Nontoxic Goiter

Nontoxic Goiter

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A nontoxic goiter is a diffuse or nodular enlargement of the thyroid gland that does not result from an inflammatory or neoplastic process and is not associated with abnormal thyroid function. Endemic goiter is defined as thyroid enlargement that occurs in more than 10% of a population, and sporadic goiter is a result of environmental or genetic factors that do not affect the general population.

The histopathology varies with etiology and age of the goiter. Initially, uniform follicular epithelial hyperplasia (diffuse goiter) is present, with an increase in thyroid mass. As the disorder persists, the thyroid architecture loses uniformity, with the development of areas of involution and fibrosis interspersed with areas of focal hyperplasia. This process results in multiple nodules (multinodular or adenomatous goiter). On nuclear scintigraphy, some nodules are hot, with high isotope uptake (autonomous) or cold, with low isotope uptake, compared with the normal thyroid tissue (as demonstrated in the images below).

The development of nodules correlates with the development of functional autonomy and reduction in thyroid-stimulating hormone (TSH) levels. Clinically, the natural history of a nontoxic goiter is growth, nodule production, and functional autonomy. However, abnormally high thyroid function resulting in thyrotoxicosis occurs in a minority of patients. The risk of malignancy is the same in a patient with a nodular goiter as with a solitary nodule.

See the images below.

United States

Iodine comes from ingestion of food. Iodine content of the soil determines the iodine content of plants and animals. Iodine is washed from the soil by water and is eventually washed out to the oceans. In general, areas with mountain ranges or heavy rainfall and flooding are iodine deficient. Iodine deficiency occurs in populations that depend on locally grown food and rely on vegetable protein rather than on animal or fish protein.

Studies have shown that iodine supplementation can eliminate cretinism and is highly effective in the prevention of endemic goiter. When urinary iodide falls below 25 micrograms per gram of creatinine, a palpable goiter occurs in 40-90% of the population, hypothyroidism occurs in 30-50% of the population, and cretinism occurs in 1-10% of the population. The seminal studies by David Marine, MD, in 1917 demonstrated the reduction in goiter among adolescent girls in Ohio from 20% to 5% by iodine supplementation.

Table salt has been supplemented in the United States since the 1920s for the prevention of cretinism and endemic goiter. The iodine intake in the United States, according to the National Health and Nutrition Examination Survey III (NHANES III), is adequate at 145 mcg/mg of creatinine. This adequate iodine intake in the United States eliminates the most common cause of endemic goiter in most populations.

Sporadic goiter is the most common cause of nontoxic goiter in the United States. The incidence of sporadic nontoxic goiter has been estimated in North America at approximately 5%. Sporadic goiter does not usually occur in people before puberty, and it does not have a peak incidence. Generally, the development of palpable thyroid nodules and goiter progressively increases with age. The prevalence of palpable nodules is approximately 5-6% in people aged 60 years, but on autopsy and ultrasonographic imaging findings, the incidence of small, nonpalpable nodules approaches 50% in people aged 60 years.


More than 2.2 billion people worldwide have some form of iodine deficiency disorder. Twenty-nine percent of the world’s population lives in a region that has iodine deficiency (primarily in Asia, Latin American, central Africa, and regions of Europe). Of those at risk, 655 million were known to have goiter. In the iodine-deficient regions of the world, goiter is more common than in the United States. The prevalence of goiter can be estimated based on the iodine intake of the population.

As reported by the World Health Organization (WHO), the United Nations Children’s Fund (UNICEF), and the International Council for the Control of Iodine Deficiency Disorders (ICCIDD), the absence of iodine deficiency (ie, median urine iodine >100 mg/dL) is associated with a goiter prevalence of less than 5%; mild iodine deficiency (ie, median urine iodine 50-99 mg/dL), with a goiter prevalence of 5-20%; moderate iodine deficiency (ie, median urine iodine 20-49 mg/dL), with a goiter prevalence of 20-30%; and severe iodine deficiency (ie, median urine iodine 20-49 mg/dL), with a goiter prevalence of greater than 30%.

Endemic goiters arising from iodine deficiency are associated with sometimes immense thyroid hypertrophy, hypothyroidism, and cretinism. Sporadic goiters are generally asymptomatic and found either by a clinician’s physical examination or by the patient’s observation of neck enlargement. Occasionally, the goiter may produce symptoms caused by pressure on anterior neck structures, including the trachea (wheezing, cough, globus hystericus [anterior neck pressure]), the esophagus (dysphagia), and the recurrent laryngeal nerve (hoarseness).

Rarely, the obstruction can be dangerous because of narrowing of the trachea and the development of tracheitis with edema and tracheomalacia, leading to severe narrowing of the airway with serious obstruction resulting in a respiratory emergency. (Tracheal compression and the results of its surgical treatment are seen in the images below.)

No convincing epidemiologic studies suggest that race plays an important role in the development of nontoxic goiter. Generally, the lower socioeconomic conditions in nonindustrialized countries resulting in iodine deficiency have a more important role than race does in the development of a goiter.

Diffuse and nodular goiter is more common in women than in men. According to the best estimate, the incidence of goiter in women is 1.2-4.3 times as great as that in men.

Sporadic goiter from dyshormonogenesis, a genetic error in proteins that are necessary for thyroid hormone synthesis, occurs during childhood. Endemic goiter due to iodine deficiency occurs during childhood, with the goiter’s size increasing with age. Other causes of sporadic goiter rarely occur before puberty and do not have a peak age of occurrence. Thyroid nodules increase in incidence with age.

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Stephanie L Lee, MD, PhD Associate Professor, Department of Medicine, Boston University School of Medicine; Director of Thyroid Health Center, Section of Endocrinology, Diabetes and Nutrition, Boston Medical Center; Fellow, Association of Clinical Endocrinology

Stephanie L Lee, MD, PhD is a member of the following medical societies: American College of Endocrinology, American Thyroid Association, Endocrine Society

Disclosure: Nothing to disclose.

Sonia Ananthakrishnan, MD Assistant Professor of Medicine, Section of Endocrinology, Diabetes and Nutrition, Boston Medical Center, Boston University School of Medicine

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.

Kent Wehmeier, MD Professor, Department of Internal Medicine, Division of Endocrinology, Diabetes, and Metabolism, St Louis University School of Medicine

Kent Wehmeier, MD is a member of the following medical societies: American Society of Hypertension, Endocrine Society, International Society for Clinical Densitometry

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.

Nontoxic Goiter

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