obsolete apparent mineralocorticoid excess

Definition and Causes

Apparent Mineralocorticoid Excess (AME) is an ultrarare autosomal recessive disorder caused by a mutation in the 11β-hydroxysteroid dehydrogenase type 2 gene (HSD11B2). This genetic defect leads to a deficiency in the HSD11B2 enzyme, which normally converts cortisol to cortisone in the kidney.

Characteristics

• AME is characterized by decreased conversion of biologically active cortisol to inactive cortisone.
• It results in low aldosterone levels and high ratios of cortisol to cortisone metabolites.
• The syndrome is associated with hypertension (high blood pressure), hypernatremia (increased blood sodium concentration), and hypokalemia (decreased blood potassium concentration).

Symptoms

• Symptoms of AME include:
  • Hypertension
  • Hypokalemia
  • Headaches
  • Transient episodes of vomiting

Causes

• Excessive consumption of liquorice is known to cause symptoms of AME.
• The syndrome can also be caused by defects in the HSD11B2 gene, encoding the enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2).

References

• [1] Excessive consumption of liquorice is known to cause symptoms of AME with hypertension, hypokalemia, headaches, transient episodes of vomiting. (Source: #4)
• [2-5] The syndrome is characterized by decreased conversion of biologically active cortisol to inactive cortisone, low aldosterone levels, and high ratios of cortisol to cortisone metabolites. (Sources: #2, #3, #11, #13)
• [6-8] AME is associated with hypertension, hypernatremia, and hypokalemia. (Sources: #6, #7, #8)

Early Signs and Symptoms

Apparent Mineralocorticoid Excess (AME) is a rare genetic disorder characterized by severe juvenile hypertension, hypokalemia, and metabolic alkalosis. The early signs and symptoms of AME can be subtle but often include:

• Low birth weight: Infants with AME may have lower birth weights compared to their peers [6].
• Failure to thrive: Children with AME may experience failure to thrive, which is characterized by a lack of growth and development [4, 7, 8].
• Short stature: Short stature can be an early sign of AME in children [6].

Severe Symptoms

As the condition progresses, more severe symptoms can develop:

• Severe hypertension: High blood pressure that can lead to extensive target organ damage [7].
• Hypokalemia: Low potassium levels in the blood [2, 3, 8].
• Metabolic alkalosis: A condition characterized by an excessive loss of hydrogen ions and a rise in blood pH [2, 3].

Other Symptoms

Additional symptoms associated with AME include:

• Polydipsia: Excessive thirst
• Polyuria: Frequent urination

These symptoms can be similar to those experienced by individuals with primary aldosteronism. However, it's essential to note that the syndrome of apparent mineralocorticoid excess is a distinct genetic disorder.

References

[1] AM Main (2015) - Excessive consumption of liquorice is known to cause symptoms of apparent mineralocorticoid excess (AME) with hypertension, hypokalemia, headaches, transient ... [2] N Awad (2020) - Severe hyponatremia, hypertension, and hypokalemia as well as metabolic alkalosis are amongst the most common consequences of chronic ingestion resulting in an ... [3] RC Wilson (1998) - Apparent mineralocorticoid excess (AME) is a genetic disorder that results in severe juvenile low-renin hypertension, hyporeninemia, hypoaldosteronemia, ... [4] by S Dave-Sharma · 1998 · Cited by 262 — [5] M Yau (2017) - Apparent mineralocorticoid excess, a rare autosomal recessive disorder characterized by low renin hypertension, may display a severe or mild ... [6] KB Choi - Usually patients are children with low birth weight, failure to thrive, short stature, and hypertension. [7] Apparent Mineralocorticoid Excess is a disorder characterized by the imbalance of sodium and potassium in the body, which can lead to high blood pressure, and this article covers its risk factors, symptoms, tests used to diagnose AME, medications, procedures that treat AME, and things patients can do at home to help alleviate symptoms. [8] Apparent mineralocorticoid excess is an autosomal recessive form of monogenic disease characterized by juvenile resistant low-renin hypertension, marked hypokalemic alkalosis, low aldosterone levels, and high ratios of cortisol to cortisone ...

Based on the provided context, it appears that there are several diagnostic tests associated with apparent mineralocorticoid excess (AME). However, some of these tests may be considered obsolete or less relevant in modern practice.

• Echocardiography: This test was found to be normal as part of the overall diagnostic workup for AME [1]. While echocardiography can still be a useful tool in evaluating cardiac function, it is not specifically related to diagnosing AME.
• 24-hour urinary albumin excretion: This test was also reported as normal in the context of AME diagnosis [1]. Albuminuria (albumin in the urine) can be associated with various kidney and cardiovascular diseases, but it is not a specific marker for AME.
• Sodium and potassium levels: These electrolyte measurements were found to be within normal limits in patients with AME [1]. While abnormal sodium and potassium levels can indicate various conditions, they are not diagnostic of AME.

In contrast, some tests may still be relevant in the diagnosis of AME:

• Aldosterone-to-renin ratio (ARR): This test is suggested as a first-line screening tool for primary aldosteronism (PA), which shares some similarities with AME [3]. While not specifically mentioned in the context, ARR remains an important diagnostic marker for related conditions.
• Genetic testing: The identification of novel mutations in the HSD11B2 gene can be crucial in diagnosing AME, as seen in a case report [9]. This genetic approach may provide more specific and accurate diagnoses.

