Today’s blog is an abstract of a paper which seems to be doing what I believe is an essential step in understanding thyroid hormone disorders. They are using computerised modelling.
I believe there is no other way to really understand because when you try to deal with all the variables (even keeping them as simple as TRH, TSH, FT4 and FT3), the interactions are beyond most human minds.
Their conclusions suggest that being Hyper, Hypo or with decent thyroid hormone levels cause three distinct ways in which these parameters interact. So the traditional simplistic ideas need to be reconsidered and they should not carry on as they have done for so long.
Such a pity that this level of understanding was not applied when first the TSH tests became available.
Nice to see it is a paper from (West) Yorkshire. We don’t see very many from there…
J Clin Pathol. 2013 Feb 19. [Epub ahead of print]
Physiological states and functional relation between thyrotropin and free thyroxine in thyroid health and disease: in vivo and in silico data suggest a hierarchical model.
Midgley JE, Hoermann R, Larisch R, Dietrich JW.
North Lakes Clinical, North Lakes Clinical, Ilkley, UK.
Understanding the exact relationship between serum thyrotropin/thyroid stimulating hormone (TSH) and free thyroxine (FT(4)) is a prerequisite for improving diagnostic reliability and clinical decision making.
We (1) retrospectively studied the relationship between TSH and FT(4) in a large unselected clinical sample (n=6641) of primary hypothyroid, euthyroid and hyperthyroid subjects, and (2) applied a mathematical model of thyroid hormone feedback control to assess the relation between structural parameters and TSH levels in the different functional states.
When separately analysing total sample and untreated subjects, the correlation slope for logTSH versus FT(4) for hypothyroid subjects was significantly different from that of the euthyroid panel and hyperthyroid subjects (the latter being compromised by reaching the TSH assay's lower detection limit). As trends between functional states changed, each functional segment appeared to become differently regulated. Theoretical modelling and sensitivity analysis revealed that the influence of various structural parameters on TSH levels also depends on the overall function of the feedback loop.
Our data suggest that the states of hypothyroidism, euthyroidism and hyperthyroidism can be regarded as differently regulated entities. The apparent complexity could be replicated by mathematical modelling suggesting a hierarchical type of feedback regulation involving patterns of operative mechanisms unique to each condition. For clinical purposes and assay evaluation, neither the standard model relating logTSH with FT(4), nor an alternative model based on non-competitive inhibition can be reliably represented by a single correlation comparing all samples for both hormones in one all-inclusive group.
PMID: 23423518 [PubMed - as supplied by publisher]
Picture is, inevitably, Ilkley Moor.