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__NOTOC__
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{{Hypoaldosteronism}}
{{Hypoaldosteronism}}
{{CMG}}; {{AE}}{{Akshun}}
{{CMG}}; {{AE}}{{Akshun}}{{SSW}}


==Overview==
==Overview==
Hypoaldosteronism is defined as decreased levels of the [[hormone]] [[aldosterone]] or a [[resistance]] of the target tissue to the actions of [[aldosterone]]. Hypoaldosteronism from decreased production is seen in conditions such as congenital isolated hypoaldosteronism, [[Primary adrenal insufficiency|primary adrenal insufficiency,]] [[diabetic nephropathy]], [[critical illness]], and [[drugs]] such as [[ACE inhibitor|ACE inhibitors]], [[NSAIDs]] and [[Calcineurin inhibitor|calcineurin inhibitors]]. [[Resistance]] of the target tissue to the actions of [[aldosterone]] is seen with [[mineralocorticoid receptor]] defects (seen in [[pseudohypoaldosteronism]]) and with [[drugs]] such as [[potassium-sparing diuretics]] and [[trimethoprim]]. Hypoaldosteronism results in reduced reabsorption of [[sodium]] in the [[principal cells]] of [[Cortical collecting duct|cortical collecting tubules]] (CCT). This leads to decreased excretion of [[potassium]] ([[hyperkalemia]]) and mild non-anion gap [[metabolic acidosis]]. On gross pathology, [[adrenal glands]] may be irregularly shrunken or hyperplastic.
Hypoaldosteronism is defined as decreased levels of the [[hormone]] [[aldosterone]] or a [[resistance]] of the target tissue to the actions of [[aldosterone]]. Hypoaldosteronism from decreased production is seen in conditions such as congenital isolated hypoaldosteronism, [[Primary adrenal insufficiency|primary adrenal insufficiency,]] [[diabetic nephropathy]], [[critical illness]], and [[drugs]] such as [[ACE inhibitor|ACE inhibitors]], [[NSAIDs]] and [[Calcineurin inhibitor|calcineurin inhibitors]]. [[Resistance]] of the target tissue to the actions of [[aldosterone]] is seen with [[mineralocorticoid receptor]] defects (seen in [[pseudohypoaldosteronism]]) and with [[drugs]] such as [[potassium-sparing diuretics]] and [[trimethoprim]]. Hypoaldosteronism results in reduced reabsorption of [[sodium]] in the [[principal cells]] of [[Cortical collecting duct|cortical collecting tubules]] (CCT). This leads to decreased excretion of [[potassium]] ([[hyperkalemia]]) and mild non-anion gap [[metabolic acidosis]]. On gross pathology, [[adrenal glands]] may be irregularly shrunken or [[hyperplastic]].


==Pathophysiology==
==Pathophysiology==
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[[image:Renin-angiotensin-aldosterone system.png|thumb|500px|center| Source:By A. Rad (me) (Own work) [GFDL (http://www.gnu.org/copyleft/fdl.html) or CC-BY-SA-3.0 (http://creativecommons.org/licenses/by-sa/3.0/)], via Wikimedia Commons]]
[[image:Renin-angiotensin-aldosterone system.png|thumb|750px|center| Source:By A. Rad (me) (Own work) [GFDL (http://www.gnu.org/copyleft/fdl.html) or CC-BY-SA-3.0 (http://creativecommons.org/licenses/by-sa/3.0/)], via Wikimedia Commons]]




