Hyperuricemia as a clue for central diabetes insipidus (Lack of V-1 effect) in the differential diagnosis of polydipsia

PURPOSE: In the differential diagnosis of patients with polyuria-polydipsia one must distinguish usually between primary polydipsia (PP) and central diabetes insipidus (CDI). The first situation is a state of volume expansion and the second of volume contraction. We evaluate whether serum uric acid determination could help to differentiate between the two conditions. PATIENTS AND METHODS: We analyzed the score of 13 consecutive patients with CDI, 7 patients with PP, and 7 patients with nephrogenic diabetes insipidus (NDI). Serum uric acid concentration was available during normonatremia without treatment with 1-desamino-8-D-arginine vasopressin (dDAVP), during mild dehydration and during treatment with dDAVP. In 8 of these patients plasma renin activity (PRA), urate, urea and creatinine clearances were also available. These data were also obtained in the patients with NDI. In 1 patient with CDI, we studied the effect on urate clearance of dDAVP, which stimulates exclusively the V-2 receptors, and of triglycyl-lysine-vasopressin (TGLV), a potent V-1-receptor agonist. RESULTS: Normonatremic polydypsic patients with CDI presented an increase in uric acid concentration (7.1 +/- 2.2 mg/dL), whereas in the PP group the value was decreased (3 +/- 0.75 mg/dL; P < 0.001). All the normonatremic PP presented a serum uric acid concentration lower than 5 mg/dL, whereas all the normonatremic CDI patients, exept 1, presented a value higher than 5 mg/dL. In both groups blood urea concentration was decreased as a consequence of high renal clearances. The hyperuricemia of CDI was related to low uric acid clearances. Patients with hypernatremia and NDI presented a lower increase in serum uric acid concentration than those with similar levels of hypernatremia and CDI (NDI: 5.7 +/- 0.8 mg/dL and CDI: 7.9 +/- 2.3 mg/dL; P <0.05) and the NDI patients presented an urate clearance corrected for creatinine clearance which was significantly higher than in CDI (9% +/- 3% and 4% +/- 1.1%; P <0.01). When the patients with CDI were treated with dDAVP and normalyzed their PRA (0.9 +/- 0.4 ng/mL/h) we observed still mild hyperuricemia compared to controls (5.5 +/- 1.4 mg/dL and 4.3 +/- 0.9 mg/dL; P <0.01) and a low fractional excretion of filtered uric acid (6.5% +/- 1.7% compared to 8.2% +/- 2% in controls; P <0.05). Acute administration of dDAVP, stimulating the V-2 receptors, in one patient with CDI, had no effect on urate clerance, while TGLV, which stimulates the V-1 receptor, increased urate clearance. CONCLUSION: The presence of an serum uric acid concentration higher than 5 mg/dL in polyuric polydipsic patients is highly suggestive of CDI. Even when these patients are treated with dDAVP many of them remain hyperuricemic, and this seems to be the consequence of a lack of V-1 receptor stimulation. (C) 1997 by Excerpta Medica, Inc.