Serum TSH measurement is the single most reliable test to diagnose all common forms of hypothyroidism and hyperthyroidism, particularly in the ambulatory setting. An elevated serum TSH concentration is present in both overt and mild hypothyroidism. In the latter, the serum FT₄ concentration is, by definition, normal. While serum TSH measurement confirms or excludes the diagnosis in all patients with primary hypothyroidism, it will not reliably identify patients with central (secondary) hypothyroidism, in whom serum TSH concentrations may be low, normal, or mildly elevated. When there is suspicion of pituitary or hypothalamic disease, the serum FT₄ concentration should be measured in addition to the serum TSH concentration.

Virtually all types of hyperthyroidism encountered in clinical practice are accompanied by suppressed serum TSH concentrations, typically less than 0.1 mIU/L. These include Graves disease, toxic adenoma and nodular goiter, subacute and lymphocytic (silent, postpartum) thyroiditis, iodine-induced hyperthyroidism, and exogenous thyroid hormone excess. Serum FT₄ measurement and serum triiodothyronine (T₃) assay in patients with a normal serum FT₄ level are indicated to further assess patients with a serum TSH level less than 0.1 mIU/L.

To diagnose hyperthyroidism accurately, TSH assay sensitivity, the lowest reliably measured TSH concentration, must be 0.02 mIU/L or less. Some less sensitive TSH assays cannot reliably distinguish patients with hyperthyroidism from those with euthyroidism. When such less sensitive TSH assays are the only ones available, a serum FT₄ assay or estimate and a total or free T₃ (FT₃) assay should be employed in addition to measurement of the serum TSH concentration. There are 2 rare types of TSH-mediated hyperthyroidism, TSH-secreting pituitary adenomas and selective pituitary resistance to thyroid hormone, that will be overlooked by serum TSH measurement alone; serum FT₄ and FT₃ concentrations should also be measured when these conditions are suspected. Finally, it is important to recognize that isolated abnormalities of the serum TSH concentration do not always connote sustained thyroid dysfunction and may be caused by other conditions and medications.

The causes of isolated TSH elevation include (1) mild (subclinical) hypothyroidism, (2) recovery from hypothyroxinemia of nonthyroid illnesses, and (3) medications such as lithium carbonate and amiodarone. (Inhibition of thyroid hormone production by these drugs may cause both transient reversible elevation of the serum TSH level and true hypothyroidism.) The causes of isolated TSH suppression include (1) mild (subclinical) hyperthyroidism, (2) recovery from overt hyperthyroidism, (3) nonthyroidal illnesses (which can cause a low serum FT₄ concentration), (4) pregnancy during the first trimester, and (5) medications, such as dopamine and glucocorticoids.