B12 and T4

[Suncrusher]

I might be an M4 now, but I know from the months I spent here as an M2 that the Step 1 forums is where all the smartest people chill. So when an attending mentioned something and I couldn't find an explanation...

We all know that when someone has concurrent B12 and folate deficiencies, you have to replete the B12 first; repleting the folate first might cause the macrocytic anemia to improve while making the neurological damage worse or more permanent. But then my GI attending said it was also important to correct thyroid levels before repleting B12 and folate. I can't seem to figure out why after reading medscape, uptodate, etc. Using google, I found an entirely unscientific site which claimed that because of T4's effects on nutrient uptake, it is important to replete T4 before repleting B12/folate, but I haven't found mention of that anywhere else. Anyone know the answer? Is my attending just crazy?

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[seminoma]

Don't remember the details, but maybe this will help point you in the right direction. Hypothyroid is associated with high plasma homocysteine. So I guess if you were to replete B12/folate without also repleting T3/T4 you might encounter problems with homocysteinemia?

 

[Psai]

hypothyroid -> low t4 t3 -> high trh tsh
high trh -> stimulates prolactin increase -> decrease gnrh
decrease gnrh -> decrease lh fsh -> decrease testosterone
androgens increase erythropoietin so decreased testosterone -> decreased erythropoietin -> decreased red blood cells

b12 and folate are part of the heme production pathway but if you don't have a signal for making rbcs then no point in being able to make heme

this is a guess i have no citations

 

[Priapism4tooLong]

hypothyroid -> low t4 t3 -> high trh tsh
high trh -> stimulates prolactin increase -> decrease gnrh
decrease gnrh -> decrease lh fsh -> decrease testosterone
androgens increase erythropoietin so decreased testosterone -> decreased erythropoietin -> decreased red blood cells

b12 and folate are part of the heme production pathway but if you don't have a signal for making rbcs then no point in being able to make heme

this is a guess i have no citations

you are so smart it blows my mind

 

[Transposony]

But then my GI attending said it was also important to correct thyroid levels before repleting B12 and folate. Anyone know the answer? Is my attending just crazy?

Maybe he was referring to anemia in hypometabolic states.
For example, in Hypothyroidism, unless you correct the hypothyroidism giving B12 and folate won't help since every process (including absorption) in the body slows down (e.g.DNA synthesis in this case).
Other hypometabolic conditions where this can happen are deficiency of glucocorticoids, testosterone, or growth hormone.
Other possibility is pernicious anemia (commonly associated with thyroid disorders) where unless you correct the cause of pernicious anemia, giving B12 (normal oral doses) won't help either.

 

[Transposony]

hypothyroid -> low t4 t3 -> high trh tsh
high trh -> stimulates prolactin increase -> decrease gnrh
decrease gnrh -> decrease lh fsh -> decrease testosterone
androgens increase erythropoietin so decreased testosterone -> decreased erythropoietin -> decreased red blood cells

b12 and folate are part of the heme production pathway but if you don't have a signal for making rbcs then no point in being able to make heme

this is a guess i have no citations

I do understand that androgens stimulates erythropoietin production.
What I don't understand is why erythropoietin needs androgens for normal RBC production?
Isn't erythropoietin released in response to hypoxia etc?

 

[Apoplexy__]

hypothyroid -> low t4 t3 -> high trh tsh
high trh -> stimulates prolactin increase -> decrease gnrh
decrease gnrh -> decrease lh fsh -> decrease testosterone
androgens increase erythropoietin so decreased testosterone -> decreased erythropoietin -> decreased red blood cells

b12 and folate are part of the heme production pathway but if you don't have a signal for making rbcs then no point in being able to make heme

this is a guess i have no citations

This made me laugh out loud with confused amusement. I feel like you can make any pathophysiological claim with enough arrows.

 

[Psai]

This made me laugh out loud with confused amusement. I feel like you can make any pathophysiological claim with enough arrows.

I have no idea what I'm doing lol

I think hypoxia is one of the signals but androgen levels contribute as well

For example blood pressure is determined by blood volume and vascular resistance but there are other factors such as sympathetic tone and heart rate. It's not just one thing but a huge system that works together

 

[Suncrusher]

Yikes. Okay, I guess it makes sense that if someone is hypometabolic enough, it's a dumb idea to try to replete everything instead of just correcting the primary hypometabolism. Thanks, everybody.

 

[solitarius]

Just start with the most obvious common link. You need B-12 for healthy nerve function. Too much thyroid taxes the nervous system. Too little thyroid may be the reason for low nervous function instead of B-12.

 

[Transposony]

Hypometabolic conditions like Hypothyroidism leads to anemia due to markedly decreased hematopoiesis since normally the need for circulating red cells depends on the cellular requirements for oxygen, which in turn are influenced by thyroid hormones. Thyroid hormones directly or indirectly, through erythropoietin, stimulate growth of erythroid colonies (BFU-E, CFU-E).

Therefore, there are three types of anemia associated with hypothyroidism:
1. Microcytic,
2. Macrocytic and
3. Normocytic.

Microcytic and macrocytic are caused by body's malabsorption of nutrients, such as iron, vitamin B12 or folic acid.
Normocytic is directly caused by a slower metabolism. However, anemia of Hypothyroidism can be of any type due to a combination of above mentioned factors.

In contrast, hypermetabolic conditions like Hyperthyroidism can lead to megaloblastic anemia due to markedly increased hematopoiesis (demand exceeds supply).
So, it's better to treat hyperthyroidism (reduce demand) and replace vitamin B12 and/or folic acid (increase supply).
It also has a higher risk of hypokalemia and fluid overload early in treatment due to increased erythropoiesis, cellular uptake of potassium, and increased blood volume.