6 Mineralocorticoid resistance

Mineralocorticoid resistance, or pseudohypoaldosteronism (PHA), is a rare cause of salt wasting in young children. It may be inherited as an autosomal dominant or recessive trait, it may occur sporadically or, rarely, it may develop secondary to other conditions. It is characterized by episodes of dehydration and hyponatraemia in the face of high aldosterone levels. In most cases, after a short period of salt supplementation no further ill effects are experienced. The condition is of great interest because it provides insights into both the mechanisms by which salt and water balance are controlled and the actions of aldosterone. This article reviews the normal physiology of aldosterone, with particular reference to its biosynthesis and its actions in specific target tissues. Current knowledge regarding the molecular mechanisms involved in aldosterone action is discussed in some detail. The clinical features of PHA are reviewed and diagnostic issues and clinical management considered. Finally, current views regarding the pathophysiology of the condition are presented. Here, considerable uncertainty remains. Whilst in many cases of PHA there is greatly reduced binding of aldosterone to its receptor, the underlying abnormality is yet to be identified; in particular, in spite of strong reasons for suspecting a defect or defects in the mineralocorticoid receptor, there is so far no direct evidence to support this hypothesis. The article concludes with a discussion of other possible explanations for the underlying abnormality in PHA.