25 ,

.
.
CC: 10 years PTA

PI:
10 years PTA
1112 5
5

2

5 years PTA

2-3 kg

PH:





Menarche 12 2-3
/ 3 pads/ 7-10
9


12

PH:

/ ,

53 65 kg 3
3,800

PH:

2 /
50

Physical examination:
GA: A Thai young female patient, well cooperative
BW 64.7 kg, Height 155.5 cm, BMI 27 kg/m2
V/S: BP 110/70 mmHg
PR 74/min, regular
RR 18/min
BT 37 C
HEENT: not pale conjunctiva, anicteric sclera,
no dry lip, no dry oral mucosa
thyroid gland normal, soft consistency
LN: no cervical, axillary, inguinal lymphadenopathy
Chest:
no palpable breast mass,
no nipple discharge

Physical examination:
Lungs:
Heart:

no adventitious sounds
apical beat at lt. 5th ICS,MCL,
no heaves, no thrills,
normal S1S2, no murmurs
Abdomen: no truncal obesity, soft, not
tender, no hepatosplenomegaly,
no abdominal mass
Extremities: no edema

Physical examination:
Skin: no skin lesions, hirsutism at back,
lower abdomen, thigh
Neurological exam:
good consciousness, good orientation
pupils 3 mm, BRTL, No VF defect,
full EOM, CN-intact
motor power grade V all
DTR 2+, no delayed relaxation phase

Problem list

Polyuria

Approach To Polyuria
Water diuresis
Excessive water intake

Solute diuresis
Abnormal ADH
secretion

Inappropriate quantity
Of ADH

Primary polydipsia

Central DI

Inappropriate qualtity
Of ADH

Nephrogenic DI

Approach To Polyuria
Solute diuresis
Organic solute
Glucose
Urea
Mannitol
Radiocontrast media

Salt diuresis
Drugs: Diuretics
NaCl load
Recovery from acute renal failure,
obstructive uropathy,
kidney transplantation

Primary polydipsia

Central DI

Nephrogenic DI

More

Abrupt onset
Persistent thirst

Insidious onset
Polyuria at daytime

throughout the day

and night associated
with a desire for
cold liquids
Polyuria at daytime
and night
Water intake and
urine output: stable
and large amounts

and night
Water intake and
urine output: stable,
but not more than 5
liters/day due to partial
defect

High/normal ECF
Physical
examination

Low

Low

Lab

PNa > 140 mEq/L

Plasma ADH: low

History

commonly is
associated with
psychiatric syndromes
May also be
produced by drugs that
cause a dry mouth
Insidious onset
Polyuria at daytime
Water intake and
urine output tend to
fluctuate widely

PNa < 140 mEq/L

Plasma ADH: low

ECF

Brenner: Brenner & Rector's The Kidney, 8th ed.

ECF

PNa > 140 mEq/L

Plasma ADH: high

J Clin Endocrinol Metab 1987; 65:561-567.

Investigations

Investigation
UA
Color:
colorless
Specific gravity:
1.003
pH:
6.5
Glucose:
negative
Protein:
negative
Ketone:
negative
WBC/HPF
3-5
RBC/HPF
0-1
Squamous Epi/HPF
2-3

Investigation
Blood
Glucose
Sodium
Potassium
Chloride
Bicarbonate
Calcium
Phosphate
Albumin

=
=
=
=
=
=
=
=

95 mg/dL (60-110)
151 mEq/L (135-150)
4 mEq/L
(3.5-5)
103 mEq/L (95-105)
28.5 mEq/L (20-30)
9.5 mg/dL (9-11)
4.1 mg/dL (2.5-4.8)
4.6 g/dL
(3.8-5)

Investigation
24 hour- urine

Volume = 11,500 ml

Investigation
Blood

Spot urine

Sodium = 146 mEq/L

Urine Na = 40 mEq/L

Plasma osmolality
= 296 mOsm/kg H2O

Urine osmolality
= 150 mOsm/kg H2O

Investigation
Blood

Spot urine

Urine osmolality = 150 mOsm/kg H2O

Sodium = 151
mEq/L

Urine Na = 40
mEq/L

Uosm/Posm = <0.5

Plasma osmolality
= 309 mOsm/kg
H2O

Urine osmolality
= 150 mOsm/kg
H2O

Approach To Polyuria
Urine volume
> 3,000 ml/24 hours
> 2-4 ml/kg/hour
Uosm/Posm < 0.9
Pure water diuresis

Combined watersolute diuresis

24-hr solute excretion

< 15 mOsm/kg BW/day
Cosm < 3 ml/min
FE osm < 3%
Water deprivation test

Uosm/Posm 0.9
Pure solute diuresis

Type of solute

Brenner: Brenner & Rector's The Kidney, 8th ed.