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*Hypoaldosteronism is defined as decreased levels of the [[hormone]] [[aldosterone]] or a resistance of the target tissue to the actions of [[aldosterone]]. Hypoaldosteronism can be due to:<ref name="pmid8015573">{{cite journal |vauthors=White PC |title=Disorders of aldosterone biosynthesis and action |journal=N. Engl. J. Med. |volume=331 |issue=4 |pages=250–8 |year=1994 |pmid=8015573 |doi=10.1056/NEJM199407283310408 |url=}}</ref>
*Hypoaldosteronism is defined as decreased levels of the [[hormone]] [[aldosterone]] or a resistance of the target tissue to the actions of [[aldosterone]]. Hypoaldosteronism can be due to:<ref name="pmid8015573">{{cite journal |vauthors=White PC |title=Disorders of aldosterone biosynthesis and action |journal=N. Engl. J. Med. |volume=331 |issue=4 |pages=250–8 |year=1994 |pmid=8015573 |doi=10.1056/NEJM199407283310408 |url=}}</ref>
** '''Aldosterone deficiency''': The deficiency in [[aldosterone]] can be due to congenital isolated hypoaldosteronism, [[primary adrenal insufficiency]], [[diabetic nephropathy]], [[critical illness]], and [[drugs]] such as [[ACE inhibitor|ACE inhibitors]], [[NSAIDs|NSAID]] and [[Calcineurin inhibitor|calcineurin inhibitors]].
** '''Aldosterone deficiency''': The deficiency in [[aldosterone]] can be due to congenital isolated hypoaldosteronism, [[primary adrenal insufficiency]], [[diabetic nephropathy]], [[critical illness]], and [[drugs]] such as [[ACE inhibitor|ACE inhibitors]], [[NSAIDs|NSAID]] and [[Calcineurin inhibitor|calcineurin inhibitors]].
** '''Aldosterone resistance''': In [[aldosterone]] resistance, the level of [[aldosterone]] is normal but there is decreased response of the target tissue to the actions of [[aldosterone]]. [[Aldosterone]] resistance is seen with [[mineralocorticoid receptor]] defects (seen in [[pseudohypoaldosteronism]]) and with [[drugs]] such as [[Potassium-sparing diuretic|potassium-sparing diuretics]] and trimethoprim.
** '''Aldosterone resistance''': In [[aldosterone]] resistance, the level of [[aldosterone]] is normal but there is decreased response of the target tissue to the actions of [[aldosterone]]. [[Aldosterone]] resistance is seen with [[mineralocorticoid receptor]] defects (seen in [[pseudohypoaldosteronism]]) and with [[drugs]] such as [[Potassium-sparing diuretic|potassium-sparing diuretics]] and [[trimethoprim]].


*Hypoaldosteronism results in reduced [[reabsorption]] of [[sodium]] in the [[principal cells]] of [[Cortical collecting ducts|cortical collecting tubules]] (CCT).  This leads to decreased [[excretion]] of [[potassium]] and mild non-anion gap [[metabolic acidosis]].
*Hypoaldosteronism results in reduced [[reabsorption]] of [[sodium]] in the [[principal cells]] of [[Cortical collecting ducts|cortical collecting tubules]] (CCT).  This leads to decreased [[excretion]] of [[potassium]] and mild non-anion gap [[metabolic acidosis]].


