Primary hyperaldosteronism pathophysiology

Jump to: navigation, search


Primary hyperaldosteronism Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Primary Hyperaldosteronism from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Diagnostic study of choice

History and Symptoms

Physical Examination

Laboratory Findings

CT scan Findings

MRI Findings

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Case Studies

Case #1

Primary hyperaldosteronism pathophysiology On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Primary hyperaldosteronism pathophysiology

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Primary hyperaldosteronism pathophysiology

CDC on Primary hyperaldosteronism pathophysiology

Primary hyperaldosteronism pathophysiology in the news

Blogs on Primary hyperaldosteronism pathophysiology

Directions to Hospitals Treating Conn syndrome

Risk calculators and risk factors for Primary hyperaldosteronism pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Syed Hassan A. Kazmi BSc, MD [2], Mehrian Jafarizade, M.D [3]

Overview

Conn's syndrome (primary hyperaldosteronism) features overproduction of aldosterone despite suppressed plasma renin activity (PRA). The resulting sodium retention produces hypertension, and elevated potassium excretion may cause hypokalemia. Patients with Conn's syndrome due to primary hyperaldosteronism may have an aldosterone producing adrenocortical adenoma (APA); classically referred to as Conn's syndrome, a unilateral hyperplasia, idiopathic hyperaldosteronism (IHA, also known as bilateral adrenal hyperplasia), familial forms (familial hyperaldosteronism types I, II, and III) have also been described, ectopic secretion of aldosterone (The ovaries and kidneys are the 2 organs described in the literature that, in the setting of neoplastic disease, can be ectopic sources of aldosterone, but this is a rare occurrence).

Pathophysiology

Renin

Basic physiology of aldosterone

Circulating aldosterone is principally made in the zona glomerulosa of the adrenal cortex (outer layer of the cortex) by a cascade of enzyme steps leading to the conversion of cholesterol to aldosterone.  

Renin angiotensin system - by Mikael Häggström, Via: Wikimedia.org[2]


Adrenal steroid synthesis pathways in adrenal cortex and related enzymes, Via: Wikimedia.org[3]

Pathogenesis

Primary hyperaldosteronism (PA) features overproduction of aldosterone despite suppressed plasma renin activity (PRA). The resulting sodium retention may lead to hypertension, and elevated potassium excretion may cause hypokalemia.

Genetics

1. Aldosterone Producing Adenoma (APA)

APAs are typically solitary, well circumscribed tumors which can cause aldosterone hypersecretion.

Somatic mutations
Gain of function mutations (KCNJ5, CACNA1D, CTNNB1 mutations)

Loss of function mutations (ATP1A1 and ATP2A3)

2. Familial hyperaldosteronism Type I (FH-I)

3. Familial hyperaldosteronism Type II (FH-II)

4. Familial hyperaldosteronism Type III

Associated Conditions

The following conditions may be found in association with primary hyperaldosteronism:

Gross Pathology

  • An aldosterone producing adenoma is usually, a unilateral, yellow, lipid-laden adenoma ranging in diameter from 5 to 35 mm.

<figure-inline>Gross adrenal adenoma.jpeg</figure-inline>

Microscopic Pathology

Microscopically, on hematoxylin and eosin section, the following findings can be observed for aldosterone producing adenomas:[23]

