Laboratory for Molecular Diagnostics
Center for Nephrology and Metabolic Disorders

Apparent mineralocorticoid excess

Apparent mineralocorticoid excess (AME) is an autosomal recessive disorder that imitates all symptoms of elevated mineralocorticoid levels, including hypertension and hypokalemia, despite rather suppressed secretion of renin and aldosterone. Due to a deficiency in cortisol to cortisone conversion in the kidney, the mineralocorticoid receptor is unspecifically stimulated by cortisol.

Clinical Findings

Apparent mineralocorticoid excess is characterized by all symptoms of hyperaldosteronism despite a rather decreased renin stimulated aldosterone secretion. The disease is marked by hypertension and hypokalemia that begin in childhood.

Spironolactone and low sodium diet relief the symptoms. Also it may respond to dexamethasone. As this remedy suppresses cortisol secretion, it ceases unspecific stimulation of the renal mineralocorticoid receptor by cortisol.

Diagnosis

The diagnosis of AME is made by increased urinary excretion of cortiol when related to plasma and cortisone. The ratio of free urinary cortisol to free urinary cortisone in an 24-hour urine collection can be measured. As cortisone levels exceed that of cortison the ration is usually in the range of 0.3-0.5.

Pathogenesis

The disease AME is caused by cortisol 11-beta-ketoreductase deficiency. This enzyme resides in epithelial cell of the distal convoluted tubule, the site where fine tuning of renal potassium secretion happens and other genes such as mineralocorticoid receptor and the sodium channel ENaC are expressed. Cortisol too can effectively stimulate the mineralocorticoid receptor, and because it is more abundant than aldosteron, it would almost replace aldosterone if there were not the enzyme in place which converts cortisol to cortisone. The latter is unable to stimulate the mineralocorticoid receptor and crosses the apical membran into the urine. If this enzyme is deficient, the mineralocoirticoid receptor action is no more regulated by aldosterone but cortisol. Hence every therapy that either blocks the mineralocorticoid receptor stimulation or cortisol production is highly effective.

Laboratory tests

Abnormal cortisol-to-cortisone in urine is pathognomonic as the reduced conversion of cortisol to cortisone leads to elevated cortisol and reduced cortisone in urine.

Management

Spironolactone, potassium substitution and sodium restriction is the treatment of choice in patients with AME. It has to be kept in mind however that in periods of increased cortisol secretion increased levels of spironolactone are required too.

Alternatively dexamethason can be used to suppress cortisol. About 60% of patients respond to that therapy. However there is a small number in whom symptoms even aggravate.

In patients with hypercalciuria and nephrocalcinosis thiazide diuretics can be used.

A kidney transplant can be used in patients with end-stage renal failure.

Symptoms

Hypertension
Hypertension is the dominating symptom in apparent mineralocorticoid excess (AME). It is typically accompanied by suppressed renin-aldosteron system (low renin and aldosteron levels), metabolic alkalosis, and hypokalemia.
Hypokalemia
Hypokalemia in AME patients is the result of excessive stimulation of the mineralocorticoid receptor.
Alkalosis
Alkalosis in AME patients is the result of excessive stimulation of the mineralocorticoid receptor.
Polyuria
Polyuria may be observed in your patients with severe AME. It is the result of a hypokalemia-induced nephrogenic diabetes insipidus and typically accompanied by polydipsia.
Polydipsia
Polydipsia is the result of excessive renal water loss, polyuria.
Failure to thrive
Failure to thrive is the result of excessive renal water and mineral losses due to polyuria.
Nephrocalcinosis
Nephrocalcinosis in AME is necessarily associated with hypertension and hypokalemia and caused by hypercalciuria.
Hypercalciuria
Hypercalciuria in AME patients is likely the cause of nephrocalcinosis.
Renal insufficiency
Protracted hyperkalemia and nephrocalcinosis lead to chronic renal failure.

Systematic

Monogenic hypertension
Apparent mineralocorticoid excess
HSD11B2
Glucocorticoid triggered hypertension
Hyperaldosteronism
Hypertension and brachydactyly syndrome
Liddle syndrome
Pseudohypoaldosteronism

References:

1.

Palermo M et al. (2004) Apparent mineralocorticoid excess syndrome: an overview.

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2.

Kamide K et al. (2006) Genetic variations of HSD11B2 in hypertensive patients and in the general population, six rare missense/frameshift mutations.

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3.

Wilson RC et al. (2001) Apparent mineralocorticoid excess.

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4.

Ferrari P et al. (2001) Juvenile hypertension, the role of genetically altered steroid metabolism.

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5.

White PC et al. (2001) 11beta-hydroxysteroid dehydrogenase and its role in the syndrome of apparent mineralocorticoid excess.

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6.

Toka HR et al. () The molecular basis of hypertension.

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Update: Sept. 26, 2018

 

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