Etiology of Goiters

• Etiology:

• Iodine deficiency:

• Is the most common cause of goiter worldwide

• In mildly and moderately iodine-deficient regions in Denmark:

• Goiter (as determined by ultrasonography) is present in 15% and 22.6% of the population, respectively

• In the United States, where significant iodine deficiency does not exist:

• Multinodular goiter, chronic autoimmune (Hashimoto’s) thyroiditis, and Graves’ disease are more common causes of goiter:

• In older adults, multinodular goiter is most common

• Other less common causes of goiter include:

• Tumors

• Thyroiditis

• Infiltrative diseases

• The risk of thyroid cancer within a multinodular goiter:

• Is approximately 3% to 5%:

• Similar to the risk in a solitary thyroid nodule

• In a series of 718 patients operated on for goiter in Pakistan:

• 3% of patients were found to have a malignancy

• In a surgical series (with potential selection bias) of 3233 patients with multinodular goiter:

• In which all patients had preoperative ultrasounds and patients who had indeterminate, suspicious, or malignant (Bethesda 3 to 6) preoperative FNA were excluded:

• 31.7% had incidental thyroid cancers:

• Of which 56% were papillary microcarcinomas

• Pathophysiology:

• In patients with iodine deficiency or chronic autoimmune (Hashimoto’s) thyroiditis:

• An increase in thyroid-stimulating hormone (TSH) secretion:

• Is the predominant cause of goiter

• In contrast, most patients with sporadic nontoxic multinodular goiters:

• Have normal serum TSH concentrations:

• In these individuals, the thyroid enlargement is probably caused by several growth factors (including TSH):

• That act over time on thyroid follicular cells:

• That have different synthetic and growth potentials

• There is often a family history of goiter:

• Suggesting that genetic factors may also play a role

• The result is diffuse and later multinodular thyroid enlargement:

• Some nodules eventually become autonomous:

• Due to activating mutations in the TSH receptor or G proteins within the thyroid follicular cells

• The following observations support this sequence of events:

• Thyroid volume is larger in older patients

• The longer the patient has a goiter:

• The larger the size of the goiter

• The larger the size of the goiter:

• The lower the serum TSH concentration

• In patients with Graves’ disease:

• TSH receptor antibodies (TRAb):

• Stimulate the TSH receptor:

• To cause thyroid growth and excessive hormonal secretion