PSEUDOHYPOALDOSTERONISM DUE TO RENAL AND MULTISYSTEM RESISTANCE TO MINERALOCORTICOIDS RESPOND DIFFERENTLY TO CARBENOXOLONE

Type I pseudohypoaldosteronism (PHA) is a hereditary syndrome of salt wasting resulting from unresponsiveness to mineralocorticoids. PHA is manifested in two clinically and genetically distinct forms, affecting either only the kidney or multiple target organs of aldosterone. We e xamined the mineralocorticoid effect of carbenoxolone (CBX) in young P HA patients with either renal or multisystem resistance to aldosterone to find out whether CBX may help reduce the requirement for a high-sa lt diet. CBX did not show any significant salt-retaining effect in two patients with multiple PHA, and did not affect the renin-aldosterone system. In contrast, CBX significantly suppressed the renin-aldosteron e system in a renal PHA patient for the whole duration of treatment, b ut without a long-term salt-retaining effect. On CBX treatment, urinar y cortisone levels decreased and the cortisol:cortisone ratio increase d, indicating that CBX inhibited 11 beta-HSD activity that metabolizes cortisol to cortisone. The complete lack of effect of CBX on the reni n-aldosterone system in multisystem PHA patients indicates that CBX do es not exert an effect via mineralocorticoid (MR) or glucocorticoid re ceptors. Examination of the structure and expression of the MR gene by Southern blot analysis and polymerase chain reaction (PCR) showed no abnormality. Whereas multiple PHA results fi om a spectrum of mutation s in the mineralocorticoid activated epithelial sodium channel subunit s, the genetic basis of renal PIPA is still unknown. The response to C BX suggests that there is at least a partly functional MR in renal PHA patients. (C) 1997 Elsevier Science Ltd.