1. Diabetes insipidus is a disorder caused by a deficiency of anti-diuretic hormone (ADH) or a failure of the kidneys to respond to ADH, resulting in the excessive production of dilute urine. 2. Central diabetes insipidus is caused by a failure of the pituitary gland to secrete adequate ADH, while nephrogenic diabetes insipidus results from the kidneys' failure to respond to circulating ADH. 3. The standard treatment is desmopressin (DDAVP), a synthetic analog of ADH, which is given intranasally and has a longer duration of action than natural ADH.

1. DIABETES INSIPIDUS
Dr. Abdelaziz Elamin
MD, PhD, FRCPCH
Professor of Child Health
consultant pediatric
endocrinologist
Sultan Qaboos University
Muscat, Oman.
azizmin@hotmail.com

2. DIABETES INSIPIDUS
 DI is a disorder resulting from deficiency of
anti-diuretic hormone (ADH) or its action and
is characterized by the passage of copious
amounts of dilute urine.
 It must be differentiated from other polyuric
states such as primary polydipsia & osmotic
duiresis. Central DI is due to failure of the
pituitary gland to secrete adequate ADH.

3. DIABETES INSIPIDUS /2
 Nephrogenic DI results when the renal
tubules of the kidneys fail to respond to
circulating ADH.
 The resulting renal concentration defect
leads to the loss of large volumes of
dilute urine. This causes cellular and
extracellular dehydration and
hypernatremia.

4. THE POSTERIOR PITUITARY
 Is composed of nerve fibers that have their
cell bodies in the supraoptic &
paraventricular nuclei of the hypothalamus.
 The neurosecretory cells in these nuclei
synthesize Oxytocin & Vasopressin which
pass down the nerve fibres to be stored in
& released from the posterior pituitary.

5. REGULATION OF ADH SECRETION
 ADH RELEASE IS STIMULATED BY:
 A PLASMA OSMOLALITY >280 mOsm/l
 A FALL IN PLASMA VOLUME
 EMOTIONAL FACTORS & STRESS
 SLEEP
 OTHER FACTORS

6. Other ADH Stimulants
CHOLINERGIC STIMULATION
a-ADRENERGIC STIMULATION
ANGIOTENSIN II
PROSTAGLANDIN E
OPIATES
NICOTINE
HISTAMINE
ETHER
PHENOBARBITONE

7. ADH SECRETION IS INHIBITED BY:
 ALCOHOL
 OROPHARYNGEAL WATER REFLEX
 b-DRENERGIC STIMULANTS
 ATRIAL NATRIURETIC FACTOR (ANF)
 PHENYTOIN

8. ADH
 THE SUPRAOPTIC NUCLEUS (SON) IS
RESPONSIBLE PREDOMINANTLY FOR
THE SYNTHESIS OF VASOPRESSIN
WHICH IS THE ADH.
 THE CLOSE STRUCTURAL SIMILARITY
OF VASOPRESSIN & OXYTOCIN
EXPLAINS THE OVERLAP OF THEIR
BIOLOGICAL ACTIONS.

9. ADH (2)
 ADH IS AN OCTAPEPTIDE LIKE OXYTOCIN.
 THE ARGININE VASOPRESSIN IS ADH IN
MAN AND OTHER MAMMALS APART FROM
THE PIG & THE HIPPOPOTAMUS WHERE
LYSINE VASOPRESSIN IS THE ADH.

10. FUNCTION OF ADH
 PRIMARY EFFECT OF ADH IS ON THE CELLS OF THE
DISTAL TUBULES & COLLECTING DUCTS OF THE
KIDNEY PROMOTING REABSORPTION OF WATER.
 THIS ACTION IS MEDIATED VIA V2-RECEPTORS
THROUGH ACTIVATION OF cAMP AND FORMATION
OF A SPECIFIC PROTEIN KNOWN AS AQUAPORIN.

11. Actions of ADH (2)
 Beside water, AVP enhances reabsorption of urea
increasing tonicity of the renal medulla allowing
more water to be re-absorbed.
 Acting on v1-receptors in peripheral vessels AVP
causes vaso-constriction & BP. Normally this is
balanced by its inhibitory effect on sympathetic
cardiac stimuli causing bradycardia

12. Actions of ADH (3)
 DURING HYPOVOLEMIA HIGH PLASMA
LEVELS OF AVP HELP MAINTAIN
TISSUE PERFUSSION.
 A LESSER SECONDARY EFFECT THAT IS
MEDIATED VIA V2 NON-RENAL
RECEPTORS IS STIMULATION OF
SYNTHESIS & RELEASE OF FACTOR VIII
& VON WILLEBRAND FACTOR.

13. CAUSES OF CENTRAL DI
 IDIOPATHIC (30% OF CASES)
 SUPRASELLAR TUMOURS (30% OF CASES)
 INFECTIONS (ENCEPHALITIS, TB, etc)
 NON-INFECTIOUS GRANULOMA (SARCOID,
HAND-SCHULLER CHRISTIAN DISEASE
 TRAUMA OR SKULL SURGERY
 LEUKAEMIA

14. CAUSES OF CENTRAL DI (2)
 AUTOIMMUNE ASSOCIATED WITH THYROIDITIS
 FAMILIAL: 2 TYPES AD & X-LINKED
INHERITANCE
 WOLFRAM SYNDROME (ALSO KNOWN AS
DIDMOAD SYNDROME) CHARACTERIZED BY DI,
DM, NERVE DEAFNESS AND OPTIC ATROPHY.