=== Hyporeninemic Hypoaldosteronism===
=== Hyporeninemic Hypoaldosteronism===
* Hyporeninemic hypoaldosteronism is most commonly seen in patients with mild to moderate [[renal insufficiency]] and [[Diabetic nephropathy|diabetic nephropathy:]]
* Hyporeninemic hypoaldosteronism is most commonly seen in patients with mild to moderate [[renal insufficiency]] and [[Diabetic nephropathy|diabetic nephropathy:]]<ref name="pmid6758113">{{cite journal |vauthors=Weidmann P |title=[Hyporeninemic hypoaldosteronism and the differential diagnosis of hyperkalemia] |language=German |journal=Schweiz Med Wochenschr |volume=112 |issue=49 |pages=1764–74 |year=1982 |pmid=6758113 |doi= |url=}}</ref><ref name="pmid3908957">{{cite journal |vauthors=Schambelan M, Sebastian A |title=[Type IV renal tubular acidosis: pathogenetic role of aldosterone deficiency and hyperkalemia] |language=French |journal=Nephrologie |volume=6 |issue=3 |pages=135–7 |year=1985 |pmid=3908957 |doi= |url=}}</ref><ref name="pmid7446728">{{cite journal |vauthors=Arruda JA, Kurtzman NA |title=Mechanisms and classification of deranged distal urinary acidification |journal=Am. J. Physiol. |volume=239 |issue=6 |pages=F515–23 |year=1980 |pmid=7446728 |doi= |url=}}</ref>
** In patients of [[renal insufficiency]], [[atrophy]] of the [[juxtaglomerular apparatus]] (JGA) leads to decreased sensing of plasma [[sodium]] concentration and renal [[perfusion pressure]].
** In patients of [[renal insufficiency]], [[atrophy]] of the [[juxtaglomerular apparatus]] (JGA) leads to decreased sensing of plasma [[sodium]] concentration and renal [[perfusion pressure]].
** With progression of the [[renal disease]] and [[atrophy]] of the [[juxtaglomerular apparatus]] (JGA) there may be inadequate [[renin]] production and release.
** With progression of the [[renal disease]] and [[atrophy]] of the [[juxtaglomerular apparatus]] (JGA) there may be inadequate [[renin]] production and release.
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===Isolated Hypoaldosteronism===
===Isolated Hypoaldosteronism===
*In isolated hypoaldosteronism, there is selective [[deficiency]] of [[aldosterone]] with normal [[cortisol]] production. Isolated hypoaldosteronism may result from dysfunction of [[zona glomerulosa]] or [[aldosterone synthase]] deficiency.  
*In isolated hypoaldosteronism, there is selective [[deficiency]] of [[aldosterone]] with normal [[cortisol]] production. Isolated hypoaldosteronism may result from dysfunction of [[zona glomerulosa]] or [[aldosterone synthase]] deficiency. <ref name="pmid15026188">{{cite journal |vauthors=Lisurek M, Bernhardt R |title=Modulation of aldosterone and cortisol synthesis on the molecular level |journal=Mol. Cell. Endocrinol. |volume=215 |issue=1-2 |pages=149–59 |year=2004 |pmid=15026188 |doi=10.1016/j.mce.2003.11.008 |url=}}</ref>
** [[Aldosterone synthase]] is an [[enzyme]] involved in the [[synthesis]] of [[aldosterone]]. Patients with [[aldosterone synthase]] [[enzyme]] [[deficiency]] (type I and type II) results in defective conversion of [[deoxycorticosterone]] to [[aldosterone]] and subsequently abnormal levels of [[aldosterone]].
** [[Aldosterone synthase]] is an [[enzyme]] involved in the [[synthesis]] of [[aldosterone]]. Patients with [[aldosterone synthase]] [[enzyme]] [[deficiency]] (type I and type II) results in defective conversion of [[deoxycorticosterone]] to [[aldosterone]] and subsequently abnormal levels of [[aldosterone]].
** Certain [[drugs]] such as [[heparin]] and [[nitric oxide]] have a direct suppressive effect on the [[zona glomerulosa]] of [[adrenal cortex]] which may lead to decrease production of [[aldosterone]].
** Certain [[drugs]] such as [[heparin]] and [[nitric oxide]] have a direct suppressive effect on the [[zona glomerulosa]] of [[adrenal cortex]] which may lead to decrease production of [[aldosterone]].
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* [[Conn syndrome pathophysiology|Conn syndrome]] is most often unilateral and leads to excessive production of [[aldosterone]] from the affected [[adrenal gland]].  
* [[Conn syndrome pathophysiology|Conn syndrome]] is most often unilateral and leads to excessive production of [[aldosterone]] from the affected [[adrenal gland]].  
* Excessive production of [[aldosterone]] causes [[hypertension]] and suppression of [[renin angiotensin aldosterone system]] ([[RAAS]]).
* Excessive production of [[aldosterone]] causes [[hypertension]] and suppression of [[renin angiotensin aldosterone system]] ([[RAAS]]).
* Patients of [[Conn syndrome pathophysiology|Conn syndrome]] who are treated with [[spironolactone]] and later undergo [[surgery]] for [[tumor]] removal may develop hypoaldosteronism.
* Patients with [[Conn syndrome pathophysiology|Conn syndrome]] who are treated with [[spironolactone]] and later undergo [[surgery]] for [[tumor]] removal may develop hypoaldosteronism.
* Patients of [[Conn syndrome pathophysiology|Conn syndrome]] have increased levels of [[aldosterone]] and decreased [[plasma renin activity]] (from suppressed [[RAAS]]) which leads to chronic suppression of contralateral [[zona glomerulosa]].
* Patients with [[Conn syndrome pathophysiology|Conn syndrome]] have increased levels of [[aldosterone]] and decreased [[plasma renin activity]] (from suppressed [[RAAS]]) which leads to chronic suppression of contralateral [[zona glomerulosa]].
* On surgical removal of aldosterone producing [[tumor]], there is sudden decline in circulating [[aldosterone]] which leads to hypoaldosteronism.
* On surgical removal of aldosterone producing [[tumor]], there is sudden decline in circulating [[aldosterone]] which leads to hypoaldosteronism.


