Sunday, 8 September 2019

What is Thyroxine binding globulin(TBG) & prealbumin combined in with Free T3


Write an essay on free T3, the most active thyroid hormone at periphery?? :_Let us first recapitulate about what  we recollect on  thyroxine-binding globulin(TBG protein ) as we read in our physiology class :- ?? Ans:-The small amounts of T3 and T4 that don't bind with thyroxine-binding globulin (TBG protein ) are referred to as “free.”  This free T4 and Free T3 in particular are active. Most of the  T3 and T4 in body bind to thyroxine-binding globulin(TBG). This is like SHBG(sex hormone binding globulin) which combines with androgens and only a small part of androgen circulates in active form (free testosterone).The serum TBG level test measures the amount of TBG in  blood. ... The illness causing the low TBG level can cause rise of Free T 3 and cause mild symptoms of hyperthyroidism. Not only Free T3 binds to globulin but the active  thyroid hormones (THs)—thyroxine (T4) and 3,5,3'-triiodothyronine (T3)  also combine with transthyretin (TTR, or prealbumin), and albumin —circulate in blood by reversibly binding to carrier proteins. Although only 0.3% or less of T3 and T4 circulates unbound, it is this free hormone fraction that is metabolically active at the tissue and cellular level.

How many types of TBG are there( globulin & albumin)??  Ans;-The 3 main proteins that carry the majority (>95%) of THs are thyroxine-binding globulin (TBG), transthyretin (TTR, or prealbumin), and albumin. A minor proportion of the Thyroxine  is bound on serum lipoproteins. Very rarely, and in the context of anti-Thyroid antibodies in autoimmune thyroid disease, immunoglobulins also may bind TH. Thyroxine  binding to TBG is characterized by low capacity but high avidity; the converse is true, I e, high capacity but low avidity, for TH binding to TTR and albumin.

Q. How to test TBG : Which methodology??
Normal Results:The normal result range will vary slightly depending on the type of technique the laboratory uses. The two main types of laboratory techniques used for the serum TBG test are electrophoresis and radioimmunoassay. Typically, the results for both types of test are measured in milligrams per 100 milliliters, or mg/100 mL.
Electrophoresis method: of determination of TBG
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During electrophoresis, a lab technician places part of   serum on specially treated paper or a gel-like substance. An electric current then runs through it. The proteins move along the paper or gel and form bands that indicate how much of each protein is in the sample. A lab can analyze these results. If the lab used electrophoresis to test  sample, then normal results will range from 10 to 24 mg/100 mL.
Radioimmunoassay method of determination of TBG
Radioimmunoassay  involves exposing a sample of blood to an antibody. That antibody will attach to TBG. The antibody has a low-level radioactive isotope attached to it. The lab can then measure the amount of radiation in the sample, which indicates the amount of TBG in  blood. If the lab used radioimmunoassay to test sample, then normal results will range from 1.3 to 2.0 mg/100 mL .The exact standards for normal results may vary depending on  lab. When to suspect thyroid disorders?? These symptoms can include:
  • constipation
  • diarrhea
  • changes in sleep pattern, such as insomnia, daytime fatigue, or prolonged sleep that isn’t refreshing
  • dry skin
  • puffy skin
  • eye problems, such as dryness, irritation, puffiness, or bulging
  • fatigue
  • weakness
  • hair loss
  • hand tremors
  • increased heart rate
  • sensitivity to cold
  • sensitivity to light
  • menstrual irregularity
  • weight changes
Can the tests of TBG be fallacious?? Ans:--Interestingly, TBG also binds numerous T4 and T3 analogues and drugs, such as phenytoin, diclofenac, fenclofenac, meclofenamate, mefenamate, diflunisal, diazepam, salicylates, and milrinone. Because some of these drugs also bind to TTR (thyroxine binding receptor) and may displace TH(thyroxine)  from the TTR(receptor)  binding site, it is at least theoretically possible that patients with either partial or complete TBG deficiency who are treated with these drugs may show some temporary increase in free TH levels..

