Mineralocorticoid excess and related syndromes

This was the topic of a recent review in Advances in Chronic Kidney Disease. Below are some take home points.

Hyperaldosteronism has deleterious effects beyond hypertension and hypokalemia such as hypertension independent LVH, myocardial fibrosis and an increase in other organ manifestations (eg hemorrhagic stroke) compared to the general population of hypertensive patients.

Sporadic primary aldosteronism

About a third are due to an adrenal adenoma for which unilateral adrenalectomy is the treatment of choice. About two thirds have bilateral adrenal hyperplasia in which the biochemical disturbances tend to be milder and for which medical management with aldosterone receptor antagonists is the treatment of choice.

Familial hyperaldosteronism type I

AKA glucocorticoid responsive hyperaldosteronism.

Reported in 1966.

Autosomal dominant.

Rare among causes of hyperaldosteronism but the most common form of monogenic hypertension.

As a result of the mutation aldosterone secretion is under the control of ACTH, thus treatment is with a glucocorticoid, preferably dexamethasone due to its long duration of action and minimal mineralocorticoid effect. Treatment may also include standard antihypertensive therapy including mineralocorticoid antagonists.

Familial hyperaldosteronism type II

Described in 1992.

Autosomal dominant.

Not suppressible by glucocorticoid.

Like sporadic hyperaldosteronism, it can be associated with adenoma or hyperplasia and the treatment is the same as in the sporadic form.

Familial hyperaldosteronism type III

Described 2008.

Not suppressible by glucocorticoid.

Massive hyperplasia.

Severe presentation with treatment resistance.

Liddle syndrome

Described 1963.

Though rare, second most common cause of monogenic hypertension.

Numerous mutations discovered, all of which cause increased activity of the epithelial sodium channel (ENaC).

Aldosterone levels low.

Treatment is with ENaC antagonists (triamterene, amiloride) but not mineralocorticoid antagonists such as spironolactone.

Apparent mineralocorticoid excess

Described 1977.

Autosomal recessive.

Third most common form of monogenic hypertension.

Local (renal tubular) deficiency of 11 beta hydroxysteroid dehydrogenase type 2 resulting in defective local conversion of cortisol to cortisone. The result is a local excess of cortisol, which has mineralocorticoid activity.

Treatment is with potassium sparing diuretics and possibly dexamethasone.

Licorice ingestion mimics this syndrome by causing inhibition of the intracellular enzyme.

Congenital adrenal hyperplasia

This is a group of diseases associated with numerous enzyme deficiencies. Only 17 alpha hydroxylase and 11 beta hydroxylase deficiencies cause mineralocorticoid excess syndromes. These result from an accumulation of precursors in the steroid biosynthetic pathway which possess mineralocorticoid activity. Glucocorticoid administration is the treatment.