Pseudohyperaldosteronism (also pseudoaldosteronism) is a medical condition which mimics the effects of elevated aldosterone (hyperaldosteronism) by presenting with

high blood pressure Hypertension, also known as high blood pressure, is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms itself. It is, however, a major ri ...

, low blood potassium levels (hypokalemia),

metabolic alkalosis Metabolic alkalosis is an acid-base disorder in which the pH of tissue is elevated beyond the normal range (7.35–7.45). This is the result of decreased hydrogen ion concentration, leading to increased bicarbonate (), or alternatively a dire ...

, and low levels of

plasma renin activity Plasma renin activity (PRA), also known as the renin (active) assay or random plasma renin, is a measure of the activity of the plasma enzyme renin, which plays a major role in the body's regulation of blood pressure, thirst, and urine output. Me ...

(PRA). However, unlike hyperaldosteronism, this conditions exhibits low or normal levels of

aldosterone Aldosterone is the main mineralocorticoid steroid hormone produced by the zona glomerulosa of the adrenal cortex in the adrenal gland. It is essential for sodium conservation in the kidney, salivary glands, sweat glands, and colon. It plays ...

in the blood. Causes include genetic disorders (e.g. apparent mineralocorticoid excess syndrome,

Liddle's syndrome Liddle's syndrome, also called Liddle syndrome, is a genetic disorder inherited in an autosomal dominant manner that is characterized by early, and frequently severe, high blood pressure associated with low plasma renin activity, metabolic alkalo ...

, and types of

congenital adrenal hyperplasia Congenital adrenal hyperplasia (CAH) is a group of Genetic disorder#Autosomal recessive, autosomal recessive disorders characterized by impaired cortisol synthesis. It results from the deficiency of one of the five enzymes required for the Biosy ...

), acquired conditions (e.g.

Cushing's syndrome Cushing's syndrome is a collection of signs and symptoms due to prolonged exposure to glucocorticoids such as cortisol. Signs and symptoms may include high blood pressure, abdominal obesity but with thin arms and legs, reddish stretch marks, ...

and

mineralocorticoid Mineralocorticoids are a class of corticosteroids, which in turn are a class of steroid hormones. Mineralocorticoids are produced in the adrenal cortex and influence salt and water balances (electrolyte balance and fluid balance). The primary ...

-producing

adrenal tumor An adrenal tumor or adrenal mass is any benign or malignant neoplasms of the adrenal gland, several of which are notable for their ability to overproduce endocrine hormones. Adrenal cancer is the presence of malignant adrenal tumors, which include ...

s), metabolic disorders, and dietary imbalances including excessive consumption of

licorice Liquorice (Commonwealth English) or licorice (American English; see spelling differences; ) is the common name of ''Glycyrrhiza glabra'', a flowering plant of the bean family Fabaceae, from the root of which a sweet, aromatic flavouring is ...

. Confirmatory diagnosis depends on the specific cause and may involve blood tests, urine tests, or

genetic testing Genetic testing, also known as DNA testing, is used to identify changes in DNA sequence or chromosome structure. Genetic testing can also include measuring the results of genetic changes, such as RNA analysis as an output of gene expression, or ...

; however, all forms of this condition exhibit abnormally low concentrations of both plasma renin activity (PRA) and plasma aldosterone concentration (PAC) which differentiates this group of conditions from other forms of

secondary hypertension Secondary hypertension (or, less commonly, inessential hypertension) is a type of hypertension which has a specific and identifiable underlying primary cause. It is much less common than essential hypertension, affecting only 5-10% of hypertens ...

. Treatment is tailored to the specific cause and focuses on symptom control, blood pressure management, and avoidance of triggers.

Presentation

The presentation of pseudohyperaldosteronism varies depending on the cause. The genetic conditions such as

and

present in childhood or earlier in life than the acquired causes which can present at any age. Adult patients present with clinical history of resistant hypertension despite typical medical therapy and lifestyle changes.

Hypertension Hypertension, also known as high blood pressure, is a Chronic condition, long-term Disease, medical condition in which the blood pressure in the artery, arteries is persistently elevated. High blood pressure usually does not cause symptoms i ...

itself is most often

asymptomatic Asymptomatic (or clinically silent) is an adjective categorising the medical conditions (i.e., injuries or diseases) that patients carry but without experiencing their symptoms, despite an explicit diagnosis (e.g., a positive medical test). P ...

. Symptoms of

hypokalemia Hypokalemia is a low level of potassium (K+) in the blood serum. Mild low potassium does not typically cause symptoms. Symptoms may include feeling tired, leg cramps, weakness, and constipation. Low potassium also increases the risk of an a ...

include fatigue, muscular weakness, and increased urine production.

