Learn to answer troublesome questions about thyroid tests

Medical Laboratory Observer, Oct, 1996 by Diana Trundle

Studies of the third-generation assays revealed that TSH was in fact suppressed in hyperthyroidism. This extended the clinical applications for the TSH assay to cover the full spectrum of thyroid disease. The TSH test had become the accepted standard test to estimate thyroid status.

Because TSH is exquisitely sensitive to changes in metabolic status, a twofold change in [T.sub.4] or F[T.sub.4] concentration causes a tenfold change in TSH concentration. This log/linear relationship, shown in Figure 2, explains why TSH is an earlier, superior indicator of subclinical or pre-clinical abnormalities of thyroid homeostasis.

The second- and third-generation TSH assays, however, are not without flaws. Along with their exquisite sensitivity and improved diagnostic capability came attendant problems of nonspecificity. Low TSH concentrations are not always indicative of hyperthyroidism. TSH is not specific for thyroid disease; it is an indirect assessment of thyroid status, an indicator of abnormalities. As with all laboratory tests, correct application and interpretation depend on knowledge of the multiple factors that affect the circulating concentrations.

The utility of the third-generation assays is their ability to distinguish extremely low TSH concentrations associated with true hyperthyroidism from suppressed values seen in nonthyroidal illnesses. Having the results of a third-generation assay is mandatory to establish and monitor the thyroxine dosage required to obliterate residual tumor cells in patients with thyroid cancer. But is a third-generation TSH assay needed for most applications? That is debatable.

Although some experts recommend the exclusive use of third-generation TSH assays, financial considerations are a strong argument for routine use of second-generation assays, which are adequate for most clinical applications. Keep in mind that the analytical goals - timeliness, cost, convenience, or accuracy - vary with the clinical situation.

Turnaround time and timeliness. How soon is the answer needed? Is the patient acutely ill? Is abnormal cardiac activity present? Is the patient scheduled for surgery? Is myxedema coma a possible diagnosis? Is the clinician trying to role out thyroid disease or confirm a clinical diagnosis of thyroid disease?

Cost or convenience may outweigh precision. If the test is used for screening an asymptomatic ambulatory population in a low-risk group, a fully automated economical assay may be adequate. A second-generation assay would meet this need.

Accuracy expectations relate to patient care decisions. The accuracy and precision required for diagnosing hypothyroidism or Graves' disease and suppressing thyroid cancer differ.

For diagnosing hypothyroidism, a first-generation assay is sufficient because one is looking at the difference between TSH concentrations of 5 and 10 mU/L. Specificity is optimal at results over 10 mU/L. Values falling in the range of 5 to 10 mU/L usually are early or preclinical hypothyroidism, but may represent the influence of nonthyroidal illness or euthyroid individuals falling outside the Gaussian distribution.