thyroid lab test question

[HiddenTruth]

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Why do alterations in TBG levels not affect free thyroid levels?
E.g: Estrogen can increase liver synth of TBG, but free thyroid levels remain normal, and total serum thyroid increases.

I always thought that the total thyroid levels remain unchanged by altering the TBG concentrations, and the levels of free Thyroud would be changed. Like in the e.g above, i would think that if you increased [TBG], that would result in an increased bound form, subsequently reducing free levels, and thus "normalizing" total thryoid levels. And this is exactly the reasoning i used for the hyperestrinic state in cirrhosis--you decrease sex binding globulin synth by liver, thus increasing free estrogen levels (oh wait, but that would also increase free testost levels--gosh im confused).

Can someone explain this. I think I am missing a huge concept, which is leading me to think the way I am. Thanks a lot.

 

[Wrigleyville]

Think of this in the same way you'd think of oxygen and hemoglobin. Changing the hemoglobin levels will alter the total O2 content of the blood, but has no affect on the amount that is carried dissolved in the blood (PO2 is not lowered by anemia-- it is still the same).

 

[dynx]

And this is exactly the reasoning i used for the hyperestrinic state in cirrhosis--you decrease sex binding globulin synth by liver, thus increasing free estrogen levels

Ditto what the poster above said and add that the reason for the hyperestrinic state in cirrhosis is that the liver is where estrogen is broken down....no breakdown = increased levels.

 

[Row Jimmy]

Yup, I agree with above posts. Conversely, someone on anabolic steroids will have decreased TBG and still have normal free levels. So, pregnancy and OCP's increase TBG and steroids decrease it but the free T levels stay normal.

 

[HiddenTruth]

I understand the analogy you made--and it makes sense that way. But, I guess I am still a bit confused. The way I am picturing it is that there is a concert agreement between the free thyroid levels (a larger pool of thyroid horm) and boung hormone to TBG--so when TBG goes up, it binds more of the T4 from the free pool, thus decreasing it. Likewise, when TBG decreases, the free pool increases. I guess these two are not connected in this way, eh? So, then I may ask, where is the "extra" thryoid hormone that is causing an increase in the total thyr levels comming from--if the free levels don't change (and TSH is subsequently normal also)?

Ok, this may clarify where i am getting confused. Like, in the HgB example you gave, the plasma O2 remains normal despite a decrease in HgB because there is a source of that O2 (inspiration) which maintains the plasma O2 levels. Anyone?

 

[Wrigleyville]

Hormones (or anything else for that matter) bound to transport proteins can not be metabolized or filtered out in the kidneys, or interact with receptors. They are protected. Only the free, unbound forms can be metabolized or elicit effects.

You are right -- there is an equilibrium between the bound and unbound form, but there is also an equilibrium between hormone production and breakdown, and that one only depends on the concentration of free hormone. If you add more of the binding protein (slowly, over time), it will act as a "sponge" for the free hormone, sopping up free hormone that otherwise would have been lost or degraded. The free hormone that the binding protein took up will be replaced by the thyroid gland faster than the free hormone is degraded, as the equilibrium between hormone production and elimination only depends on the free, unbound form.

So yes, the binding hormone takes hormone out of the free pool, but that is relatively quickly replaced by the thyroid gland, as stealing from the free, unbound pool disrupts the equilibrium in favor of increased hormone production and decreased breakdown

 

[HiddenTruth]

Hormones (or anything else for that matter) bound to transport proteins can not be metabolized or filtered out in the kidneys, or interact with receptors. They are protected. Only the free, unbound forms can be metabolized or elicit effects.

You are right -- there is an equilibrium between the bound and unbound form, but there is also an equilibrium between hormone production and breakdown, and that one only depends on the concentration of free hormone. If you add more of the binding protein (slowly, over time), it will act as a "sponge" for the free hormone, sopping up free hormone that otherwise would have been lost or degraded. The free hormone that the binding protein took up will be replaced by the thyroid gland faster than the free hormone is degraded, as the equilibrium between hormone production and elimination only depends on the free, unbound form.

So yes, the binding hormone takes hormone out of the free pool, but that is relatively quickly replaced by the thyroid gland, as stealing from the free, unbound pool disrupts the equilibrium in favor of increased hormone production and decreased breakdown

Thanks a lot to all those have replied.