Addison's disease pathophysiology

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

Normal Physiology of Adrenal Glands

Hypothalamic–pituitary–adrenal axis

  • The paraventricular nucleus of the hypothalamus, secrete corticotropin-releasing hormone (CRH).
  • It stimulates the anterior lobe of the pituitary gland. to secrete adrenocorticotropic hormone (ACTH)
  • ACTH, in turn, acts on the adrenal cortex, which produces glucocorticoid hormones (mainly cortisol in humans) in response to stimulation by ACTH.
  • Glucocorticoids in turn act back on the hypothalamus and pituitary (to suppress CRH and ACTH production) in a negative feedback cycle.

Cortisol

Harmone Type of class Function
Cortisol Glucocorticoids
  • Helps maintain blood pressure and cardiovascular function
  • Helps slow the immune system's inflammatory response
  • Helps balance the effects of insulin in breaking down sugar for energy
  • Helps regulate the metabolism of proteins, carbohydrates, and fats
  • Helps maintain proper arousal and sense of well-being
Aldosterone Mineralocorticoids
  • Maintain blood pressure and water and salt balance in the body by helping the kidney retain sodium and excrete potassium

Pathophysiology

Addison's disease occurs when the adrenal glands do not produce enough of the hormone cortisol and, in some cases, the hormone aldosterone. Causes of adrenal insufficiency can be grouped by the way in which they cause the adrenals to produce insufficient cortisol. These are adrenal dysgenesis (the gland has not formed adequately during development), impaired steroidogenesis (the gland is present but is biochemically unable to produce cortisol) or adrenal destruction (disease processes leading to the gland being damaged).

Causes Definition Pathophysiology
Adrenal dysgenesis Gland has not formed adequately during development
Impaired steroidogenesis
  • The gland is present but is biochemically unable to produce cortisol
  • To form cortisol, the adrenal gland requires cholesterol, which is then converted biochemically into steroid hormones.
  • Interruptions in the delivery of cholesterol
Adrenal destruction
  • Disease processes leading to the gland being damaged


References

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