Hyperaldosteronism

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Resident
Survival
Guide

Hyperaldosteronism Main page

Patient Information

Overview

Classification

1- Primary hyperaldosteronism
2- Secondary hyperaldosteronism
3- Pseudohyperaldosteronism causes (low renin)

Differentiating diagonsis

History and symptoms

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

This page contains general information about hyperaldosteronism. For more information on specific types, please visit the pages on primary hyperaldosteronism.

Synonyms and Keywords: Aldosteronism

Overview

Hyperaldosteronism is a clinical scenario of mineralocorticoid excess with resistant hypertension, hypokalemia, and metabolic alkalosis due to increased hydrogen ion excretion. Aldosteronism may be classified into three types, primary hyperaldosteronism (Conn's syndrome), secondary hyperaldosteronism, and pseudohyperaldosteronism. Primary hyperaldosteronism can caused by aldosterone-secreting adenoma, bilateral hyperplasia of the adrenal glands, and ectopic secretion of aldosterone from ovaries and kidneys. Primary hyperaldosteronism features overproduction of aldosterone despite suppressed plasma renin activity (PRA). The resulting Na+ retention produces hypertension, and increased K+ excretion may cause hypokalemia. Secondary hyperaldosteronism is caused by high renin and subsequently aldosterone level, such as renovascular causes and reninoma. Pseudohyperaldosteronism is the clinical presentation of hyperaldosteronism such as resistant hypertension, hypokalemia, and metabolic alkalosis due to factors other than renin and aldosterone. The treatment should be prescribed for the blockade of aldosterone effects, or based on underlying disease.

Classification

Aldosteronism and mineralocorticoid excess may be classified into three types, primary hyperaldosteronism (conn's syndrome), secondary hyperaldosteronism, and pseudohyperaldosteronism. The different types of mineralocorticoid excess are described below.


Primary hyperaldosteronism (conn's syndrome)

Primary hyperaldosteronism causes categorizes as below table: [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15]

Primary hyperaldosteronism Category Diseases
Adrenal causes Aldosterone-secreting adrenal adenoma
Idiopathic hyperaldosteronism
Extra-adrenal causes Ectopic secretion of aldosterone
Familial hyperaldosteronism Familial hyperaldosteronism type I
  • Glucocorticoid-remediable aldosteronism [GRA]
Familial hyperaldosteronism II
Familial hyperaldosteronism type III
  • Associated with the germline mutation in the KCNJ5 potassium channel)
Other Pure aldosterone-producing adrenocortical carcinomas
Unilateral adrenal hyperplasia

Secondary hyperaldosteronism

Secondary hyperaldosteronism causes are categorized as below, and each specific disease is described in the related micro-chapter. [16][17][18][19][20][21]

Category Diseases
Secondary hyperaldosteronism Genetic mutation Bartter and Gitelman syndromes (hyperplasia of the juxtaglomerular apparatus, the source of renin in the kidney)
Endocrine causes Cushing syndrome
  • The main pathogenetic mechanism is linked to the excess

of cortisol which saturates 11-HSD2 activity,

Ectopic ACTH production (Secondary to carcinomas such as lung cancer)
Renovascular Kidney transplant
Renin-secreting juxtaglomerular cell tumors
Scleroderma renal crisis
Malignant hypertension
Tumors Reninoma
Intravascular hypovolemia

Pseudohyperaldosteronism causes (low renin)

Pseudohyperaldosteronism causes are classified as below: [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15]

