EFFECT OF FLUDROCORTISONE AND SPIRONOLACTONE ON SODIUM AND POTASSIUM LOSSES IN SECRETORY DIARRHEA

The response of the colon to aldosterone is believed to be an importan t adaptive mechanism to excessive sodium losses in diarrhea. However, the degree to which mineralocorticoid activity actually influences fec al output of sodium in people with diarrhea is unknown. To gain insigh t into this question, 10 normal people were treated with placebo, flud rocortisone (an aldosterone agonist), and spironolactone (an aldostero ne antagonist) during three experimental periods lasting nine days. On days 5-8, diarrhea was induced by ingestion of phenolphthalein. Diet was controlled. Fecal sodium was 40 meq/day on placebo and 29 meq/day on fludrocortisone, consistent with mineralocorticoid stimulation of i ntestinal sodium absorption. However, contrary to our expectations, sp ironolactone therapy was also associated with a fall in fecal sodium o utput, to 28 meq/day. To explain this paradoxical effect of spironolac tone, we suggest that sodium depletion caused by spironolactone's natr iuretic action on the kidney caused the release of an unknown stimulan t of intestinal sodium absorption, whose action more than overcame the reduced colonic absorption resulting from inhibition of aldosterone a ctivity by spironolactone. This interpretation implies that the intest inal adaptation to sodium depletion in diarrhea involves both aldoster one and an aldosterone independent factor, working in concert to reduc e fecal sodium output.