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Diagnosis and Treatment of NTIS

Last Updated: · Doctors


I am an intensivist and I'm very confused about the literature about NTSI or "euthyroid sick syndrome". As we now are used to use some kind of endocrine replacement therapy (fe. hydrocortisone, vasopressine) on a routine basis, we are currently reevaluating our approach to the NTSI. I read with great interest your article in J Endocrinol Invest 2003. One problem for me (as a non-endocrinologist): most of the literature discusses total T4 and T3 levels, but today we recieve from our laboratory results of FREE-T3- and T4-levels (chemilumineszenz-method). Is it possible with the free hormone levels to better evaluate, if there is a (chemical) hypothyroidism; or are there still a lot of analytic interferences that make the interpreation of the laboratory results difficult ?

  • What will be the usual pictures of FREE-T3/T4 in NTSI ?
  • Could you recommend levels of free-T4 or T3, below that you would start replacemant therapy?

In our small experience, we have seen two groups of ICU-patients

  1. Isolated low free-T3 levels and normal TSH
  2. Low free-T3, +/- low freeT4, in combination with low TSH

What is your recommendation for a practical approach in ICU:

  • Replacement therapy only if free-T4 is under a certain limit?
  • How would a low TSH influence your approach?

I thank you very much for helping us!

Rolf Ensner


Please note that I come from a particular point of view, believing that these patients have a deficient supply of thyroid hormone, will probably benefit from replacement, and that there is no proven danger in treatment.

The hallmark if NTIS is observation of a low T4, best estimated by a method that is believed to provide, or correlate with, free T4, in the setting of severe illness. Usually TSH is normal or low (rarely elevated), and T3 or free T3 is usually even more dramatically suppressed. Since low T3 alone has not been shown to correlate with bad outcome, I think one depends on a low free T4 as the test. In my mind any free T4 level clearly below normal in this setting brings up possible treatment, more urgently as the T4 becomes lower. The TSH level is more of a guide to causation, than to therapy. People talk about confusion with the low TSH of hyperthyroidism, but that is, in this setting, usually a rather bizarre consideration. We have given patients 30 ug T3 bid, and started 100ug T4, and followed blood levels closely. Obviously T3 is the required drug, if any, and T4 will only be supplemental as recovery proceeds. Unfortu nately proof that this approach is correct is not available. Best regards,

L De Groot, MD