Hyperaldosteronism

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]

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

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	Category	Diseases
	Adrenal causes	Aldosterone-secreting adrenal adenoma (APA-benign tumor, 50-60%)
		Idiopathic hyperaldosteronism (IHA-Bilateral hyperplasia of the adrenal gland, 40-50%)
	Extra-adrenal causes	Ectopic secretion of aldosterone (ovaries and kidneys)
	Familial hyperaldosteronism	Familial hyperaldosteronism type I (glucocorticoid-remediable aldosteronism [GRA])
		Familial hyperaldosteronism II (the familial occurrence of APA or bilateral idiopathic hyperplasia or both)
		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	Genetic mutation	Bartter and Gitelman syndromes	Hyperplasia of the juxtaglomerular apparatus (the source of renin in the kidney),
		Liddle syndrome or pseudohypoaldosteronism type 1	due to resistance to the actions of aldosterone
	Endocrine causes	Cushing syndrome
		Ectopic ACTH production
	Renovascular	Kidney transplant
		Renin-secreting juxtaglomerular cell tumors
		Scleroderma renal crisis
		Malignant hypertension
	Tumors	Reninoma
	Intravascular hypovolemia	heart failure, hepatic cirrhosis, and nephrotic syndrome

Pseudohyperaldosteronism causes:

Pseudohyperaldosteronism causes	Disease	Etiology	Clinical features	Labratory
				Elevated mineralocorticoid	Renin	Aldosterone	Other	Treatment
Endogenous causes	17 alpha-hydroxylase deficiency	Mutations in the CYP17A1 gene	Ambiguous genitalia in male Hypertension Primary amenorrhea Absence of secondary sexual characteristics Minimal body hair	Deoxycorticosterone (DOC)	↓	↓	Cortisol ↓	Corticosteroids
	11β-hydroxylase deficiency	Mutations in the CYP11B1 gene	Ambiguous genitalia in female Hypertension and hypokalemia Virilization				Cortisol ↓
	Apparent mineralocorticoid excess syndrome (AME)	Genetic or acquired defect of 11-HSD Cortisone decreases and cortisol accumulates and binds to aldosterone receptors	Severe juvenile hypertension Hypercalciuria, nephrocalcinosis, polyuria (due to hypokalemia-induced nephrogenic diabetes insipidus) Renal failure	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	Hypertension Hypokalemia	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) Proximal muscle weakness A round face often referred to as a "moon face" Excess sweating Headache	Cortisol has mineralocorticoid effects	↓	↓ if excess cortisol saturates 11-HSD2 enzyme activity ↑ in direct activation of renin angiotensin system activation by glucocorticoids	Urinary free cortisol markedly ↑↑	Pasireotide, Cabergoline, Ketoconazole, and Metyrapone Adrenalectomy
	Insensitivity to glucocorticoids (Chrousos syndrome)	Mutations in glucocorticoid receptor (GR) gene	Hypertension Adrenal hyperandrogenism	Deoxycorticosterone (DOC)	↓	↓	Cortisol	Dexamethasone
	Aldosterone-secreting adrenocortical carcinoma			Cortisol has mineralocorticoid effects	↓	↓ if excess cortisol saturates 11-HSD2 enzyme activity ↑ in direct activation of renin angiotensin system activation by glucocorticoids	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	Hypertension Hyperkalemia 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
	Hypersodic diets
	Water intossications
	Licorice ingestion				↓	↓	Urinary free cortisol Moderate ↑
	grapefruit
	Contraceptives
	Some progestins
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)
  • 17 alpha hydroxylase deficiency
  • 11 beta hydroxylase deficiency
• 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

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