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The thyroid gland plays an integral role in normal development and metabolism in humans. Diseases of the thyroid gland have a familial tendency and are more common in females. The thyroid gland depends on adequate levels of dietary iodine to synthesize thyroid hormones. In the circulation the thyroid hormones are highly bound (>99%) to binding proteins including thyroid-binding globulin, thyroid-binding prealbumin, and albumin. It is the free hormone that is active in the cells. Specific cellular deiodinases convert T4 to T3; T3 binds to the thyroid nuclear receptor and elicits the cellular response.

The hypothalamic-pituitary-thyroid axis is under classic negative feedback control. The hypothalamus produces a tripeptide, thyrotropin-releasing hormone (TRH), which stimulates the pituitary to release thyroid-stimulating hormone (TSH), and TSH stimulates the thyroid follicle to release T4 and Tr Thyroxine is converted by a specific pituitary deiodinase to T3, and the T3 exerts a negative influence on TSH production.

Thyroid Function Tests

Thyroid-Stimulating Hormone

The development of ultrasensitive TSH assays has had a profound impact on thyroid function testing. These new assays allow differentiation between normal and low levels of TSH. This increase in assay sensitivity has changed clinical practice and improved the usefulness of this assay as a screening test. The American College of Obstetricians and Gynecologists recommends routine TSH testing among women more than 18 years old.


A total T4 level is a good measure of circulating T4 in patients with normal binding proteins, and it gives an idea of the amount of free hormone. A number of factors influence thyroid-binding proteins. Estrogen can significantly increase thyroid-binding proteins and hence increase the total amount.


Antithyroglobulin and antimicrosomal (or antithyroid per-oxidase) antibodies are important in evaluating subjects for the presence of Hashimoto's thyroiditis, especially if there is any question about the diagnosis. In subjects with subclinical hypothyroidism (high ultrasensitive TSH, normal free T4), high levels of these antibodies suggest a high risk of progression to clinical hypothyroidism. Thyroid-stimulating antibodies are often seen in Graves' disease.

The clinical manifestations of overt hyperthyroidism are directly related to the action of excess free T4. Hyperthyroidism has a number of different causes, including excess production and release of thyroid hormone (as seen in Graves' disease), an autonomous nodule, and toxic multi-nodular goiter; excess release of thyroid hormone from a damaged gland (as seen in thyroiditis); and excess ingestion of exogenous thyroid hormone.

The signs and symptoms of hyperthyroidism are multiple and depend on the age of the patient, underlying cause, and absolute level of hormone. The classic findings include heat intolerance, weight loss, nervousness, increased sweating, tachycardia, diarrhea, and tremor. Other manifestations may be disease specific, such as pretibial myxedema, diffusely enlarged goiter, and the eye changes of Graves' disease. The elderly patient may present differently, with flat affect, weakness, weight loss, high-output cardiac failure, or atrial fibrillation, which is known as apathetic hyperthyroidism.


The signs and symptoms associated with hypothyroidism are primarily determined by circulating T4 levels. Hypothyroidism has a number of causes, including autoimmune destruction of the thyroid (as seen with Hashimoto's thyroiditis), ablation of functional thyroid after surgery or therapy with radioactive iodine, hypothalamic pituitary dysfunction, and congenital abnormalities in thyroid hormone synthesis.

The clinical manifestations of overt hypothyroidism include cold intolerance, lethargy, weight gain, hypothermia, hyperlipidemia, hair loss, constipation, and bradycardia. Untreated patients with long-standing hypothyroidism may pass into a hypothermic, stuporous state that may be fatal. This is referred to as myxedema coma. Autoimmune thyroiditis may be associated with other autoimmune diseases including diabetes mellitus, Addison's disease, hypoparathyroidism, premature ovarian failure, pernicious anemia, and vitiligo.

The treatment of overt hypothyroidism requires replacement with levothyroxine. The use of combinations of thyroid hormones, thyroid extract, or T3 should be discouraged as primary treatment. The usual replacement dose of levothyroxine is 1.6 :g/kg per day. Therapy may be initiated at anywhere

Subclinical Hypothyroidism

An elevated TSH level with a normal free T4 level defines subclinical hypothyroidism. This condition has a number of causes, including autoimmune thyroiditis, iatrogenic destruction of the thyroid, and congenital abnormalities.

Patients with subclinical hypothyroidism have a higher frequency of lipid abnormalities, including abnormalities of lipoprotein, and a recent study suggests increased progression of coronary artery plaques. Other manifestations that have been attributed to subclinical hypothyroidism.

Pregnancy and Hypothyroidism

The elevated estrogen levels in pregnancy cause profound increases in thyroid-binding proteins. In the hypothyroid patient, the dose of levothyroxine may need to be increased to maintain the euthyroid state. It is important to monitor TSH levels during pregnancy; checking the TSH level once each trimester is probably sufficient. Occasionally, hypothyroidism can improve during pregnancy, probably because of the immune modulation of pregnancy, and the dose of levothyroxine may need to be lowered.

Postpartum Thyroiditis

Postpartum thyroiditis occurs in 5-9% of women after the birth of a child. This condition is characterized by varying degrees of transient hyperthyroidism and hypothyroidism. These patients can experience multiple symptoms during the period of transient abnormal function.