Copeptin stimulation by combined intravenous arginine and oral LevoDopa/Carbidopa in healthy short children and children with the polyuria-polydipsia syndrome.

Abstract

Stimulated copeptin may provide an alternative to water deprivation testing (WDT) in the evaluation of polyuria-polydipsia syndrome (PPS). Though best studied, arginine stimulation alone produces a modest copeptin response in children. We investigated the effectiveness of the arginine + LevoDopa/Carbidopa stimulation test (ALD-ST) for copeptin. 47 healthy short children (controls), 10 children with primary polydipsia and 10 children with AVP deficiency received arginine hydrochloride (500 mg/Kg intravenously over 30 minutes) and Levodopa/carbidopa (10:1 ratio; 175 mg of L-Dopa/m2 BSA) orally. Serum copeptin was measured at 0 60, 90 and 120 minutes. In controls, ALD-ST increased copeptin from a median of 7.0 pMol/L (IQR 5.0-10.0) to a peak of 44.0 pMol/L (IQR 21.4-181.0) between 60-120 minutes (p<0.001). Copeptin peak was higher in subjects who experienced nausea or vomiting (57%) than in those who did not (131.0 pMol/L [IQR 42.5-193.8] vs 22.7 pMol/L [IQR 16.0-33.7], p<0.001). While subjects with primary polydipsia had similar baseline (8.5 pMol/L [IQR 8.0-11.0]) and stimulated (125.2 pMol/L [IQR 87.6-174.0]) copeptin levels as controls, subjects with AVP deficiency had lower baseline (2.5 pMol/L [IQR 2.0-3.1]) and peak levels (4.6 pMol/L [IQR 2.4-6.0]). A peak copeptin of ≥9.3 pMol/L best predicted absence of complete or partial AVP deficiency with a sensitivity of 100% and specificity of 80%. ALD-ST induced a robust peak copeptin in healthy short children and children with primary polydipsia. Nausea/vomiting, a side effect of ALD-ST, amplified the copeptin response. The ALD-ST may be a suitable initial screening test in children with PPS.