24 hr-solute excretion
=
Uosm x urine volume (liters)
BW (kg)
Cosm
=
Osmolal clearance
=
Uosm x urine volume
Posm x 1440

FEosm

=
=

Fractional excretion of osmolal

Uosm/Posm x 100
UCr/PCr
Brenner: Brenner & Rector's The Kidney, 8th ed.

Solute diuresis
< 0.4
Organic solute
Urine osmolal gap
< 200
Urea diuresis
> 200
Radiocontrast
Mannitol
Glucose
Urine pH < 7
Drug anions
Ketonuria

2 (UNa + UK)
Uosm

> 0.6
Electrolyte diuresis

Major anion ?
UNa+ UK >> UCl

Urine pH > 8
Bicarbonaturia

UNa+ UK UCl
Diuretics
NaCl load
Recovery from ARF,
Obstructive uropathy,
Kidney transplantation
Loss of medullary
hypertonicity
Brenner: Brenner & Rector's The Kidney, 8th ed.

Further investigations ?

15.15
dDAVP 1 ug sc

Time

10.15

11.15

12.15

13.15

16.15

osmolarity
Urine

150

140

138

166

291

osmolarity
BW

63.2

62.8

62.5

62.3

62.1

Serum

296

299

310

% change
= 75.30

Water deprivation test

INDICATION
Differential

diagnosis of Polyuria

Central Diabetes Insipidus (CDI)

Nephrogenic Diabetes Insipidus (NDI)
Primary Polydipsia (PP)

The Scientific Advisory Committee of the Diabetes Insipidus Foundation, Inc.

CONTRAINDICATIONS

Other causes of polyuria

Diuretics
Hypercalcaemia, hypokalaemia
Anterior pituitary hormone deficiency

Renal insufficiency
Uncontrolled diabetes mellitus
Hypovolemia of any cause
Uncorrected deficiency of adrenal or thyroid
hormone.

The Scientific Advisory Committee of the Diabetes Insipidus Foundation, Inc.

SIDE EFFECTS
Risk

of excessive dehydration
True CDI or NDI

The Scientific Advisory Committee of the Diabetes Insipidus Foundation, Inc.

Procedure
1. Initiation depends on the severity of the DI
routine cases, NPO after dinner,
Severe polyuria and polydipsia, NPO 6 AM
2. Start of the test
Plasma osmolality, Plasma AVP level, Serum electrolytes,
Urine osmolality
3. Measure urine volume and osmolality hourly or with each voided urine
4. Stop the test when
Body weight decreases by 3%,
Orthostatic blood pressure changes,
Urine osmolality reaches a plateau (i.e., <10% change over two or
three consecutive measurements)
Serum Na+ >145 mmol /L.

Brenner: Brenner and Rector's The Kidney, 8th ed. 2007

Procedure
5. End of the test
Plasma, plasma AVP, Serum electrolytes
Urine osmolality

6. When stop If

Plasma Na+ <146 mmol/L

Plasma osmolality <300 mOsm/kg
Infusion of hypertonic saline (3% NaCl at a rate of 0.1

ml/kg/min for 12 hr) to reach these endpoints

7. AVP (5 U) or dDAVP (1 g) SC and continue

following urine osmolality and volume for an
additional 2 h
Brenner: Brenner and Rector's The Kidney, 8th ed. 2007

Interpretation
1. Urine osmolality after dDAVP
>50% increase Central DI (CDI)
<10% increase Nephrogenic DI (NDI)

Primary polydipsia (PP).

2. DDx.
NDI and PP
10%50% increase
Relation between

Plasma AVP levels and Plasma osmolality

Plasma AVP levels and Urine osmolality

Brenner: Brenner and Rector's The Kidney, 8th ed. 2007

Brenner: Brenner and Rector's The Kidney, 8th ed. 2007

Cause of central diabetes

insipidus in this patient?

