Another useful article

[diogenes]

Tania Smith has written another useful article in thyroidpatients.ca entitled Normal FT3:FT4 thyroid hormone ratios in large populations. It deals with the variation in FT3/FT4 ratios in health and the changes in incipient thyroid failure. These ratios are a crude approximation to T4 to T3 conversion, but good enough to draw valid conclusions. Useful to know if the ratios you get on T4 therapy are within this range or not. From the ratios in health from about 0.2 to o.5, one wonders if the healthypatients with ratio 0.2 will be the poor converters when on T4 only.

[Lora7again]

Is this the link?

thyroidpatients.ca/2020/10/...

[diogenes Remembering in reply to Lora7again]

Yes

[sy28]

This is so helpful, Diogenes. Thank you.

[Tythrop]

I am very interested in this,, my question is as follows:-

does it mean that for someone with readings for TSH/ft4/ft3 ALL at, say, 8% in range(in other words level at percentage in-range,) would amount to a deviation from the findings of these studies of healthy subjects?

So that low and level figures in percentage "in range" terms could be an indication of lack of thyroid health?

[diogenes Remembering in reply to Tythrop]

I don't think that follows. The three parameters are linked together, and if a person is healthy, the 3 could be anywhere within range, according to their genetic makeup. The sample you describe could well be healthy, but would be in the far-out area of normal distributions. ie in or near the 5% limits of the lower range cutoff.

[Tythrop in reply to diogenes]

Ta

[jimh111]

Interesting article. Allow me to get on my hobby horse! I have an inbuilt distrust of ratios because being able to calculate a ratio with a high degree of precision may lull us into a false confidence in the result.

We should beware any ratio with TSH because TSH varies during the day academic.oup.com/jcem/artic... and to a much greater extent during the menstrual cycle pubmed.ncbi.nlm.nih.gov/290... . Also, TSH bioactivity varies considerably, the result we get from the immunoassay does not tell us how much ‘oomph’ the TSH has. TSH increases with age because it loses bioactivity as we get older, more TSH is needed for the same effect.

Looking at the first chart (Gullo’s Table 2) we see that the AVERAGE fT3:fT4 ratio is stable at around 0.31 – at least when TSH is within its reference interval. However, the references intervals for the ratio are wide (e.g. 0.27 – 0.37) with the potential to overlap with unhealthy subjects. Indeed, the chart that follows shows a very wide reference interval in healthy controls (0.20 – 0.50).

Bianco’s team assert that ‘Defending plasma T3 is a biological priority’ ncbi.nlm.nih.gov/pmc/articl... and looking at Gullo’s Table 2 we can see fT3 has a narrower reference interval (3.85 – 4.93) than the fT3:fT4 ratio (0.27 – 0.37). It is more useful to observe fT3 than ratios.

A more important concern is that ratios do not address the issue of where the T3 is coming from. T3 at receptors comes from the serum and from type-2 deiodinase (D2) which regulates local T3 levels in organs such as the brain. When hormone levels fall TSH rises and this stimulates the thyroid to secrete proportionally more T3 and D2 to produce more T3.

In the case of thyroid failure, we can theoretically at least replace the T3 and T4 that came from the thyroid. We lose the dynamic response of the thyroid but should be able to restore normal TSH, fT3 and fT4 levels. This should work well and indeed many patients do reasonably well even on levothyroxine monotherapy.

TSH is central to this homeostasis mechanism. We replace serum T3 and T4 and a normal TSH manages peripheral deiodinase. What if TSH becomes subnormal? Perhaps the patient has a TSH = 1.5, fT3 = 3.41 and fT4 =11.0 giving the same 0.31 fT3:fT4 ratio. We can supply levothyroxine and liothyronine to restore fT3 to 4.34 and fT4 to 13.9. However, this will push a subnormal TSH down even further perhaps to e.g. TSH = 0.3. Consequently, this low TSH will reduce D2 activity considerably and organs dependent upon D2, such as the brain, will suffer local hypothyroidism.

An additional factor is that when TRH stimulation of the pituitary is low the pituitary produces TSH isoforms of reduced bioactivity. There is less TSH with less activity. If TSH secretion is subnormal restoring serum fT3 and fT4 levels will not be sufficient to overcome hypothyroidism in all tissues.

In my example above where TSH = 1.5, fT3 = 3.41 and fT4 =11.0 the fT3:fT4 ratio is the same as in the healthy controls (0.31). This illustrates why we should not pay much attention to ratios.

[Tythrop in reply to jimh111]

I love all this stuff. Its great that people are intetested even if they disagree. This is how progress is made. Apathy and prejudice is the enemy it seems to me.

[jimh111 in reply to Tythrop]

It was a difficult post to make because I needed to go into a lot of detail but didn't want to highjack this topic. I will put up a separate post on subnormal TSH sometime in the future and this will allow a separate discussion.

The whole topic of interpreting TFTs is far more complicated than previously thought, we are trying to infer what is going on in cells by looking at hormone levels in the blood.

[Tythrop in reply to jimh111]

Yes this is so right. Blood is different to brain /digestive system etc

[diogenes Remembering]

I'm afraid I don't agree fundamentally so perhaps we'll leave this as a polite disagreement.