Hyperaldosteronism
Hyperaldosteronism Main page |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mehrian Jafarizade, M.D [2]
This page contains general information about Hyperaldosteronism. For more information on specific types, please visit the pages on Primary hyperaldosteronism, and Secondary hyperaldosteronism.
Synonyms and keywords: Aldosteronism
Overview
Classification
Aldosteronism and mineralocorticoid excess may be classified into two types, primary hyperaldosteronism (conn's syndrome) and secondary hyperaldosteronism. The different types of aldosteronism described in the below table:
Primary hyperaldosteronism (conn's syndrome)
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
| |
Familial hyperaldosteronism II
| ||
Familial hyperaldosteronism type III
| ||
Other | Pure aldosterone-producing adrenocortical carcinomas | |
Unilateral adrenal hyperplasia |
Secondary hyperaldosteronism
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
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 | Disease | Etiology | Clinical features | Labratory | ||||
---|---|---|---|---|---|---|---|---|
Elevated mineralocorticoid | Renin | Aldosterone | Other | Treatment | ||||
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
|
|
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 can reverse the clinical picture reactivating the renin aldosterone | |
Cushing’s syndrome | The main pathogenetic mechanism is linked to the excess
of cortisol which saturates 11-HSD2 activity, allowing cortisol to bind MR. A similar picture is also related to over secretion of cortisol by adrenocortical carcinomas. In some cases the disease is associated with secondary hyperaldosteronism due to a direct activation of the renin angiotensin system by glucocorticoids. |
Rapid weight gain, particularly of the trunk and face with limbs sparing (central obesity)
|
Cortisol has mineralocorticoid effects | ↓ |
|
Urinary free cortisol markedly ↑↑ |
| |
Insensitivity to glucocorticoids (Chrousos syndrome) | Mutations in glucocorticoid receptor (GR) gene |
|
Deoxycorticosterone (DOC) | ↓ | ↓ | Cortisol | Dexamethasone | |
Aldosterone-secreting adrenocortical carcinoma | Multifactorial | Cortisol has mineralocorticoid effects | ↓ |
|
Urinary free cortisol markedly ↑↑ | |||
Geller’s syndrome | mutation of MR that alters its specificity and allows progesterone to bind MR | severe hypertension particularly during pregnancy | ↓ | ↓ | ||||
Gordon’s syndrome (Pseudohypoaldosteronism type 2) | Mutations of at least four genes have been identified, including WNK1 and WNK4 |
|
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 MR and blocks 11-HSD2 at the level of classical target tissues of aldosterone | ↓ | ↓ | Urinary free cortisol Moderate ↑ | ||||
grapefruit | High assumption of naringenin, a component of grapefruit, can also block 11-HSD | |||||||
Contraceptives | Estrogens can retain sodium and water by different mechanisms, causing increased blood pressure values and suppressing the renin aldosterone system. However, contraceptives usually cause hypertension through a secondary hyperaldosteronism due to the stimulation of the synthesis of angiotensinogen | |||||||
Particular causes of hypertension | Sclerosis of juxtaglomerular apparatus (diabetic microangiopathy and/or of the elderly) | |||||||
FANS | ||||||||
B-Adrenergic agonists | ||||||||
Aging | ||||||||
Low-renin essential hypertension | ||||||||
Autonomic dysfunction | ||||||||
Partial/total nephrectomy or removal of renal tissue |
Differentiating Diagnosis
Hyperaldosteronism should be differentiated from other diseases causing hypertension and hypokalemia for example:
- Renal artery stenosis
- Cushing's syndrome
- Congenital adrenal hyperplasia (CAH)
- Liddle's syndrome
- Diuretic use
- Licorice ingestion
- Renin-secreting tumors
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
Primary hyperaldosteronism may be suspected in the following scenarios:
- Patients with a history of spontaneous or unprovoked hypokalemia along with hypertension.
- Patients who develop severe and/or persistent hypokalemia while on low to moderate doses of potassium-wasting diuretics.
- Patients with a history of treatment-refractory/-resistant hypertension (HTN).
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 primary hyperaldosteronism (PA) include:[1][2][3][4][5][6]
- Headaches
- Facial flushing
- Weakness
- Visual impairment
- Impaired consciousness
- Seizures (hypertensive encephalopathy)
- Constipation
- Polyuria and polydipsia (because of impaired renal concentrating ability)
- Weakness
Less Common Symptoms
Less common symptoms of Conn's syndrome (primary hyperaldosteronism) include:[7][8]
References
- ↑ 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.
- ↑ Mattsson C, Young WF (2006). "Primary aldosteronism: diagnostic and treatment strategies". Nat Clin Pract Nephrol. 2 (4): 198–208, quiz, 1 p following 230. doi:10.1038/ncpneph0151. PMID 16932426.
- ↑ 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.
- ↑ Unwin RJ, Luft FC, Shirley DG (2011). "Pathophysiology and management of hypokalemia: a clinical perspective". Nat Rev Nephrol. 7 (2): 75–84. doi:10.1038/nrneph.2010.175. PMID 21278718.
- ↑ 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.
- ↑ 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.
- ↑ Moeller J, Muniz B (1967). "[Hypokalemic ileus and aldosteronism]". Med Klin (in German). 62 (52): 2019–24. PMID 5596496.
- ↑ Failor RA, Capell PT (2003). "Hyperaldosteronism and pheochromocytoma: new tricks and tests". Prim. Care. 30 (4): 801–20, viii. PMID 15024897.