<figure-inline>Adenoma adrenal.jpg</figure-inline>


References

  1. Williams GH (2005). "Aldosterone biosynthesis, regulation, and classical mechanism of action". Heart Fail Rev. 10 (1): 7–13. doi:10.1007/s10741-005-2343-3. PMID 15947886.
  2. <https://commons.wikimedia.org/w/index.php?curid=8458370>
  3. "File:Adrenal Steroids Pathways.svg - Wikimedia Commons".
  4. Young WF (2007). "Primary aldosteronism: renaissance of a syndrome". Clin. Endocrinol. (Oxf). 66 (5): 607–18. doi:10.1111/j.1365-2265.2007.02775.x. PMID 17492946.
  5. Scholl UI, Healy JM, Thiel A, Fonseca AL, Brown TC, Kunstman JW, Horne MJ, Dietrich D, Riemer J, Kücükköylü S, Reimer EN, Reis AC, Goh G, Kristiansen G, Mahajan A, Korah R, Lifton RP, Prasad ML, Carling T (2015). "Novel somatic mutations in primary hyperaldosteronism are related to the clinical, radiological and pathological phenotype". Clin. Endocrinol. (Oxf). 83 (6): 779–89. doi:10.1111/cen.12873. PMC 4995792. PMID 26252618.
  6. Choi M, Scholl UI, Yue P, Björklund P, Zhao B, Nelson-Williams C, Ji W, Cho Y, Patel A, Men CJ, Lolis E, Wisgerhof MV, Geller DS, Mane S, Hellman P, Westin G, Åkerström G, Wang W, Carling T, Lifton RP (2011). "K+ channel mutations in adrenal aldosterone-producing adenomas and hereditary hypertension". Science. 331 (6018): 768–72. doi:10.1126/science.1198785. PMC 3371087. PMID 21311022.
  7. Scholl UI, Healy JM, Thiel A, Fonseca AL, Brown TC, Kunstman JW, Horne MJ, Dietrich D, Riemer J, Kücükköylü S, Reimer EN, Reis AC, Goh G, Kristiansen G, Mahajan A, Korah R, Lifton RP, Prasad ML, Carling T (2015). "Novel somatic mutations in primary hyperaldosteronism are related to the clinical, radiological and pathological phenotype". Clin. Endocrinol. (Oxf). 83 (6): 779–89. doi:10.1111/cen.12873. PMC 4995792. PMID 26252618.
  8. Fernandes-Rosa FL, Williams TA, Riester A, Steichen O, Beuschlein F, Boulkroun S, Strom TM, Monticone S, Amar L, Meatchi T, Mantero F, Cicala MV, Quinkler M, Fallo F, Allolio B, Bernini G, Maccario M, Giacchetti G, Jeunemaitre X, Mulatero P, Reincke M, Zennaro MC (2014). "Genetic spectrum and clinical correlates of somatic mutations in aldosterone-producing adenoma". Hypertension. 64 (2): 354–61. doi:10.1161/HYPERTENSIONAHA.114.03419. PMID 24866132.
  9. Monticone S, Hattangady NG, Nishimoto K, Mantero F, Rubin B, Cicala MV, Pezzani R, Auchus RJ, Ghayee HK, Shibata H, Kurihara I, Williams TA, Giri JG, Bollag RJ, Edwards MA, Isales CM, Rainey WE (2012). "Effect of KCNJ5 mutations on gene expression in aldosterone-producing adenomas and adrenocortical cells". J. Clin. Endocrinol. Metab. 97 (8): E1567–72. doi:10.1210/jc.2011-3132. PMC 3410264. PMID 22628608.
  10. 10.0 10.1 Monticone S, Hattangady NG, Penton D, Isales CM, Edwards MA, Williams TA, Sterner C, Warth R, Mulatero P, Rainey WE (2013). "a Novel Y152C KCNJ5 mutation responsible for familial hyperaldosteronism type III". J. Clin. Endocrinol. Metab. 98 (11): E1861–5. doi:10.1210/jc.2013-2428. PMC 3816265. PMID 24037882.
  11. Oki K, Plonczynski MW, Luis Lam M, Gomez-Sanchez EP, Gomez-Sanchez CE (2012). "Potassium channel mutant KCNJ5 T158A expression in HAC-15 cells increases aldosterone synthesis". Endocrinology. 153 (4): 1774–82. doi:10.1210/en.2011-1733. PMC 3320257. PMID 22315453.
  12. Åkerström T, Maharjan R, Sven Willenberg H, Cupisti K, Ip J, Moser A, Stålberg P, Robinson B, Alexander Iwen K, Dralle H, Walz MK, Lehnert H, Sidhu S, Gomez-Sanchez C, Hellman P, Björklund P (2016). "Activating mutations in CTNNB1 in aldosterone producing adenomas". Sci Rep. 6: 19546. doi:10.1038/srep19546. PMC 4728393. PMID 26815163.
  13. Scholl UI, Healy JM, Thiel A, Fonseca AL, Brown TC, Kunstman JW, Horne MJ, Dietrich D, Riemer J, Kücükköylü S, Reimer EN, Reis AC, Goh G, Kristiansen G, Mahajan A, Korah R, Lifton RP, Prasad ML, Carling T (2015). "Novel somatic mutations in primary hyperaldosteronism are related to the clinical, radiological and pathological phenotype". Clin. Endocrinol. (Oxf). 83 (6): 779–89. doi:10.1111/cen.12873. PMC 4995792. PMID 26252618.
  14. 14.0 14.1 Stowasser M, Gordon RD (2001). "Familial hyperaldosteronism". J. Steroid Biochem. Mol. Biol. 78 (3): 215–29. PMID 11595502.
  15. 15.0 15.1 Jackson RV, Lafferty A, Torpy DJ, Stratakis C (2002). "New genetic insights in familial hyperaldosteronism". Ann. N. Y. Acad. Sci. 970: 77–88. PMID 12381543.
  16. Lafferty AR, Torpy DJ, Stowasser M, Taymans SE, Lin JP, Huggard P, Gordon RD, Stratakis CA (2000). "A novel genetic locus for low renin hypertension: familial hyperaldosteronism type II maps to chromosome 7 (7p22)". J. Med. Genet. 37 (11): 831–5. PMC 1734468. PMID 11073536.
  17. Torpy DJ, Gordon RD, Lin JP, Huggard PR, Taymans SE, Stowasser M, Chrousos GP, Stratakis CA (1998). "Familial hyperaldosteronism type II: description of a large kindred and exclusion of the aldosterone synthase (CYP11B2) gene". J. Clin. Endocrinol. Metab. 83 (9): 3214–8. doi:10.1210/jcem.83.9.5086. PMID 9745430.
  18. "Genetics of primary hyperaldosteronism".
  19. Malinow KC, Lion JR (1979). "Hyperaldosteronism (Conn's disease) presenting as depression". J Clin Psychiatry. 40 (8): 358–9. PMID 468762.
  20. Apostolopoulou K, Künzel HE, Gerum S, Merkle K, Schulz S, Fischer E, Pallauf A, Brand V, Bidlingmaier M, Endres S, Beuschlein F, Reincke M (2014). "Gender differences in anxiety and depressive symptoms in patients with primary hyperaldosteronism: a cross-sectional study". World J. Biol. Psychiatry. 15 (1): 26–35. doi:10.3109/15622975.2012.665480. PMID 22568586.
  21. Astegiano M, Bresso F, Demarchi B, Sapone N, Novero D, Palestro G, Resegotti A, Pellicano R, Rizzetto M (2005). "Association between Crohn's disease and Conn's syndrome. A report of two cases". Panminerva Med. 47 (1): 61–4. PMID 15985978.
  22. Kim YA, Lee SS (2003). "Conn's syndrome associated with Behcet's disease". J. Korean Med. Sci. 18 (1): 145–7. doi:10.3346/jkms.2003.18.1.145. PMC 3054990. PMID 12589107.
  23. "Aldosterone-producing adenoma and other surgically correctable forms of primary aldosteronism".

Linked-in.jpg