Hereditary thyroxine binding globulin deficiency is a genetic condition that usually does not cause any health problems.
Thyroxine-binding globulin (TBG) is a glycoprotein that binds the thyroid hormones T4 and T3 in the bloodstream with an affinity 100 times greater than thyroxine-binding prealbumin (TBPA).
Under normal conditions, TBG non-covalently binds almost the entire concentration of T3 and T4 in plasma. The portion of the thyroid hormone that remains unfixed is responsible for producing biological activity.
TBG is produced in the liver and its synthesis is increased by the action of estrogens.
This can decrease with treatment with androgens or glucocorticoids and in some liver diseases, there may also be hereditary variations of it.
TBG blood test
These tests may be done to diagnose thyroid problems.
If the test is performed by electrophoresis, normal values can range from 10 to 24 mg/100 mL, while radioimmunoassay usually gives normal values of 1.3 to 2.0 mg/100 mL. and normal value ranges may vary slightly between laboratories.
An increased level of TBG may be due to:
-Acute intermittent porphyria (a rare metabolic disorder).
– Hypothyroidism (underactive thyroid).
– Liver disease.
-P regnancy (TBG levels are normally elevated during pregnancy and are elevated in newborns).
The decrease in TBG levels may be due to:
– Hepatic cirrhosis.
– Acute illness.
– Hyperthyroidism (overactive thyroid).
– Nephrotic syndrome.
– Stress from surgery.
Thyroid hormones play an important role in regulating growth, brain development, and the rate of chemical reactions in the body (metabolism).
Researchers have identified two forms of hereditary thyroxine-binding globulin deficiency: the complete form (TBG-CD), which results in a total loss of thyroxine-binding globulin, and the partial form (TBG-PD), which reduces the amount of this protein or its structure is altered.
Neither of these conditions cause problems with thyroid function. They are usually identified during routine blood tests that measure thyroid hormones.
Although hereditary thyroxine-binding globulin deficiency does not cause any health problems, it can be confused with more serious thyroid disorders (such as hypothyroidism).
Therefore, it is important to diagnose hereditary thyroxine binding globulin deficiency to avoid unnecessary treatment.
The full form of hereditary thyroxine-binding globulin deficiency, TBG-CD, affects approximately 1 in 15,000 newborns worldwide.
The partial form, TBG-PD, affects approximately 1 in 4,000 newborns.
Hereditary thyroxine binding globulin deficiency is due to mutations in the SERPINA7 gene. This gene provides instructions for making thyroxine binding globulin.
Also, non-inherited forms of thyroxine-binding globulin deficiency have been described, which are more common than the hereditary form.
Nonhereditary thyroxine binding globulin deficiency can occur with a variety of diseases and is a side effect of some medications.
Hereditary thyroxine-binding globulin deficiency has an X-linked pattern of inheritance. The SERPINA7 gene is located on the X chromosome, which is one of the two sex chromosomes.
In males (who have only one X chromosome), a mutation in the only copy of the gene in each cell causes partial or complete hereditary thyroxine-binding globulin deficiency.
In females (who have two X chromosomes), a mutation in one of the two copies of the gene in each cell reduces the amount of thyroxine-binding globulin.
However, your levels of this protein are usually within the normal range.
To date, approximately 27 different mutations have been identified that play a role in the etiology of the hereditary form of complete TBG deficiency.
These mutations appear to be caused by a nucleotide substitution or by a frame shift.
Missense mutations have been the only type identified so far in an inherited form of partial TBG deficiency.
Acquired forms of TBG deficiency are attributable to impaired synthesis and degradation of the molecule.
Patients with hyperthyroidism have been found to have an increased rate of TBG turnover.
In terminal illness, interleukin-6 appears to play a role in altering TBG levels.
It has been found thatTBG levels also vary with fluctuations in sex hormones.
For example, estrogen is known to cause an increase in TBG, while androgens have been found to decrease TBG levels.
SNPs are mutations in which there is a substitution of nucleotide a for a different nucleotide, often a pyrimidine nucleotide substituting for another pyrimidine nucleotide.
For example, a SNP can replace the nucleotide cytosine (C) with the nucleotide thymine (T) in a certain stretch of DNA.
In the presence of TBG, there would only be a 10% drop in T4 and a 40% drop in T3. Therefore, TBG plays a role in preventing thyroid hormone fluctuations.
Central hypothyroidism can be congenital or acquired. Some critically ill euthyroid patients with nonthyroidal illness may also have low FT4, low T4, and low TSH.
However, most of these patients have elevated levels of reverse T3, (T3reverse) due to reduced metabolism of reverse T3. These abnormalities usually resolve with resolution of nonthyroidal illnesses.
-Pappa T, Ferrara AM, Refetoff S. Inherited defects of thyroxine-binding proteins. Best Practice Res Clin Endocrinol Metab. 2015 Oct;29(5):735-47.
-Refetoff S. Inherited thyroxine-binding globulin abnormalities in man. Endocr Rev. 1989 Aug;10(3):275-93.
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