Non-thyroidal illness syndrome is a manifestation of hypothalamic-pituitary dysfunction, and in view of current evidence, should be treated with appropriate replacement therapies

Crit Care Clin. 2006 Jan;22(1):57-86, vi. doi: 10.1016/j.ccc.2005.10.001.


This article documents the role of hypothalamic hypothyroidism and decreased T4-->T3 conversion as the cause of low T4 and T3 in non-thyroidal illness syndrome (NTIS). This article also presents the arguments for administration of replacement triiodothyronine (T3) and thyroxine (T4) hormone in patients who have NTIS. It is impossible to be certain at this time that it is beneficial to replace hormone, or whether this could be harmful. Only a prospective study will be adequate to prove this point, and probably this would need to involve hundreds of patients. If effective, thyroid hormone replacement will be one of many beneficial treatments given the patient, rather than a single magic bullet, which would reverse all the metabolic changes going wrong in these severely ill patients.

Publication types

  • Review

MeSH terms

  • Biological Transport / physiology
  • Cytokines / metabolism
  • Euthyroid Sick Syndromes / drug therapy
  • Euthyroid Sick Syndromes / physiopathology*
  • Growth Hormone-Releasing Hormone / therapeutic use
  • Hormone Replacement Therapy / methods
  • Humans
  • Hypothalamo-Hypophyseal System / physiopathology*
  • Stress, Physiological
  • Thyroid Hormones / deficiency
  • Thyroid Hormones / metabolism
  • Thyroid Hormones / physiology
  • Thyroid Hormones / therapeutic use*
  • Thyrotropin / analysis
  • Thyrotropin / physiology
  • Thyrotropin / therapeutic use
  • Thyrotropin-Releasing Hormone / therapeutic use
  • Thyroxine / analysis
  • Thyroxine / deficiency
  • Thyroxine / physiology
  • Thyroxine-Binding Proteins / metabolism
  • Triiodothyronine / analysis
  • Triiodothyronine / deficiency
  • Triiodothyronine / physiology


  • Cytokines
  • Thyroid Hormones
  • Thyroxine-Binding Proteins
  • Triiodothyronine
  • Thyrotropin-Releasing Hormone
  • Thyrotropin
  • Growth Hormone-Releasing Hormone
  • Thyroxine