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Submitted on December 4, 2007
Accepted on March 17, 2008
Academic Unit of Diabetes, Endocrinology & Metabolism, and Department of Automatic Control & Systems Engineering, The University of Sheffield, Sheffield S1 3JD, UK; Chemical Pathology, Royal Hallamshire Hospital, Sheffield S10 2JF, UK; Department of Endocrinology, Christie Hospital, Manchester M20 4BX, United Kingdom
* To whom correspondence should be addressed. 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 optimising thyroid hormone replacement therapy we have used modern assays for FT4 and FT3 to investigate circadian rhythmicity.
Setting: University Hospital.
Design and subjects: Cross sectional study in 33 healthy individuals with 24 hour blood sampling (TSH in 33 and FT4 and FT3 in 29 individuals) and cosinor analysis.
Results: 100% of individuals 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 0404h. The group cosinor model predicts that TSH hormone levels remain above the mesor between 2020 h and 0820 h and for FT3 from 2200 h to 1000 h. Cross correlation of FT3 with TSH showed that the peak correlation occurred with a delay of 0.5–2.5 hours. 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.
Conclusion: FT3 shows a circadian rhythm with a periodicity that lags behind TSH suggesting the periodic rhythm of FT3 is due to the proportion of T3 derived from the thyroid. Optimising thyroid hormone replacement may need to take these rhythms into account.
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