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Experts debate thyroid hormone treatment for the euthyroid sick patient
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The Endocrine Society 92nd Annual Meeting
SAN DIEGO — Should the euthyroid sick patient be treated with thyroid hormone? This question sparked a debate between Greet H. Van den Berghe, MD, PhD, and Elaine M. Kaptein, MD.
Van den Berghe maintained the pro position, and suggested that a combination of thyrotropin-releasing hormone (TRH) plus growth hormone-releasing peptide (GHRP) may provide benefit to a subgroup of euthyroid sick patients, more specifically, the prolonged, critically ill patients in the ICU, provided these patients receive an adequate amount of nutrition.
Kaptein presented the con position, and concluded that available data in favor of thyroid hormone treatment for the euthyroid patient are “somewhere between ineffective and harmful,” and treatment may actually increase mortality.
"To be honest, I think we agree more than we disagree about thyroid hormone therapy for these patients," Van den Berghe, of the Catholic University of Leuven, Belgium, said at the debate. "Strong data to support one or the other side of the argument are simply not there."
Much of the debate focused on the lack of data about thyroid hormone treatment in the euthyroid sick patient.
Kaptein questioned whether there is ever an indication for thyroid hormone therapy in this patient population. She discussed the results of a literature review that revealed only about 30 studies that examined thyroid hormone therapy (T3 and T4) in obese or euthyroid sick patients, including very few randomized controlled trials, of which several used pharmacological doses of thyroid hormone.
“There is no conclusive evidence to date, and T3 may induce hyperthyroidism,” said Kaptein, of the University of Southern California Medical Center.
Further, based on available evidence, she did not recommend T3 and T4 therapy for obesity during caloric deprivation to increase weight loss, in nonthyroidal illness or postoperatively to improve morbidity and mortality.
Van den Berghe reviewed data on the only four existing small randomized controlled trials that examined thyroid hormone treatment in euthyroid sick patients in the ICU. Two trials examined the use of pharmacological T3, and showed no change in mortality; the other two trials examined use of T4, and also showed no change, with potentially an increase in mortality with high-dose T4. No study thus far has addressed the question, with enough statistical power, whether or not low circulating levels of T3 and T4 should be normalized in prolonged, critically ill, adequately fed, ICU patients, Van den Berghe said.
"Absence of evidence, therefore, is not evidence of absence," she said.
"For ICU patients, the randomized controlled trials have been performed in the wrong patient population, in the wrong phase of illness - acute instead of prolonged - while patients were fasted whereas feeding can reverse part of the syndrome, and it may have been the wrong hormone, as treatment with either T4 or T3 is very difficult to dose correctly in ICU patients," she said.
Kaptein and Van den Berghe both discussed the need for future research to determine whether thyroid hormone or other therapies are beneficial in the euthyroid sick patient.
“Our most important need is randomized controlled trials with adequate sample sizes and appropriate endpoints,” Kaptein said.
For more information:
- Kaptein EM and Van den Berge GH. D2: The euthyroid sick patient should be treated with thyroid hormone. Presented at: The Endocrine Society 92nd Annual Meeting and Expo; June 19-22, 2010; San Diego.