New Bianco article

[diogenes]

This is another, not yet published in full, abstract from Bianco's lab. It finally brings FT3 measurement into patient diagnosis.

,REVIEW article

Front. Endocrinol.

Thyroid Endocrinology

 doi: 10.3389/fendo.2022.1044691

This article is part of the Research Topic(Re)defining Hypothyroidism: The Key to Patient-centered Treatment 

T3 levels and thyroid hormone signaling

Federico Salas-Lucia1* and Antonio C. Bianco1

The clinical availability of tissue-specific biomarkers of thyroid hormone (TH) action constitutes a “holy grail” for the field. Scientists have investigated several TH-dependent markers, including the tissue content of triiodothyronine (T3)—the active form of TH. The study of animal models and humans indicates that the T3 content varies among different tissues, mostly due to the presence of low-affinity, high-capacity cytoplasmic T3 binding proteins. Nonetheless, given that T3 levels in the plasma and tissues are in equilibrium, T3 signaling is defined by the intracellular free T3 levels. The available techniques to assess tissue T3 are invasive and not clinically applicable. However, the tracer kinetic studies revealed that serum T3 levels can accurately predict tissue T3 content and T3 signaling in most tissues, except for the brain and pituitary gland. This is true not only for normal individuals but also for patients with hypo or hyperthyroidism, but not for patients with non-thyroidal illness syndrome. Given this direct relationship between serum and tissue T3 contents and T3 signaling in most tissues, clinicians managing patients with hypothyroidism could refocus attention on monitoring serum T3 levels. Future clinical trials should aim at correlating clinical outcomes with serum T3 levels. 

[PaulRobinson]

Thanks Diogenes.

Quite positive! Even if it feels a bit like baby steps, when most of us want some serious marching towards change.

Best wishes, Paul

[DippyDame]

However, the tracer kinetic studies revealed that serum T3 levels can accurately predict tissue T3 content and T3 signaling in most tissues, except for the brain and pituitary gland. 

What happens when a patient has a form of Thyroid Hormone Resistance ( RTH)...is that the exception referrred in the reference to "most tissues"?

If all things are equal does serum T3 level not "automatically" reflect/predict tissue level.

Is it not the case that the problem (undermedication) arises when the T3 does not reach the nuclei of the cells where it becomes active eg when a form of RTH exists. And, for those patients, there is no method of measuring tissue/ cellular T3 and therefore no way of monitoring dose requirement .....beyond trial, error and good old fashioned clinical evaluation!

The patients FT3 level may be high but their cellular level remains low and consequently their well-being also remains low....until a supraphysiological dose of T3 , adequate to relieve symptoms, is taken. If they are lucky!

The idea of such a large dose of T3 tends to send medics running for the hills.....consequently the patient remains in poor health because they are left undermedicated Or worse....their body slowly shuts down.

Here we all understand the importance of monitoring serum T3 levels...leaving the following statement by the authors on the platform, after the train has departed!

Given this direct relationship between serum and tissue T3 contents and T3 signaling in most tissues, clinicians managing patients with hypothyroidism could refocus attention on monitoring serum T3 levels.

Most medics are also left behind on that platform because they focussed on TSH and missed the important T3 express!

More specifically and back to my point,....the authors say available techniques to assess tissue T3 are invasive and not clinically applicable. 

Is it impossible to make "it available"....or is that not viable due to the limited cohort involved?

Those of us with a form of RTH would benefit hugely were someone to discover a method of acurately measuring cellular T3....since it cannot be predicted by serum level T3.

I'm fortunate I can self medicate with a supraphysiological dose of T3....but it was not always so. My bio explains.

For various reasons many cannot....this is madness!

The problem is the word "most" in the first quote above

It strikes me that a greater understanding of T3 amongst the medical profession is vital

That lack of knowledge, low cellular T3 and medic's fear of T3 almost ruined my life....

I wonder how many patients are suffering ( often in silence) because their cellular T3 level is, and remains, far too low!

[jimh111]

I'm sure brain T3 action could be measured using EEG, especially during sleep when there is little external distraction.

Another marker is ankle reflex time which can be measured very accurately with fancy cameras.

It's a shame there is a little more thought given to determining thyroid hormone action. If all else fails they could resort to asking the patient!

As DippyDame notes the problem occurs when serum fT3 does not reflect hormone action, in which case carefully monitoring fT3 is barking up the wrong tree.

[diogenes Remembering in reply to jimh111]

Never must any advance in thyroid diagnosis fall into the trap of "range fever", that is diagnosing by any old placement in the reference range. Successful diagnosis must, as the other post indicates, be primarly patient symptom-oriented as a necessary task.