ReviewInterpretation of thyroid function tests
Section snippets
Thyroid function tests
The choice of first-line thyroid function tests depends on local arrangements and laboratory protocols. In many laboratories, a highly sensitive TSH assay (second or third generation, with a limit of detection <0·1 mU/L)1 alone is used for initial screening, which is satisfactory so long as its limitations are appreciated. At an increased cost, the sensitive TSH measurement can be combined with a single measurement of total or free thyroid hormone concentrations to address these limitations. T3
Low TSH, raised free T3 or T4
There are six patterns of thyroid function tests. Low TSH, accompanied by raised free T4 and T3 concentrations (panel 2), indicates primary hyperthyroidism, most commonly caused by Graves' disease, multinodular goitre, or toxic nodule. In these cases TSH should be undetectable and thyroid tissue should not be tender. Clinical criteria can usually separate the three common causes of primary hyperthyroidism, however, there is no definitive test for Graves' disease. Thyroid ophthalmopathy and a
Low TSH, normal free T3 or T4
Low TSH and normal free T3 and T4 test results are usually seen with thyroxine ingestion (panel 3). A less common alternative is subclinical primary hyperthyroidism, typically seen in elderly people. Further investigation normally reveals a multinodular goitre. If TSH is wholly suppressed, this situation can require treatment since the risk of atrial fibrillation22 and osteoporosis is increased.23
Among patients in hospital, high-dose steroid or dopamine and dobutamine infusions, both of which
Low or normal TSH, low free T3 or T4
Low or normal TSH and low free T3 or T4 test results represent a typical pattern in unwell patients with nonthyroidal illness, the most common combination of results being a low free T3 with a TSH in the normal range (panel 4). However, in individuals without obvious concomitant disease, pituitary disease with second hypothyroidism should be considered.4
Nonendocrinologists are frequently surprised to find TSH in the normal range in this situation, since the pituitary fails to respond adequately
Raised TSH, low free T4 or T3
This combination of results always indicates primary hypothyroidism (panel 5). In iodine sufficient areas, almost all cases are due to thyroablative therapy for thyrotoxicosis or thyroid cancer (by radioiodine or surgery) or, if they arise spontaneously, autoimmune thyroiditis (manifest as atrophic thyroiditis or Hashimoto's disease).26 Hypothyroidism can develop 20 years or more after radioiodine therapy. Hyperthyroidism can also develop years after thyroid surgery27 or carbimazole-induced
Raised TSH, normal free T4 or T3
This is the pattern of thyroid function normally seen with mild thyroid failure (subclinical hypothyroidism) (panel 6). It is common in the population, affecting 5–10% of all women, and in most cases is associated with positive anti-TPO antibodies. Subclinical hypothyroidism is caused by autoimmune hypothyroidism that has not yet progressed to severe thyroid impairment,46 although it can also follow radioiodine treatment or thyroidectomy.
Although subclinical autoimmune hypothyroidism is by far
Normal or raised TSH, raised free T4 or T3
Normal or raised TSH and raised free T4 or T3 values is an unusual pattern of thyroid function tests, which is often artifactual but is sometimes seen in two rare but clinically important conditions (see below and panel 7). If results of the free T4 and T3 assays are widely discordant with each other, or with the clinical status, then antithyroid hormone (anti-T4 and anti-T3) antibodies interfering with the assay should be suspected. Interference can cause considerable confusion, since it is
Summary of common pitfalls
Panel 8 summarises the five most common circumstances in which modern thyroid function tests are wrongly interpreted. Amiodarone therapy is frequently cited by general physicians as rendering thyroid function tests difficult to interpret, but in fact the impact of amiodarone on TSH concentration rarely leads to a grossly erroneous misunderstanding of the patient's thyroid status. If TSH alone is used as the initial screening test, for thyroid function testing, the most important circumstance in
Conclusion
In most cases, interpretation of thyroid function tests with free hormone assays and TSH is straightforward. However, unusual conditions can generate common patterns of thyroid function, easily confused with more straightforward diseases (Panel 2, Panel 5, Panel 6), and unusual patterns of test results (Panel 3, Panel 4, Panel 7). One or more of the following features should prompt further investigation: (1) abnormal thyroid function in childhood; (2) familial disease; (3) thyroid function
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