Dear All,

 

Let us have some intellectual debate about this controversial issue !!

 

In our lab, if TSH is suppressed to <0.05 mU/L then FT3 is added automatically regardless of what has caused the suppression of TSH. Inevitably some thyroxine treated patients with suppressed TSH will get both FT4 & FT3 measured, and from extensive observations the pattern of TFTs is mostly TSH <0.05 mU/L, high FT4 but FT3 within normal range. I have also noticed that in T4 treated patients with normal TSH and FT4 results when FT3 get measured, it is usually low. 

 

To illustrate this phenomenon, here are two examples from our TFTs routine yesterday of T4 treated patients:

 

FT3          4.7      pmol/L     (   3.1-6.8   )       

FT4        H 27.2     pmol/L     (  11.0-22.0  )

TSH        L <0.05    miu/L      (  0.30-5.00  )

 

FT3          4.0      pmol/L     (   3.1-6.8   )

FT4          21.4     pmol/L     (  11.0-22.0  )

TSH        L <0.05    miu/L      (  0.30-5.00  )

 

You can see how the TSH suggests T4 over-replacement in both cases but FT3 is well within normal limits and FT4 is high in the first example and at high end of normal in the second example.

 

This low T3/T4 ratio in T4 monotherapy has been well documented in the literature and has led some authors to advocate the use of combination T3 + T4 therapy.

 

The prevalent theory backed by some experimental evidence is that T4 is a prohormone and it has to undergo peripheral deiodination into T3 the active form of thyroid hormone that binds nuclear receptors inducing regulatory effects on gene expressions. Iodothyrionine deiodinases is ubiquitous family of enzymes present in most tissues and it is difficult to see how they can be completely deficient in hypothyroid patients. What we measure in TFTs is blood T3 level which may be relatively low in hypothyroid patients treated with T4 replacement despite achieving normal TSH. However the active T3 is produced by peripheral tissues as required and this peripherally formed T3 may not all find its way to the circulating pool giving a high T4/T3 ratio and the impression that the patient may be T3 deficient whilst in reality the tissues are well satisfied as evidenced by normal TSH. Another factor for the low circulating T3 pool is the lack of directly secreted T3 by thyroid gland in hypothyroid patients which normally amounts to 20% of total circulating T3 pool. This relatively low T3 in T4 treated patients has led some authors to suggest that adding T3 therapy will give better physiological levels of circulating T3 and provide the best symptomatic relief in hypothyroid patients.

 

I think that TSH is still the best guide to adequacy of thyroxine replacement therapy and that measuring T3 is going to give false impression of under-replacement in some cases. It could also be used as false evidence for the need to add T3 to T4 treated patients even when TSH indicate tissue euthyroidism.

 

I will be interested in hearing your views and observations on this matter.

 

Best regards,

 

 

Mohammad

 

 

Dr. M. A. Al-Jubouri

MBChB, FRCP Edin, FRCPath

Consultant Chemical Pathologist

Clinical Director of Pathology

St. Helens & Knowsley Teaching Hospitals

 

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