in older men. Personality changes and psychopathology, muscular weakness, and systemic symptoms all lead to quality of life changes. Associated oculopathy may be symptomatic, especially with double vision. Rarely it may progress to affect the integrity of the cornea and may even endanger vision.

Associated dermopathy is uncommon and is usually minimally symptomatic, but it may be symptomatic to become debilitating.

Associated hypokalemic periodic paralysis, most commonly seen in Asian males, may be sudden, dramatic, and concerning but usually runs a benign course of recovery after a few hours of skeletal muscle paralysis.

A higher risk of associated immunologic diseases, such as adrenal insufficiency, each has their own associated morbidity and mortality, especially if undiagnosed.

Bahn RS, Burch HB, Cooper DS, et al. Hyperthyroidism and other Causes of Thyrotoxicosis: Management Guidelines of the American Thyroid Association and American Association of Clinical Endocrinoloigists. Endocr Pract. 2011 May-Jun. 17(3):456-520. [Medline].

Abraham-Nordling M, Törring O, Hamberger B, et al. Graves’ disease: a long-term quality-of-life follow up of patients randomized to treatment with antithyroid drugs, radioiodine, or surgery. Thyroid. 2005 Nov. 15(11):1279-86. [Medline].

Nakamura H, Noh JY, Itoh K, Fukata S, Miyauchi A, Hamada N. Comparison of methimazole and propylthiouracil in patients with hyperthyroidism caused by Graves’ disease. J Clin Endocrinol Metab. 2007 Jun. 92(6):2157-62. Epub 2007 Mar 27. [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.

Vanderpump M. Cardiovascular and cancer mortality after radioiodine treatment of hyperthyroidism. J Clin Endocrinol Metab. 2007 Jun. 92(6):2033-5. [Medline].

Cawood T, Moriarty P, O’Shea D. Recent developments in thyroid eye disease. BMJ. 2004 Aug 14. 329(7462):385-90. [Medline].

Cooper DS. Antithyroid drugs. N Engl J Med. 2005 Mar 3. 352(9):905-17. [Medline].

deGroot LJ, Larsen RP, Hennemann G. Undefined. The Thyroid and Its Diseases. 1996. 371-489.

Franklyn JA, Maisonneuve P, Sheppard M, et al. Cancer incidence and mortality after radioiodine treatment for hyperthyroidism: a population-based cohort study. Lancet. 1999 Jun 19. 353(9170):2111-5. [Medline].

Mestman JH. Hyperthyroidism in pregnancy. Best Pract Res Clin Endocrinol Metab. 2004 Jun. 18(2):267-88. [Medline].

Sarlis NJ, Gourgiotis L. Thyroid emergencies. Rev Endocr Metab Disord. 2003 May. 4(2):129-36. [Medline].

Schwartz KM, Fatourechi V, Ahmed DD, Pond GR. Dermopathy of Graves’ disease (pretibial myxedema): long-term outcome. J Clin Endocrinol Metab. 2002 Feb. 87(2):438-46. [Medline].

Weetman AP. Graves’ disease. N Engl J Med. 2000 Oct 26. 343(17):1236-48. [Medline].

Bernard Corenblum, MD, FRCPC Professor of Medicine, Director, Endocrine-Metabolic Testing and Treatment Unit, Ovulation Induction Program, Department of Internal Medicine, Division of Endocrinology, University of Calgary Faculty of Medicine, Canada

Disclosure: Nothing to disclose.

Oluyinka S Adediji, MD, MBBS Consulting Staff, Department of Adult and General Medicine, Health Services Incorporated, Montgomery, Alabama

Oluyinka S Adediji, MD, MBBS is a member of the following medical societies: American College of Physicians, American Medical Association

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Yoram Shenker, MD Chief of Endocrinology Section, Veterans Affairs Medical Center of Madison; Interim Chief, Associate Professor, Department of Internal Medicine, Section of Endocrinology, Diabetes and Metabolism, University of Wisconsin at Madison

Yoram Shenker, MD is a member of the following medical societies: American Heart Association, Central Society for Clinical and Translational Research, Endocrine Society

Disclosure: Nothing to disclose.

George T Griffing, MD Professor Emeritus of Medicine, St Louis University School of Medicine

George T Griffing, MD is a member of the following medical societies: American Association for the Advancement of Science, International Society for Clinical Densitometry, Southern Society for Clinical Investigation, American College of Medical Practice Executives, American Association for Physician Leadership, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical and Translational Research, Endocrine Society

Disclosure: Nothing to disclose.

Steven R Gambert, MD Professor of Medicine, Johns Hopkins University School of Medicine; Director of Geriatric Medicine, University of Maryland Medical Center and R Adams Cowley Shock Trauma Center

Steven R Gambert, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for Physician Leadership, American College of Physicians, American Geriatrics Society, Endocrine Society, Gerontological Society of America, Association of Professors of Medicine

Disclosure: Nothing to disclose.

Paul Killian, MD Former Chief of Endocrine Service, Former Associate Professor, Department of Internal Medicine, Harlem Hospital, Harlem Hospital Center

Paul Killian, MD is a member of the following medical societies: American College of Physicians-American Society of Internal Medicine, American Diabetes Association, and Endocrine Society

Disclosure: Nothing to disclose.

Diffuse Toxic Goiter (Graves Disease)

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