Thyroxine-binding globulin

Thyroxine-binding globulin (TBG) binds Thyroid hormone in circulation. It is one of three proteins (along with transthyretin and albumin) responsible for carrying the thyroid hormones thyroxine (T4) and 3,5,3’-triiodothyronine (T3) in the bloodstream. Of these three proteins, TBG has the highest affinity for T4 and T3, but is present in the lowest concentration. Despite its low concentration, TBG carries the majority of T4 in serum. Due to the very low serum concentration of T4 & T3, TBG is rarely more than 25% saturated with its ligand. Unlike transthyretin and albumin, TBG has a single binding site for T4/T3. TBG is synthesized primarily in the liver as a 54 kDa protein. Genomically, TBG is a serpin, although it has no inhibitory function like many other members of this class of proteins.

Role in Diagnosis

TBG tests are sometimes used in finding the reason for elevated or diminished levels of thyroid hormone. This is done by measuring resin binding to labeled thyroid hormone, which only happens when the labeled thyroid hormone is free.

The patient's serum is mixed with the labeled thyroid hormone; then, the resin is added to the whole mixture, to measure the amount of free labeled thyroid hormone. So, for instance, if the patient is truly hypothyroid, and TBG levels are normal, then there are many sites open for binding on the TBG, since the total thyroid hormone level is low. Therefore, when the labeled hormone is added, it will mostly bind to the TBG, leaving little of it left for binding to the resin. Conversely, if the patient is truly hyperthyroid, and TBG levels are normal, the patient's endogenous hormone will saturate the TBG binding sites more, leaving less room for the labeled hormone, which allows greater binding to the resin.

In the situations described above, TBG testing is not very useful. However, total thyroid hormone levels point to hypothyroidism or hyperthyroidism, without the expected symptoms, the utility of TBG testing becomes more evident, since TBG production can be modified by other factors such as estrogen, corticosteroids, or liver failure. If, for example, the TBG level is high, which can occur when estrogen levels are high, the TBG will bind more thyroid hormone, decreasing the free hormone available in the blood, which leads to stimulation of TSH, and the production of more thyroid hormone. In this case, the total thyroid hormone level will be high. However, when labeled hormone is added, since TBG is so high, it will bind to the TBG, leaving little free labeled hormone for uptake into the resin. Conversely, in the presence of corticosteroids, which lower TBG levels, the total thyroid hormone (bound and free) in the blood will be low. However, when the labeled hormone is added, since so little TBG is available in the blood, only a small portion of it will bind, leaving plenty available for uptake by the resin.