15. CAUSES OF NEPHROGENIC DI
 PRIMARY FAMILIAL: X-LINKED RECESSIVE
THAT IS SEVERE IN BOYS & MILD IN GIRLS
 SECONDARY TO:
 CHRONIC PYELONEPHRITIS
 HYPOKALEMIA
 HYPERCALCEMIA
 SICKLE CELL DISEASE
 PROTEIN DEPRIVATION

16. CAUSES OF NEPHROGENIC DI/2
 SECONDARY CAUSES continued:
 AMYLOIDOSIS
 OTHER RENAL DISEASES (chronic renal failure,
obstructive uropathy, polycystic disease)
 SJOGREN SYNDROME
 DRUGS (Lithium, Colchicine, Fluoride, Cidofovir,
Demeclocycline, Methoyflurane)

17. CLINICAL FEATURES
 POLYURIA, POLYDIPSIA & THIRST
 NOCTURIA OR NOCTURNAL ENURESIS
 HYPERNATREMIC DEHYDRATION
 ANOREXIA, CONSTIPATION & FTT
 HYPERTHERMIA & LACK OF SWEATING
 SYMPTOMS OF UNDERLYING CAUSE

18. COMPLICATIONS
 HYPERNATREMIC DEHYDRATION & ITS
NEUROLOGICAL SEQUELEA
 GROWTH RETARDATION
 HYDRONEPHROSIS (DUE TO EXCESSIVE
URINE OUTPUT)

19. DIAGNOSTIC WORKUP
• CAREFUL HISTORY & EXAMINATION
DOCUMENT PRESENCE OF POLYURIA
(USUALLY 4-15 L/24h)
 PRACTICALLY SMILTANEOUS
MEASUREMENT OF PLASMA & URINE
OSMOLALTY ESTABLISH THE DIAGNOSIS
IN MOST CHILDREN WITH SEVERE DI
MAKING A WATER DEPRIVATION TEST
UNNECESSARY

20. DIAGNOSTIC WORKUP (2)
 URINALYSIS & MICROSCOPY TOGETHER
WITH PLASMA ELECTROLYTES HELP
EXCLUDE MOST OF THE CAUSES OF
POLYURIA
 IN A NORMAL WELL HYDRATED SUBJECT
PLASMA OSMOLALITY IS <290 mOsml/l AND
URINE OSMOLALITY IS 300-450 mOsmol/l

21. DIAGNOSTIC WORKUP (3)
 IN PATIENTS WITH DI & FREE EXCESS
TO WATER PLASMA OSMOLALITY IS
>295 mOsmol/l & URINE OSOLALITY IS
50-150 mOsmol/l.
 IN PATIENTS WITH DI & FREE EXCESS
TO WATER PLASMA OSMOLALITY IS
>295 mOsmol/l & URINE OSOLALITY IS
50-150 mOsmol/l.

22. WATER DEPRIVATION TEST
 WATER DEPRIVATION TEST IS NEEDED
FOR PATIENTS WITH PARTIAL AVP
DEFICIENCY & ALSO TO
DIFFERENTIATE DI FROM PRIMARY
POLYDIPSIA WHICH IS VERY RARE IN
CHILDREN

23. WATER DEPRIVATION TEST (2)
 SHOULD BE DONE IN THE MORNING UNDER
OBSERVATION
 8 HOURS FAST IS ENOUGH FOR CHILDREN
 WEIGH THE CHILD HOURLY AND MEASURE
PLASMA & URINE OSMOLALITY EVERY 2 HOURS
 IN NORMAL SUBJECTS PLASMA OSMOLALITY
HARDLY RISES (< 300) BUT THE URINE OUTPUT IS
REDUCED & ITS OSMOLALITY RISES (800-1200)

24. WATER DEPRIVATION TEST (3)
 PATIENTS WITH PRIMARY POLYDIPSIA
START WITH LOW NORMAL PLASMA
OSMOLALITY (280) BUT URINE/PLASMA
OSMOLALITY RATIO RISES TO >2 AFTER
DEHYDRATION.
 IN PATIENTS WITH DI THE PLASMA BUT NOT
THE URINE OSMOLALITY RISES AND U/P
OSMOLALITY RATIO REMAINS < 1.5

25. WATER DEPRIVATION TEST (4)
 AT THE END OF THE TEST, ADH IS GIVEN
(20 mg DDAVP INTRNASALLY OR 2 mg
I.M.) AND FLUID INTAKE ALLOWED.
 CONCENTRATION OF THE DILUTE URINE
CONFIRMS CENTRAL DI AND FAILURE
SUGGEST NEPHROGENIC CAUSES

26. TREATMENT
 DESMOPRESSIN (DDAVP) A SYNTHETIC
ANALOG IS SUPERIOR TO NATIVE AVP
BECAUSE:
 IT HAS LONGER DURATION OF ACTION (8-
10 h vs 2-3 h)
 MORE POTENT
 ITS ANTIDIURETIC ACTIVITY IS 3000
TIMES GREATER THAN ITS PRESSOR
ACTIVITY

27. DDAVP
 USUALLY GIVEN INTRANASALLY BUT
CAN BE GIVEN ORALLY OR I.M. FOR
COMATOSE PATIENTS OR DURING
SURGERY.
 DDAVP CAN ALSO BE USED IN MILD
HAEMOPHILIA OR VON WILLEBRAND
DISEASE AND AS TREATMENT FOR
NOCTURNAL ENURESIS IN CHILDREN

28. TREATMENT OF NEPHROGENIC DI
 PROVISION OF ADEQUATE FLUIDS &
CALORIE
 LOW SODIUM DIET
 DIURETICS
 HIGH DOSE OF DDAVP
 CORRECTION OF UNDERLYING CAUSE
 DRUGS (Indomethacin, Chlorprooramide,
Clofibrate & Carbamazepine)