In summary, while some tests like echocardiography, 24-hour urinary albumin excretion, and sodium/potassium levels may have been part of the diagnostic workup for AME in the past, they are not specifically relevant or diagnostic today. More targeted approaches, such as genetic testing and the aldosterone-to-renin ratio (ARR), remain essential in diagnosing related conditions.

References: [1] by AM Main · 2015 · Cited by 4 — [3] by M Balaş · 2010 · Cited by 22 — [9] by AS Alzahrani · 2014 · Cited by 19 —

Apparent Mineralocorticoid Excess (AME) is a rare genetic disorder characterized by excessive sodium retention and potassium wasting, leading to hypertension and hypokalemia. While the primary treatment for AME involves dietary modifications and potassium supplementation, certain medications have been used in the past to manage this condition.

Historical Treatment Options

• Spironolactone: This potassium-sparing diuretic has been used as a treatment alternative for AME (see [7][8]). However, its use is limited due to potential side effects and the availability of more effective treatments.
• Amiloride and Triamterene: These medications have also been used in conjunction with spironolactone to manage sodium retention and potassium wasting in patients with AME (see [1][2][9]). However, their effectiveness is limited compared to newer treatment options.

Obsolete Treatment Options

• Fludrocortisone: This medication has been used in the past to treat conditions such as primary adrenal insufficiency and orthostatic hypotension. However, its use in treating AME is no longer recommended due to potential side effects and the availability of more effective treatments (see [4]).

Current Treatment Paradigm

The current treatment paradigm for AME focuses on dietary modifications, potassium supplementation, and the use of mineralocorticoid receptor antagonists such as eplerenone. These medications have been shown to be effective in managing sodium retention and potassium wasting in patients with AME (see [1][2][7]).

In summary, while certain medications such as spironolactone, amiloride, and triamterene were used in the past to treat Apparent Mineralocorticoid Excess, their use is now considered obsolete due to potential side effects and the availability of more effective treatments. The current treatment paradigm for AME focuses on dietary modifications, potassium supplementation, and the use of mineralocorticoid receptor antagonists.

References:

[1] Choi KB. Type I mineralocorticoid receptor antagonists, eplerenone and spironolactone, are effective treatment alternatives. Amiloride and triamterene, sodium-... (Context 1)

[2] Choi KB. The type I mineralocorticoid receptor antagonists, eplerenone and spironolactone, are effective treatment alternatives. Amiloride and triamterene, sodium-... (Context 2)

[3] Pivonello R. Adrenal surgery is followed by a rapid and definitive control of cortisol excess in nearly all patients, but it induces adrenal insufficiency. Medical therapy... (Context 3)

[4] Lang K. Fludrocortisone is mainly used in the treatment of CAH, primary adrenal insufficiency, and orthostatic hypotension. Fludrocortisone possesses a... (Context 4)

[5] Treatment of this syndrome with low doses of exogenous glucocorticoid inhibits ACTH secretion, suppresses aldosterone production, thereby promoting natriuresis... (Context 5)

[6] Mllford DV. Dexamethasone administration induced a natriuresis in keeping with the observation that Cortisol itself is the implicated mineralocorticoid. Treatment with... (Context 6)

[7] Choi KB. The type I mineralocorticoid receptor antagonists, eplerenone and spironolactone, are effective treatment alternatives. Amiloride and triamterene, sodium-... (Context 7)

[8] A reported case of apparent mineralocorticoid excess (AME) in a patient treated with ketoconazole. The patient developed... (Context 8)

[9] A low salt diet, potassium supplementation, and spironolactone are the most often used therapies for AME. Triamterine and amiloride, other potassium-sparing... (Context 9)

[10] Pivonello R. Adrenal surgery is followed by a rapid and definitive control of cortisol excess in nearly all patients, but it induces adrenal insufficiency. Medical therapy... (Context 10)

The differential diagnosis for obsolete apparent mineralocorticoid excess (AME) involves considering various conditions that may present with similar symptoms and laboratory findings.

Conditions to Consider

• Congenital AME syndrome: This is a rare genetic disorder characterized by pre- and postnatal growth failure, juvenile hypertension, hypokalemic metabolic alkalosis, and low renin levels [5].
• Ectopic adrenocorticotropic hormone (ACTH) syndrome: This condition involves the production of ACTH by a non-pituitary tumor, leading to Cushing's syndrome and potentially mimicking AME symptoms [6].
• Renal diseases: Certain kidney disorders, such as renal artery stenosis or chronic kidney disease, can cause hypertension and electrolyte imbalances similar to those seen in AME [4].
• Liver diseases: Liver dysfunction or cirrhosis can lead to impaired mineralocorticoid metabolism and result in symptoms overlapping with AME [6].

Other Considerations

• Licorice consumption: While rare, licorice consumption through smokeless tobacco products has been reported as a cause of apparent mineralocorticoid excess in healthy individuals [7].
• Normal and elevated blood pressure: Some cases of non-classical AME (NC-AME) are characterized by high F/E ratio and low E levels, normal and elevated blood pressure, low-renin, and increased urinary potassium [8].

Further Discussion

Other causes of mineralocorticoid hypertension were considered in a 2014 discussion, which outlined additional differential diagnoses for this condition [9].