External links

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Further reading

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citations =
*cite journal | author=Cheng SY |title=Partial amino acid sequence of human thyroxine-binding globulin. Further evidence for a single polypeptide chain |journal=Biochem. Biophys. Res. Commun. |volume=79 |issue= 4 |pages= 1212–8 |year= 1978 |pmid= 414747 |doi=
*cite journal | author=Shirotani T, Kishikawa H, Wake N, "et al." |title=Thyroxine-binding globulin variant (TBG-Kumamoto): identification of a point mutation and genotype analysis of its family |journal=Endocrinol. Jpn. |volume=39 |issue= 6 |pages= 577–84 |year= 1993 |pmid= 1294376 |doi=
*cite journal | author=Bertenshaw R, Sarne D, Tornari J, "et al." |title=Sequencing of the variant thyroxine-binding globulin (TBG)-San Diego reveals two nucleotide substitutions |journal=Biochim. Biophys. Acta |volume=1139 |issue= 4 |pages= 307–10 |year= 1992 |pmid= 1515456 |doi=
*cite journal | author=Bertenshaw R, Takeda K, Refetoff S |title=Sequencing of the variant thyroxine-binding globulin (TBG)-Quebec reveals two nucleotide substitutions |journal=Am. J. Hum. Genet. |volume=48 |issue= 4 |pages= 741–4 |year= 1991 |pmid= 1901689 |doi=
*cite journal | author=Imamura S, Mori Y, Murata Y, "et al." |title=Molecular cloning and primary structure of rat thyroxine-binding globulin |journal=Biochemistry |volume=30 |issue= 22 |pages= 5406–11 |year= 1991 |pmid= 1903654| doi=10.1021/bi00236a012
*cite journal | author=Janssen OE, Takeda K, Refetoff S |title=Sequence of the variant thyroxine-binding globulin (TBG) in a Montreal family with partial TBG deficiency |journal=Hum. Genet. |volume=87 |issue= 2 |pages= 119–22 |year= 1991 |pmid= 1906047| doi=10.1007/BF00204164
*cite journal | author=Yamamori I, Mori Y, Seo H, "et al." |title=Nucleotide deletion resulting in frameshift as a possible cause of complete thyroxine-binding globulin deficiency in six Japanese families |journal=J. Clin. Endocrinol. Metab. |volume=73 |issue= 2 |pages= 262–7 |year= 1991 |pmid= 1906892 |doi=
*cite journal | author=Li P, Janssen OE, Takeda K, "et al." |title=Complete thyroxine-binding globulin (TBG) deficiency caused by a single nucleotide deletion in the TBG gene |journal=Metab. Clin. Exp. |volume=40 |issue= 11 |pages= 1231–4 |year= 1991 |pmid= 1943753 |doi=
*cite journal | author=Waltz MR, Pullman TN, Takeda K, "et al." |title=Molecular basis for the properties of the thyroxine-binding globulin-slow variant in American blacks |journal=J. Endocrinol. Invest. |volume=13 |issue= 4 |pages= 343–9 |year= 1990 |pmid= 2115061 |doi=
*cite journal | author=Mori Y, Takeda K, Charbonneau M, Refetoff S |title=Replacement of Leu227 by Pro in thyroxine-binding globulin (TBG) is associated with complete TBG deficiency in three of eight families with this inherited defect |journal=J. Clin. Endocrinol. Metab. |volume=70 |issue= 3 |pages= 804–9 |year= 1990 |pmid= 2155256 |doi=
*cite journal | author=Takeda K, Mori Y, Sobieszczyk S, "et al." |title=Sequence of the variant thyroxine-binding globulin of Australian aborigines. Only one of two amino acid replacements is responsible for its altered properties |journal=J. Clin. Invest. |volume=83 |issue= 4 |pages= 1344–8 |year= 1989 |pmid= 2495303| doi=10.1172/JCI114021
*cite journal | author=Mori Y, Seino S, Takeda K, "et al." |title=A mutation causing reduced biological activity and stability of thyroxine-binding globulin probably as a result of abnormal glycosylation of the molecule |journal=Mol. Endocrinol. |volume=3 |issue= 3 |pages= 575–9 |year= 1989 |pmid= 2501669 |doi=
*cite journal | author=Flink IL, Bailey TJ, Gustafson TA, "et al." |title=Complete amino acid sequence of human thyroxine-binding globulin deduced from cloned DNA: close homology to the serine antiproteases |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=83 |issue= 20 |pages= 7708–12 |year= 1986 |pmid= 3094014| doi=10.1073/pnas.83.20.7708
*cite journal | author=Janssen OE, Chen B, Büttner C, "et al." |title=Molecular and structural characterization of the heat-resistant thyroxine-binding globulin-Chicago |journal=J. Biol. Chem. |volume=270 |issue= 47 |pages= 28234–8 |year= 1996 |pmid= 7499319 |doi=
*cite journal | author=Mori Y, Miura Y, Oiso Y, "et al." |title=Precise localization of the human thyroxine-binding globulin gene to chromosome Xq22.2 by fluorescence in situ hybridization |journal=Hum. Genet. |volume=96 |issue= 4 |pages= 481–2 |year= 1995 |pmid= 7557975| doi=10.1007/BF00191811
*cite journal | author=Miura Y, Mori Y, Yamamori I, "et al." |title=Sequence of a variant thyroxine-binding globulin (TBG) in a family with partial TBG deficiency in Japanese (TBG-PDJ) |journal=Endocr. J. |volume=40 |issue= 1 |pages= 127–32 |year= 1994 |pmid= 7951486 |doi=
*cite journal | author=Hayashi Y, Mori Y, Janssen OE, "et al." |title=Human thyroxine-binding globulin gene: complete sequence and transcriptional regulation |journal=Mol. Endocrinol. |volume=7 |issue= 8 |pages= 1049–60 |year= 1993 |pmid= 8232304| doi=10.1210/me.7.8.1049
*cite journal | author=Akbari MT, Kapadi A, Farmer MJ, "et al." |title=The structure of the human thyroxine binding globulin (TBG) gene |journal=Biochim. Biophys. Acta |volume=1216 |issue= 3 |pages= 446–54 |year= 1994 |pmid= 8268226 |doi=
*cite journal | author=Mori Y, Miura Y, Takeuchi H, "et al." |title=Gene amplification as a cause of inherited thyroxine-binding globulin excess in two Japanese families |journal=J. Clin. Endocrinol. Metab. |volume=80 |issue= 12 |pages= 3758–62 |year= 1996 |pmid= 8530630 |doi=
*cite journal | author=Carvalho GA, Weiss RE, Vladutiu AO, Refetoff S |title=Complete deficiency of thyroxine-binding globulin (TBG-CD Buffalo) caused by a new nonsense mutation in the thyroxine-binding globulin gene |journal=Thyroid |volume=8 |issue= 2 |pages= 161–5 |year= 1998 |pmid= 9510125 |doi=

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