===Mineralocorticoid Resistance===
===Mineralocorticoid Resistance===
Mineralocorticoid resistance is characterized by a decrease in response to the hormone [[aldosterone]]. In mineralocorticoid resistance the level of [[aldosterone]] may be normal or supranormal. It is due to this reason mineralocorticoid resistance is also known as [[pseudohypoaldosteronism]]. Mineralocorticoid resistance can be further categorized into:<ref name="pmid13545877">{{cite journal |vauthors=CHEEK DB, PERRY JW |title=A salt wasting syndrome in infancy |journal=Arch. Dis. Child. |volume=33 |issue=169 |pages=252–6 |year=1958 |pmid=13545877 |pmc=2012226 |doi= |url=}}</ref><ref name="pmid11498583">{{cite journal |vauthors=Wilson FH, Disse-Nicodème S, Choate KA, Ishikawa K, Nelson-Williams C, Desitter I, Gunel M, Milford DV, Lipkin GW, Achard JM, Feely MP, Dussol B, Berland Y, Unwin RJ, Mayan H, Simon DB, Farfel Z, Jeunemaitre X, Lifton RP |title=Human hypertension caused by mutations in WNK kinases |journal=Science |volume=293 |issue=5532 |pages=1107–12 |year=2001 |pmid=11498583 |doi=10.1126/science.1062844 |url=}}</ref><ref name="pmid23453970">{{cite journal |vauthors=Wakabayashi M, Mori T, Isobe K, Sohara E, Susa K, Araki Y, Chiga M, Kikuchi E, Nomura N, Mori Y, Matsuo H, Murata T, Nomura S, Asano T, Kawaguchi H, Nonoyama S, Rai T, Sasaki S, Uchida S |title=Impaired KLHL3-mediated ubiquitination of WNK4 causes human hypertension |journal=Cell Rep |volume=3 |issue=3 |pages=858–68 |year=2013 |pmid=23453970 |doi=10.1016/j.celrep.2013.02.024 |url=}}</ref>
[[Mineralocorticoid]] resistance is characterized by a decrease in response to the hormone [[aldosterone]]. In [[mineralocorticoid]] resistance the level of [[aldosterone]] may be normal or supranormal. It is due to this reason [[mineralocorticoid]] resistance is also known as [[pseudohypoaldosteronism]]. [[Mineralocorticoid]] resistance can be further categorized into:<ref name="pmid13545877">{{cite journal |vauthors=CHEEK DB, PERRY JW |title=A salt wasting syndrome in infancy |journal=Arch. Dis. Child. |volume=33 |issue=169 |pages=252–6 |year=1958 |pmid=13545877 |pmc=2012226 |doi= |url=}}</ref><ref name="pmid11498583">{{cite journal |vauthors=Wilson FH, Disse-Nicodème S, Choate KA, Ishikawa K, Nelson-Williams C, Desitter I, Gunel M, Milford DV, Lipkin GW, Achard JM, Feely MP, Dussol B, Berland Y, Unwin RJ, Mayan H, Simon DB, Farfel Z, Jeunemaitre X, Lifton RP |title=Human hypertension caused by mutations in WNK kinases |journal=Science |volume=293 |issue=5532 |pages=1107–12 |year=2001 |pmid=11498583 |doi=10.1126/science.1062844 |url=}}</ref><ref name="pmid23453970">{{cite journal |vauthors=Wakabayashi M, Mori T, Isobe K, Sohara E, Susa K, Araki Y, Chiga M, Kikuchi E, Nomura N, Mori Y, Matsuo H, Murata T, Nomura S, Asano T, Kawaguchi H, Nonoyama S, Rai T, Sasaki S, Uchida S |title=Impaired KLHL3-mediated ubiquitination of WNK4 causes human hypertension |journal=Cell Rep |volume=3 |issue=3 |pages=858–68 |year=2013 |pmid=23453970 |doi=10.1016/j.celrep.2013.02.024 |url=}}</ref>
* '''Pseudohypoaldosteronism type I''':  
* '''Pseudohypoaldosteronism Type I''':  
** The decrease in response to aldosterone is due to heterozygous or homozygous inactivating mutations in the [[mineralocorticoid receptor]]. These patients are also resistant to mineralocorticoid therapy.
** The decrease in response to [[aldosterone]] is due to heterozygous or homozygous inactivating [[mutations]] in the [[mineralocorticoid receptor]]. These patients are also resistant to [[mineralocorticoid]] therapy.
* '''Pseudohypoaldosteronism Type II''':  
* '''Pseudohypoaldosteronism Type II''':  
** This is an extremely rare disorder. It is speculated that these patients have mutations in the genes encoding proteins of the serine threonine [[kinase]] family (WKNK1 or WNK4 kinases). Pseudohypoaldosteronism Type II  is characterized by low or low-normal [[plasma renin activity]] and [[aldosterone]] concentrations, leading to [[hyperkalemia]] and [[metabolic acidosis]] with normal [[renal]] function. Pseudohypoaldosteronism type II is also known as Gordon’s syndrome.
** This is an extremely rare disorder. It is speculated that these patients have [[mutations]] in the [[genes]] encoding proteins of the serine threonine [[kinase]] family (WKNK1 or WNK4 kinases). Pseudohypoaldosteronism Type II  is characterized by low or low-normal [[plasma renin activity]] and [[aldosterone]] concentrations, leading to [[hyperkalemia]] and [[metabolic acidosis]] with normal [[renal]] function. Pseudohypoaldosteronism type II is also known as [[Gordon syndrome|Gordon’s syndrome]].
* '''Pseudohypoaldosteronism type III''':  
* '''Pseudohypoaldosteronism Type III''':  
** This condition presents with [[transient]] mineralocorticoid resistance. Pseudohypoaldosteronism type III is seen in patients with underlying [[renal]] conditions with decreased [[GFR]]. The exact cause is unknown but is thought to be related to increased levels of [[TGF beta|TGF]]-β.
** This condition presents with [[transient]] [[mineralocorticoid]] resistance. Pseudohypoaldosteronism type III is seen in patients with underlying [[renal]] conditions with decreased [[glomerular filtration rate]]. The exact cause is unknown but is thought to be related to increased levels of [[TGF beta|TGF]]-β.


