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has someone experience in T4 levels?
It is very well described for TSH a circadian rhythm, but there is
not so clear for T4, or at least, I have not found so many literature
I have 12-h T4 levels of a relatively high sample of healthy young
people in basal conditions showing a profile with significantly
higher levels at 10 am and 12am related to 8am, but the difference is
at maximum 0.60mcg/l. Can those differences be considered as
clinically significant?, Can it be considered as a circadian rhythm?
Has someone any paper that could helps me?
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You can try to model your data to explore if a (significant) circadian
rhythm is present.
The following strategy can be used:
1. The first and very simple model could be a constant (time invariant)
This model will give you same model predictions at every time point.
The number of parameters in this model is equal to one (baseline):
Effect (T4 levels) = Baseline.
2. More complex models can then be used to describe time tendencies
(circadian rhythms) in the data.
Those models use periodic functions (i.e., cosine functions)  or
several other functions .
3. Model predictions, residual plots, AIC value, minimum value of the
objective function obtained from the
very basic model can be compared with those obtained from the complex
models to evaluate if model
complexity is supported by the data.
In particular, periodic functions are really easy to implement in NONMEM
(see documentation from the recent
intermediate NONMEM workhops) and Winnonlin (see example in page 743 in
and Pharmacodynamic Data Analysis: Concepts and Applications, by
Gabrielsson and Weiner; 2nd edition).
 Hempel G et al. Population pharmacokinetic-pharmacodynamic modeling
of moxonidine using 24-hour
ambulatory blood pressure measurements. Clin. Pharmacol. Ther. 1998; 64:
 Chakraborty et al. Mathematical modelling of circadian cortisol
concentrations using indirect response models:
comparison of several methods. J. Pharmacokin. Biopharm. 1999; 27: 23-43.
Hope this help.
Inaki F. Troconiz
Farmacia y Tecnologia Farmaceutica
Facultad de Farmacia
Universidad de Navarra
Tph: +34 948 42 56 00 ext. 6507
Fax: +34 948 42 56 49
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