Question 2

Compare and contrast central and nephrogenic diabetes insipidus.

Please tabulate your answer under the following headings: definition, etiology, clinical features, investigations, and specific management.
(100% marks)

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College answer

Aim: To explore the clinical entities of Diabetes Insipidus.

Key sources include: Paper 2015.1 Q29, CanMEDS Medical Expert.

Discussion: This question is similar in content to the previously published SAQ. Candidates did well if they were able to demonstrate the pathophysiology particularly in nephrogenic DI.

There was a knowledge gap for many candidates. Management of sodium issues, the requirement for paired serum and urine samples and a discussion of correction strategies of water/sodium balance were contained in the better answers.

Generic answers that did not address the headings asked or omitted specific details of the investigations and rationale were unsuccessful. To improve the answers, familiarity with the Glossary of terms using compare and contrast to state how the aetiology and clinical features are different between the two pathologies.


Question 29 from the first paper of 2015 was actually about SIADH and cerebral salt wasting, rather than diabetes insipidus. Still, it's all sodium, innit. The historical SAQs interrogating the trainee's understanding of DI were Question 5.2 from the first paper of 2018 and Question 17 from the first paper of 2018, in both of which investigations and management were expected. This "compare and contrast" question does work best as a table, and the examiners specifically asked you to tabulate your answer and gave you the headings, so there's probably no excuse for failing to use that structure:

Heading Central DI Nephrogenic DI
  • Inadequate release of vasopressin
  • Inadequate renal response to vasopressin
  • Stroke or ICH (eg. SAH, pituitary apoplexy)
  • Meningitis
  • Neoplasm (eg. mets or pituitary adenoma)
  • Trauma (eg. TBI, base of skull fracture)
  • Gestational (placental vasopressinase)
  • Idiopathic congenital and autoimmune forms account for ~ 50%
  • Drug-induced:
    • Lithium
    • Foscarnet
    • Clozapine
    • Amphotericin
  • Congenital (eg. aquaporin-2 gene mutation)
  • Post-obstructive
  • Hypercalcemia
  • Hypokalemia
  • Polydipsia
  • Polyuria
  • Hypernatremia
  • Plus whatever features are characteristic of the primary pathology (eg. the diplopia of a pituitary adenoma)

Diagnosis of DI:

  • Paired serum and urine osmolality (urine expected to be low, serum expected to be high)
  • Serum sodium
  • Water deprivation test, or the alternative hypertonic saline infusion test (to exclude primary polydipsia)

Discrimination between different causes of DI:

  • Measurement of plasma vasopressin (depressed in central DI)
  • Measurement of plasma copeptin (depressed in central DI)
  • DDAVP challenge (no effect in nephrogenic DI)
  • DDAVP (desmopressin) IV, s/c, orally, or intranasally
  • Free water or 5% dextrose to correct water deficit
  • Cease causative drug
  • Low sodium diet
  • Thiazide diuretics
  • Amiloride
  • Indomethacin


Makaryus, Amgad N., and Samy I. McFarlane. "Diabetes insipidus: diagnosis and treatment of a complex disease." Cleveland Clinic journal of medicine 73.1 (2006): 65.

Bendz, Hans, and Mattias Aurell. "Drug-induced diabetes insipidus: incidence, prevention and management." Drug safety 21.6 (1999): 449-456.

Christ-Crain, Mirjam, et al. "Diabetes insipidus." Nature reviews Disease primers 5.1 (2019): 54.

Pivonello, Rosario, et al. "Central diabetes insipidus and autoimmunity: relationship between the occurrence of antibodies to arginine vasopressin-secreting cells and clinical, immunological, and radiological features in a large cohort of patients with central diabetes insipidus of known and unknown etiology." The Journal of Clinical Endocrinology & Metabolism 88.4 (2003): 1629-1636.

Ananthakrishnan, Sonia. "Gestational diabetes insipidus: diagnosis and management." Best Practice & Research Clinical Endocrinology & Metabolism 34.5 (2020): 101384.

Khositseth, Sookkasem, et al. "Hypercalcemia induces targeted autophagic degradation of aquaporin-2 at the onset of nephrogenic diabetes insipidus.Kidney international 91.5 (2017): 1070-1087.

Khositseth, Sookkasem, et al. "Autophagic degradation of aquaporin-2 is an early event in hypokalemia-induced nephrogenic diabetes insipidus." Scientific reports 5.1 (2015): 18311.