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Month-to-month variations in serum thyrotropin and thyroxine concentrations in normal subjects

(July 2002)

The background of the study. The reference ranges for serum thyrotropin (TSH) and thyroxine (T4) in normal subjects are broad, which helps to explain the high frequency of subclinical thyroid disease (high or low serum TSH concentrations and normal serum T4 concentrations). The variations are due to analytical and biologic variation, which may include circadian and seasonal variation both within and between subjects. This study was done to determine the extent of variation within and between normal subjects over a one-year period.

How the study was done. The study subjects were 16 normal men living in Denmark. Blood samples for measurement of serum TSH and T4 were collected between 9 am and noon monthly for 12 months. The samples were analyzed at the end of the study. The analytical coefficients of variation of the assays ranged from 2 to 4 percent.

The results of the study. There were substantial variations within subjects and even larger variations between subjects for all measurements, so that thyroid function was unique in each man. The variation for each man was approximately half that for the group as a whole, indicating that an individual man could have substantial changes in serum TSH or T4 concentrations, yet the values remain within the group or reference range.

There was a weak positive correlation between serum TSH and T4 concentrations. Based on the analytical and within-subject variations, highly precise (90 percent accurate) definition of these interrelationships would require repeated measurements. Based on these same variations, to be significant at the 5 percent level the measured serum TSH concentration would need to change on average by 0.75 mU/L, and the respective change in serum T4 would need to be 2.2 µg/dl (28 nmol/L).

The conclusions of the study. Serum TSH and T4 concentrations vary substantially from month to month in individual normal subjects and even more so between normal subjects.

The original article. Andersen S, Pedersen KM, Bruun NH, Laurberg P. Narrow individual variations in serum T4 and T3 in normal subjects: a clue to the understanding of subclinical thyroid disease. J Clin Endocrinol Metab 2002;87:1068-72.

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