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A comprehensive search of the medical literature was performed on Endocrinology texts, UpToDate®, and These resources were queried for general content. PubMed was accessed for specific references during January 2008.

Disorders of the thyroid gland are a common problem encountered in a primary care setting. Normal thyroid function is essential to many cellular and metabolic processes which are important throughout the life cycle. Abnormalities of function may lead to a wide variety of nonspecific and subtle or overt signs and symptoms. Among the disorders that present to the primary care provider are hypothyroidism, hyperthyroidism, thyroid nodules, goiter, thyroid cancers, and even nonthyroidal illness. The routine screening for thyroid disease is not recommended by most consensus groups, thus the primary care provider must recognize the need for evaluation of thyroid function when appropriate.

The thyroid is an endocrine gland controlled by a feedback loop involving the hypothalamus, pituitary gland, and the thyroid gland. The hypothalamus produces thyrotropin-releasing hormone (TRH) which stimulates the pituitary gland to produce thyroid-stimulating hormone (TSH). TSH controls the formation and release of the hormones serum thyroxine (T4) and serum triiodothyronine (T3). All of T4 is made in the thyroid gland while only 20% of T3 is formed in the thyroid. Eighty percent of T3 is formed by the deiodination of T4 to T3 in the peripheral tissue (predominately in the liver and kidneys) in the presence of 5′ monodeiodinase. Serum T3 and T4 regulate the release or suppression of the TRH and TSH from hypothalamus and pituitary, respectively, in a feedback loop.1

Nearly all of T3 and T4 isprotein-bound by thyroxine-binding protein or albumin. The unbound portion of thyroid hormone is referred to as free T4 and free T3 which are the physiologically active forms of hormone. Protein binding is important in regulation of uptake by tissues and for providing a reserve of hormone.1

Testing for thyroid abnormalities varies depending on the clinical situation but generally begins with the evaluation of the TSH and free T4 levels. Other tests of thyroid function may be necessary. The measurement of Total T4 and Total T3 is seldom indicated. Free T4 and free T3 will be referred to as T4 and T3 throughout this text.

Hypothyroidism is the manifestation of a deficiency of thyroid hormones. The symptoms may vary from severe as seen with myxedema coma to absent as with subclinical hypothyroidism.


There are many different causes of hypothyroidism including autoimmune disorders, iatrogenic causes, and secondary to other disease processes. Table 27-1 illustrates many of the conditions that may cause hypothyroidism.1

Table 27-1. Conditions Resulting in Hypothyroidism

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