Clinical Assessment of Posterior Pituitary Function by Direct Measurement of Plasma Vasopressin Levels during Hypertonic Saline Infusion Yutaka OISO,

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1 Clinical Assessment of Posterior Pituitary Function by Direct Measurement of Plasma Vasopressin Levels during Hypertonic Saline Infusion Yutaka OISO, Yasumasa IWASAKI, Kazuyuki YAMAUCHI, Kensuke TAKATSUKI, Akio TOMITA, Kyuji KAMOI1), Fumihiko KURIMOTO2) and Hyoichiro SAKURAI2) The First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan Department of Internal Medicine, Nagaoka Red Cross Hospital, Nagaoka, Japan l) Mitsubishiyuka Laboratory of Medical Science Co., Ltd., Tokyo, Japan2) Clinical usefulness of a radioimmunoassay of plasma arginine vasopressin concentration (AVP) during hypertonic saline infusion for the assessment of posterior pituitary function was studied in comparison with the conventional water deprivation test. Infusion of 5% saline at a rate of 0.05m1/kg/min for 120min in 15 normal subjects induced an elevation of plasma osmolality (Posm) from ± 0.7 to ± 2.1mOsm/kg with a resultant increase in AVP from 2.4 ± 0.4 to 9.9 ± 2.2pg/ml. During the infusion, a highly significant correlation between AVP and Posm was observed with a regression line expressed as AVP = 0.40 (Posm ). In 22 polyuric patients, on the other hand, the infusion induced a marked elevation of Posm from ± 2.5 to ± 2.9mOsm/kg,

2 but caused a slight (<5.8pg/m1) or no increase in AVP from the basal levels (0.5 ± 0.1pg/m1). A conventional water deprivation test was carried out in ten patients with neurogenic diabetes insipidus, including one who had coincidental nephrogenic diabetes insipidus. As would be expected, urine osmolality (Uosm) did not rise beyond Posm in seven of them. However, two of three other patients, who had a complete lack of AVP response to the hypertonic saline, were able to concentrate their urine with a maximal Uosm/Posm of 1.3 and 1.1 respectively. The concurrent decrease in creatinine clearance to 49 and 57% of the initial values, respectively, indicated that a marked reduction in glomerular filtration rate due to severe dehydration was responsible for the unexpected concentration of urine in the patients with totally impaired AVP secretion. Based on these results, we conclude that the direct measurement of AVP during hypertonic saline infusion is an essential procedure for the accurate evaluation of posterior pituitary function.

3 Table 1. Clinical data of patients with polyuria. Fig. 1. Method of 5% saline infusion test.

4 Fig. 2. Effect of 5% saline infusion on plasma arginine vasopressin (AVP), plasma osmolality (Posm) and serum sodium (S-Na) in healthy adults. Significantly different from baseline levels by paired-t analysis: a: p<0.02, b: p<0.01, c: p<0.005, d: p<0.001.

5 Fig. 3. Relationship of plasma arginine vasopressin (AVP) to plasma osmolality (Posm) in healthy adults.

6 Fig. 4. Effect of 5% saline infusion on plasma vasopressin (AVP), plasma osmolality and serum sodium (S-Na) in patients with polyuria. Significantly different from baseline levels by paired-t analysis: b: p<0.01, d: p< Fig. 5. Relationship of plasma arginine vasopressin (AVP) to plasma osmolality (Posm) during 5% saline infusion in patients with polyuria.

7 Fig. 6. Maximum urine osmolality (Uosm)/plasma osmolality (Posm) ratio after dehydration plotted against the change in plasma arginine vasopressin (AVP) during 5% saline infusion in patients with polyuria.

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10 1) Berliner, R.W. and Davidson, D.G.: Production of hypertonic urine in the absence of pituitary antidiuretic hormone. J. Clin. Invest., 35: 690, ) Carter, A.C. and Robbins, J.: The use of hypertonic saline infusions in the differential diagnosis of diabetes insipidus and psychogenic polydipsia. J. Clin. Endocrinol., 7: , ) Dashe, A.M., Cramm, R.E., Crist, C.A., Habener, J.F. and Solomon, D.H.: A water deprivation test for the differential diagnosis of polyuria. J.A.M.A., 185: , ) del Greco, F. and de Wardener, H.E.: The effect on urine osmolarity of a transient reduction in glomerular filtration rate and solute output during a water diuresis. J. Physiol., 131: , ) de Wardener, H.E. and Herxheimer, A.: The effect of a high water intake on the kidney's ability to concentrate the urine in man. J. Physiol., 139: 42-52, ) Gellai, M., Edwards, B.R. and Valtin, H.: Urinary concentrating ability during dehydration in the absence of vasopressin. Amer. J. Physiol., 237: F100 F104, ) Gennari, F.J.: Serum osmolality, uses and limitations. New Engl. J. Med., 310: , ) Kleeman, C.R., Maxwell, M.H. and Witlin, S.: Functional Isosthenuria. Arch. Intern. Med., 101: , ) McConnel, R.F.Jr., Lorentz, W.B.Jr., Berger, M., Smith, E.H., Carvajal, H.F. and Travis, L.B.: The mechanism of urinary concentration in nephrogenic diabetes insipidus. Pediat. Res., 11: 33-36, ) Miller, M., Dalakos, T., Moses, A.M., Fellerman, H. and Streeten, D.H.P.: Recognition of partial defects in antidiuretic hormone secretion. Ann. Intern. Med., 73: , ) Moses, A.M. and Streeten, D.H.P.: Differentiation of polyuric states by measurement of responses to changes in plasma osmolality induced by hypertonic saline infusions. Amer. J. Med., 42: , ) Moses, A.M., Scheinman, S.J. and Oppenheim, A.: Marked hypotonic polyuria resulting from nephrogenic diabetes insipidus with partial sensitivity to vasopressin. J. Clin. Endocrinol. Metab., 59: , ) Oiso, Y., Gaskill, M., Stamoutsos, B., Lindheimer, M. and Robertson, G.L.: Vasopressin immunoactivity in Brattleboro rats with hereditary hypothalamic diabetes insipidus. Clin. Res., 29: 708A, ) Robertson, G.L., Mahr, E.A., Athar, S. and Sinha, T.: Development and clinical application of new method for the radioimmunoassay of arginine vasopressin in human plasma. J. Clin. Invest., 52: , ) Robertson, G.L.: The regulation of vasopressin function in health and disease. Rec. Prog. Horm. Res., 33: , 1977.

11 61: , ) Vaamonde, C.A., Presser, J.I. and Clapp, W.: Effect of high fluid intake on the renal concentrating mechanism of normal man. J. Appl. Physiol., 36: , ) Zerbe, R.L. and Robertson, G.L.: A comparison of plasma vasopressin measurements with a standard indirect test in the differential diagnosis of polyuria. New Engl. J. Med., 305: , 1981.

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