Diffuse Toxic Goiter (Graves Disease)

Updated: Jul 27, 2015
  • Author: Bernard Corenblum, MD, FRCPC; Chief Editor: George T Griffing, MD  more...
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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.


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.