DIABETES INSIPIDUS

Dr. Abdelaziz Elamin

MD, PhD, FRCPCH
Professor of Child Health
consultant pediatric
endocrinologist
Sultan Qaboos University
Muscat, Oman.
azizmin@hotmail.com
 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.
 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.
 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.
 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
 Other ADH Stimulants

CHOLINERGIC STIMULATION
a-ADRENERGIC STIMULATION
ANGIOTENSIN II
PROSTAGLANDIN E
OPIATES
NICOTINE
HISTAMINE
ETHER
PHENOBARBITONE
 ADH SECRETION IS INHIBITED BY:

 ALCOHOL
 OROPHARYNGEAL WATER REFLEX
 b-DRENERGIC STIMULANTS
 ATRIAL NATRIURETIC FACTOR (ANF)
 PHENYTOIN
 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.
 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.
 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.
 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
 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.
 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
 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.
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
 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)
 CLINICAL FEATURES

 POLYURIA, POLYDIPSIA & THIRST

 NOCTURIA OR NOCTURNAL ENURESIS
 HYPERNATREMIC DEHYDRATION
 ANOREXIA, CONSTIPATION & FTT
 HYPERTHERMIA & LACK OF SWEATING
 SYMPTOMS OF UNDERLYING CAUSE
 COMPLICATIONS

 HYPERNATREMIC DEHYDRATION & ITS

NEUROLOGICAL SEQUELEA

 GROWTH RETARDATION

 HYDRONEPHROSIS (DUE TO EXCESSIVE

URINE OUTPUT)
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
 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
 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.
 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
 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)
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
 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
 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
 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
 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)