Narrow Individual Variations in Serum T4 and T3 in Normal Subjects: A Clue to the Understanding of Subclinical Thyroid Disease
Stig Andersen, Klaus Michael Pedersen, Niels Henrik Bruun and Peter Laurberg
The width of the individual 95% confidence intervals were approximately half that of the group for all variables. Accordingly, the index of individuality was low: T4 = 0.58; T3 = 0.54; free T4 index = 0.59; TSH = 0.49.
One test result described the individual set point with a precision of plus or minus 25% for T4, T3, free T4 index, and plus or minus 50% for TSH. The differences required to be 95% confident of significant changes in repeated testing were (average, range): T4 = 28, 11–62 nmol/liter; T3 = 0.55, 0.3–0.9 nmol/liter; free T4 index = 33, 15–61 nmol/liter; TSH = 0.75, 0.2–1.6 mU/liter.
A test result within laboratory reference limits is not necessarily normal for an individual
Our data indicate that each individual had a unique thyroid function. The individual reference ranges for test results were narrow, compared with group reference ranges used to develop laboratory reference ranges. Accordingly, a test result within laboratory reference limits is not necessarily normal for an individual. Because serum TSH responds with logarithmically amplified variation to minor changes in serum T4 and T3, abnormal serum TSH may indicate that serum T4 and T3 are not normal for an individual.
A condition with abnormal serum TSH but with serum T4 and T3 within laboratory reference ranges is labeled subclinical thyroid disease. Our data indicate that the distinction between subclinical and overt thyroid disease (abnormal serum TSH and abnormal T4 and/or T3) is somewhat arbitrary. For the same degree of thyroid function abnormality, the diagnosis depends to a considerable extent on the position of the patient’s normal set point for T4 and T3 within the laboratory reference range.