When to test TSH under combi (LT-4 / LT-3) therapy - Thyroid UK

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When to test TSH under combi (LT-4 / LT-3) therapy

Freddyy profile image
17 Replies

Hi,

We often hear that Levothyroxin needs ~ 6 weeks to build up in the body, therefore it’s not wise to test TSH before 6 weeks from adjusting dosage.

This time baseline is probably not true in case you take a combi LT-4 / LT-3 .

Does anyone have experience with tsh testing while on combi therapy?

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Freddyy profile image
Freddyy
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SeasideSusie profile image
SeasideSusieRemembering

Freddyy

No point in testing just TSH whatever thyroid hormone replacement you take, you need TSH, FT4 and FT3 for a full picture. TSH is a pituitary hormone, it's FT4 and FT3 that are the thyroid hormones which tell us how our hormone levels are reacting to our thyroid meds.

Taking T3 normally lowers FT4 and will also lower, even suppress, TSH, so really TSH becomes unimportant, it's FT3 that is the most important test when taking T3.

I take a combination of Levo and T3 and when I was tweaking them to find my optimal doses, I found that I needed 6-8 weeks after changing either Levo or T3 for levels of FT4 and FT3 to settle.

Freddyy profile image
Freddyy in reply to SeasideSusie

Thank you.

You are right since T3 contribute to a sustained reduction of TSH beyond 24 hours even by a single dose of liothyronine, but FT3 won’t have a steady level.

If the FT3 baseline (own produced/ converted t3, before a Patient start taking cytomel) is 5 pmol/l, will this portion get reduced after starting cytomel ? Or it will be a fixed portion and the added cytomel will accumulate over it ?

SeasideSusie profile image
SeasideSusieRemembering in reply to Freddyy

If the FT3 baseline (own produced/ converted t3, before a Patient start taking cytomel) is 5 pmol/l, will this amount get reduced after starting cytomel ? Or it will be a fixed portion and the added cytomel will accumulate over it ?

I'm afraid I can't answer that.

SmallBlueThing profile image
SmallBlueThing in reply to Freddyy

If the T4 is cut by too much, I suppose the fT3 would be affected and drop. I believe fT3 helps in the conversion, so fT3 would be higher than just the T3's contribution, with ideal dosing.

I recall reading about the variation during the day in fT3 for healthy subjects being quite variable. I've had hospital tests five hours after my dose, with no concerns over timing from any staff.

diogenes profile image
diogenesRemembering in reply to Freddyy

If conversion is working, however inefficiently, then giving T3 will suppress TSH, lower thyroid production of T4 and T3 and probably inhibit conversion. It won't be a fixed x (T3 you make) + y (T3 you add) will equal x +y.

Freddyy profile image
Freddyy in reply to diogenes

I don’t think adding T3 will inhibit conversion...

Do you have any study that points out to that ?

diogenes profile image
diogenesRemembering in reply to Freddyy

It's simple enzyme kinetics. The conversion enzymes work at a certain rate that depends on the steadystate concentrations of T4 and T3. If you add T3, then the enzymes will automatically slow down because of the back effects of the extra T3 - ie they "think" they needn't work so hard.

Freddyy profile image
Freddyy in reply to diogenes

Actually the opposite is true !

The deiodinse enzymes d1, d2 and d3 are impaired because of reduced T3 !

In hypothyroidism or iodine deficiency, when T4 production is reduced, D1 activity is reduced, while that of D2 is increased due to the fact that T4- induced ubiquitination and proteasomal degradation of D2 is reduced, since the efficiency of T4 to T3 by D2 is double that of D1, the shifting of ratio in favor of D2 increases the efficiency of activation whatever residual T4 can be formed.

So in conclusions these enzymes are T4 dependent and not T3 !

diogenes profile image
diogenesRemembering in reply to Freddyy

Sorry, you can't deny elementary enzyme kinetics of the relation between substrate and product. The impairment of deiodinases by T3 reduction: depends on which you mean. If you have any working thyroid left at all, then the gland deiodinase actually works harder to keep T3 production there up, which otherwise would fall owing to lack of T4, whilst at the same time the tissue deiodinases are downgraded in activity because of the lack of T4 substrate. It's this that keeps FT3 fairly steady whilst the thyroid is dying. See the paper in The Lancet I mentioned in my last post. If no thyroid, then the kinetics comparing combined therapy v T4 monotherapy will work as I indicated.

MaisieGray profile image
MaisieGray in reply to Freddyy

If taking exogenous T3 has a negative effect on TSH, which in turn has a negative effect on the production of endogenous thyroid hormone, T4 in particular, (assuming that there is some residual thyroid function), would that therefore reduce the amount of converted T3 because there is less endogenous T4 to make it?

diogenes profile image
diogenesRemembering in reply to MaisieGray

See my reply to Freddyy. With some thyroid left, the remnant switches to producing more T3 to counteract the fall in T4 production, which knocks on to a lower conversion of the T4 to T3 in the tissues. Thus the FT3 is nearly maintained. This thyroid switch is stimulated by higher TSH. So adding T3 will lower the TSH, and switch off the thyroid T3 production. The T3 therapy will then substitute for the T3 the thyroid was making, but it won't be an effect of one on one.

MaisieGray profile image
MaisieGray in reply to diogenes

Thank you for clarifying the action. Is the net effect all dependent on/affected by variables though - ie how much thyroid/function is remaining, how much T3 we supplement with, which particular tissues we're talking about, efficiency of conversion etc?

diogenes profile image
diogenesRemembering in reply to MaisieGray

Yes, it is a highly interactive system between thyroid and body, unique for each person. As are the changes that occur, and how they do so, when the thyroid declines and dies. Back to individual experience and individual treatment of that experience. There is no formula.

MaisieGray profile image
MaisieGray in reply to diogenes

diogenes Excellent! Thank You again for confirming this.

Freddyy profile image
Freddyy in reply to diogenes

There is no evidence that the conversion will be inhibited, adding a moderate amount of T3 ( not more than 12.5 mcg ) and maintaining an appropriate LT-4 dosage can bring awesome results.

I am not a fan of only-T3 therapy, i take 125 T4 + 12.5 T3 ( split in two doses ) and i feel much better.

The goal is to reflect the natural T4/T3 ratio.

A healthy thyroid produces daily 80- 100 mcg T4 and 30-40 mcg T3.

diogenes profile image
diogenesRemembering in reply to Freddyy

Well, there is a simple answer. I don't talk about inhibition of conversion in the way of enzyme decline, only the influence of exogenous T3 on the conversion of T4 to T3 by what enzyme is there. Furthermore, it can only be the case that T3 added + T3 made fully represents the addition if the enzyme working was far from saturation in the absence of the added T3. This will not be the case as it is highly inefficient, and the body doesn't work inefficiently in this way. So Q: if you add T3 to a system already making T3, will the result for T3 be a simple addition? A: no.

Freddyy profile image
Freddyy in reply to diogenes

That’s a good observation, however when we add T3, we do that only after we make sure that the body needs more T3 hormones.

So at the end, it’s a sort of complex balanced distribution.

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