I have to clarify my previous remark. It
seems that 1 in 15,000
individuals (in most countries) does not have "measurable"
TBG, in other
words absence of TBG is not exceedingly rare. Therefore, it
appears
reasonable to have some laboratories able to perform TBG quantitation
(not
TBG affinity for T4 or TBG binding capacity). The cases with
strong
suspicion of complete TBG deficiency (in contrast with merely
decreased
TBG) could be referred to some research labs that can easily find out
the
mutations in the TBG gene or alterations of its promoter. The
"abnormal"
TBG often have "geographical" names (similar to hemoglobins
of the past).
TBG is X-linked, therefore complete TBG deficiency is found mostly
in
males. I do not think that TBG quantitation should be performed in
all
individuals with decreased T4 and measurement of "free T4"
is more common.
The Valentine' Day poetry of Prof. Ekins is greatly
appreciated!
AOV
Also in conclusion, I should also clarify my previous remarks
(directed to Adrian Vladutiu). Graham Beastall's original
message questioned the value of continuing with TBG assays. The
consensus view seems to be that such assays are of little diagnostic
value per se, although Graham (in an e-mail to me of 13th Feb
which may not have been generally circulated) indicated that they may
occasionally be of value to unravel certain difficult diagnostic
problems. I take this to mean that a knowledge of the TBG
concentration may be helpful in clarifying apparently contradictory
results - and I agree that such knowledge can be useful.
I also agree with Adrian Vladutiu that it would be a pity if no
research laboratory were available to which anomalous samples could be
sent for detailed investigation of their TBG content and the
properties of the TBG they contain. TBG is a bizarre
protein in that its total absence (which, for the reasons given by
Adrian Vladutiu, is generally confined to males) has no apparent
physiological effect. Are therefore its presence in human serum,
and the increase in its concentration in pregnancy, merely
genetic accidents without purpose? Is this also true of other specific
hormone binding proteins present in blood ? And why does the rise in
corticosteroid-binding globulin (CBG) in pregnancy occur only in
mammalian species with haemochorial or haemoendothelial placentae (see
Seal VS and Doe RP. "Corticosteroid-binding globulin:
Biochemistry, physiology and phylogeny. In Pincus G, Nadac T, Tait JF;
Eds. Steroid Dynamics. Academic Press, New York; 63-90, 1966)?
These questions underlay my hypothesis (see Ekins R .
"Roles of serum thyroxine- binding proteins and maternal thyroid
hormones in fetal development" [Hypothesis] Lancet i. 1129-1132,
1985) that TBG's role is to ensure adequate transport of maternal T4
to the fetus (prior to the development of the fetal thyroid), in which
I postulated that a supply of T4 is of crucial importance
to early fetal neurological development (as is now increasingly
accepted). (This hypothesis stemmed in part from collaborative studies
- with Dr Peter Pharoah and Prof Kevin Connolly - in New Guinea
where in certain regions some 15% of children are born neurological
cretins.)
Hence my instant poem. I'm delighted it was appreciated by
Adrian Vladutiu, albeit I had, of course, another, fairer, recipient
in
mind.
--
Roger Ekins
Molecular Endocrinology
University College London Medical School
London W1N 8AA
Fax +44 20 7580 2737
Phone +44 20 7679 9410