Endocrine Abstracts (2019) 65 S4.2 | DOI: 10.1530/endoabs.65.S4.2

Thyroid hormone in inflammation

Anne H van der Spek, Eric Fliers & Anita Boelen


Amsterdam University Medical Center, Amsterdam, Netherlands


Thyroid hormone levels are strongly affected by inflammation. In a wide spectrum of diseases, ranging from critical illness in the ICU to ischemic stroke, a decrease in circulating T3 and T4 is observed without the expected increase in TSH. This disruption of the negative feedback system of the hypothalamicpituitarythyroid (HPT) axis is accompanied by various changes in thyroid hormone metabolism at the cellular and tissue level. Collectively, these changes in thyroid hormone metabolism are known as the non thyroidal illness syndrome (NTIS). The changes in HPT axis feedback are due to increased local bioavailability of T3 in the hypothalamus. This is due to changes in the activity of deiodinase enzymes, which can activate or inactivate thyroid hormone, resulting in increased local T3 concentrations. Besides these changes in circulating thyroid hormones and the HPT axis, NTIS also results in profound changes in cellular thyroid hormone metabolism. These changes are cell type and timing specific and are independent of changes in circulating thyroid hormone, meaning that tissue thyroid levels can differ significantly from serum concentrations. Innate immune cells are important thyroid hormone target cells that play a crucial role during inflammation and infection. In neutrophils, the thyroid hormone inactivating type 3 deiodinase is essential for adequate function both in vivo and in vitro. In macrophages, the thyroid hormone activating type 2 deiodinase plays an important role. A lack of D2, resulting in lower intracellular T3 concentrations, impairs pro-inflammatory macrophage function. A lack of the thyroid hormone receptor alpha, which modulates the effects of T3, also results in impaired macrophage function and shifts the cells towards a more anti-inflammatory phenotype. Inflammation and infection have profound effects on both central and peripheral thyroid hormone metabolism. Adequate regulation of intracellular thyroid hormone concentrations is crucial for optimal function of neutrophils and macrophages during inflammation.

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