Underestimation of Thyroid Dysfunction Risk Due to Regression Dilution Bias in a Long-Term Follow-Up: Tehran Thyroid Study (TTS)

Thyroid dysfunction is linked with mortality and particular diseases. Intra-individual variability of measured thyroid function parameters may bias its association with outcomes, the so called "regression dilution" bias. Single measurements of thyroid function parameters result in underestimation of real associations between outcome rates with the "usual life-long levels" of the aforesaid parameters. The aim of this study was to examine the intra-individual variability of FT4 and TSH of study cohorts in the Tehran Thyroid Study (TTS) and to investigate the extent of the risk underestimation during the 4 phases (Ph) of TTS, with median follow-up of 4, 7, and 10 years between the Ph2-Ph1, Ph3-Ph1, and Ph4-Ph1 intervals; respectively. We estimated regression dilution ratios (RDRs) by the Rosner method of linear regression of repeated measures for FT4 and TSH. RDR1, RDR2, and RDR3 were obtained by regressing the repeated measures of the aforesaid parameters of the last 3 TTS follow-ups on the baseline measurements. Calculations showed 0.64 RDR1, 0.58 RDR2, and 0.52 RDR3 for TSH; and 0.62 RDR1, 0.57 RDR2, and 0.55 RDR3 for FT4. A single measurement-based risk estimation in the TTS was underestimated for FT4 about 61.2, 76.5, and 80.4%; and for TSH as 55.8, 73.1 and 93% after 4, 7, and 10 years of follow-up; respectively. In conclusion, using only single measurements of TSH and FT4 the association between thyroid function and outcome rates is considerably underestimated, especially after a long follow-up period.