Nonthyroidal illness in critically ill children

Abstract

This review summarizes recent literature on non-thyroidal illness syndrome (NTI) and outcome of pediatric critical illness, to provide insight in pathophysiology and therapeutic implications.Recent findings: NTI is typically characterized by lowered triiodothyronine levels without compensatory TSH rise. Although NTI severity is associated with poor outcome of pediatric critical illness, it remains unclear whether this association reflects an adaptive protective response or contributes to poor outcome. Recently, two metabolic interventions that improved outcome also altered NTI in critically ill children. These studies shed new light on the topic, as the results suggested that the peripheral NTI component, with inactivation of thyroid hormone, may represent a beneficial adaptation, whereas the central component, with suppressed TSH-driven thyroid hormone secretion, may be maladaptive. There is currently insufficient evidence for treatment of NTI in children. However, the recent findings raised the hypothesis that reactivation of the central NTI component could offer benefit, which should be tested in RCTs. Summary: NTI in critically ill children can be modified by metabolic interventions. The peripheral, but not the central, component of NTI may be a beneficial adaptive response. These findings open perspectives for the development of novel strategies to improve outcome of critical illness in children.

Non-thyroidal illness syndrome and SARS-CoV-2-associated multisystem inflammatory syndrome in children

“…NTIS has been reported in the context of infection, sepsis, trauma, burns, Extended author information available on the last page of the article myocardial infarction, and malignancy [10][11][12][13]. This condition has also been described in fasting states in otherwise healthy individuals [10][11][12][13].…”

“…Several changes in thyroid hormones (TH) occur during severe acute illness and are collectively referred to as non-thyroidal illness syndrome (NTIS) [10]. NTIS has been reported in the context of infection, sepsis, trauma, burns, Extended author information available on the last page of the article myocardial infarction, and malignancy [10][11][12][13]. This condition has also been described in fasting states in otherwise healthy individuals [10][11][12][13].…”

Central hypothyroidism improves with age in very young children with Prader‐Willi syndrome

“…The majority of previous studies utilized healthy controls as a reference; however, this may have created a bias when evaluating thyroid hormone levels in PWS children because thyroid hormone levels are affected by the nutritional status and/or body composition. For example, undernutrition has been shown to decrease FT4 levels without an increase in TSH levels, 13,14 which is of critical importance in PWS children, the majority of whom have difficulties in feeding, often necessitating enteral feeding 2 . Even when feeding difficulties cease, a significant proportion of subjects are still under strict energy intake restrictions as part of a nutritional intervention that may cause growth restrictions 21,22 .…”

“…These findings indicate that the HPT axis is altered in PWS children, possibly due to hypothalamic dysfunctions; however, control values in these studies were based on age‐ and sex‐matched healthy reference populations. As accumulating evidence has shown that the thyroid hormone status is affected by body composition 6,11,12 and the nutritional status 13,14 in paediatric populations, thyroid hormone levels in PWS children may be affected by a low body weight (BW), low body mass index (BMI) and/or an impaired nutritional status, which are characteristic of infants with PWS; therefore, comparisons between PWS subjects and healthy controls may create a bias, resulting in misinterpretations of the thyroid hormone status in very young children with PWS. In addition, GH treatment has been shown to enhance the conversion of T4 to T3 and reduce T4 levels; 15,16 therefore, combined analysis of GH‐treated and GH‐untreated subjects may also cause misunderstandings of thyroid hormone status in PWS.…”

Correlation of Nonthyroidal Illness Syndrome with Extubation Outcome in Mechanically Ventilated Children: A Prospective Cohort Study

“…Although there is an association between severe NTIS and poor clinical outcomes, it is unclear whether this association is due to a protective adaptation to critical illness through reduction of energy expenditure or is simply a direct cause of poor outcomes. 3 Pediatric patients were excluded from studies examining thyroid function and its relationship with disease severity, prognosis, and outcomes since most studies have been conducted in adults focusing primarily on surgical patients. 4 The extubation failure rate in pediatric patients has been found to be in the range of 2 to 20% and is associated with the pediatric intensive care unit (PICU) service and patient characteristics.…”