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Free Triiodothyronine Has a Distinct Circadian Rhythm That Is Delayed but Parallels Thyrotropin Levels

Academic Unit of Diabetes (W.R., A.P.W., R.J.R.), Endocrinology & Metabolism, and Department of Automatic Control and Systems Engineering (R.F.H.), The University of Sheffield, Sheffield S1 3JD, United Kingdom; Chemical Pathology (N.S.), Royal Hallamshire Hospital, Sheffield S10 2JF, United Kingdom; and Department of Endocrinology (K.D., S.S.), Christie Hospital, Manchester M20 4BX, United Kingdom

Address all correspondence and requests for reprints to: Professor Richard J. M. Ross, University of Sheffield, Room 112 Floor M, Royal Hallamshire Hospital, Glossop Road, Sheffield, S10 2JF, United Kingdom. E-mail: r.j.ross{at}sheffield.ac.uk.

Context: TSH is known to have a circadian rhythm, but the relationship between this and any rhythm in T₄ and T₃ has not been clearly demonstrated.

Objective: With a view to optimizing thyroid hormone replacement therapy, we have used modern assays for free T₄ (FT4) and free T₃ (FT3) to investigate circadian rhythmicity.

Setting: The study was performed at a university hospital.

Design and Subjects: This was a cross-sectional study in 33 healthy individuals with 24-h blood sampling (TSH in 33 and FT4 and FT3 in 29 individuals) and cosinor analysis.

Results: Of the individuals, 100% showed a sinusoidal signal in TSH, for FT4 76%, and for FT3 86% (P < 0.05). For FT4 and FT3, the amplitude was low. For TSH the acrophase occurred at a clock time of 0240 h, and for FT3 approximately 90 minutes later at 0404 h. The group cosinor model predicts that TSH hormone levels remain above the mesor between 2020 and 0820 h, and for FT3 from 2200–1000 h. Cross correlation of FT3 with TSH showed that the peak correlation occurred with a delay of 0.5–2.5 h. When time-adjusted profiles of TSH and FT3 were compared, there was a strong correlation between FT3 and TSH levels ( = 0.80; P < 0.0001). In contrast, cross correlation revealed no temporal relationship between FT4 and TSH.

Conclusions: FT3 shows a circadian rhythm with a periodicity that lags behind TSH, suggesting that the periodic rhythm of FT3 is due to the proportion of T₃ derived from the thyroid. Optimizing thyroid hormone replacement may need to take these rhythms into account.

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