Pseudohypoaldosteronism: Decreased Aldosterone Levels With Age Without Significant Change in Urinary Sodium Excretion

Abstract

To clarify age-related changes in the plasma renin activity (PRA)-aldosterone (ALDO) system in relation to urinary sodium (Na) excretion in pseudohypoaldosteronism type I (PHA), we followed a patient with PHA serially by measuring the hormonal balance and urinary electrolyte excretion for 5 years. The patient was diagnosed as PHA mainly on the basis of extremely high PRA (170 ng/ml/h) and ALDO (1670 ng/dl) despite massive urinary Na excretion, a normal ALDO/PRA ratio (mean value = 11), and the ineffectiveness of 9 alpha-fluorocortisol (Florinef) to reduce urinary Na excretion and PRA-ALDO. The pattern of reduction in PRA-ALDO with age in this patient was almost identical with that of normal infants and children and was most remarkable during the first 18 months of life. During this period, there were statistically significant correlations between age and each of the following values: PRA (r = -0.753, n = 9, P less than 0.05), ALDO (r = -0.736, n = 11, P less than 0.01) and urinary ALDO excretion (r = -0.840, n = 9, P less than 0.01). But the reduction of PRA-ALDO in this patient was not the result of increased urinary Na excretion with age. Although PRA and ALDO values in this patient did decrease with age, they were still high compared with age-matched controls, suggesting a marginal state of Na balance. Thus, we conclude that PRA-ALDO levels in PHA decrease with age in the same pattern as in normal infants and children without a significant change in urinary Na excretion, possibly through increased renal conservation of Na, the mechanism of which should be clarified in a future study.

Type I Pseudohypoaldosteronism Includes Two Clinically and Genetically Distinct Entities with either Renal or Multiple Target Organ Defects

“…In our index cases the aldosterone and PRA levels were highest in the first few months of life and decreased notably during the first 2 yr, but remained significantly elevated. Other patients with renal PHA show similar decreases in aldosterone in the first 2 yr of life (11,25,26). The urinary sodium excretion appears to remain constant during the same period indicating an increased renal conservation of sodium with age (26).…”

“…Other patients with renal PHA show similar decreases in aldosterone in the first 2 yr of life (11,25,26). The urinary sodium excretion appears to remain constant during the same period indicating an increased renal conservation of sodium with age (26). It should be noted that tubular transport mechanisms in healthy children improve with increasing age (31).…”

“…The renin-angiotensin system appears to be intact in both forms of PHA. Acute changes in sodium intake (sodium depletion or repletion) result in concomitant changes in aldosterone and PRA (our case with multiple PHA, 9,12,16,25,26,34). Aldosterone biosynthetic capacity also appears to be normal in both forms of PHA (our cases, and Ref.…”