Pseudohyperaldosteronism causes Disease Etiology Clinical features Labratory Treatment
Elevated mineralocorticoid Renin Aldosterone Other
Endogenous causes 17 alpha-hydroxylase deficiency Mutations in the CYP17A1 gene Deoxycorticosterone (DOC) Cortisol Corticosteroids
11β-hydroxylase deficiency Mutations in the CYP11B1 gene Cortisol
Apparent mineralocorticoid excess syndrome (AME) Genetic or acquired defect of 11-HSD gene Cortisol has mineralocorticoid effects Urinary free cortisone ↓↓ Dexamethasone and/or mineralocorticoid blockers
Liddle’s syndrome (Pseudohyperaldosteronism type 1) Mutation of the epithelial sodium channels (ENaC) gene in the distal renal tubules No extra mineralocorticoid presents, and mutations in Na channels mimic aldosterone mechanism Cortisol Amiloride or triamterene
Cushing’s syndrome
  • The main pathogenetic mechanism is linked to the excess

of cortisol which saturates 11-HSD2 activity,

Rapid weight gain, particularly of the trunk and face with limbs sparing (central obesity) Cortisol has mineralocorticoid effects
  • ↓ if excess cortisol saturates 11-HSD2 enzyme activity
Urinary free cortisol markedly ↑↑
  • Adrenalectomy
Insensitivity to glucocorticoids (Chrousos syndrome) Mutations in glucocorticoid receptor (GR) gene Deoxycorticosterone (DOC) Cortisol Dexamethasone
Cortisol-secreting adrenocortical carcinoma Multifactorial

Rapid weight gain, particularly of the trunk and face with limbs sparing (central obesity)

Cortisol has mineralocorticoid effects
  • ↓ if excess cortisol saturates 11-HSD2 enzyme activity
Urinary free cortisol markedly ↑↑ Surgery
Geller’s syndrome Mutation of mineralocorticoid (MR) receptor that alters its specificity and allows progesterone to bind MR Severe hypertension particularly during pregnancy Progesterone has mineralocorticoid effects - mineralocorticoid blockers
Gordon’s syndrome (Pseudohypoaldosteronism type 2) Mutations of at least four genes have been identified, including WNK1 and WNK4
  • Normal renal function
No excess mineralocorticoid; an increased activity of the thiazide-sensitive Na–Cl co-transporter in the distal tubule Normal Hyperkalemia thiazide diuretics and/or dietary sodium restriction
Exogenous causes Corticosteroids with mineralocorticoid activity Fludrocortisone or fluoroprednisolone can mimic the action of aldosterone, Medications such as fludrocortisone - Change the treatment
Licorice ingestion Glycyrrhetinic acid that binds mineralocorticoid receptor and blocks 11-HSD2 at the level of classical target tissues of aldosterone - Urinary free cortisol Moderate ↑ Discontinue licorice
Grapefruit High assumption of naringenin, a component of grapefruit, can also block 11-HSD - - Discontinue grapefruit
Estrogens Estrogens can retain sodium and water by different mechanisms, causing:
  • Increased blood pressure values and suppressing the renin aldosterone system, on the other side inducing secondary hyperaldosteronism due to the stimulation of the synthesis of angiotensinogen
- - Discontinue estrogens

Other less common causes of pseudohyperaldosteronism are:

Differentiating Diagnosis

Hyperaldosteronism should be differentiated from other diseases causing hypertension and hypokalemia for example:[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15]

 
 
 
 
 
 
 
 
Hypertension and Hypokalemia
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Plasma renin activity
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Normal or High (Plasma Renin/Aldosterone ratio <10
 
 
 
 
 
 
 
 
 
 
 
Suppressed (Plasma Renin/Aldosterone ratio >20
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
*Renin-secreting tumors
*Diuretic use
*Renovascular hypertension
*Coarctation of aorta
*Malignant phase hypertension
 
 
 
 
 
 
 
 
 
 
 
Urinary aldosterone
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Elevated
 
Normal
 
 
Low
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Conn's syndrome (Primary aldosteronism)
 
Profound K+ depletion
 
 
• 17 alpha hydroxylase deficiency
• 11 beta hydroxylase deficiency
• Liddle's syndrome
• Licorice ingestion
• Deoxycortisone producing tumor
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Add Mineralocrticoid antagonist for 8 weeks
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
BP response
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No BP response
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
• Deoxycorticosterone excess( Tumor, 17 alpha hydroxylase and 11 beta hydroxylase deficiency)
• Licorice ingestion
•Glucocorticoid resistance
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Liddle's syndrome)

