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Differentiating AVP deficiency and primary polydipsia: a clinical and biochemical perspective

Year 2025, Volume: 7 Issue: 5, 576 - 582, 15.09.2025
https://doi.org/10.38053/acmj.1705329

Abstract

Aims: The polyuria–polydipsia syndrome encompasses three major disorders—arginine vasopressin (AVP) deficiency, AVP resistance, and primary polydipsia. This study aimed to differentiate AVP deficiency from primary polydipsia by evaluating clinical features, biochemical markers, and anterior pituitary hormone levels, using the water deprivation test as the primary diagnostic modality.
Methods: This retrospective observational study included 34 adult patients with polyuria–polydipsia syndrome who underwent a standardized inpatient water deprivation test. Patients were categorized into AVP deficiency (complete or partial) or primary polydipsia based on urine osmolality responses to dehydration and desmopressin. Clinical data, daily fluid intake, and nocturia frequency were recorded. Serum electrolytes and anterior pituitary hormones (LH, GH) were analyzed.
Results: AVP deficiency was diagnosed in 76.4% of patients (58.8% complete, 17.6% partial), while 23.5% had primary polydipsia. LH and GH levels were significantly higher in the primary polydipsia group (p=0.011 and p=0.028, respectively), whereas AVP deficiency was associated with lower gonadotropin levels, especially in postoperative cases. Serum sodium, chloride, and magnesium levels were significantly lower in primary polydipsia (p<0.05), reflecting dilutional hyponatremia. Urine osmolality was significantly higher in primary polydipsia (p=0.011), indicating preserved concentrating ability. Nocturia occurred in 96.2% of patients with AVP deficiency versus 12.5% in primary polydipsia (p<0.001).
Conclusion: The water deprivation test remains a valuable diagnostic tool for differentiating AVP deficiency from primary polydipsia. These retrospective findings may serve as predictive indicators in the differential diagnosis, particularly in clinical settings where water deprivation tests and copeptin testing are not readily available. Incorporating nocturia frequency, serum electrolytes, and anterior pituitary hormone levels particularly LH and GH may improve diagnostic precision and facilitate individualized management.

References

  • Refardt J, Winzeler B, Christ-Crain M. Diabetes insipidus: an update. Endocrinol Metab Clin North Am. 2020;49(3):517-531. doi:10.1016/j.ecl. 2020.05.012
  • Sailer CO, Winzeler B, Christ-Crain M. Primary polydipsia in the medical and psychiatric patient: characteristics, complications and therapy. Swiss Med Wkly. 2017;147:w14514. doi:10.4414/smw.2017.14514
  • Teare H, Argente J, Dattani M, et al. Challenges and improvement needs in the care of patients with central diabetes insipidus. Orphanet J Rare Dis. 2022;17(1):58. doi:10.1186/s13023-022-02191-2
  • Atila C, Yıldız BO, Güler S, et al. Psychopathological characteristics in patients with arginine vasopressin deficiency (central diabetes insipidus) and primary polydipsia compared to healthy controls. Eur J Endocrinol. 2024;190(5):354-362. doi:10.1093/ejendo/lvae040
  • Itagaki E, Ozawa S, Yamaguchi S, et al. Increases in plasma ACTH and cortisol after hypertonic saline infusion in patients with central diabetes insipidus. J Clin Endocrinol Metab. 2001;86:5749-5754.
  • Flynn K, Thomas L, Jackson P, et al. Central and nephrogenic diabetes insipidus: updates on diagnosis and management. Front Endocrinol (Lausanne). 2025;15:1479764. doi:10.3389/fendo.2024.1479764
  • Bologna K, Cesana-Nigro N, Refardt J, et al. Effect of arginine on the hypothalamic-pituitary-adrenal axis in individuals with and without vasopressin deficiency. J Clin Endocrinol Metab. 2020;105(3):e884-e892. doi:10.1210/clinem/dgaa157
  • 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: 10.1056/NEJMoa1803760
  • Pires BF, Andrade M, Silva T, et al. Primary polydipsia and sIDH Type D due to water-electrolytic disturbance in a schizophrenic patient: a case report and systematic review. Open J Psychiatry. 2025;15(1):1-15.
  • Pedrosa W, Drummond JB, Soares BS, Ribeiro-Oliveira A Jr. A combined outpatient and inpatient overnight water deprivation test is effective and safe in diagnosing patients with polyuria-polydipsia syndrome. Endocr Pract. 2018;24(11):963-972. doi:10.4158/ep-2018-0238
  • Pivonello R, Faggiano A, Filippella M, et al. Hypothalamus-pituitary-adrenal axis in central diabetes insipidus: ACTH and cortisol responsiveness to CRH administration. J Endocrinol Invest. 2002;25(10): 932-937. doi:10.1007/BF03344064
  • Ho KK; 2007 GH Deficiency Consensus Workshop Participants. Consensus guidelines for the diagnosis and treatment of adults with GH deficiency II: a statement of the GH Research Society in association with the European Society for Pediatric Endocrinology, Lawson Wilkins Society, European Society of Endocrinology, Japan Endocrine Society, and Endocrine Society of Australia. Eur J Endocrinol. 2007;157(6):695-700. doi:10.1530/EJE-07-0631
  • Atila C, Lustenberger S, Yıldız BO, et al. Relationship between plasma urea and copeptin in response to arginine stimulation in healthy adults, patients with vasopressin deficiency, and primary polydipsia. Pituitary. 2025;28(1):18. doi:10.1007/s11102-024-01489-7
  • Trimpou P, Olsson DS, Ehn O, Ragnarsson O. Diagnostic value of the water deprivation test in the polyuria-polydipsia syndrome. Hormones (Athens). 2017;16(4):414-422. doi:10.14310/horm.2002.1762
  • Winzeler B, Cesana-Nigro N, Refardt J, et al. Arginine-stimulated copeptin measurements in the differential diagnosis of diabetes insipidus: a prospective diagnostic study. Lancet. 2019;394(10198):587-595. doi:10.1016/S0140-6736(19)31255-3

