Could this explain lower than expected TSH?

[Mollyfan]

I have just read this study and would be interested in any interpretations of it.

It says that they found a negative correlation between age and TSH after levo withdrawal and suggested this was due to reduced pituitary DIO2 with age ( I am not sure about the mechanism). This suggests that as we age, our TSH does not rise as far in response to low T4 as it did when we were younger.

It goes on to say that the presence of a DIO2 polymorphism under 60 years is also associated with a lower rise in TSH.

could this explain why TSH appears lower than it “should be” for the level of T4 in some people and why TSH is not a good measure of thyroid function?

pubmed.ncbi.nlm.nih.gov/366...

I would love your ideas!

[helvella]

Interesting. Having a 23andme test, I checked mine - which is T/T. (Might not have been done on all versions of 23andme testing.)

Interesting that they are pointing at TSH not rising to "its putative target" in 70% of A/T and 76% of A/A variants. But I think it significant that it didn't in 44% of TT (wild type homozygous). So A/T and A/A make it more so - but 44% is a lot in whom it is failing to reach that putative target despite not having the A/T or A/A variants.

I'd put it as "yet another" reason TSH testing is not a good measure.

Shame that, as so often, the full paper is behind a paywall.

[jimh111]

We need to see the full paper to make sense of this study.

Generally TSH rises with age. I guess this is due to the thyroid getting weaker. This study seems to show pituitary D2 reduces with age. This is neat in healthy people because reduced D2 will raise TSH a little further (than the decline in thyroid secretion) and so induce the thyroid to secrete proportionally more T3. Age related thyroidal decline is neatly compensated for!

The subjects in this study had no thyroid. They found TSH didn't rise so much in older people when levothyroxine was withdrawn. Perhaps the pituitary is aging?

The rest of the abstract is confusing. They seem to be saying the age related decline in TSH response to (L)T4 withdrawal was absent in those homozgous for the polymorphism. Yet they say TSH didn't reach its target in more of the subjects with the polymorphism. This seems contradictory unless there are different 'targets' for each group. We need to see the study, and hopefully it has some pretty graphs to make things clear.

[helvella in reply to jimh111]

Pretty graphs should be mandatory.

All the better if they also make sense and communicate the information well.

[Mollyfan in reply to jimh111]

Thank you for your comments, I agree that it is very confusing!

I found this article which states that, for the same T4 level in untreated hypothyroidism, the TSH in the elderly is less raised. They suggest that the pituitary becomes less responsive to lower T4 levels as we age which fits with the other study.

researchgate.net/publicatio...

[jimh111 in reply to Mollyfan]

TSH less increased even though D2 is reduced also meaning T3 in the pituitary will be lower - a double effect. In healthy people a mildly failed thyroid will push up TSH and lead to higher T3 secretion somewhat compensating. However, if there is no functioning thyroid this can't happen and so a lower TSH will be needed - or some T3. Need to see the paper so we can quantify these effects, to see if they matter.

[Mollyfan in reply to jimh111]

I was confused by the last bit too, but I think what they are saying is that age is associated with reduced D2 in the pituitary and a lower TSH is all patients. AND, in addition in younger people who still have lots of D2, the polymorphism reduces TSH as well. Once we get over 60 and the D2 has reduced in the pituitary the effects of a poorly functioning D2 disappear because there is less to make a difference.

Clear as mud eh?

Does anyone have access to the full paper. I resent having to pay $55!