The patients reported developed lithium carbonate toxicity while being maintained on a constant sodium and fluid intake. Negative sodium balance was observed in both patients coincident with the onset of lithium carbonate toxicity. Negative sodium balance was also observed in lithium carbonate-toxic rats.
The renal response to the mineralocorticoid deoxycorticosterone acetate (DOC) was evaluated in groups of control and lithium carbonate-treated rats in order to further explore the renal mechanisms involved in lithium carbonate toxicity. In established lithium carbonate toxicity, a blunted response to the sodium retaining properties of DOC was present.
Accordingly, these observations demonstrate a pathogenic cycle in lithium carbonate toxicity. Mineralocorticoid blockade induced by already toxic concentrations of lithium carbonate promotes renal sodium wasting which in turn leads to further lithium carbonate retention and increased toxicity.