==Genetics==
==Genetics==
*[[Genes]] involved in the [[pathogenesis]] of hypoaldosteronism include [[mutation]] in [[CYP11B2]] gene and NR3C2 gene.
*[[Genes]] involved in the [[pathogenesis]] of hypoaldosteronism include [[mutation]] in [[CYP11B2]] gene and NR3C2 gene.<ref name="pmid1594605">{{cite journal |vauthors=Pascoe L, Curnow KM, Slutsker L, Rösler A, White PC |title=Mutations in the human CYP11B2 (aldosterone synthase) gene causing corticosterone methyloxidase II deficiency |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=89 |issue=11 |pages=4996–5000 |year=1992 |pmid=1594605 |pmc=49215 |doi= |url=}}</ref><ref name="pmid9814506">{{cite journal |vauthors=Portrat-Doyen S, Tourniaire J, Richard O, Mulatero P, Aupetit-Faisant B, Curnow KM, Pascoe L, Morel Y |title=Isolated aldosterone synthase deficiency caused by simultaneous E198D and V386A mutations in the CYP11B2 gene |journal=J. Clin. Endocrinol. Metab. |volume=83 |issue=11 |pages=4156–61 |year=1998 |pmid=9814506 |doi=10.1210/jcem.83.11.5258 |url=}}</ref><ref name="pmid15134805">{{cite journal |vauthors=White PC |title=Aldosterone synthase deficiency and related disorders |journal=Mol. Cell. Endocrinol. |volume=217 |issue=1-2 |pages=81–7 |year=2004 |pmid=15134805 |doi=10.1016/j.mce.2003.10.013 |url=}}</ref>
*'''CYP11B2 gene''' is located on chromosome 8q24.
*'''CYP11B2 gene''' is located on chromosome 8q24.
**[[Mutation]] in [[CYP11B2]] gene is transmitted in [[autosomal recessive]] pattern.
**[[Mutation]] in [[CYP11B2]] gene is transmitted in [[autosomal recessive]] pattern.
**The [[CYP11B2]] gene encodes for the [[enzyme]] [[aldosterone synthase]] (previously known as corticosterone methyloxidase).  
**The [[CYP11B2]] gene encodes for the [[enzyme]] [[aldosterone synthase]] (previously known as corticosterone methyloxidase).  
**[[Aldosterone synthase]] catalyses the conversion of 11 deoxycorticosterone to [[aldosterone]]. The following flowchart depicts the various steps carried out by the [[enzyme]] [[aldosterone synthase]]:  
**[[Aldosterone synthase]] catalyses the conversion of [[11-deoxycorticosterone]] to [[aldosterone]]. The following flowchart depicts the various steps carried out by the [[enzyme]] [[aldosterone synthase]]:  




