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.
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.
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.
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.
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.
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.
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 in AME patients is the result of excessive stimulation of the mineralocorticoid receptor.
Alkalosis in AME patients is the result of excessive stimulation of the mineralocorticoid receptor.
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 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 in AME is necessarily associated with hypertension and hypokalemia and caused by hypercalciuria.
Hypercalciuria in AME patients is likely the cause of nephrocalcinosis.
Protracted hyperkalemia and nephrocalcinosis lead to chronic renal failure.
|Apparent mineralocorticoid excess|
|Glucocorticoid triggered hypertension|
|Hypertension and brachydactyly syndrome|
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