Differentiating AVP deficiency and primary polydipsia: a clinical and biochemical perspective

Year 2025, Volume: 7 Issue: 5, 576 - 582, 15.09.2025
https://doi.org/10.38053/acmj.1705329

Abstract

Aims: The polyuria–polydipsia syndrome encompasses three major disorders—arginine vasopressin (AVP) deficiency, AVP resistance, and primary polydipsia. This study aimed to differentiate AVP deficiency from primary polydipsia by evaluating clinical features, biochemical markers, and anterior pituitary hormone levels, using the water deprivation test as the primary diagnostic modality.
Methods: This retrospective observational study included 34 adult patients with polyuria–polydipsia syndrome who underwent a standardized inpatient water deprivation test. Patients were categorized into AVP deficiency (complete or partial) or primary polydipsia based on urine osmolality responses to dehydration and desmopressin. Clinical data, daily fluid intake, and nocturia frequency were recorded. Serum electrolytes and anterior pituitary hormones (LH, GH) were analyzed.
Results: AVP deficiency was diagnosed in 76.4% of patients (58.8% complete, 17.6% partial), while 23.5% had primary polydipsia. LH and GH levels were significantly higher in the primary polydipsia group (p=0.011 and p=0.028, respectively), whereas AVP deficiency was associated with lower gonadotropin levels, especially in postoperative cases. Serum sodium, chloride, and magnesium levels were significantly lower in primary polydipsia (p<0.05), reflecting dilutional hyponatremia. Urine osmolality was significantly higher in primary polydipsia (p=0.011), indicating preserved concentrating ability. Nocturia occurred in 96.2% of patients with AVP deficiency versus 12.5% in primary polydipsia (p<0.001).
Conclusion: The water deprivation test remains a valuable diagnostic tool for differentiating AVP deficiency from primary polydipsia. These retrospective findings may serve as predictive indicators in the differential diagnosis, particularly in clinical settings where water deprivation tests and copeptin testing are not readily available. Incorporating nocturia frequency, serum electrolytes, and anterior pituitary hormone levels particularly LH and GH may improve diagnostic precision and facilitate individualized management.

Ethical Statement

This study was approved by the Ethics Committee of Ankara Bilkent City Hospital (E1-23-3947) and conducted in accordance with the Declaration of Helsinki.