{{Family tree/start}}
{{Family tree/start}}
{{Family tree | | | | A01 | | | |A01= 11 Deoxycorticosterone}}
{{Family tree | | | | A01 | | | |A01= [[11 Deoxycorticosterone]]}}
{{Family tree | | | | |!| | | | | }}
{{Family tree | | | | |!| | | | | }}
{{Family tree | | | | B01 | | | |B01= Corticosterone}}
{{Family tree | | | | B01 | | | |B01= [[Corticosterone]]}}
{{Family tree | | | | |!| | | | | }}
{{Family tree | | | | |!| | | | | }}
{{Family tree | | | | C01 | | | |C01= 18 Hydroxycorticosterone}}
{{Family tree | | | | C01 | | | |C01= [[18 Hydroxycorticosterone]]}}
{{Family tree | | | | |!| | | | | }}
{{Family tree | | | | |!| | | | | }}
{{Family tree | | | | D01 | | | |D01= Aldosterone}}
{{Family tree | | | | D01 | | | |D01= [[Aldosterone]]}}
{{Family tree/end}}
{{Family tree/end}}


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**NR3C2 [[gene]] is located on [[chromosome]] 4q31.1-31.2; which is the long (q) arm of [[chromosome 4]] at position 31.1-31.2
**NR3C2 [[gene]] is located on [[chromosome]] 4q31.1-31.2; which is the long (q) arm of [[chromosome 4]] at position 31.1-31.2
**NR3C2 [[gene]] encodes for [[mineralocorticoid receptor]].
**NR3C2 [[gene]] encodes for [[mineralocorticoid receptor]].
**[[Mutation]] in NR3C2 [[gene]] can be transmitted in autosomal recessive or autosomal dominant pattern.
**[[Mutation]] in NR3C2 [[gene]] can be transmitted in [[autosomal recessive]] or [[autosomal dominant]] pattern.
**[[Mutated]] NR3C2 [[gene]] leads to defective [[mineralocorticoid receptor]] and presents with [[resistance]] to the actions of [[aldosterone]].
**[[Mutated]] NR3C2 [[gene]] leads to defective [[mineralocorticoid receptor]] and presents with [[resistance]] to the actions of [[aldosterone]].


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*[[Pernicious anemia]]
*[[Pernicious anemia]]
*[[Myasthenia gravis]]
*[[Myasthenia gravis]]
*Chronic [[candidiasis]]
*[[Candidiasis|Chronic candidiasis]]
*[[Sjögren's syndrome|Sjögren syndrome]]
*[[Sjögren's syndrome|Sjögren syndrome]]
*[[Chronic active hepatitis]]
*[[Chronic active hepatitis]]
*[[Hypothyroidism]]
*[[Hypothyroidism]]
*[[Graves' disease|Graves]] hyperthyroidism
*[[Graves' disease|Graves hyperthyroidism]]
*[[Adrenoleukodystrophy]]
*[[Adrenoleukodystrophy]]


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{{WH}}
{{WH}}
{{WS}}
{{WS}}
[[Category:Disease]]
[[Category:Endocrinology]]
[[Category:Nephrology]]
[[Category:Emergency medicine]]
[[Category:Medicine]]
[[Category:Up-To-Date]]

Latest revision as of 14:07, 31 July 2018

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Akshun Kalia M.B.B.S.[2]Sargun Singh Walia M.B.B.S.[3]

Overview

Hypoaldosteronism is defined as decreased levels of the hormone aldosterone or a resistance of the target tissue to the actions of aldosterone. Hypoaldosteronism from decreased production is seen in conditions such as congenital isolated hypoaldosteronism, primary adrenal insufficiency, diabetic nephropathy, critical illness, and drugs such as ACE inhibitors, NSAIDs and calcineurin inhibitors. Resistance of the target tissue to the actions of aldosterone is seen with mineralocorticoid receptor defects (seen in pseudohypoaldosteronism) and with drugs such as potassium-sparing diuretics and trimethoprim. Hypoaldosteronism results in reduced reabsorption of sodium in the principal cells of cortical collecting tubules (CCT). This leads to decreased excretion of potassium (hyperkalemia) and mild non-anion gap metabolic acidosis. On gross pathology, adrenal glands may be irregularly shrunken or hyperplastic.

