Narrow Individual Variations in Serum T4 and T3 in Normal Subjects: A Clue to the Understanding of Subclinical Thyroid Disease

S Andersen, KM Pedersen, NH Bruun… - The Journal of Clinical …, 2002 - academic.oup.com
S Andersen, KM Pedersen, NH Bruun, P Laurberg
The Journal of Clinical Endocrinology & Metabolism, 2002academic.oup.com
High individuality causes laboratory reference ranges to be insensitive to changes in test
results that are significant for the individual. We undertook a longitudinal study of variation in
thyroid function tests in 16 healthy men with monthly sampling for 12 months using standard
procedures. We measured serum T4, T3, free T4 index, and TSH. All individuals had
different variations of thyroid function tests (P< 0.001 for all variables) around individual
mean values (set points)(P< 0.001 for all variables). The width of the individual 95 …
High individuality causes laboratory reference ranges to be insensitive to changes in test results that are significant for the individual. We undertook a longitudinal study of variation in thyroid function tests in 16 healthy men with monthly sampling for 12 months using standard procedures. We measured serum T4, T3, free T4 index, and TSH. All individuals had different variations of thyroid function tests (P < 0.001 for all variables) around individual mean values (set points) (P < 0.001 for all variables). 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. 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.
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