Addison's disease pathophysiology: Difference between revisions

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{{CMG}} ; {{AE}} {{ADG}}
{{CMG}} ; {{AE}} {{ADG}}
==Overview==
==Overview==
The [[hypothalamus]] releases [[corticotropin-releasing hormone]] (CRH), which stimulates the [[pituitary gland]] to release [[Adrenocorticotropic hormone|corticotropin]] ([[ACTH]]). [[Adrenocorticotropic hormone|ACTH]] travels via the [[blood]] to the [[adrenal gland]], where it stimulates the release of [[cortisol]]. [[Cortisol]] is secreted by the [[Adrenal cortex|cortex]] of the [[adrenal gland]] from a region called the [[zona fasciculata]] in response to [[Adrenocorticotropic hormone|ACTH]]. Elevated levels of [[cortisol]] exert [[negative feedback]] on the [[Pituitary gland|pituitary]], which decreases the amount of [[Adrenocorticotropic hormone|ACTH]] released from the [[pituitary gland]]. Addison's disease results when the [[Adrenal gland|adrenal glands]] do not produce enough [[cortisol]] and [[aldosterone]].
The [[hypothalamus]] releases [[corticotropin-releasing hormone]] (CRH), which stimulates the [[pituitary gland]] to release [[Adrenocorticotropic hormone|corticotropin]] ([[ACTH]]). [[Adrenocorticotropic hormone|ACTH]] travels via the [[blood]] to the [[adrenal gland]], where it stimulates the release of [[cortisol]]. [[Cortisol]] is secreted by the [[Adrenal cortex|cortex]] of the [[adrenal gland]] from a region called the [[zona fasciculata]] in response to [[Adrenocorticotropic hormone|ACTH]]. Elevated levels of [[cortisol]] exert [[negative feedback]] on the [[Pituitary gland|pituitary]], which decreases the amount of [[Adrenocorticotropic hormone|ACTH]] released from the [[pituitary gland]]. Addison's disease results when the [[Adrenal gland|adrenal glands]] do not produce enough [[cortisol]] and [[aldosterone]].


==Normal Physiology of Adrenal Glands==
==Normal Physiology of Adrenal Glands==
===Hypothalamic–pituitary–adrenal axis===
===Hypothalamic–pituitary–adrenal axis===
*The paraventricular nucleus of the hypothalamus, secrete corticotropin-releasing hormone (CRH).
*The [[paraventricular nucleus]] of the [[hypothalamus]] [[Secrete|secretes]] [[corticotropin-releasing hormone]] ([[CRH]]).
*It stimulates the anterior lobe of the pituitary gland. to secrete adrenocorticotropic hormone (ACTH)
*[[Corticotropin-releasing hormone|CRH]] stimulates the anterior lobe of the [[pituitary gland]], which leads to the release of [[adrenocorticotropic hormone]] ([[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.  
*[[ACTH]], in turn, acts on the [[adrenal cortex]], which produces [[glucocorticoid]] [[Hormone|hormones]] (mainly [[cortisol]] in humans).  
*Glucocorticoids in turn act back on the hypothalamus and pituitary (to suppress CRH and ACTH production) in a negative feedback cycle.
*Glucocorticoids, in addition to having [[physiological]] functions in the body, also have a [[negative feedback]] effect on the [[hypothalamus]] and [[Pituitary gland|pituitary]] (suppression of [[Corticotropin-releasing hormone|CRH]] and [[ACTH]] production).
[[Image:HPA Axis Diagram (Brian M Sweis 2012).png|center|500px]]
[[Image:HPA Axis Diagram (Brian M Sweis 2012).png|center|500px]]



Revision as of 18:50, 8 September 2017

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]

Overview

The hypothalamus releases corticotropin-releasing hormone (CRH), which stimulates the pituitary gland to release corticotropin (ACTH). ACTH travels via the blood to the adrenal gland, where it stimulates the release of cortisol. Cortisol is secreted by the cortex of the adrenal gland from a region called the zona fasciculata in response to ACTH. Elevated levels of cortisol exert negative feedback on the pituitary, which decreases the amount of ACTH released from the pituitary gland. Addison's disease results when the adrenal glands do not produce enough cortisol and aldosterone.

Normal Physiology of Adrenal Glands

Hypothalamic–pituitary–adrenal axis

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

Genetics

  • Hereditary factors sometimes play a key role in the development of autoimmune adrenal insufficiency.[1]
  • Common genetic conditions associated with addison's diseases include:
    • Familial glucocorticoid insufficiency may be associated with a recessive gene pattern.
    • Adrenomyeloneuropathy is known to be X-linked
  • Addison disease is associated with a variety of autoimmune conditions that have been linked to genetic factors.
  • Patients with autoimmune polyglandular failure might develop diabetes mellitus, pernicious anemia, and hypothyroidism secondary to antibodies which develop in adrenal glands.

Associated conditions

Addison's disease is commonly seen associated with conditions such as:

  • Autoimmune hypoparathyroidism resulting in hypocalcemia
  • Vitiligo
  • Premature ovarian failure
  • Pernicious anemia
  • Myasthenia gravis
  • Chronic candidiasis
  • Sjögren syndrome
  • Chronic active hepatitis
  • Diabetes mellitus type 1
  • Hypothyroidism
  • Hashimoto thyroiditis
  • Graves hyperthyroidism
  • Adrenoleukodystrophy

References

  1. Michels AW, Eisenbarth GS (2010). "Immunologic endocrine disorders". J. Allergy Clin. Immunol. 125 (2 Suppl 2): S226–37. doi:10.1016/j.jaci.2009.09.053. PMC 2835296. PMID 20176260.

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