Causes

This condition has several known causes including genetic disorders, acquired conditions, metabolic derangements, and dietary imbalances. All causes mimic the effects of elevated aldosterone without raising aldosterone levels but achieve this through varying mechanisms.

Genetic forms

Genetic disorders that lead to this condition include

apparent mineralocorticoid excess Apparent mineralocorticoid excess syndrome (AME) is an autosome, autosomal dominance (genetics), recessive disorder causing hypertension (high blood pressure), hypernatremia (increased blood sodium concentration) and hypokalemia (decreased blood p ...

(AME), and two types of

(CAH). * Liddle's syndrome is

autosomal dominant In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the Phenotype, effect of a different variant of the same gene on Homologous chromosome, the other copy of the chromosome. The firs ...

disorder affecting epithelial sodium channels (

ENaC The epithelial sodium channel (ENaC), (also known as amiloride-sensitive sodium channel) is a membrane-bound ion channel that is selectively permeable to sodium ions (). It is assembled as a heterotrimer composed of three homologous subunits α ...

) in the distal tubules of the kidneys. In this disorder, a gain of function mutation decreases ENaC degradation leading to increased renal absorption of sodium and water. * Apparent mineralocorticoid excess genetic forms include

autosomal recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the Phenotype, effect of a different variant of the same gene on Homologous chromosome, the other copy of the chromosome. The firs ...

disorders with mutations lowering the activity of the enzyme 11-beta-hydroxysteroid dehydrogenase type 2 (11-β-HSD2). These mutations limit the ability of 11-β-HSD2 to transform active cortisol to the less active

cortisone Cortisone is a pregnene (21-carbon) steroid hormone. It is a naturally-occurring corticosteroid metabolite that is also used as a pharmaceutical prodrug. Cortisol is converted by the action of the enzyme corticosteroid 11-beta-dehydrogenase ...

. Excess cortisol is then able to bind and activate mineralocorticoid receptors due to receptor cross-reactivity leading to aldosterone-like effects. * Congenital adrenal hyperplasia is an autosomal recessive disorder with multiple types, two of which lead to pseudohyperaldosteronism. Deficiency of 11-beta-hydroxylase blocks the conversion of 11-deoxycorticosterone (DOC) to

corticosterone Corticosterone, also known as 17-deoxycortisol and 11β,21-dihydroxyprogesterone, is a 21-carbon steroid hormone of the corticosteroid type produced in the cortex of the adrenal glands. In the very rare case of congenital adrenal hyperplasia due ...

leading to an excess of DOC which acts as a mineralocorticoid similar to aldosterone. Deficiency of 17-alpha-hydroxylase blocks the conversion of

pregnenolone Pregnenolone (P5), or pregn-5-en-3β-ol-20-one, is an endogenous steroid and precursor/metabolic intermediate in the biosynthesis of most of the steroid hormones, including the progestogens, androgens, estrogens, glucocorticoids, and mineraloc ...

and

progesterone Progesterone (; P4) is an endogenous steroid and progestogen sex hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species. It belongs to a group of steroid hormones called the progestogens and is the ma ...

to their 17-a-hydroxy forms leading to increased mineralocorticoid production.

Acquired forms

Some causes of pseudohyperaldosteronism can be acquired throughout life with examples including

s and ectopic ACTH syndrome. * Adrenal tumor subtypes include adrenal adenomas that produce 11-deoxycorticosterone (DOC) leading to increased mineralocorticoid activity without elevated aldosterone. * Ectopic ACTH syndrome describes conditions leading to excess production of

adrenocorticotropic hormone Adrenocorticotropic hormone (ACTH; also adrenocorticotropin, corticotropin) is a polypeptide tropic hormone produced by and secreted by the anterior pituitary gland. It is also used as a medication and diagnostic agent. ACTH is an important ...

(ACTH) subsequently leading to mineralocorticoid production. This can arise in ectopic forms of

associated with small-cell lung cancers and other ACTH-producing tumors. The excess ACTH can saturate the 11-β-HSD2 enzyme leading to decreased conversion of cortisol to cortisone and increased mineralocorticoid effects.

Metabolic and dietary forms

Metabolic causes include conditions of

glucocorticoid Glucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every vertebra ...

resistance and from mineralocorticoid excess which can occur following high-dose corticosteroid therapy. Dietary causes include overconsumption of

-containing products.

Glycyrrhetinic acid Enoxolone (International Nonproprietary Name, INN, British Approved Name, BAN; also known as glycyrrhetinic acid or glycyrrhetic acid) is a pentacyclic triterpenoid derivative of the beta-amyrin type obtained from the hydrolysis of glycyrrhizic a ...

in licorice inhibits the 11-β-HSD2 enzyme resulting in inappropriate stimulation of the

mineralocorticoid receptor The mineralocorticoid receptor (or MR, MLR, MCR), also known as the aldosterone receptor or nuclear receptor subfamily 3, group C, member 2, (NR3C2) is a protein that in humans is encoded by the ''NR3C2'' gene that is located on chromosome 4q31 ...

by cortisol leading to aldosterone-like effects.

