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Letters to the Editor |
Washington Hospital Center Washington, DC 20010
In his review of the euthyroid sick syndrome (ESS), Dr. DeGroot (1) cites a litany of circumstantial evidence ostensibly supporting a state of underlying hypothyroidism in patients with systemic illness, which in his view justifies treatment with thyroid hormone. DeGroot argues with the dogma against such treatment espoused by Chopra et al. (2) by stating that "there is no factual basis for this dogma," while failing to fully acknowledge that there is no factual basis for treatment either. Surely, a causal relationship cannot be inferred from the association of low serum T4 and risk of death, as severity of illness correlates directly with either low T4 or risk of death. While he cites the study of Maldonado et al. (3), he overlooks their finding that only low T3 significantly and independently predicted survival beyond what was clinically apparent to intensivist physicians. By definition, the ESS or "low T3 syndrome" is characterized by low TT3. Recently, Chopra (4) observed normal free T3 in 83% of ESS patients and concluded it might be responsible for maintaining their euthyroid state. DeGroot would have us conclude that there is also low FT4 in ESS, but his own literature review concludes that FT4 may be low, normal, or elevated.
Our concept of metabolic status in the ESS is that patients are indeed euthyroid during caloric deprivation, acute illness, surgery, and dozens of other models, and that the changes in thyroid function tests reflect effects by the various cytokines, circulating inhibitors, etc., as have been reviewed (1, 5–7). DeGroot calls the normal to low TSH levels in these situations "inappropriately low," rather than considering them appropriate because the patients are euthyroid. He postulates that ESS patients are hypothyroid on the basis of low TRH with secondarily low TSH, while ignoring the fact that observed changes in iodothyronines occur too rapidly in acute illness to be on a hypothalamic/pituitary basis. Indeed, studies by Faber et al. (8) indicated that pituitary function was normal in critical illness in the absence of dopamine therapy. DeGroot cites the increases in TSH that may be seen with recovery (9) as "strongly suggesting" that the patients are recovering from a hypothyroid state. This could be true in some states of prolonged systemic illness that may lead to relative thyroid hormone deficiency as a result of chronically low degrees of TSH-driven thyroid hormone biosynthesis. In patients such as those with prolonged coma, thyroid hormone therapy might be warranted, and in this context Van den Berghe et al. (10) carefully make the distinction between effects of acute vs. prolonged systemic illness. But how can thyroid hormone treatment be justified by DeGroot for all patients with altered thyroid function tests of the ESS, which simply reflect acute homeostatic mechanisms when he acknowledges that hypothyroidism may take 2–3 weeks to actually develop? While the review cites studies showing reduced TRH biogenesis, this does not refute a concept of ESS as homeostatic in nature, nor does it imply that the patients are, by definition, hypothyroid. DeGroot suggests the possibility of treating such patients with recombinant human TSH to normalize their serum T4, but wouldn’t L-thyroxine be both considerably more practical and cost-effective?
Finally, DeGroot admits that "proof that tissues are chemically hypothyroid is clearly lacking," yet he concludes that thyroid hormone treatment "may be beneficial" and proceeds to give guidelines for such therapy. He avers that "there is no clear evidence that administration of replacement T3 ... is disadvantageous," choosing to ignore critical analyses that caution us otherwise (5–7, 11). We agree with DeGroot when he "cannot envision that replacement of T3 or T4 would cure all patients", but the contention that such treatment would cure any is bewildering. He seems to eschew the premise and the evidence that it is the underlying illness (causing the ESS) that needs curing, not the aberrated thyroid function tests. In treating the ESS with thyroid hormone, DeGroot asserts that he would "do no evil," but confesses uncertainty as to whether benefit or harm might ensue. We do agree with him on one point, i.e. that large, prospective, carefully controlled studies are needed. To treat with thyroid hormones without such data would certainly not be doing "evil," but could instead represent a misguided attempt to do good that is inconsistent with primum non nocere, a dogma that few would characterize as dangerous.
Footnotes
Address correspondence to: Leonard Wartofsky, Department of Medicine, Washington Hospital Center, 110 Irving Street, NW, Washington, DC 20010-2975.
Received January 22, 1999.
References
This article has been cited by other articles:
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  D. I. Spratt, M. Frohnauer, H. Cyr-Alves, R. S. Kramer, F. L. Lucas, J. R. Morton, D. F. Cox, K. Becker, and J. T. Devlin Physiological effects of nonthyroidal illness syndrome in patients after cardiac surgery Am J Physiol Endocrinol Metab, July 1, 2007; 293(1): E310 - E315. [Abstract] [Full Text] [PDF]
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