cortisol physiology

see also:

• adrenocorticotropic hormone (ACTH)
• corticosteroids

• cortisol is a glucocorticoid hormone produced by the cortex of the adrenal glands and is a key component of the physiologic stress response

• cortisol is 11-beta,17-alpha,21-trihydroxypregn-4-ene-3,20-dione
• it is “inactivated” by 11-beta-hydroxysteroid dehydrogenase to the inactive cortisone

• amygdala:
  • in response to emotive stress, sends signals to stimulate the hypothalamus
• hypothalamus:
  • corticotrophin-releasing hormone, CRH, is secreted from the paraventricular nucleus of the hypothalamus
• anterior pituitary gland:
  • CRH stimulates the anterior pituitary gland to release adrenocorticotropic hormone (ACTH)
• adrenal cortex:
  • ACTH is a tropic hormone that stimulates the zona fasciculate layer of the adrenal cortex to release glucocorticoids, such as cortisol
• negative feedback loop:
  • cortisol inhibits the production of CRH and ACTH

• steroid hormones such as cortisol are fat soluble and can cross cellular membranes
• once inside the cell, cortisol binds to the glucocorticoid receptor and dissociates the Hsp90 from the receptor, and the cortisol-receptor complex then enters the nucleus and affects gene transcription

• fear, anxiety, etc are processed by the amygdala to stimulate the hypothalamus which then activates the sympNS which stimulates the adrenal glands to secrete:
  • epinephrine (adrenaline)
  • cortisol
• when the threat passes, the above are switched off and the parasympNS is activated and further reduces the stress response

• cortisol helps maintain an adequate supply of glucose to provide energy for the brain via:
  • liver: increased gluconeogenesis and decreased glycogen synthesis
  • muscles: decreased glucose uptake and consumption and increased protein degradation which helps supply glucogenic amino acids to allow gluconeogenesis to occur
  • adipose tissue: increased lipolysis to provide FFAs and glycerol as an energy source for non-brain cells
  • pancreas: decreased insulin and increased glucagon secretion
    • glucagon increases liver glycogenolysis, liver gluconeogenesis, liver ketogenesis, lipolysis, as well as decreases lipogenesis
  • enhances the activity of glucagon, epinephrine, and other catecholamines

• glucorticosteroids are anti-inflammatory and decrease the immune response

• cortisol potentiates the vasoconstrictive effect of epinephrine

• cortisol with epinephrine help form memories from highly emotive events but may lead to poor memory of other unrelated events
• has a significant impact on vigilance and cognition
• inhibits the retrieval of already stored information
• long term elevated levels create deficits in memory and attention and can lead to “steroid dementia”

• multiple effects on fetal development
• maturation of the lung and production of surfactant
• necessary for normal brain development
• etc.

• this may cause Addison's disease or an acute Addisonian crisis which may result in:
  • the shocked hypotensive patient or hypotension
  • hyponatraemia
  • hyperkalaemia
• low serum cortisol levels may be caused by:
  • diurnal variation (high in the morning, low at midnight)
  • corticosteroids
  • decreased cortisol binding globulin
  • sudden cessation of exogenous corticosteroids may result in acute Addisonian crisis
  • pituitary failure
  • adrenal failure
• Ix of a morning low cortisol level:
  • short Synacthen test (SST):
    • cortisol level measured in am then an IM dose of Synacthen is given and a repeat serum cortisol sample is taken 30 and 60 minutes later
    • a response to Synacthen resulting in a rise in cortisol to over 420 excludes primary adrenal failure but the cause may still be pituitary failure which would be suggested by a low morning serum ACTH level
    • an inadequate response indicates primary adrenal failure

• high serum cortisol levels are seen in:
  • stress
  • exogenous corticosteroids including prednisolone, hydrocortisone, cortisone
  • increased cortisol binding globulin levels (pregnancy, OCP)
  • Cushing's syndrome:
    • pituitary
    • adrenal
    • ectopic ACTH
• if this is prolonged, it may result in the clinical features of Cushing's syndrome:
  • see Cushing's syndrome