Diagnosis

In patients with hypertension, diagnostic clues pointing to pseudohyperaldosteronism can be found on routine labwork. These include low serum potassium (hypokalemia), elevated serum sodium (

hypernatremia Hypernatremia, also spelled hypernatraemia, is a high concentration of sodium in the blood. Early symptoms may include a strong feeling of thirst, weakness, nausea, and loss of appetite. Severe symptoms include confusion, muscle twitching, and ...

), and elevated serum

bicarbonate In inorganic chemistry, bicarbonate (IUPAC-recommended nomenclature: hydrogencarbonate) is an intermediate form in the deprotonation of carbonic acid. It is a polyatomic anion with the chemical formula . Bicarbonate serves a crucial bioche ...

(metabolic alkalosis). Urine studies may show elevated urine potassium (

kaliuresis Kaliuresis () or kaluresis () is the condition of excreting potassium in the urine. Thiazide diuretics are used to treat patients with heart failure. Their goal is to decrease the amount of salt (sodium chloride) in the body by decreasing the amou ...

). To further differentiate between hyperaldosteronism and pseudohyperaldosteronism, studies including plasma renin activity (PRA) and plasma aldosterone concentration (PAC) can be obtained. Pseudohyperaldosteronism will exhibit low levels of both PRA and PAC while hyperaldosteronism will demonstrate elevated PAC. Confirmatory tests to diagnose the specific forms of pseudohyperaldosteronism vary depending on the cause. The genetic conditions such as Liddle's syndrome and CAH can be confirmed with genetic tests for the affected genes. CAH can also be confirmed by analyzing enzyme levels following ACTH stimulation testing. AME can be diagnosed with a 24 hour urine collection exhibiting an increased ratio of urinary cortisol to urinary cortisone.

Treatment

Specific treatment of pseudohyperaldosteronism depends on the inciting cause. General management focuses on countering the effects of excess mineralocorticoid activity to achieve adequate

blood pressure Blood pressure (BP) is the pressure of Circulatory system, circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. When used without qualification, the term ...

control and avoid end-organ damage and

cardiovascular In vertebrates, the circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the body. It includes the cardiovascular system, or vascular system, that consists of the heart a ...

mortality. In some cases, specific antihypertensive medications may be recommended. In Liddle's syndrome, ENaC-binding potassium-sparing diuretics (e.g.

amiloride Amiloride, sold under the trade name Midamor among others, is a medication typically used with other medications to treat high blood pressure or swelling due to heart failure or cirrhosis of the liver. Amiloride is classified as a potassium-spar ...

triamterene Triamterene (traded under names such as Dyrenium and Dytac) is a potassium-sparing diuretic often used in combination with thiazide diuretics for the treatment of high blood pressure or swelling. The combination with hydrochlorothiazide, is kno ...

) are used to counter the excess ENaC activity. In AME, the mineralocorticoid receptor-binding

potassium-sparing diuretic Potassium-sparing diuretics or antikaliuretics refer to drugs that cause diuresis without causing potassium loss in the urine. They are typically used as an adjunct in management of hypertension, cirrhosis, and congestive heart failure. The ster ...

s (e.g.

spironolactone Spironolactone, sold under the brand name Aldactone among others, is classed as a diuretic medication. It can be used to treat edema, fluid build-up due to hepatic cirrhosis, liver disease or kidney disease. It is also used to reduce risk o ...

eplerenone Eplerenone, marketed under brand name Inspa or Espler, is an aldosterone antagonist used primarily in the treatment of heart failure with reduced ejection fraction (HFrEF), particularly following myocardial infarction. It may also be considered ...

) are used to limit aldosterone receptor activity. Other medications such as

glucocorticoids Glucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every vertebra ...

are added in AME and CAH to inhibit ACTH and further cortisol production. Lifestyle changes such as a

low sodium diet A low sodium diet is a diet that includes no more than 1,500 to 2,400 mg of sodium per day. The human minimum requirement for sodium in the diet is about 500 mg per day, which is typically less than one-sixth as much as many diets "seaso ...

are also used for managing

hypertension Hypertension, also known as high blood pressure, is a Chronic condition, long-term Disease, medical condition in which the blood pressure in the artery, arteries is persistently elevated. High blood pressure usually does not cause symptoms i ...

, and cessation of

intake is recommended in cases of licorice overconsumption.

References

External links

{{Medical resources , DiseasesDB = 7471 , ICD10 = I15.1 , ICD9 = , ICDO = , OMIM = 177200 , MedlinePlus = , eMedicineSubj = , eMedicineTopic = , MeshID = D056929 , Orphanet = 526 Hypertension