Q  Which drugs cause  falsely high TBG levels?? Ans;-Many different medications and drugs can affect  TBG levels. Some of these are medications that are  frequently taken , such as aspirin and birth control pills containing estrogen. Other medications that can affect serum TBG levels include:
  • hormones
  • opiates
  • opioids
  • Depakote
  • Depakene
  • Dilantin
  • phenothiazines
  • prednisone

Q. These medications temporarily before TBG test. What is Thyroxine-binding globulin (TBG) deficiency?? Ans;- It  is a nonharmful condition that is either acquired or inherited. The only known complications associated with TBG deficiency are those stemming from the primary disorders that cause the acquired form of this condition. Complications could also potentially result from erroneously administered treatment if TBG deficiency is misdiagnosed as another disorder.


Inherited or acquired variations in the concentration and/or affinity of these proteins may produce substantial changes in serum total TH levels measured by commercially available assays. [1Notably, these changes do not result in illness (ie, hypothyroidism or hyperthyroidism), because the concentration of the free TH does not change.

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When TBG Deficincy occurs?? Ans:-TBG deficiency usually accompanies an underlying illness. A low TBG level itself  doesn’t cause symptoms. The illness causing the low TBG level can cause symptoms, however. if Free T3, FreT4 are high . What happens  to  Thyroid in TBG Deficiency??
Thyroid-binding globulin (TBG) deficiency does not cause thyroid disease. The homeostatic mechanism of equilibrium dynamics between TBG-bound and free TH is as follows:
·         First, any decrease in TBG levels initially increases the concentration of the free hormone
·         Subsequently, the tendency to cause hyperthyroidism is counterbalanced by the tendency to shut off TSH secretion and hence decrease the TH secretory rate from the thyroid gland
·         Finally, the total TH concentration in the serum decreases until the concentration of the free hormone is restored to normal
This equilibrium is achieved extremely rapidly and on a physicochemical level. If chronic, the decreased extrathyroidal pool of TH may lead to small, transient declines in circulating free TH levels, thus resulting in transient TSH stimulation of the thyroid. The latter mechanism may explain the moderate elevation in serum thyroglobulin levels observed in up to one third of patients with TBG deficiency. Because TBG deficiency is not an acute process, a state of resultant hypothyroidism does not occur. Total T4 and T3 may be low in states of TBG deficiency, but the free T4, free T3, and TSH levels remain normal.
eMedicine LogoPatients may have constitutional symptoms unrelated to thyroxine-binding globulin (TBG) deficiency (eg, fatigue, weight gain, constipation, drowsiness, somnolence, low energy, dry skin, edema) that prompt them to seek medical advice. These symptoms are highly common in the general population and usually lead to extensive investigations, including TFTs and the ultimate diagnosis of TBG deficiency.
Most individuals with TBG deficiency are expected to be asymptomatic. Others present to their health-care provider because of conflicting findings from a thyroid function screening test (eg, low total thyroid hormone and normal TSH levels).
Identifying medical and nutritional states that may be associated with a secondary deficiency of TBG is very important, because this may indicate important coexisting disease. A family history of TBG deficiency is suggestive of an inherited state.

In physical examination no specific findings are associated with inherited deficiency of thyroxine-binding globulin (TBG) upon physical examination. In secondary deficiency of TBG, any clinical findings are attributable to the underlying illness.


What is thyroxine-binding globulin (TBG) deficiency & its clinical symp ?? Ans:-Serum TBG Level interpretations??  The most important aspect of dealing with thyroxine-binding globulin (TBG) deficiency is to recognize and correctly diagnose this condition in order to avoid unnecessary treatment for a mistaken diagnosis of hypothyroidism.  A firm diagnosis of secondary TBG deficiency may also be important when it indicates the coexistence of a previously unrecognized or underestimated serious general medical disease. Prompt evaluation of the possible causative condition is mandatory.
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D/D of diagnosis for TBG deficiency??

 Ans:-Differential diagnosis for TBG deficiency includes euthyroid sick syndrome and hypothyroidism. It  can help  us to diagnose TSH, free T4, and free T3 levels are normal, but total T4 and total T3 levels are low. Serum thymoglobulin levels are mildly to moderately elevated in one third of patients.
When TBG is decreased??   Ans:-Thyroxine-binding globulin (TBG) levels vary, and can be interpreted, as follows:
·         These levels are decreased in patients with secondary TBG deficiency and incomplete acquired deficiency, but they are undetectable in cases of complete TBG deficiency (males only)
·         The finding of undetectable TBG in female patients denotes laboratory error or the very rare occurrence of Homozygosity for TBG gene mutations and TBG mutations in females with Turner syndrome (XO karyotype)   . In patients with qualitative defects, the TBG concentration may be normal


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