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NBME 20 Answers

nbme20/Block 2/Question#26
A male newborn is found to have a decreased ...
Thyroid hormone-binding globulin deficiency🔍

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 +7  upvote downvote
submitted by monoloco(113),

Decreased total, normal free (unbound) = Thyroid hormone-binding globulin deficiency

 +5  upvote downvote
submitted by sugaplum(157),

This is apparently congenital thyroid binding globulin deficiency

"Thyroxine-binding globulin deficiency — Thyroxine-binding globulin (TBG) deficiency is characterized by low serum total T4 but normal free T4 and TSH; the diagnosis is confirmed by measuring TBG concentrations. These infants have normal thyroid function and do not require treatment." - uptodate *can't find in FA, maybe it is in there somewhere?

hhsuperhigh  The only thing I can relate to this is FA P331 " TBG in pregnancy, OCP use (estrogen increases TBG) increases total T3/T4", so here is the opposite situation, which TBG decreases, and total T3/T4 decreases... +4  
jawnmeechell  Goljan talks about this (around 33 mins into his endocrine lecture) in relation to increased androgens causing decreased TBG +1  

 +2  upvote downvote
submitted by step1soon(24),

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

A deficiency in TH-binding proteins is suspected when abnormally low serum total TH concentrations are encountered in clinically euthyroid subjects in the presence of normal serum thyrotropin (ie, thyroid-stimulating hormone [TSH]). More specifically, low TBG is suggested because this protein carries the majority of the serum TH.

Several states of deficiency of this protein have been described that are either inherited or acquired. Thyroid function tests (TFTs) in patients with TBG deficiency show normal TSH and free T4, but low total T4 and, occasionally, low total T3 serum concentrations. The most important clinical aspect of TBG deficiency states is recognition of these disorders and avoidance of unnecessary and potentially harmful TH replacement therapy.

 +0  upvote downvote
submitted by alimd(0),

about 70% of the circulating thyroid is bound to thyroid-binding globulin (tbg). the remainder of the bound protein is attached to thyroxine-binding prealbumin (transthyretin) and albumin. Large variations in tbg do not normally affect the free form. a rare congenital deficiency or excess of tbg drastically alters the bound fraction but because the free fraction is normal, the individuals are all euthyroid.

 +0  upvote downvote
submitted by waterloo(21),

If you think about it this way, his free T4 is normal and his TSH is normal. Would any other option allow this to happen?

A step further would be, why is his free serum T4 okay but his T3 and T4 dec. His total T4 must be decreased then, which one of those can cause that while keeping free T4 normal.

 +0  upvote downvote
submitted by whossayin(13),

why can't "organification defect in T3 and T4" be the answer?

sugaplum  I think if it was organification defect you wouldn't have a normal T4 level in the serum. +4  
divya  because there would be an overall decrease in serum T3, T4 and increase in serum TSH levels. +  

This is how my brain farted while I was doing this question.... I wanted to choose TBG deficiency, but I kept thinking that if TBG is deficient, that means there are less or no binding proteins in the blood. And how can the free T4 be normal? Shouldn't free T4 increase if there were less T4 binding protein? ...

adong  free T4 wouldn't increase because it would be sensed by the pituitary and TSH would drop until free T4 normalizes +  

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