Pathophysiology

Physiology


Source:By A. Rad (me) (Own work) [GFDL (http://www.gnu.org/copyleft/fdl.html) or CC-BY-SA-3.0 (http://creativecommons.org/licenses/by-sa/3.0/)], via Wikimedia Commons


Pathogenesis

Hyporeninemic Hypoaldosteronism

Hyperreninemic Hypoaldosteronism

Isolated Hypoaldosteronism

Postadrenalectomy Hypoaldosteronism

Postadrenalectomy hypoaldosteronism is seen in patients with Conn syndrome who undergo surgery for tumor removal:[12][13][14][15][16][17][18]

Mineralocorticoid Resistance

Mineralocorticoid resistance is characterized by a decrease in response to the hormone aldosterone. In mineralocorticoid resistance the level of aldosterone may be normal or supranormal. It is due to this reason mineralocorticoid resistance is also known as pseudohypoaldosteronism. Mineralocorticoid resistance can be further categorized into:[19][20][21]

Genetics


 
 
 
11 Deoxycorticosterone
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Corticosterone
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
18 Hydroxycorticosterone
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Aldosterone
 
 
 


Associated Conditions

Gross Pathology

Image courtesy: PathologyOutlines.com
Image courtesy: PathologyOutlines.com

Microscopic Pathology

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Image courtesy: PathologyOutlines.com

