The major hormone secreted by the thyroid is thyroxine(T₄) which is converted in many tissues to the more potent triiodothyronine (T₃). Both are bound reversibly to plasma proteins, primarily thyroxine-binding globulin (TBG). Only the free (unbound) fraction enters cells and produces biological effects. T₄  secretion is stimulated by thyroid-stimulating hormone (TSH).  In-turn, TSH secretion is inhibited by T₄ , forming a negative feedback loop that keeps free T₄ levels within a narrow normal range.

Diagnosis of thyroid disease is based on clinical findings, palpation of the thyroid, and measurement of plasma TSH and thyroid hormones (Arch Intern Med 160:1573, 2000).

1. Thyroid palpation determines the size and consistency of the thyroid gland and the presence of nodules, tenderness, or a thrill.
2. Plasma TSH is the initial test of choice in most patients with suspected thyroid disease, except when thyroid function is not in a steady state(Endocrinol Metab Clin North Am 30:245, 2001). TSH levels are elevated even in mild primary hypothyroidism and are suppressed to less than 0.1 mU/ml even in mild hyperthyroidism.

Thus, a normal plasma TSH level excludes hyperthyroidism and primary hypothyroidism. Because even slight changes in thyroid hormone levels affect TSH secretion, abnormal TSH levels are not specific for clinically important thyroid disease. Changes in plasma TSH lag behind changes in plasma T₄, and TSH levels may be misleading when plasma T₄ levels are rapidly changing, as during treatment of hyperthroidism.

• Plasma TSH is mildly elevated (upto 20 mU/ml) in some euthyroid patients with nonthyroidal illness and in mild (also known as subclinical hypothyroidism).
• TSH levels may be suppressed to less than 0.1 mU/ml in severe nonthyroidal illness, in mild (also known as subclinical) hyperthyroidism, and during treatment with dopamine or high doses of glucocortocoids. Also, TSH levels remain less than 0.1 mU/ml for some time after hyperthyroidism is corrected.
• TSH levels are usually within the reference range in secondary hypothyroidism and are not useful for detection of this rare form of hypothyroidism.

3. Plasma free T₄ confirms the diagnosis and assesses the severity of hyperthyroidism when plasma TSH is less than 0.1 mU/ml. It is also used to diagnose secondary hypothyroidism and adjust T₄ therapy in patients with pituitary disease. Most laboratories measure free T₄  by analog immunoassays. Older tests, such as total T₄  assays or T₄ index, are less reliable and should no longer be used.
4. Free T₄ measured by equilibrium dialysis is the most reliable measure of thyroid status, but results seldom are rapidly available. It is needed only in rare cases in which the diagnosis is not clear from measurement of plasma TSH and free T₄ by analog immunoassay.
5. Effect of nonthyroidal illness on thyroid function tests (Endocrinol Metab Clin North Am 31:159, 2002). Many illnesses alter thyroid tests without causing true thyroid dysfunction (the nonthyroidal illness or euthyroid sick syndrome). These changes must be recognized to avoid mistaken diagnosis and therapy.
   • the low T₃ syndrome occurs in many illnesses, during starvation, and after trauma or surgery. Conversion of T₄ to T₃ is decreased, and plasma T₃ levels are low. Plasma T₄ and TSH levels are normal. This may be an adoptive response to illness, and thyroid hormone therapy is not beneficial.
   • the low T₄ syndrome occurs in severe illness. Plasma total T₄ levels fall as a result of decreased levels of TBG and perhaps inhibition of T₄ binding to TBG. When measured by commonly available analog immuoassays, free T₄ may be low. However, plasma free T₄, measured by equilibrium dialysis usually remains normal. TSH levels decrease early in severe illness, sometimes to less than 0.1 mU/ml. During recovery they rise, sometimes to levels higher than the normal range (although rarely >20 mU/ml).
6. A number of drugs affect thyroid function tests. Iodine-containing drugs (Amiodarone and radiographic contrast media) may cause hyperthyroidism in susceptible patients. In general, plasma TSH levels are a reliable guide to determining whether true hyperthyroidism or hypothyroidsm is present.

Reference: “The Washington Manual of medical therapeutics”