The TSH reference interval is still controversial. One reason is that TSH measurement is dependent on the method used. Different concentrations can be obtained from different assays. Therefore, when monitoring a patient, we recommend using the same assay from the same laboratory.
Another reason for varying reference intervals is the variation in study results and expert opinion. A review of data from NHANES III suggests that the upper limit of the reference interval is close to 4 mIU/L.2 The National Academy of Clinical Biochemists has suggested a much lower cutoff of 2.5 mIU/L.3 In 2012, the American Association of Clinical Endocrinologists (AACE) and the American Thyroid Association (ATA) suggested using the reference interval established by any given laboratory that is using a third generation TSH assay. If this is not available, the next option would be to use the NHANES III range of 0.45-4.12 mIU/L.4
Most clinical laboratories have not lowered the upper cutoff for TSH based on observations that “22 to 28 million more Americans would be diagnosed with hypothyroidism without any clinical or therapeutic benefit from this diagnosis.”5 Surveys of academic clinical endocrinologists have shown that many physicians may monitor patients more frequently once the TSH rises above the 2.5 to 3.0 mIU/L cutoff, but few will treat until the TSH is significantly higher (eg, 10 mIU/L or more) or unless other significant cofactors (eg, antithyroid antibodies, low free T4) are present.
Different TSH clinical cutoffs are used for pregnant women. These cutoffs are based on clinical studies showing adverse health effects of maternal hypothyroidism for both mother and infant. The ATA released guidelines in 2011 that specify lower cutoffs for TSH during pregnancy.6 If a lab does not have its own trimester-specific TSH reference intervals, then the ATA suggests using a TSH reference interval of 0.1–2.5 mIU/L during the first trimester, 0.2–3.0 mIU/L during the second trimester, and 0.3–3.0 mIU/L during the third trimester. Not all those who have a TSH above the trimester-specific cutoff need treatment, but they should all be evaluated further (eg, TPO antibody testing) and monitored more closely.
Low TSH values (below the laboratory’s reference interval) do not always indicate hyperthyroidism and a need to treat. Low values might indicate a need for further evaluation, especially when symptoms of hyperthyroidism are present.