Increased inflammatory cytokines, which occurs in response to virtually any illness, has long been speculated to play a role in derangements of deiodinase expression. Over the last decades, several studies have attempted to elucidate the mechanisms underlying the changes on circulating thyroid hormones in NTIS. In contrast, type 3 deiodinase (D3) catalyzes the inactivation of both T4 and T3. The conversion of T4 to T3 is catalyzed by type 1 (D1) and type 2 (D2) deiodinases via outer-ring deiodination. The early phase seems to reflect changes occurring primarily in the peripheral thyroid hormone metabolism, best seen in humans since 80–90% of the circulating T3 are derived from the pro-hormone T4. The pathophysiological mechanisms are poorly understood but the acute and chronic changes in pituitary–thyroid function are probably the consequence of the action of multiple factors. Affected individuals have low T3, elevated rT3, and inappropriately normal TSH levels. The non-thyroidal illness syndrome (NTIS) refers to changes in serum thyroid hormone levels observed in critically ill patients in the absence of hypothalamic–pituitary–thyroid primary dysfunction. Thyroid Section, Endocrine Division, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brasil.
