ELECTROLYTE QUIZ

The Answer
The answer is A, discontinue lithium.

The Question

A 35 year-old man with bipolar disorder treated on lithium, is referred to you for chronic polyuria and polydipsia. He complains that he has to void once every hour.

Laboratory studies:

Serum sodium                     146 mEq/L

Blood urea nitrogen               35 mg/dL

Serum creatinine                    1.9 mg/dL

Serum osmolality                 305 mOsm/kg

24-hr urine volume                  5 L

Urine sodium                         28 mEq/L

Urine osmolality                   190 mOsm/kg

Which of the following might be appropriate in the management of this patient?

(A)      Discontinue lithium

(B)      Demeclocycline

(C)      Vasopressin V2 receptor antagonist

(D)      Fluid restriction

(E)      Furosemide

Explanation

Lithium is the most common cause of drug-induced diabetes insipidus. In a report by Bendz and Aurell from Sweden in Drug Safety from 1999 they report that lithium was the cause in 159 of 359 reports in the WHO data base of drug induced causes of DI.

Lithium carbonate reduces the sensitivity of renal tubules to ADH by reducing V2 receptor density or aquaporin-2 expression. Lithium impairs the ADH-stimulatory effect on adenylate cyclase resulting in less cyclic adenosine monophosphate, which, in turn decreases the water absorption through pores in basolateral membrane of collecting tubules.  Long-term treatment of rats with lithium causes a marked decrease in the expression of the aquaporin-2 protein in the medullary collecting duct cells and results in severe nephrogenic diabetes insipidus. Lithium-induced polyuria is also partially due to an enhancement of renal prostaglandin action. Dysregulation of amiloride-sensitive sodium channel (ENaC) may be responsible for increased sodium excretion associated with lithium treatment.

Patients taking lithium, especially long-term therapy, can develop an irreversible concentrating defect that can persist to varying degrees after lithium is discontinued.