Tissue thyroid hormone metabolism is differentially regulated during illness in mice

Abstract

Illness induces major modifications in central and peripheral thyroid hormone (TH) metabolism, so-called nonthyroidal illness syndrome (NTIS). As a result, organ-specific changes in local TH availability occur depending on the type and severity of illness. Local TH availability is of importance for the regulation of the tissue-specific TH target genes and determined by the interplay between deiodinating enzymes, TH transport and TH receptor (TR) expression. In the present study, we evaluated changes in TH transport, deiodination and TR expression, the resulting tissue TH concentrations and the expression of TH target genes in liver and muscle in three animal models of illness. We induced (1) acute systemic inflammation by intraperitoneal injection of bacterial endotoxin (LPS), (2) chronic local inflammation by a turpentine injection in the hind limb and (3) severe pneumonia and sepsis by intranasal inoculation with We found that all aspects of peripheral TH metabolism are differentially regulated during illness, depending on the organ studied and severity of illness. In addition, tissue TH concentrations are not equally affected by the decrease in serum TH concentrations. For example, the decrease in muscle TH concentrations is less severe than the decrease observed in liver. In addition, despite lower TH concentrations in muscle in all three models, muscle T action is differentially affected. These observations help to understand the complex nature of the nonthyroidal illness syndrome.

Hypothesis: Mechanisms That Prevent Recovery in Prolonged ICU Patients Also Underlie Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

“…The relative sequence and importance of these various mechanisms in depressing the HPT axis and thyroid hormone function in different tissues and phases of critical illness are the subject of most NTIS publications (10,104,105). Notwithstanding the effect of other mechanisms, alterations in the activity of the deiodinase enzymes lead to a decrease in T3 and an increase in rT3 and thus a reduction in thyroid hormone function in peripheral tissues during prolonged critical illness [based on biopsies on ICU patients who died (142) and studies on mice (143,144)]. Circulating thyroid hormone concentrations, however, only reveal the "tip of the iceberg" of the alterations occurring at the tissue level (141,145), which thus are often missed altogether in clinical settings (146).…”

Early induction of hepatic deiodinase type 1 inhibits hepatosteatosis during NAFLD progression

“…The expression of hepatic Dio1 is influenced by cytokines and nutritional status, and it is markedly up-regulated by T 3 [ 2 , 11 ]. Previous research has found low levels of Dio1 expression in the livers of mice after acute and chronic inflammation, as well as rodents and patients with NASH [ 2 , 12 , 13 ]. In this study, we examined the role of intrahepatic regulation of the thyroid hormone by Dio1 during the different phases of NAFLD progression.…”

Serum thyroxine and thyrotropin concentrations decrease with severity of nonthyroidal illness in cats and predict 30‐day survival outcome

“…[1][2][3] This condition, known as the nonthyroidal illness syndrome (NTIS, previously termed "sick euthyroid syndrome"), is not a primary thyroid disorder but instead results from changes in secretion of TSH, as well as altered secretion, transport, metabolism, tissue uptake, and action of the thyroid hormones. [3][4][5][6] A likely adaptive response to the systemic illness, NTIS attempts to decrease peripheral tissue energy expenditure and minimize metabolic demands during the stress of the illness. [3][4][5] Nonthyroidal illness can have marked effects on thyroid function tests.…”