Pseudohyperaldosteronism

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Pseudohyperaldosteronism
Other namesPseudoaldosteronism

Pseudohyperaldosteronism (also pseudoaldosteronism) is a medical condition which mimics the effects of elevated aldosterone (hyperaldosteronism) by presenting with high blood pressure, low blood potassium levels (hypokalemia), metabolic alkalosis, and low levels of plasma renin activity (PRA). [1] [2] However, unlike hyperaldosteronism, this conditions exhibits low or normal levels of aldosterone in the blood. [1] [2] Causes include genetic disorders (e.g. apparent mineralocorticoid excess syndrome, Liddle's syndrome, and types of congenital adrenal hyperplasia), acquired conditions (e.g. Cushing's syndrome and mineralocorticoid-producing adrenal tumors), metabolic disorders, and dietary imbalances including excessive consumption of licorice. [1] [3] [4] Confirmatory diagnosis depends on the specific cause and may involve blood tests, urine tests, or genetic testing; 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. [1] [2] Treatment is tailored to the specific cause and focuses on symptom control, blood pressure management, and avoidance of triggers. [1]

Contents

Presentation

The presentation of pseudohyperaldosteronism varies depending on the cause. The genetic conditions such as Liddle's syndrome and congenital adrenal hyperplasia present in childhood or earlier in life than the acquired causes which can present at any age. [1] [4] [2] Adult patients present with clinical history of resistant hypertension despite typical medical therapy and lifestyle changes. [1] [4] Hypertension itself is most often asymptomatic. [4] Symptoms of hypokalemia include fatigue, muscular weakness, and increased urine production. [4] [2]

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. [1]

Genetic forms

Genetic disorders that lead to this condition include Liddle's syndrome, apparent mineralocorticoid excess (AME), and two types of congenital adrenal hyperplasia (CAH). [1] [2]

Acquired forms

Some causes of pseudohyperaldosteronism can be acquired throughout life with examples including adrenal tumors and ectopic ACTH syndrome. [5]

Metabolic and dietary forms

Various edible products containing licorice. Excessive consumption of licorice can lead to pseudohyperaldosteronism due to the plant's high concentrations of Glycyrrhetinic acid. 2013.02-402-022aP Liquorice products tue05feb2013.jpg
Various edible products containing licorice. Excessive consumption of licorice can lead to pseudohyperaldosteronism due to the plant's high concentrations of Glycyrrhetinic acid.

Metabolic causes include conditions of glucocorticoid resistance [8] and from mineralocorticoid excess which can occur following high-dose corticosteroid therapy. [1] Dietary causes include overconsumption of licorice-containing products. [3] [9] Glycyrrhetinic acid in licorice inhibits the 11-β-HSD2 enzyme resulting in inappropriate stimulation of the mineralocorticoid receptor by cortisol leading to aldosterone-like effects. [3] [9]

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), and elevated serum bicarbonate (metabolic alkalosis). [1] Urine studies may show elevated urine potassium (kaliuresis). To further differentiate between hyperaldosteronism and pseudohyperaldosteronism, studies including plasma renin activity (PRA) and plasma aldosterone concentration (PAC) can be obtained. [1] [2] Pseudohyperaldosteronism will exhibit low levels of both PRA and PAC while hyperaldosteronism will demonstrate elevated PAC. [1] 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. [1] [4] CAH can also be confirmed by analyzing enzyme levels following ACTH stimulation testing. [1] AME can be diagnosed with a 24 hour urine collection exhibiting an increased ratio of urinary cortisol to urinary cortisone. [1]

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 control and avoid end-organ damage and cardiovascular mortality. [1] In some cases, specific antihypertensive medications may be recommended. In Liddle's syndrome, ENaC-binding potassium-sparing diuretics (e.g. amiloride or triamterene) are used to counter the excess ENaC activity. [4] [10] [2] In AME, the mineralocorticoid receptor-binding potassium-sparing diuretics (e.g. spironolactone or eplerenone) are used to limit aldosterone receptor activity. [1] Other medications such as glucocorticoids are added in AME and CAH to inhibit ACTH and further cortisol production. [1] Lifestyle changes such as a low sodium diet are also used for managing hypertension, [1] [2] and cessation of licorice intake is recommended in cases of licorice overconsumption. [1] [3]

See also

References

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  2. 1 2 3 4 5 6 7 8 9 10 11 Mubarik, Ateeq; Anastasopoulou, Catherine; Riahi, Shayan; Aeddula, Narothama R. (2020), "Liddle Syndrome", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID   30725596 , retrieved 2020-10-21
  3. 1 2 3 4 Sabbadin, Chiara; Bordin, Luciana; Donà, Gabriella; Manso, Jacopo; Avruscio, Giampiero; Armanini, Decio (2019). "Licorice: From Pseudohyperaldosteronism to Therapeutic Uses". Frontiers in Endocrinology. 10: 484. doi: 10.3389/fendo.2019.00484 . ISSN   1664-2392. PMC   6657287 . PMID   31379750.
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  5. 1 2 3 4 Choi, Kyu Bok (June 2007). "Hypertensive Hypokalemic Disorders". Electrolytes & Blood Pressure. 5 (1): 34–41. doi:10.5049/EBP.2007.5.1.34. ISSN   1738-5997. PMC   3894504 . PMID   24459498.
  6. Wada, N.; Kubo, M.; Kijima, H.; Yamane, Y.; Nishikawa, T.; Sasano, H.; Koike, T. (October 1995). "A case of deoxycorticosterone-producing adrenal adenoma". Endocrine Journal. 42 (5): 637–642. doi: 10.1507/endocrj.42.637 . ISSN   0918-8959. PMID   8574286.
  7. Sontia, Bruno; Mooney, Jan; Gaudet, Lise; Touyz, Rhian M. (2008-02-14). "Pseudohyperaldosteronism, Liquorice, and Hypertension". The Journal of Clinical Hypertension. 10 (2): 153–157. doi:10.1111/j.1751-7176.2008.07470.x. ISSN   1524-6175. PMC   8109973 . PMID   18256580.
  8. Martinez-Aguayo, Alejandro; Fardella, Carlos (2009). "Genetics of hypertensive syndrome". Hormone Research. 71 (5): 253–259. doi: 10.1159/000208798 . hdl: 10533/135775 . ISSN   1423-0046. PMID   19339789. S2CID   11267816.
  9. 1 2 Makino, Toshiaki (2014). "3-Monoglucuronyl glycyrrhretinic acid is a possible marker compound related to licorice-induced pseudoaldosteronism". Biological & Pharmaceutical Bulletin. 37 (6): 898–902. doi: 10.1248/bpb.b13-00997 . ISSN   1347-5215. PMID   24882402.
  10. Hanukoglu, Israel; Hanukoglu, Aaron (2016-04-01). "Epithelial sodium channel (ENaC) family: Phylogeny, structure-function, tissue distribution, and associated inherited diseases". Gene. 579 (2): 95–132. doi:10.1016/j.gene.2015.12.061. ISSN   0378-1119. PMC   4756657 . PMID   26772908.