This document provides information about diabetes insipidus (DI), including its history, signs and symptoms, diagnostic workup, pathophysiology, types, and treatment. DI is characterized by excessive thirst and urination of large volumes of diluted urine. The most common type is central DI, caused by a deficiency of arginine vasopressin (ADH). Diagnostic workup involves tests of urine and blood osmolality and ADH levels. Central DI results from lack of ADH production in the brain, while nephrogenic DI involves kidney insensitivity to ADH due to issues with aquaporin channels. Treatment depends on the type, with desmopressin used to treat central DI and th

1. Diabetes Insipidus.
Valmiki K. Seecheran | Year V MBBS Student
University of the West Indies, Cave Hill Campus.
Dr. Krishnamurthy |PICU | Senior Pediatric Clerkship.
April 24th 2014.

2. History.
• ‘Diabainein’(Greek) which means, go through/
siphon.
– 16th century the word precipitated into ‘Diabetes’.
• ‘Insipidus’ comes from the French word
‘insipide’ which thereby means tasteless.
– This is because D.I has no glycosuria ( excretion of
glucose into urine).

3. Objectives.
• To understand signs and symptoms.
• To understand the work-up investigations.
• To understand the pathophysiology.
• To understand the various types of D.I.
• To understand management and treatment.

4. Introduction | DI.
• Characterized by:
– Excessive thirst.
– Excretion of large amounts of severely diluted urine.
– Reduction of fluid intake has no effect on the
concentration of urine.
• Various types of DI:
– Most common type is Central DI.
• Deficiency of Arginine Vasopressin (ADH).
– 2nd type is Nephrogenic DI.
• Kidneys insensitive to ADH.

5. Signs & Symptoms.
• Excessive urination and thirst.
• Interferes with appetite, eating, weight gain
and growth.
• Dehydration and hypokalaemia.

6. Work up.
• 24 hour urine collection.
• Serum electrolytes and glucose.
• Plasma and Urine Osmolality.
• Plasma ADH levels.
• Anticipatory results
– Hypernatremia .
– Urinalysis shows dilute urine with low specific
gravity.
– Urine osmolarity levels are low.

7. Work up.
• Fluid deprivation test. (Miller-Moses test)
– Excessive intake of fluid (primary polydipsia).
• Urine osmolality should increase and stabilize at above 280
Osm/kg with fluid restriction, while a stabilization at a lower
level indicates DI.
– Defect in ADH production.
• Desmopressin stimulation. Patient consumes water only
when thirsty, this can lead to sudden fluid accumulation.
• If the Desmopressin reduces urine output and increases
urine osmolarity, ADH production was deficient.
• MRI + testing of other hormones of pituitary.
– Defect in kidney’s response to ADH.
• Renal pathology.

8. Physiology.
• Hypothalamus.
– regulation of urine production. Also produces
ADH in supra-optic and para-ventricular nuclei.
– In addition, sensation of thirst is regulated in the
ventromedial nucleus by sensing increases in
serum osmolarity and relaying this information to
the cortex.
• ADH is transported to posterior lobe of
pituitary gland.

9. Physiology.
• ADH increases water permeability in collecting
ducts and distal convoluted tubules.
• Aquaporin (2)
• ADH binds to G-protein coupled receptors
increasing cyclic AMP and couples with protein
kinase A stimulating translocation of aquaporin in
distal convoluted tubules and distal tubules.
• The transcribed channels allow water into
collecting duct cells.
• Increase in permeability for reabsorption
increases concentration of urine.

10. Pathophysiology.
• Neurogenic/central DI.
– Lack of vasopressin production in brain.
– Vasopressin acts to increase intravascular volume and
decrease urine output.
– Low ADH causes increase urine production and
volume depletion.
• 25% of cases are idiopathic.
• 20% of cases are benign suprasellar tumours.
• 17% of cases are due to trauma.
• 10% of cases are due to neurosurgery.

11. Pathophysiology.
• Nephrogenic .
– Lack of Aquaporin channels in the distal collecting duct
(decreased surface expression and transcription).
– As a result, kidney is insensitive to vasopressin.
• Major causes
– Hereditary.
• AVPR2 – malfunction of vasopressin receptor.
• AQP2 – malfunction of aquaporin.
– Osmotic.
• Hypokalaemia.
• Renal cystic disease.
– Acquired.
• Lithium toxicity.
• Hypercalcemia.

12. Classification.
• Neurogenic.
• Nephrogenic.
• Dipsogenic*
– Defect in thirst mechanism. Results in increased
fluid intake that suppresses vasopressin secretion
and increases urine output.
• Gestational*
– Women produce vasopressinase in the placenta
which breaks down ADH.

13. Treatment.
• Nephrogenic.
– Treat underlying medical aetiology and replace free water deficit.
– Hydrochlorothiazide – create mild hypervolemia to encourage salt and
water uptake in proximal tubule. Combined with amiloride to prevent
hypokalaemia.
– Thiazide diuretic will decrease DCT reabsorption of sodium and water.
Subsequently decreases plasma volume and thus lowers GFR and
hence augments absorption of sodium and water in proximal nephron.
Less fluid reaches the distal nephron so overall fluid conservation is
obtained.
• Central DI.
– Desmopressin.
• Intranasal.
• Oral tablets.

14. Thank you.