Secondary adrenal insufficiency pathophysiology: Difference between revisions

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==Overview==
==Overview==
Secondary adrenal insufficiency is caused by the processes occurring outside [[adrenal glands]]: [[pituitary]] causes, drugs, genetic causes.These disease processes causes the decreased production of [[adrenocorticotrophic hormone]] ([[ACTH]]).
Secondary adrenal insufficiency is caused by the processes occurring outside [[adrenal glands]]: [[pituitary]] causes, [[Drug|drugs]], [[Genetics|genetic]] causes.These disease processes causes the decreased production of [[adrenocorticotrophic hormone]] ([[ACTH]]).
 


==Pathophysiology==
==Pathophysiology==
* [[Hypothalamus]] produces [[corticotropin releasing hormone]] ([[CRH]]) that stimulates pituitary gland's corticotrophes to release [[adrenocorticotroph hormone]] ( [[ACTH]]).
* [[Hypothalamus]] produces [[corticotropin releasing hormone]] ([[CRH]]) that stimulates [[pituitary gland]]'s corticotrophs to release [[adrenocorticotrophic hormone]] ( [[ACTH]]).
* [[Anterior pituitary]][[gland]'s corticotrophe cells produce ACTH that in turn stimulates adrenal cortex's zona glomerulosa to produce [[cortisol]].
* [[Anterior pituitary]] [[gland]]'s [[Corticotrophs|corticotroph cells]] produce [[ACTH]] that in turn stimulates [[adrenal cortex]]'s [[zona glomerulosa]] to produce [[cortisol]].
* [[Cortisol]] is produced by [[zona glomerulosa]] of the [[adrenal gland]] and provides feedback to [[pituitary]] and [[hypothalamus]].
* [[Cortisol]] is produced by [[zona glomerulosa]] of the [[adrenal gland]] and provides feedback to [[pituitary]] and [[hypothalamus]].


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===Pathogenesis===
===Pathogenesis===


*Secondary adrenal insufficiency is caused by the processes occurring outside [[adrenal glands]]: [[pituitary]] causes, drugs, genetic causes.
* Secondary adrenal insufficiency is caused by the processes occurring outside [[adrenal glands]]: [[pituitary]] causes, [[Drug|drugs]], and [[Genetics|genetic]] causes.
*These disease processes causes the decreased production of [[adrenocorticotrophic hormone]] ([[ACTH]]).
* These disease processes causes the decreased production of [[adrenocorticotrophic hormone]] ([[ACTH]]).
*[[Chronic steroid]] therapy causes suppression of [[hypothalamic pituitary adrenal axis]] ([[HPA]]) axis.
* Chronic [[steroid]] therapy causes suppression of [[hypothalamic pituitary adrenal axis]] ([[HPA]]) axis.
*In some cases of adrenal insufficiency, [[hyponatremia]] is seen due to an abnormal increase in [[antidiuretic hormone]]([[ADH]]) which in turn caused due to deficiency of cortisol due to decreased excretion of free water. The feedback loop causes secretion of [[corticotropin-releasing hormone]] ([[CRH]]), again an [[ADH]] [[secretagogue]]. There is a negative feedback on [[CRH]] and [[ACTH]] by [[cortisol]]. In adrenal insufficiency, this effect is removed and [[cortisol]] inhibits [[ADH]] excretion directly showing the reciprocal relation of [[ADH]] increase when [[cortisol]] is low. [[ADH]] inappropriate secretion leads to more water absorption leading to [[hyponatremia]].<ref name="pmid25699130">{{cite journal |vauthors=Jessani N, Jehangir W, Behman D, Yousif A, Spiler IJ |title=Secondary adrenal insufficiency: an overlooked cause of hyponatremia |journal=J Clin Med Res |volume=7 |issue=4 |pages=286–8 |year=2015 |pmid=25699130 |pmc=4330026 |doi=10.14740/jocmr2041w |url=}}</ref>
* In some cases of [[adrenal insufficiency]], [[hyponatremia]] is seen due to an abnormal increase in [[antidiuretic hormone]]([[ADH]]) which in turn caused due to deficiency of cortisol due to decreased excretion of free water. The feedback loop causes secretion of [[corticotropin-releasing hormone]] ([[CRH]]), again an [[ADH]] [[secretagogue]]. There is a negative feedback on [[CRH]] and [[ACTH]] by [[cortisol]]. In adrenal insufficiency, this effect is removed and [[cortisol]] inhibits [[ADH]] excretion directly showing the reciprocal relation of [[ADH]] increase when [[cortisol]] is low. [[ADH]] inappropriate secretion leads to more water absorption leading to [[hyponatremia]].<ref name="pmid25699130">{{cite journal |vauthors=Jessani N, Jehangir W, Behman D, Yousif A, Spiler IJ |title=Secondary adrenal insufficiency: an overlooked cause of hyponatremia |journal=J Clin Med Res |volume=7 |issue=4 |pages=286–8 |year=2015 |pmid=25699130 |pmc=4330026 |doi=10.14740/jocmr2041w |url=}}</ref>