References

  1. ↑ Schnermann J, Levine DZ (2003). "Paracrine factors in tubuloglomerular feedback: adenosine, ATP, and nitric oxide". Annu. Rev. Physiol. 65: 501–29. doi:10.1146/annurev.physiol.65.050102.085738. PMID 12208992.
  2. ↑ Castrop H (2007). "Mediators of tubuloglomerular feedback regulation of glomerular filtration: ATP and adenosine". Acta Physiol (Oxf). 189 (1): 3–14. doi:10.1111/j.1748-1716.2006.01610.x. PMID 17280552.
  3. ↑ Hall JE (1991). "Control of blood pressure by the renin-angiotensin-aldosterone system". Clin Cardiol. 14 (8 Suppl 4): IV6–21, discussion IV51–5. PMID 1893644.
  4. ↑ White PC (1994). "Disorders of aldosterone biosynthesis and action". N. Engl. J. Med. 331 (4): 250–8. doi:10.1056/NEJM199407283310408. PMID 8015573.
  5. ↑ Weidmann P (1982). "[Hyporeninemic hypoaldosteronism and the differential diagnosis of hyperkalemia]". Schweiz Med Wochenschr (in German). 112 (49): 1764–74. PMID 6758113.
  6. ↑ Schambelan M, Sebastian A (1985). "[Type IV renal tubular acidosis: pathogenetic role of aldosterone deficiency and hyperkalemia]". Nephrologie (in French). 6 (3): 135–7. PMID 3908957.
  7. ↑ Arruda JA, Kurtzman NA (1980). "Mechanisms and classification of deranged distal urinary acidification". Am. J. Physiol. 239 (6): F515–23. PMID 7446728.
  8. ↑ Kater CE, Biglieri EG, Brust N, Chang B, Hirai J (1982). "Regulation of the mineralocorticoid hormones in adrenocortical disorders with adrenocorticotropin excess". Clin Exp Hypertens A. 4 (9–10): 1749–58. PMID 6291814.
  9. ↑ Aguilera G, Fujita K, Catt KJ (1981). "Mechanisms of inhibition of aldosterone secretion by adrenocorticotropin". Endocrinology. 108 (2): 522–8. doi:10.1210/endo-108-2-522. PMID 6256154.
  10. ↑ Singer DR, Shirley DG, Markandu ND, Miller MA, Buckley MG, Sugden AL, Sagnella GA, MacGregor GA (1991). "How important are suppression of aldosterone and stimulation of atrial natriuretic peptide secretion in the natriuretic response to an acute sodium load in man?". Clin. Sci. 80 (4): 293–9. PMID 1851063.
  11. ↑ Lisurek M, Bernhardt R (2004). "Modulation of aldosterone and cortisol synthesis on the molecular level". Mol. Cell. Endocrinol. 215 (1–2): 149–59. doi:10.1016/j.mce.2003.11.008. PMID 15026188.
  12. ↑ Kawasaki T, Uezono K, Ueno M, Noda Y, Kumamoto K, Kawano Y, Ogata M, Fukiyama K, Omae T, Bartter FC (1980). "Influence of unilateral adrenalectomy on renin-angiotensin-aldosterone system in primary aldosteronism". Jpn Heart J. 21 (5): 681–92. PMID 7001091.
  13. ↑ Kempers MJ, Lenders JW, van Outheusden L, van der Wilt GJ, Schultze Kool LJ, Hermus AR, Deinum J (2009). "Systematic review: diagnostic procedures to differentiate unilateral from bilateral adrenal abnormality in primary aldosteronism". Ann. Intern. Med. 151 (5): 329–37. PMID 19721021.
  14. ↑ Huang WT, Chau T, Wu ST, Lin SH (2010). "Prolonged hyperkalemia following unilateral adrenalectomy for primary hyperaldosteronism". Clin. Nephrol. 73 (5): 392–7. PMID 20420801.
  15. ↑ Gadallah MF, Kayyas Y, Boules F (1998). "Reversible suppression of the renin-aldosterone axis after unilateral adrenalectomy for adrenal adenoma". Am. J. Kidney Dis. 32 (1): 160–3. PMID 9669438.
  16. ↑ Biglieri EG, Slaton PE, Silen WS, Galante M, Forsham PH (1966). "Postoperative studies of adrenal function in primary aldosteronism". J. Clin. Endocrinol. Metab. 26 (5): 553–8. doi:10.1210/jcem-26-5-553. PMID 4287160.
  17. ↑ Groth H, Vetter W, Stimpel M, Greminger P, Tenschert W, Klaiber E, Vetter H (1985). "Adrenalectomy in primary aldosteronism: a long-term follow-up study". Cardiology. 72 Suppl 1: 107–16. PMID 3902226.
  18. ↑ Yorke E, Stafford S, Holmes D, Sheth S, Melck A (2015). "Aldosterone deficiency after unilateral adrenalectomy for Conn's syndrome: a case report and literature review". Int J Surg Case Rep. 7C: 141–4. doi:10.1016/j.ijscr.2015.01.013. PMC 4336421. PMID 25604311.
  19. ↑ CHEEK DB, PERRY JW (1958). "A salt wasting syndrome in infancy". Arch. Dis. Child. 33 (169): 252–6. PMC 2012226. PMID 13545877.
  20. ↑ Wilson FH, Disse-Nicodème S, Choate KA, Ishikawa K, Nelson-Williams C, Desitter I, Gunel M, Milford DV, Lipkin GW, Achard JM, Feely MP, Dussol B, Berland Y, Unwin RJ, Mayan H, Simon DB, Farfel Z, Jeunemaitre X, Lifton RP (2001). "Human hypertension caused by mutations in WNK kinases". Science. 293 (5532): 1107–12. doi:10.1126/science.1062844. PMID 11498583.
  21. ↑ Wakabayashi M, Mori T, Isobe K, Sohara E, Susa K, Araki Y, Chiga M, Kikuchi E, Nomura N, Mori Y, Matsuo H, Murata T, Nomura S, Asano T, Kawaguchi H, Nonoyama S, Rai T, Sasaki S, Uchida S (2013). "Impaired KLHL3-mediated ubiquitination of WNK4 causes human hypertension". Cell Rep. 3 (3): 858–68. doi:10.1016/j.celrep.2013.02.024. PMID 23453970.
  22. ↑ Pascoe L, Curnow KM, Slutsker L, Rösler A, White PC (1992). "Mutations in the human CYP11B2 (aldosterone synthase) gene causing corticosterone methyloxidase II deficiency". Proc. Natl. Acad. Sci. U.S.A. 89 (11): 4996–5000. PMC 49215. PMID 1594605.
  23. ↑ Portrat-Doyen S, Tourniaire J, Richard O, Mulatero P, Aupetit-Faisant B, Curnow KM, Pascoe L, Morel Y (1998). "Isolated aldosterone synthase deficiency caused by simultaneous E198D and V386A mutations in the CYP11B2 gene". J. Clin. Endocrinol. Metab. 83 (11): 4156–61. doi:10.1210/jcem.83.11.5258. PMID 9814506.
  24. ↑ White PC (2004). "Aldosterone synthase deficiency and related disorders". Mol. Cell. Endocrinol. 217 (1–2): 81–7. doi:10.1016/j.mce.2003.10.013. PMID 15134805.

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