Endocrine Abstracts

The “sick euthyroid syndrome” or “non-thyroidal illness syndrome” (NTIS) occurs in a large proportion of hospitalized patients and comprises a variety of alterations in the hypothalamus-pituitary-thyroid (HPT) axis that are observed during illness. One of the hallmarks of NTIS is decreased plasma triiodothyronine (T3) levels, in severe illness accompanied by low plasma thyroxine (T4) and increased plasma reverse T3 (rT3) concentrations. Downregulation of hypophysiotropic thyrotropin releasing hormone (TRH) neurons in the paraventricular nucleus (PVN) of the hypothalamus and of thyrotropin (TSH) production in the pituitary gland points to altered feedback regulation during illness. The extent of the NTIS correlates with prognosis, but at this stage there is no proof for causality of this association. The changes in thyroid hormone (TH) metabolism are organ-specific, occur in a time-dependent manner and depend on the severity of illness. Acute alterations in plasma TH concentrations are a reflection of altered TH binding, uptake and metabolism by deiodinating enzymes, as well as by concomitant macronutrient restriction. Acute NTIS appears to be adaptive and probably beneficial, and may be considered part of the acute phase response to systemic illnesses. However, the pathogenesis of NTIS is different in prolonged critical illness when patients continue to depend on intensive medical care. In this prolonged critical illness, hypothalamic thyrotropin releasing hormone (TRH) expression is suppressed, explaining persistently reduced TSH secretion and TH release in spite of low plasma TH. At present there is no evidence-based consensus or guideline advocating thyroid hormone treatment of NTIS in the critically ill patients. Adequately powered RCTs should be performed to define whether active management of NTIS, e.g. using hypothalamic neuropeptides including TRH, may yield clinical benefit in terms of outcome.