Non-thyroidal Illness Syndrome

  • Lisa D. Madison
  • Stephen H. LaFranchi


Non-thyroidal illness is the term used to describe the changes in thyroid hormone and thyroid-stimulating hormone (TSH) with acute illness not caused by an intrinsic abnormality of thyroid function. In children, non-thyroidal illness is most commonly seen in acutely ill patients admitted to pediatric or neonatal intensive care units (ICUs). The characteristic decrease in thyroid hormone levels also can be seen with starvation, trauma, or surgical procedures. Non-thyroidal illness probably occurs with any severe illness, and the pattern of changes in thyroid hormones correlates with the severity of illness. Typically, the first changes are a decrease in serum triiodothyronine (T3) and a rise in reverse T3 (rT3) levels. This disorder has been referred to as the low-T3 syndrome or the euthyroid sick syndrome. However, as there is disagreement about whether patients truly are “euthyroid,” non-thyroidal illness syndrome (NTIS) is the term preferred at present.

The changes in thyroid hormone and TSH concentrations with NTIS are believed to be an adaptive mechanism, in that they protect the body from high metabolic demands in the face of starvation or acute illness. However, there are certain clinical situations where this concept has been challenged, with the belief that the changes are maladaptive and clinical improvement may be seen with treatment with triiodothyronine (l-T3) or levothyroxine (l-T4). In particular, there is some evidence that preterm babies <27 weeks’ gestation may show improvement in IQ scores with l-T4 treatment and that infants and children undergoing cardiac surgery may show improved post-op cardiac function with l-T3 treatment. Further research is needed to resolve these issues.


Non-thyroidal illness syndrome—thyroid hormone changes Thyroxine (T4) Free T4 (FT4) Triiodothyronine (T3) Free T3 (FT3) Reverse T3 (rT3) Thyroid-stimulating hormone (TSH) Thyrotropin-releasing hormone (TRH) Thyroxine-binding globulin (TBG) Transthyretin Albumin Hypothalamic–pituitary–thyroid (HPT) axis Central hypothyroidism Leptin Paraventricular nucleus Tanycyte Cytokines Cortisol Deiodinase type 1 (D1) Deiodinase type 2 (D2) Deiodinase type 3 (D3) Thyroid hormone receptor (THR) Thyroid hormone transporters Monocarboxylate transporter 8 (MCT8) Heparin Dopamine Glucocorticoids Furosemide Salicylates Preterm infants Neurodevelopmental outcome Cardiac–renal insufficiency Cystic fibrosis Psychiatric disorders Depression Bipolar disorder Attention-deficit hyperactivity disorder (ADHD) 


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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Pediatrics – EndocrinologyDoernbecher Children’s Hospital, Oregon Health and Science UniversityPortlandUSA

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