Central DI

Hereditary
Familial
Wolfram's syndrome

Drug/toxin-induced
Granulomatous

Histiocytosis X, Sarcoidosis

Neoplastic

Primary: craniopharyngioma, germinoma, lymphoma,

leukemia, meningioma, pituitary tumor

Secondary: metastases most often due to lung
cancer

Brenner: Brenner & Rector's The Kidney, 7th ed.

Central DI
Infectious

(meningitis, tuberculosis,
encephalitis)
Trauma (neurosurgery, deceleration
injury)
Vascular (cerebral hemorrhage/infarction,
brain death)
Inflammatory/autoimmune (lymphocytic
infundibuloneurohypophysitis)
Idiopathic
Brenner: Brenner & Rector's The Kidney, 7th ed.

Differential Diagnosis
Inflammatory/autoimmune

(lymphocytic
infundibuloneurohypophysitis)
Intracranial tumors: Craniopharyngioma,
Germinoma
Idiopathic

Neurohypophysis 3 parts
1. Magnocellular neurons: paired
supraoptic nuclei (SON),paired
paraventricular nuclei(PVN)
2. Supraopticneurohypophyseal tract
3. Posterior pituitary : neurosecretary
granules,membrane-bound packets of
hormones stored
Blood supply from inferior
hypophyseal artery and artery of the
trabecula( a branch of superior
hypophyseal artery

SCN

William textbook of Endocrinology

Vasopressin
Supraoptic

nucleus 80%-90% of neurons producing

vasopressin
Paraventriculer nucleus (PVN)
Parvocellular divisions producing CRH,TRH and
Somatostatinmedian eminence,brain
stem,spinal cord
Suprachiasmatic nucleus also synthesized
vasopressin

William textbook of

Action of AVP

V1 receptor
1.Vascular smooth muscle vasoconstriction
2. Platelet enhance adhesion
3. Liver glycogenolysis
4. CNS neurotransmitter,neuromodulator , role unclear

V2 receptor
1.Collecting tubule, TAL: basolateral membrane
2.Endothelial : release VWF, vasodilation

V3 receptor : anterior pituitary corticotrope ACTH

Endocrinology 5th edition Leslie J. DeGroot et. al.

Chemical structures
9-amino acid

1-deamino-8-D-arginine vasopressin.

Two-amino acid substitute of AVP that

has potent antidiuretic activity but no
vasopressor activity

William textbook of

Regulation of Vasopressin release

Osmoregulation
- Infusion hypertonic saline(855 mmol/l):increase
plasma AVP at plasma osmolarity = 284 mOsm/kg
- Primary osmoreceptors cells in OVLT, anterior
hypothalamus
- Very sensitive : small increase 1% increase
vasopressin level

Pressure and volume regulations

- Baroreceptors : carotid sinus,aortic arch via IX,X
- Less sensitive : require 10-15% change to stimulus
release of vasopressin

William textbook of

Renal effect

Basolateral

Apical

Water resorption
Loop of Henle ,CCT

V2 Receptor

Principle cell of collecting duct

aquaporin shift to apical
membrane facilitate water
reabsorbtion by osmotic
gradient depend on
hypertonic medullary
interstitium

Medullary interstitial
blood vvs (vasa recta)
High osmolarity
Journal of the American College of Cardiology, Volume 48, Issue 12, Pages 2397-2409

Diabetes insipidus
Disorder

of a large volume of urine (diabetes)

that is hypotonic,dilute and tasteless (insipid)

AVP

disturbances in production or action of the

hormone,manifest as clinical problems in sodium
and water balance

Urine

>40ml/kg/day in adults
>100 ml/kg/day in infants
William textbook of

Four mechanisms AVP produce large

volumes of dilute urine and polydipsia

Hypothalamic(central or neurohypophyseal) DI with inability to

secrete and usually to synthesize vasopressin in the
neurohypophyseal system

Nephrogenic DI wherein there is an in appropriate renal response

to vasopressin

Transient diabetes insipidus of pregnancy produced by the

accelerated metabolism of vasopressin

Primary polydipsia wherein the initial pathophysiology is the

ingestion of fluid rather than the excretion of fluid

William textbook of Endocrinology,1