Patients with nontoxic goiter are usually asymptomatic and seek medical advice because of a thyroid mass. Goiters are more common in women than men (=4:1). Sporadic goiters from dyshormonogenesis and endemic goiter due to iodine deficiency are usually first noted during childhood and continue to grow 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. The natural history of nontoxic goiter is characterized by slow, often progressive or intermittent growth, with many patients eventually becoming symptomatic.

Although most goiters are present for years, sudden, rapid growth of a discrete nodule or thyroid lobe, as previously mentioned, should suggest possible hemorrhage into a nodule or dedifferentiation to a poorly differentiated thyroid carcinoma, anaplastic carcinoma, or possible lymphoma. Benign goiters are rarely painful or grow quickly unless recent hemorrhage into a nodule has occurred. Some goiters, especially in patients with chronic lymphocytic thyroiditis, may cause a choking sensation or pain radiating to the ear.

Symptoms may be caused by compression of structures in the neck and superior mediastinum. Obstructive symptoms are more likely to occur in patients with a substernal goiter. As the substernal goiter continues to grow, the thoracic inlet may become occluded, a phenomenon known as the thyroid cork. This is because substernal goiter is confined between the sternum and the vertebral bodies and may displace or impinge on the trachea, esophagus, recurrent laryngeal nerve, and, rarely, the superior vena cava or the cervical sympathetic chain. Tracheal compression is generally asymptomatic until critical narrowing has occurred (=75% of cross-sectional area) to about 4 mm. Nocturnal or positional dyspnea and dyspnea with exertion suggest that they are caused by substernal goiter. Anxiety when raising one's arm above one's head with a reddened face and distended neck veins (positive Pemberton sign) suggests superior mediastinal obstruction. Upper respiratory tract infection or hemorrhage into a nodule or cyst may exacerbate upper airway obstruction and result in acute respiratory distress. Dysphagia occurs in about 20% of patients with substernal goiters. Ischemia and stretching of the recurrent laryngeal nerve with vocal cord dysfunction may cause hoarseness in about 4% of patients with benign substernal goiters, but cancer is more likely in these patients. Compression of the venous outflow through the thoracic inlet and sympathetic chain, causing Horner's syndrome, may rarely occur.58 59

Review of the possible causative factors of goiter and the differential diagnosis of nontoxic goiter include family history of benign or malignant thyroid disorder, a history of living in an endemic goiter area or of intake of goitrogens, a history of radiation exposure or, rarely, metastases from other organs to the thyroid gland. The last one occurs most often in patients with lung cancer, breast cancer, hypernephroma, and melanoma.

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