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
Department of Endocrinology (S.A., N.H.B., P.L.) and Clinical Biochemistry (K.M.P.), Aalborg Hospital, Aalborg, Denmark DK-9000
Address all correspondence and requests for reprints to: Stig Andersen, M.D., Department of Endocrinology and Medicine, Aalborg Hospital, DK-9000 Aalborg, Denmark. E-mail: . stiga{at}dadlnet.dk
Abstract
High individuality causes laboratory reference ranges to beinsensitive to changes in test results that are significantfor the individual. We undertook a longitudinal study of variationin thyroid function tests in 16 healthy men with monthly samplingfor 12 months using standard procedures. We measured serum T4,T3, free T4 index, and TSH. All individuals had different variationsof thyroid function tests (P < 0.001 for all variables) aroundindividual mean values (set points) (P < 0.001 for all variables).The width of the individual 95% confidence intervals were approximatelyhalf that of the group for all variables. Accordingly, the indexof individuality was low: T4 = 0.58; T3 = 0.54; free T4 index= 0.59; TSH = 0.49. One test result described the individualset point with a precision of plus or minus 25% for T4, T3,free T4 index, and plus or minus 50% for TSH. The differencesrequired to be 95% confident of significant changes in repeatedtesting were (average, range): T4 = 28, 11–62 nmol/liter;T3 = 0.55, 0.3–0.9 nmol/liter; free T4 index = 33, 15–61nmol/liter; TSH = 0.75, 0.2–1.6 mU/liter. Our data indicatethat each individual had a unique thyroid function. The individualreference ranges for test results were narrow, compared withgroup reference ranges used to develop laboratory referenceranges. Accordingly, a test result within laboratory referencelimits is not necessarily normal for an individual. Becauseserum TSH responds with logarithmically amplified variationto minor changes in serum T4 and T3, abnormal serum TSH mayindicate that serum T4 and T3 are not normal for an individual.A condition with abnormal serum TSH but with serum T4 and T3within laboratory reference ranges is labeled subclinical thyroiddisease. Our data indicate that the distinction between subclinicaland overt thyroid disease (abnormal serum TSH and abnormal T4and/or T3) is somewhat arbitrary. For the same degree of thyroidfunction abnormality, the diagnosis depends to a considerableextent on the position of the patient’s normal set pointfor T4 and T3 within the laboratory reference range.
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