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>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 ------ACB discussion List Information-------- This is an open discussion list for the academic and clinical community working in clinical biochemistry. Please note, archived messages are public and can be viewed via the internet. Views expressed are those of the individual and they are responsible for all message content. ACB Web Site http://www.acb.org.uk List Archives http://www.jiscmail.ac.uk/lists/ACB-CLIN-CHEM-GEN.html List Instructions (How to leave etc.) http://www.jiscmail.ac.uk/