Diabetes insipidus and polyuria-polydipsia

The organising idea is the vasopressin-water balance axis. Hypothalamic osmoreceptors sense a rising plasma osmolality, the posterior pituitary releases arginine vasopressin, and vasopressin acts on the renal collecting duct to reabsorb water and concentrate the urine. Diabetes insipidus breaks this axis in one of two places: at the source, where no vasopressin is made (central), or at the kidney, where vasopressin cannot act (nephrogenic). Primary polydipsia is the mirror image — the axis is intact, but a flood of drunk water suppresses vasopressin and mimics the same dilute polyuria. Knowing which link is broken is the fastest route to the right test and the right drug. [1] [4]

This page covers the full breadth of the paediatric polyuria-polydipsia syndrome: the physiology of vasopressin and aquaporin-2, the three-way classification, congenital and acquired causes, the presentation from the failure-to-thrive infant to the child after brain surgery, the water-deprivation test, the copeptin tests that have largely replaced it, and the divided management. It cross-links to the SIADH leaf for the opposite disorder of water balance rather than repeating it here. [1] [2]

Overview & Definition

Diabetes insipidus is the passage of large volumes of inappropriately dilute urine because the kidney fails to concentrate it. In children, polyuria means a urine output above roughly 2 litres per square metre per day, or more than 40 to 50 millilitres per kilogram per day. The urine is hypotonic (osmolality typically below 300 milliosmoles per kilogram), and the child compensates by drinking — the polydipsia that gives the syndrome its name. [3] [5]

The word "insipidus" means tasteless, distinguishing this dilute urine from the sweet urine of diabetes mellitus, and the two diseases share nothing but the polyuria. This is the first fork in every assessment: a high glucose points to osmotic diuresis from diabetes mellitus, while a low urine osmolality with a normal glucose points to a water diuresis and the polyuria-polydipsia syndrome. [5] [10]

An international working group has renamed the two forms of diabetes insipidus to reduce the dangerous confusion with diabetes mellitus. Central diabetes insipidus is now arginine vasopressin deficiency (AVP-D), and nephrogenic diabetes insipidus is arginine vasopressin resistance (AVP-R). The older names remain in wide clinical use, so a fellowship candidate should recognise both and understand why the change was made. [2]

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1. [1]Christ-Crain M; Bichet DG; Fenske WK; et al Diabetes insipidus. Nat Rev Dis Primers, 2019.PMID 31395885
2. [2]Arima H, Cheetham T, Christ-Crain M, et al. Changing the name of diabetes insipidus: a position statement of The Working Group for Renaming Diabetes Insipidus. Eur J Endocrinol, 2022.PMID 36239119
3. [3]Dabrowski E; Kadakia R; Zimmerman D Diabetes insipidus in infants and children. Best Pract Res Clin Endocrinol Metab, 2016.PMID 27156767
4. [4]Di Iorgi N; Napoli F; Allegri AE; et al Diabetes insipidus--diagnosis and management. Horm Res Paediatr, 2012.PMID 22433947
5. [5]Fenske W; Allolio B Clinical review: Current state and future perspectives in the diagnosis of diabetes insipidus: a clinical review. J Clin Endocrinol Metab, 2012.PMID 22855338
6. [6]Timper K; Fenske W; Kühn F; et al Diagnostic Accuracy of Copeptin in the Differential Diagnosis of the Polyuria-polydipsia Syndrome: A Prospective Multicenter Study. J Clin Endocrinol Metab, 2015.PMID 25768671
7. [7]Fenske W; Refardt J; Chifu I; et al A Copeptin-Based Approach in the Diagnosis of Diabetes Insipidus. N Engl J Med, 2018.PMID 30067922
8. [8]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.PMID 31303316
9. [9]Bockenhauer D; Bichet DG Pathophysiology, diagnosis and management of nephrogenic diabetes insipidus. Nat Rev Nephrol, 2015.PMID 26077742
10. [10]Robertson GL Diabetes insipidus: Differential diagnosis and management. Best Pract Res Clin Endocrinol Metab, 2016.PMID 27156759
11. [11]Djermane A; Elmaleh M; Simon D; et al Central Diabetes Insipidus in Infancy With or Without Hypothalamic Adipsic Hypernatremia Syndrome: Early Identification and Outcome. J Clin Endocrinol Metab, 2016.PMID 26588450