==Genetics==
==Genetics==
*Secondary adrenal insufficiency is also caused by genetic disorders.
*Secondary adrenal insufficiency is also caused by genetic disorders.
**Combined pituitary hormone deficiency (CPHD)
**Combined [[Pituitary gland|pituitary]] hormone deficiency (CPHD)
**[[Proopiomelanocortin]] deficiency ([[POMC]])<ref name="urlProopiomelanocortin Deficiency - GeneReviews® - NCBI Bookshelf">{{cite web |url=https://www.ncbi.nlm.nih.gov/books/NBK174451/ |title=Proopiomelanocortin Deficiency - GeneReviews® - NCBI Bookshelf |format= |work= |accessdate=}}</ref>
**[[Proopiomelanocortin]] deficiency ([[POMC]])<ref name="urlProopiomelanocortin Deficiency - GeneReviews® - NCBI Bookshelf">{{cite web |url=https://www.ncbi.nlm.nih.gov/books/NBK174451/ |title=Proopiomelanocortin Deficiency - GeneReviews® - NCBI Bookshelf |format= |work= |accessdate=}}</ref>


*POMC deficiency is transmitted in [[autosomal recessive]] transmission pattern.
*[[POMC]] deficiency is transmitted in [[autosomal recessive]] transmission pattern.
*Genes involved in the pathogenesis of [[POMC]] deficiency include [[POMC]] gene.
*Genes involved in the pathogenesis of [[POMC]] deficiency include [[POMC]] gene.
*Genes involved in the pathogenesis of CPHD include PROP-1 where [[ACTH]] deficiency occurs in the end after [[GH]], [[Prolactin]], [[TSH]], [[LH]]/[[FSH]] deficiencies. Other genes in CPHD include HESX1, LHX3, LHX4 and SOX3.
*Genes involved in the pathogenesis of CPHD include [[PROP1|PROP-1]] where [[ACTH]] deficiency occurs in the end after [[GH]], [[Prolactin]], [[TSH]], and [[LH]]/[[FSH]] deficiencies. Other genes in CPHD include [[HESX1]], [[LHX3]], LHX4 and [[SOX3]].


==Associated Conditions==
==Associated Conditions==
*[[Hypopituitarism]]
*[[Hypopituitarism]]
*[[Adrenal crisis]]
*[[Adrenal hemorrhage]]
*[[Hyponatremia]]


==Gross Pathology==
==Gross Pathology==

Latest revision as of 21:10, 15 November 2017

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Amandeep Singh M.D.[2]

Overview

Secondary adrenal insufficiency is caused by the processes occurring outside adrenal glands: pituitary causes, drugs, genetic causes.These disease processes causes the decreased production of adrenocorticotrophic hormone (ACTH).

Pathophysiology

Production of cortisol- Source :NIH, https://www.niddk.nih.gov/health-information/endocrine-diseases/adrenal-insufficiency-addisons-disease

Pathogenesis

Genetics

Associated Conditions

Gross Pathology

  • The gross pathology features are dependent on the cause. For the gross pathology, when secondary adrenal insufficiency is caused by hypopituitarism, click here.

Microscopic Pathology

  • The microscopic pathology features are dependent on the cause. For the microscopic pathology when the cause is hypopituitarism, click here.
Histopathological image of nonfunctioning pituitary adenoma. Hematoxylin & eosin stain showing basophilic appearance of the cells.
Histopathological image of nonfunctioning pituitary adenoma. Hematoxylin & eosin stain showing basophilic appearance of the cells. Source: By Jensflorian (Own work) [CC BY-SA 3.0 (http://creativecommons.org/licenses/by-sa/3.0)], via Wikimedia Commons

References

  1. Jessani N, Jehangir W, Behman D, Yousif A, Spiler IJ (2015). "Secondary adrenal insufficiency: an overlooked cause of hyponatremia". J Clin Med Res. 7 (4): 286–8. doi:10.14740/jocmr2041w. PMC 4330026. PMID 25699130.
  2. "Proopiomelanocortin Deficiency - GeneReviews® - NCBI Bookshelf".

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