Hypothyroidism can be a primary disorder that results from disease in the thyroid gland itself or a secondary or tertiary disorder. In most cases, hypothyroidism occurs as a primary disorder and results from the loss of thyroid tissue, which leads to inadequate production of thyroid hormones (primary hypothyroidism). It is most frequently autoimmune in origin but can also be related to iodine deficiency. Secondary hypothyroidism, which occurs in only 5% of cases, is caused by a failure of the pituitary gland to stimulate the thyroid gland or a failure of the target tissues to respond to the thyroid hormones. Tertiary hypothyroidism is caused by failure of the hypothalamus to produce thyroid-releasing factor.

The most common cause of goitrous hypothyroidism in North America is Hashimoto's disease, which causes defective iodine binding and defective thyroid hormone production. Hashimoto's disease is common in the same family and is considered an autoimmune disorder leading to chronic inflammation of the thyroid gland and hypothyroidism but can also lead to hyperthyroidism.

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