Critical illness–related corticosteroid insufficiency

The best known feature that suggests a possible underlying adrenal insufficiency is low blood pressure despite resuscitation with intravenous fluids, requiring vasopressor drugs. Several blood test abnormalities can suggest corticosteroid insufficiency, such as hypoglycemia, hyponatremia, hyperkalemia, hypercalcemia, neutropenia, eosinophilia, hyperprolactinemia, and hypothyroidism. ==Physiology==

In acute states of severe stress, cortisol secretion by the adrenal gland increases up to sixfold, parallel to the severity of the condition. There is also an increase in the number and affinity of glucocorticoid receptors. Furthermore, anaesthesia drugs like etomidate could interfere with the HPA axis. The secretion also loses its normal diurnal pattern of morning peak levels and evening and night time troughs. Nevertheless, secretion remains pulsatile and there is a marked variation in blood samples from the same individual. 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. 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. 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. ==Diagnosis==

The exact diagnostic tests and cut-off values to diagnose critical illness-related corticosteroid insufficiency are not agreed upon. In the CORTICUS study, ACTH stimulation testing predicted mortality whereas baseline cortisol levels did not. However, possible benefits of corticosteroid therapy do not seem to be completely predicted by ACTH stimulation testing. For these reasons, guidelines currently do not recommend that ACTH stimulation testing should guide the decision whether or not to administer corticosteroids. Cortisol immunoassays on the other hand have been shown to be prone to both over- and underestimation. ==Treatment==

In adults with septic shock and refractory hypotension despite resuscitation with intravenous fluids and vasopressors, hydrocortisone is the preferred corticosteroid. It can be divided in several doses or administered as a continuous infusion. Historically, higher doses of steroids were given, but these have been suggested to be harmful compared to the lower doses which are advocated today. In the CORTICUS study, hydrocortisone hastened the reversal of septic shock, but did not influence mortality, with an increased occurrence of septic shock relapse and hypernatremia. Several factors (such as lack of statistical power due to slow recruitment) could have led a false-negative finding on mortality in the CORTICUS study; thus, more research is needed. ==See also==