Is T3/T4 ratio significant?

[muppetme]

just a question really. My T3 is top of range, and my T4 more middling... I don't want to be taking more T3 than I need, and have tried to reduce it previously when my T4 was higher but it didn't suit me. Now circumstance has set my T4 lower (NHS endo meddling), should I try a tweak lower for my T3? that would put my ratio back to where it was when I felt fine, but with both T4 & T3 doses slightly lower...🤔

[greygoose]

Well, as with most things thyroid, I don't think enough research has ever been done to give an answer to that question? But I'm pretty sure that ratios are of no significance to a hypo. You need what you need. Other wise, people like me, on T3 mono-therapy would be pretty ill!

[muppetme in reply to greygoose]

Ahhh! 🤪good point. That's a definitive answer

[Hashihouseman in reply to muppetme]

…..definitive for someone but an answer that doesn’t reflect the evidence, it may suit some individuals to have abnormal thyroid balance but the statistical normal ratio is 0.3 which stems from the normal euthyroid range NOT the lab range or the thyroid patient range, the 0.3 or thereabouts is derived from a fT4 of about 15 and a fT3 of between 4.4-4.8 for example and which if coinciding with a euthyroid normal TSH of between 1.0- 2.5 would tell you that someone was in all probability euthyroid or generally well treated. I have experimented for years with all this and taking a lead from the large scale population data for healthy thyroid have found that 0.3 really is the sweet spot. Whereas GPs and endocrinologists are sanguine about more or less any values in the Lab Ranges, which are far too wide and doesn’t reflect euthyroid normal. Euthyroid normal range is much more narrow but routine testing of thyroid patients seldom if ever include T3 and T4 with TSH so people dont know where they are or where they will likely feel better. OK, caveat this by observing that some individuals may have their thyroid set points or be treated and symptom free outside the euthyroid norm but the norm is the norm and probably the best place to aim for unless symptoms strongly suggest otherwise. It is also worth noting that some of these large scale population studies have shown a significant association with cardiovascular issues on ratios from typical replacement with Levothyroxine (Anderson et al 2019), that if no other is a good reason to aim for the 0.3 ratio regardless of whether replacement includes T3 and T4 because regular monitoring of fT3 & fT4 will show the balance of replacement and conversion going on in the body. Someone on T4 alone or even T3 alone may have a normal fT3:fT4 ratio almost by luck but I suspect some (not all) people on replacement would benefit from adjusting for it which may mean adding T3 and or T4 and titrating the doses accordingly. Now I wait for the backlash…..

[jimh111]

In healthy people the fT3 / fT4 ratio will vary as fT4 (or fT3) varies, so the ratio doesn't mean much. It does give an indication of how well T4 is converting to T3, at least when fT4 is middling.It's always good to see if you can get better with normal thyroid hormone levels but ultimately it's the clinical response that is definitive not blood test results. So, try a liothyronine reduction but put it back up if you get worse. You could try it a couple of times to rule out random events.

Blood T3 levels peak three hours after taking liothyronine but T3 action generally takes much longer (except when the T3 dose is large). So, the recommendation to take liothyronine around three hours before the blood test is either stupidity or more likely sabotage.

[Hashihouseman in reply to jimh111]

Further to what I just posted above, the large scale data suggests that the narrow range of ft3ft4 and the dependent ratio does not change much! This taken from the large population studies which would have data from blood sampling over highly variable timing and circumstances and yet show tight normal range. I have also seen other eminent professor published papers (which I can’t find right now !) but which talk about the body seeking to maintain fT3 in a very tight range and that fT4 is metabolically subservient to that, which again implies that the ratio is likely to be very stable, because that’s the allostatic imperative! Beyond data we also know that having fT3 even a little out of whack feels uncomfortable to say the least and fT4 out of whack is a much more insidious beast….. So follow the normal ratio unless it really doesn’t work for you!

[jimh111 in reply to Hashihouseman]

This is the review you have in mind doi.org/10.1111/cen.12538 . It perhaps over states the extent to which T3 is kept stable.

This paper shows individual variations in (total) T3 and T4 researchgate.net/publicatio... . Individual reference intervals are about half as wide as the population ones. For similar TSH levels fT3 and fT4 will tend to act in a see-saw manner, this will have a substantial effect on the fT3 / fT4 ratio. This is why I think we shouldn't pay much attention to ratios, rather look to the fT3 level.

Another consideration, always overlooked, is that type-2 deiodinase (D2) converts T4 to T3 in the endoplastic reticulum which is close to the cell nucleus. This T3 remains close to the nucleus (and receptors) for several hours and so is likely to have more effect than T3 from type-1 deiodinase or tablets. If you are taking more T3 than the thyroid secretes, e.g. > 6 mcg T3 the fT3 figure is less relevant for tissues that rely on local D2 activity.

[radd]

muppettme

The ratio of T4:T3 can only apply to those not medicating T3-only.

The performance of the three thyroid hormone conversion enzymes (deiodinases) will be influenced by the ratio, and behave accordingly in trying to keep to your individualised best. This can result in excess hormones being turned to inactive metabolites should either become too far out-of-balance.

Our best indicator of a good ratio is a long lasting reduction in symptoms, but when we get lost in the mess thyroid hormone imbalances can create it can be useful to use both test results and calculations to see how the body is utilising the meds.

Numbers-in-range give a general guide to safe limits of thyroid hormone levels. Ratio offers indication of the amount of T4 we have in relation to the amount of T3.

[muppetme]

Thanks all - appreciate your thoughts.