SHBG levels in different conditions?

[amakhosidlo]

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Someone explain to me why liver failure increases SHBG? And how an increase in the level of a binding globulin alters the free level? (To contrast, in pregnant women total T4 levels increase, but so do TBG levels, which is why free T4/3 doesn't change and women stay (Reasonably) Euthymic?

And I thought the reason you have gynoecomastia in liver failure was because you have a decreased ability to metabolize 17-ketosteroids and testosterone, so it's peripherally converted to estrogen?

 

[frankyazz]

Someone explain to me why liver failure increases SHBG? And how an increase in the level of a binding globulin alters the free level? (To contrast, in pregnant women total T4 levels increase, but so do TBG levels, which is why free T4/3 doesn't change and women stay (Reasonably) Euthymic?

And I thought the reason you have gynoecomastia in liver failure was because you have a decreased ability to metabolize 17-ketosteroids and testosterone, so it's peripherally converted to estrogen?

Pregnancy increases synthesis of TBG. You have an increase in total T4 due to an increase in TBG, but free levels remain normal...If free levels are normal, then you are euthymic. Completely different from what you stated, and I hope you see the difference; increased total T4 does NOT cause an increase in TBG.

As to my understanding, liver failure causes hyperestrinism due to the inability of the liver to metabolize estrogen.

 

[MrBeauregard]

Someone explain to me why liver failure increases SHBG? And how an increase in the level of a binding globulin alters the free level? (To contrast, in pregnant women total T4 levels increase, but so do TBG levels, which is why free T4/3 doesn't change and women stay (Reasonably) Euthymic?

And I thought the reason you have gynoecomastia in liver failure was because you have a decreased ability to metabolize 17-ketosteroids and testosterone, so it's peripherally converted to estrogen?

Binding proteins act as transport proteins for hormones in the blood. Binding proteins always have 2/3 of their available binding sites bound to their respective hormone. If the level of a binding protein is increased, since 2/3 of the sites are always occupied, it will bind more of the hormone, thus decreasing the free (read: active) levels in the blood. If less hormone is free, less will bind the receptor. The opposite is also true: a decrease in the amount of a binding protein means that more free/active hormone will circulate and thus more hormone will bind its receptor.

And frankyazz was correct about the inability of the liver to metabolize estrogens, thus leading to hyperestrinism and gynecomastia.

The patient would also be euthyroid, not euthymic.

 

[amakhosidlo]

Pregnancy increases synthesis of TBG. You have an increase in total T4 due to an increase in TBG, but free levels remain normal...If free levels are normal, then you are euthymic. Completely different from what you stated, and I hope you see the difference; increased total T4 does NOT cause an increase in TBG.

As to my understanding, liver failure causes hyperestrinism due to the inability of the liver to metabolize estrogen.

Right, right sorry I mis-spoke. The increase in total is due to an increase in TBG spurred on by estrogen, and free levels don't change.

Still at a loss, though, as to why liver failure increases SHBG?

 

[Go Ducks]

Still at a loss, though, as to why liver failure increases SHBG?

As Frankyazz correctly said, liver failure causes an increase in estrogen levels because estrogen is normally eliminated via the liver. Estrogen has the direct effect of increasing SHBG.

The increased estrogen is also responsible for the spider angiomas and the gynecomastia seen with liver failure.

 

[usmlesuccess]

doesn't estrogen also increase transferrin? Does estrogen increase the levels of ALL serum binding proteins?