SALT LOSS AND MINERALOODRTICOID RESISTANCE IN AN INFANT: A VARIANT OF PSUEDOHYPOALDOSTERONISM

Abstract

Gas Chromatography/Mass Spectrometry (GC/MS) analysis of urinary steroid derivatives has extended our understanding of a variety of metabolic disease states. GC/MS was used to evaluate a suspected case of adrenal hyperplasia. A 4 week-old male presented with failure to thrive, absence of excessive virilization, hyponatremia (Na 120 mmol/L) and hyperkalanic metabolic acidosis. Serum 17-OHP and urinary 17-ketosteroids and pregnanetriol were normal. Treatment with IV saline and IM DOCA resulted in improvement, but α-fluorocortisone alone was ineffective and NaCl supplements at doses of 8mmol/kg/day were needed. Plasma aldosterone was 840 pmol/L (27 ng/dL); PRA was 125ng/ml/hr after 5 months of treatment. An older brother with salt losing in infancy had responded to sodium and α-fluorocortisone and was considered to be an 18 hydroxylase complex deficiency. GC analysis confirmed the normalcy of glucocorticoid and androgen pathways as well as an abnormal elevation of THB. In addition, there was a marked elevation of THA (TH corticosterol), confirmed by MS, which has not been previously reported. In contrast with other cases of pseudohypoaldosteronism and abnormalities in aldosterone biosynthesis, the present combination of features suggests problems in both aldosterone synthesis and tubular insensitivity to mineralocorticoids. The latter may possibly result from competitive inhibition by THA.