The 3% hypertonic saline infusion test for the differential diagnosis of diabetes insipidus and primary polydipsia: assessment of diagnostic accuracy

AIM: assessment of the diagnostic accuracy of a 3% hypertonic saline infusion test in relation to a set of clinical and laboratory data (including a water deprivation test and MRI data) for differential diagnoses of diabetes insipidus (DI) and primary polydipsia (PP).

METHODS: An interventional cross-sectional study was carried out at Endocrinology Research Centre From September 2021 to September 2023 ninety patients with polyuria-polydipsia syndrome were included. In order to assess the diagnostic characteristics, all the subjects underwent two tests with osmotic stimulation: a 3% hypertonic saline infusion test and a water deprivation test. Adverse events were assessed.

RESULTS: Based on the results of clinical, anamnestic, laboratory and instrumental data, and the results of a water deprivation test, a final diagnosis of DI was made in 48 (53%) patients and PP in 42 (47%) patients. The agreement between the two samples is significant — Kappa = 0.823, 95% CI (0.707, 0.939). The operational parameters of the 3% hypertonic saline infusion test are: sensitivity 98% (95% CI: 89%; 100%); specificity 98% (95% CI: 87%; 100%), positive and negative predictive values 98% (95% CI: 89%–100%) and 98% (95% CI: 87%–100%). Respectively. Chills occurred significantly more often (31% vs. 12%), and dizziness and headache were more pronounced during the 3% hypertonic saline infusion test. The median duration of the water deprivation test in patients was 11 hours, and median duration of 3% hypertonic saline infusion test was 1.5 hour (P<0.001).

CONCLUSION: The 3% hypertonic saline infusion test has a high overall diagnostic accuracy 98%; 95% CI 92% to 100%)) in relation to the classical set of clinical, laboratory and instrumental data of patients (including a water deprivation test), However, it is important the advantage of the latter is its short duration and, as a consequence, better tolerability and probably better compliance, while no significant differences in adverse events frequencies during the tests were identified.

1. Christ-Crain M, Fenske W. Copeptin in the diagnosis of vasopressin-dependent disorders of fluid homeostasis. Nat Rev Endocrinol. 2016;12(3):168-176. doi: https://doi.org/10.1038/nrendo.2015.224

2. Verbalis JG. Disorders of body water homeostasis. Best Pract Res Clin Endocrinol Metab. 2003;17(4):471-503. doi: https://doi.org/10.1016/S1521-690X(03)00049-6

3. Bockenhauer D, Bichet DG. Pathophysiology, diagnosis and management of nephrogenic diabetes insipidus. Nat Rev Nephrol. 2015;11(10):576-588. doi: https://doi.org/10.1038/nrneph.2015.89

4. Epstein FH, Kleeman CR, Hendrikx A. The influence of bodily hydration on the renal concentrating process. J Clin Invest. 1957;36(5):629-634. doi: https://doi.org/10.1172/JCI103462

5. Robertson GL. Diabetes Insipidus. Endocrinol Metab Clin North Am. 1995;24(3):549-572. doi: https://doi.org/10.1016/S0889-8529(18)30031-8

6. Fenske W, Allolio B. Current state and future perspectives in the diagnosis of diabetes insipidus: A clinical review. J Clin Endocrinol Metab. 2012. doi: https://doi.org/10.1210/jc.2012-1981

7. Pigarova EA, Dzeranova LK, Zhukov AY, et al. Electrolyte disorders after endoscopic transnasal neurosurgical interventions. Endocrine surgery. 2019;13(1):42-55. (In Russ.). doi: https://doi.org/10.14341/serg10205

8. Miller M. Recognition of Partial Defects in Antidiuretic Hormone Secretion. Ann Intern Med. 1970;73(5):721. doi: https://doi.org/10.7326/0003-4819-73-5-721

9. Fenske W, Refardt J, Chifu I, et al. A Copeptin-Based Approach in the Diagnosis of Diabetes Insipidus. N Engl J Med. 2018;379(5):428-439. doi: https://doi.org/10.1056/NEJMoa1803760

10. Dedov II, Melnichenko GA, Pigarova EA, et al. Federal clinical guidelines for the diagnosis and treatment of diabetes insipidus in adults. Obesity and metabolism. 2018;15(2):56-71. (In Russ.)]. doi: https://doi.org/10.14341/omet9670

11. Baylis PH, Robertson GL. Plasma Vasopressin Response to Hypertonic Saline Infusion to Assess Posterior Pituitary Function. J R Soc Med. 1980;73(4):255-260. doi: https://doi.org/10.1177/014107688007300408

12. Gellai M, Edwards BR, Valtin H. Urinary concentrating ability during dehydration in the absence of vasopressin. Am J Physiol Physiol. 1979;237(2):F100-F104. doi: https://doi.org/10.1152/ajprenal.1979.237.2.F100

13. Li C, Wang W, Kwon T-H, et al. Downregulation of AQP1, -2, and -3 after ureteral obstruction is associated with a long-term urine-concentrating defect. Am J Physiol Physiol. 2001;281(1):F163-F171. doi: https://doi.org/10.1152/ajprenal.2001.281.1.F163

14. Rebrova OYu, Fediaeva VK. Assessment of risk of bias in the cross-sectional studies of diagnostic tests: the russian- language version of the questionnaire QUADAS. Medical Technologies. Assessment and Choice. 2017;1:42-55. (In Russ.).