>I agree that measurement of TBG should be retained in some laboratories
>because individuals without TBG are not that rare and new mutations in the
>gene for TBG are described every year (or so it seems).
>Subjects without TBG have been mistakenly treated for hypothyroidism
>not so long ago (Clin Chem 40: 2323, 1994).
>Adrian Vladutiu
Well I'm not sure that this is a good argument for retaining TBG
assays. The measurement of FT4 was/is intended, inter alia, to
obviate the incorrect treatment that subjects with low serum T4
(resulting from a genetic lack of TBG - typically young boys) have
sometimes received. The possibility of such occurrences can only be
eliminated by insisting that all patients with low serum T4 are
tested for TBG or, more sensibly, FT4. But obviously this implies
that it would be better and more economical for FT4 to be initially
determined in all patients suspected of thyroid abnormality.
The same argument applies in the case of subjects with genetic
variants of TBG. Adrian Vladutiu's comment implies that in the case
of patients with abnormal T4 we should not only be measuring the
serum TBG concentration per se but the protein's T4 binding capacity
and affinity. This doesn't seem a sensible strategy
But I must again emphasize that the assumption underlying the
clinical measurement of FT4 is that the free hormone hypothesis
(i.e. that the FT4 concentration as measured in vitro determines T4's
physiological effects in vivo) is valid, and that this assumption is
questionable. For example, all reliable modern methods (including
the symmetric dialysis methods developed by Alex Ross and his
colleagues in the Netherlands) show a reduction in FT4 in pregnancy,
though values generally lie within the normal reference range. This
observation conflicts with the teachings of the free hormone
hypothesis.
--
Roger Ekins
Molecular Endocrinology
University College London Medical School
London W1N 8AA
Fax +44 20 7580 2737
Phone +44 20 7679 9410
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