History and symptoms

History

Hyperaldosteronism may be suspected in the following scenarios:

Patients with profound hypokalemia report fatigue, muscle weakness, cramping, headaches, and palpitations. They can also have polydipsia and polyuria from hypokalemia-induced nephrogenic diabetes insipidus. Long-standing HTN may lead to cardiac, retinal, renal, and neurologic problems, with all the associated symptoms and signs. Patients with primary hyperaldosteronism may have subclinical systolic dysfunction, more bradycardia, higher blood pressure and vascular resistance values than those with the secondary hyperaldosteronism. Plasma renin activity has been found to be lower in primary than in secondary hyperaldosteronism.

Common Symptoms

Common symptoms of Hyperaldosteronism include:[22][23][24][25][26][27]

Hypertension related symptoms

Hypokalemia related symptoms

Less Common Symptoms

Less common symptoms of hyperaldosteronism include:[28][29]

References

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  19. Whorwood CB, Sheppard MC, Stewart PM (1993). "Licorice inhibits 11 beta-hydroxysteroid dehydrogenase messenger ribonucleic acid levels and potentiates glucocorticoid hormone action". Endocrinology. 132 (6): 2287–92. PMID 8504732. doi:10.1210/endo.132.6.8504732. 
  20. CHRISTY NP, LARAGH JH (1961). "Pathogenesis of hypokalemic alkalosis in Cushing's syndrome". N. Engl. J. Med. 265: 1083–8. PMID 13879332. doi:10.1056/NEJM196111302652203. 
  21. Funder JW, Carey RM, Mantero F, Murad MH, Reincke M, Shibata H, Stowasser M, Young WF (2016). "The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline". J. Clin. Endocrinol. Metab. 101 (5): 1889–916. PMID 26934393. doi:10.1210/jc.2015-4061. 
  22. Rubidge CJ, O'Dowd PB, Powell SJ (1973). "Difetarsone in the treatment of Trichuris trichiura infections". S. Afr. Med. J. 47 (23): 991–2. PMID 4714286. 
  23. Mattsson C, Young WF (2006). "Primary aldosteronism: diagnostic and treatment strategies". Nat Clin Pract Nephrol. 2 (4): 198–208; quiz, 1 p following 230. PMID 16932426. doi:10.1038/ncpneph0151. 
  24. Di Tullio M, Alli C, Avanzini F, Bettelli G, Colombo F, Devoto MA, Marchioli R, Mariotti G, Radice M, Taioli E (1988). "Prevalence of symptoms generally attributed to hypertension or its treatment: study on blood pressure in elderly outpatients (SPAA)". J Hypertens Suppl. 6 (1): S87–90. PMID 3216243. 
  25. Unwin RJ, Luft FC, Shirley DG (2011). "Pathophysiology and management of hypokalemia: a clinical perspective". Nat Rev Nephrol. 7 (2): 75–84. PMID 21278718. doi:10.1038/nrneph.2010.175. 
  26. Bautista J, Gil-Neciga E, Gil-Peralta A (1979). "Hypokalemic periodic paralysis in primary hyperaldosteronism. Subclinical myopathy with atrophy of the type 2A muscle fibers". Eur. Neurol. 18 (6): 415–20. PMID 546663. 
  27. Bortolotto LA, Cesena FH, Jatene FB, Silva HB (2003). "Malignant hypertension and hypertensive encephalopathy in primary aldosteronism caused by adrenal adenoma". Arq. Bras. Cardiol. 81 (1): 97–100, 93–6. PMID 12908077. 
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  29. Failor RA, Capell PT (2003). "Hyperaldosteronism and pheochromocytoma: new tricks and tests". Prim. Care. 30 (4): 801–20, viii. PMID 15024897. 

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