Diabetes insipidus either from: Vasopressin deficiency (central) Vasopressin insensitivity in kidney (nephrogenic)

1. Presented by:
Anish Dhakal

2. Diabetes Insipidus
• Manifests with polyuria and polydipsia
• Can result from either
– Vasopressin deficiency (central)
– Vasopressin insensitivity in kidney (nephrogenic)

4. Classification
• Central DI
Genetic defects
Malformations: septo- optic dysplasia,
holoprosencephaly, anencephaly
Neurological insults: Head trauma, neurosurgery,
infection , brain death
Infiltrative disorders: sarcoidosis, histiocytosis
CNS Tumors : Craniopharyngioma, germinoma,
pinealoma

5. • Nephrogenic DI
Genetic : 90% X-linked recessive & 10% autosomal
recessive and dominant
Acquired : Hypokalemia, hypercalcemia,
obstructive uropathy, nephrocalcinosis

6. Clinical features
• Polyuria
– Nocturia and urine output suggest it
– Urine output > 2L/m2 /day or 5ml/kg/hr suggests
polyuria
• Polydipsia

7. Signs in Infants:
• Crying
• Irritability
• Growth retardation
• Hyperthermia
• Weight loss
• failure to thrive

8. Signs in children:
• Enuresis
• Anorexia
• Growth defects
• Fatigability

9. • Acquired form
– Present later in life
– Hypernatremia and
polyuria
– Developmental delay and
behavioral abnormalities
are less common
• Congenital NDI
– Massive polyuria
– Volume depletion
– Hypernatremia
– Hyperthermia
– Irritability and crying
– Constipation, Poor weight gain
– Developmental delay and mental
retardation
– Enuresis
– Diminished appetite and poor food
intake
– Hyperactivity and short-term memory
problems
Clinical features
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10. Investigations
• Initial investigations :
– Urine sugar and early morning specific gravity or
osmolality.
– Blood gas , urea, electrolytes calcium and
creatinine
• High plasma osmolality (> 300mOsm/kg or
serum sodium > 146 mmol/L) and low urine
osmolality (< 300 mOsm /kg, urine specific
gravity < 1.005 ) suggests DI

11. • Normal plasma osmolality and low urine
osmolality ( < 800 mOsm/kg ) should undergo
water deprivation test.
• Urine osmolality > 800 mOsm/kg ( specific
gravity > 1.010) excludes DI
• MRI of Hypothalamic- pituitary region and
Anterior pituitary
• Renal imaging and serum electrolytes

12. • Indicated when
– Child with polyuria, low urinary osmolality and normal plasma osmolality
• Renal failure and Renal tubular acidosis should be excluded before test
• Principle
– Is to restrict the water intake of the polyuric patient until serum sodium has risen
sufficiently to cause endogenous release of ADH
• ↑ the plasma osmolality > 300mOsm/kg to allow for maximum renal
concentration
– If the urine osmolality increase to a normal high value the cause of polyuria is
Polydipsia
– If there is no response either CDI or NDI
• Child weighed and target weight loss calculated i.e. 5% of total body weight
Water Deprivation Test
12

13. • Start water deprivation early in morning
• Stopped when
a. Urine osmolality ↑ > 700mOsm/kg (or specific gravity >
1.010) excludes DI
b. Plasma osmolality ↑ > 300mOsm/kg (or serum sodium
above 145 mmol/l) Target achieved
c. Weight loss > 5% ( risk of dehydration)
• Body weight, urine output, urine & blood osmolality monitored
hourly
 Plasma osmolality rises above normal i.e. > 300 mOsm/kg with
urine osmolality < 300 mOsm/kg with  Diagnostic of DI (Need
vasopressin response test)
 Plasma osmolality > 300 mOsm/kg with urine osmolality
between 300-700mOsm/kg Partial central or nephrogenic DI

14. Vasopressin response test
• To differentiate complete central DI from
Nephrogenic DI
• Urine osmolality is measured one and four
hour after vasopressin injection.
• Increase in urine osmolality by more than 50%
of baseline levels : Diagnostic of central DI
• Lower increase suggests: Nephrogenic DI

15. Management of Central DI
• Fluid Therapy
– If intact thirst mechanism, free access to fluid
– Can maintain plasma osmolality and sodium in
although at great inconvenience
– Neonates and young infants best treated solely
with fluid therapy (3 L/m2/24 hr of nutritive fluid)
– Use of vasopressin analogs in obligate high fluid
intaker is difficult (risk of hyponatremia)

16. Management of Central DI
• Vasopressin Analogs (DDAVP)
– Best treatment in older children
– Available in intranasal preparation and as tablets
– Intranasal (2.5 -10mg 12 hrly) administered by
rhinal tube (allowing dose titration) or by nasal
spray.
– Oral tablets (50-200 µg 12 hrly)
– One urine output before giving next dose to
prevent the fluid overload

17. • Aqueous Vasopressin
– Acute onset following neurosurgery best managed
with continuous infusion of synthetic aqueous
vasopressin
– Total fluid intake limited to 1 L/m2/24 hr during
antidiuresis
– Dosage 1.5 mU/kg/hr IV (results in blood
vasopressin concentration of 10 pg /mL)
Contd..
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18. • Maintenance of adequate fluid intake &
access to free water
• Minimizing urine output by limiting solute
load with a low osmolar, low sodium diet
– Na intake in older pts 0.7 mEq/kg/24hr
Treatment of Nephrogenic DI
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19. • Removal of offending drugs or pathology
• Ensure intake of adequate calories and avoid
severe dehydration
– Foods with the highest ratio of caloric content to
osmotic load (Na <1 mmol/kg/24 hr)
Contd..

20. • Administering medications directed at ↓ ing urine output
• Thiazide diuretics
– Hydrochlorthiazide 2-3mg/kg/24hr
– Induce Na loss & stimulate proximal tubule reabsorption of water
– Paradoxical effect (↓ed delivery of free water to collecting ducts
and distal tubules)
• K+ sparing diuretics
– Amiloride 0.3 mg/kg/24 hr in 3 divided dose
• If inadequate response to diuretics add Indomethacin
2mg/kg/24 hr
– Additive effect in reducing water excretion
– Monitor renal function deterioration of renal fxn over time
Contd..

21. Nelson Textbook of Pediatrics, 20th edition
Ghai Essential Pediatrics, 8th edition
B. Daniel, Evaluation of patients with Polyuria,
https://www.uptodate.com/contents/evaluation-
of-patients-with-polyuria?search=diabetes
S. Richard, Clinical manifestations and causes of
central diabetes insipidus,
https://www.uptodate.com/contents/clinical-
manifestations-and-causes-of-central-diabetes-
insipidus
•