Critical illness-related corticosteroid insufficiency pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Pathophysiology

In acute states of severe stress, cortisol secretion by the adrenal gland increases up to six-fold, parallel to the severity of the condition.[1] This is partly due to an increased secretion of corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH). Several cytokines have been also shown to interfere with the HPA axis at multiple levels.[2] There is also an increase in the number and affinity of glucocorticoid receptors.[3] Levels of corticosteroid-binding globulin (CBG) and albumin, which normally bind cortisol, are decreased, resulting in increased levels of free cortisol.[1] Furthermore, anaesthesia drugs like etomidate could interfere with the HPA axis.[4] The secretion also loses its normal diurnal pattern of morning peak levels and evening and night time troughs.[5] Nevertheless, secretion remains pulsatile and there is a marked variation in blood samples from the same individual.[6]

High blood levels of cortisol during critical illness could theoretically be protective because of several reasons. They modulate metabolism (for example, by inducing high blood sugar levels, thereby providing energy to the body). They also suppress excessive immune system activation and exert supporting effects on the circulatory system.[2][7] Increased susceptibility to infections, hyperglycemia (in patients already prone to stress hyperglycemia), gastrointestinal bleeding, electrolyte disturbances and steroid-induced myopathy (in patients already prone to critical illness polyneuropathy) are possible harmful effects.

Blood levels of dehydroepiandrosterone increase, and levels of dehydroepiandrosterone sulfate decrease in response to critical illness.[8][9][10]

In the chronic phase of severe illness, cortisol levels decrease slowly and return to normal when the patient recovers. ACTH levels are however low, and CBG levels increase.

References

  1. 1.0 1.1 Hamrahian AH, Oseni TS, Arafah BM (2004). "Measurements of serum free cortisol in critically ill patients". N. Engl. J. Med. 350 (16): 1629–38. doi:10.1056/NEJMoa020266. PMID 15084695. Unknown parameter |month= ignored (help)
  2. 2.0 2.1 Marik PE, Zaloga GP (2002). "Adrenal insufficiency in the critically ill: a new look at an old problem". Chest. 122 (5): 1784–96. PMID 12426284. Unknown parameter |month= ignored (help)
  3. name=http://www.ncbi.nlm.nih.gov/pubmed?term=18695699
  4. Duthie DJ, Fraser R, Nimmo WS (1985). "Effect of induction of anaesthesia with etomidate on corticosteroid synthesis in man". Br J Anaesth. 57 (2): 156–9. PMID 2982387. Unknown parameter |month= ignored (help)
  5. Cooper MS, Stewart PM (2003). "Corticosteroid insufficiency in acutely ill patients". N. Engl. J. Med. 348 (8): 727–34. doi:10.1056/NEJMra020529. PMID 12594318. Unknown parameter |month= ignored (help)
  6. Venkatesh B, Mortimer RH, Couchman B, Hall J (2005). "Evaluation of random plasma cortisol and the low dose corticotropin test as indicators of adrenal secretory capacity in critically ill patients: a prospective study". Anaesth Intensive Care. 33 (2): 201–9. PMID 15960402. Unknown parameter |month= ignored (help)
  7. Van den Berghe G, de Zegher F, Bouillon R (1998). "Clinical review 95: Acute and prolonged critical illness as different neuroendocrine paradigms". J. Clin. Endocrinol. Metab. 83 (6): 1827–34. PMID 9626104. Unknown parameter |month= ignored (help)
  8. Arlt W, Hammer F, Sanning P; et al. (2006). "Dissociation of serum dehydroepiandrosterone and dehydroepiandrosterone sulfate in septic shock". J. Clin. Endocrinol. Metab. 91 (7): 2548–54. doi:10.1210/jc.2005-2258. PMID 16608898. Unknown parameter |month= ignored (help)
  9. Marx C, Petros S, Bornstein SR; et al. (2003). "Adrenocortical hormones in survivors and nonsurvivors of severe sepsis: diverse time course of dehydroepiandrosterone, dehydroepiandrosterone-sulfate, and cortisol". Crit. Care Med. 31 (5): 1382–8. doi:10.1097/01.CCM.0000063282.83188.3D. PMID 12771606. Unknown parameter |month= ignored (help)
  10. Vermes I, Beishuizen A (2001). "The hypothalamic-pituitary-adrenal response to critical illness". Best Pract. Res. Clin. Endocrinol. Metab. 15 (4): 495–511. doi:10.1053/beem.2001.0166. PMID 11800520. Unknown parameter |month= ignored (help)

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