[Non thyroidal illnesses (NTIS)]

Abstract

Abnormalities in the circulating levels of thyroid hormones, without evidence of coexisting thyroid or pituitary gland disease can be observed in all general diseases. These nonthyroidal illnesses (NTIS) are the result of complex mechanisms that combine the effect of some drugs, cytokines, nutritional and endocrine factors at all levels of the thyrotropic axis, from the hypothalamus to the cellular transporters and nuclear receptors of thyroid hormones. The patterns of NTIS depend on the underlying disease and its severity. Thirtyfive years after the initial description, the pathophysiological significance of these anomalies remains controversial. One of the dilemma of NTIS is whether the hormone responses represent an adaptive and normal, physiologic response to conserve energy and protect against hypercatabolism in case of aggression, or whether it is a maladaptive response contributing to a worsening of the disease. This debate is not just a theoretical question, because in the first case the process must be respected, in the other case a vigorous treatment to restore circulating thyroid hormone levels is justified. There have been very few clinical studies designed to address whether the substitution with thyroid hormone is advantageous, and there is at current time no permissive evidence for the use of thyroid hormone replacement in patients with NTIS. But the clinical context, the choice of the molecule or of the dose and the way of administration were not necessarily the most relevant. Theoretically, stimulation of thyreotrope axis used a continuous infusion of TRH seems to provide clinical benefit. With the expectation that randomized clinical trials will provide demonstration of NTIS treatment efficiency, the question might remain unanswered for several more years.