References

  • Refardt J, Winzeler B, Christ-Crain M. Diabetes insipidus: an update. Endocrinol Metab Clin North Am. 2020;49(3):517-531. doi:10.1016/j.ecl. 2020.05.012
  • Sailer CO, Winzeler B, Christ-Crain M. Primary polydipsia in the medical and psychiatric patient: characteristics, complications and therapy. Swiss Med Wkly. 2017;147:w14514. doi:10.4414/smw.2017.14514
  • Teare H, Argente J, Dattani M, et al. Challenges and improvement needs in the care of patients with central diabetes insipidus. Orphanet J Rare Dis. 2022;17(1):58. doi:10.1186/s13023-022-02191-2
  • Atila C, Yıldız BO, Güler S, et al. Psychopathological characteristics in patients with arginine vasopressin deficiency (central diabetes insipidus) and primary polydipsia compared to healthy controls. Eur J Endocrinol. 2024;190(5):354-362. doi:10.1093/ejendo/lvae040
  • Itagaki E, Ozawa S, Yamaguchi S, et al. Increases in plasma ACTH and cortisol after hypertonic saline infusion in patients with central diabetes insipidus. J Clin Endocrinol Metab. 2001;86:5749-5754.
  • Flynn K, Thomas L, Jackson P, et al. Central and nephrogenic diabetes insipidus: updates on diagnosis and management. Front Endocrinol (Lausanne). 2025;15:1479764. doi:10.3389/fendo.2024.1479764
  • Bologna K, Cesana-Nigro N, Refardt J, et al. Effect of arginine on the hypothalamic-pituitary-adrenal axis in individuals with and without vasopressin deficiency. J Clin Endocrinol Metab. 2020;105(3):e884-e892. doi:10.1210/clinem/dgaa157
  • 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: 10.1056/NEJMoa1803760
  • Pires BF, Andrade M, Silva T, et al. Primary polydipsia and sIDH Type D due to water-electrolytic disturbance in a schizophrenic patient: a case report and systematic review. Open J Psychiatry. 2025;15(1):1-15.
  • Pedrosa W, Drummond JB, Soares BS, Ribeiro-Oliveira A Jr. A combined outpatient and inpatient overnight water deprivation test is effective and safe in diagnosing patients with polyuria-polydipsia syndrome. Endocr Pract. 2018;24(11):963-972. doi:10.4158/ep-2018-0238
  • Pivonello R, Faggiano A, Filippella M, et al. Hypothalamus-pituitary-adrenal axis in central diabetes insipidus: ACTH and cortisol responsiveness to CRH administration. J Endocrinol Invest. 2002;25(10): 932-937. doi:10.1007/BF03344064
  • Ho KK; 2007 GH Deficiency Consensus Workshop Participants. Consensus guidelines for the diagnosis and treatment of adults with GH deficiency II: a statement of the GH Research Society in association with the European Society for Pediatric Endocrinology, Lawson Wilkins Society, European Society of Endocrinology, Japan Endocrine Society, and Endocrine Society of Australia. Eur J Endocrinol. 2007;157(6):695-700. doi:10.1530/EJE-07-0631
  • Atila C, Lustenberger S, Yıldız BO, et al. Relationship between plasma urea and copeptin in response to arginine stimulation in healthy adults, patients with vasopressin deficiency, and primary polydipsia. Pituitary. 2025;28(1):18. doi:10.1007/s11102-024-01489-7
  • Trimpou P, Olsson DS, Ehn O, Ragnarsson O. Diagnostic value of the water deprivation test in the polyuria-polydipsia syndrome. Hormones (Athens). 2017;16(4):414-422. doi:10.14310/horm.2002.1762
  • Winzeler B, Cesana-Nigro N, Refardt J, et al. Arginine-stimulated copeptin measurements in the differential diagnosis of diabetes insipidus: a prospective diagnostic study. Lancet. 2019;394(10198):587-595. doi:10.1016/S0140-6736(19)31255-3
There are 15 citations in total.

Details

Primary Language English
Subjects Endocrinology
Journal Section Research Articles
Authors

Beril Turan Erdoğan 0000-0003-1391-0647

Muzaffer Serdar Deniz 0000-0002-8905-3955

Belma Özlem Tural Balsak 0000-0002-1348-7706

Çağlar Keskin 0000-0001-5503-4468

Burçak Polat 0000-0002-7729-5586

Oya Topaloğlu 0000-0003-2501-935X

Reyhan Ersoy 0000-0002-7437-1176

Bekir Çakır 0000-0001-7526-8827

Publication Date September 15, 2025
Submission Date May 23, 2025
Acceptance Date August 14, 2025
Published in Issue Year 2025 Volume: 7 Issue: 5

Cite

AMA Turan Erdoğan B, Deniz MS, Tural Balsak BÖ, et al. Differentiating AVP deficiency and primary polydipsia: a clinical and biochemical perspective. Anatolian Curr Med J / ACMJ / acmj. September 2025;7(5):576-582. doi:10.38053/acmj.1705329

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