DR AMRO

1. DI, SIADH AND CSWS
Amro al tarawneh

2. Similarities – What’s in common?
Central neurogenic diabetes insipidus (CNDI), syndrome of
inappropriate secretion of antidiuretic hormone (SIADH), and
cerebral salt-wasting syndrome (CSWS(
ALL affect both sodium and water balance; however, they
have differences in pathophysiology, diagnosis,
and treatment.

3. Antidiuretic hormone (ADH(
 A polypeptide synthesized
in the supraoptic and
paraventricular nuclei in
the hypothalamus.
 Secretory granules
containing ADH migrate
down into the posterior
lobe of the pituitary,
where they are stored and
released after appropriate
stimuli.

4. Anatomy of pitutary
 Situated in the pituatry fossa
limited anterior , posterior ,
inferior by bony constituents of
sella turcica “ depression in the
body of sphenoid bone “
 Demarcated laterally , superiorly
by reflection of dura and sella
turcica
Don’t injury me ,,, I will flood your
ICU

5. Antidiuretic hormone (ADH(
 ADH increase the
permeability of the renal
distal tubule and
collecting ducts to water
 Less free water is
excreted in urine
 Urine volume is
decreased
 Concentration of urine
is increased

6. Antidiuretic hormone (ADH(

7. Diabetes Insipidus
A hormone disorder that
occurs when the body
doesn’t produce enough
antidiuretic hormone (ADH)
or doesn't use the hormone
effectively “ urinary system
doesn’t responed >>
excretion of excessive
quantities of very dilute, but
otherwise normal urine.

8. Diabetes Insipidus – Types
Types:
1. Central DI, a primary deficiency of ADH
2. Nephrogenic DI, caused by an inappropriate renal
response to ADH
3. Gestational DI , only during pregnancy when enzyme
from placenta destroys ADH in the mother

9. Central DI
 The cause of central diabetes insipidus in adults is
usually damage to the pituitary gland or hypothalamus
 Idiopathic - 30%
 Malignant or benign tumors of the brain or pituitary - 25% “
craniopharyngoma , metastatic carcinoma “
 Cranial surgery - 20% “
 Head trauma - 16% “ skull fracture , hge , concussion “
 Inflammation : meningitis , TB , syphilis
 Vascular : sclerosis , thrombosis of unknown
 Brain infarction , shehan’s syndrome

10. Post Surgical Central DI
 Postsurgical diabetes insipidus results
from inflammatory edema around the
hypothalamus or posterior pituitary
and resolves with resolution of the
edema. It may also be secondary to
damage to the supraoptic and
paraventricular neurons of the
hypothalamus, the pituitary stalk, or
Pituitary Vasculature
 The neurohypophysis is supplied by
the inferior hypophyseal arteries
terminal branches of the
meningohypophyseal trunk, which
arises from the cavernous portion
of the internal carotid artery

11. Diabetes Insipidus - Symptoms
Characterized by:
 Excessive thirst that may be intense or uncontrollable, usually
with the need to drink large amounts of water
 Excessive urine volume That is hypotonic, dilute and tasteless
(insipid) , dehydration .
 Excessive urination, often needing to urinate every hour
throughout the day and night ” nocturia “

12. Central DI - Diagnosis

13. Complication
 Hypernatremia , hyperosmolarity , dehydration
if sufficient water intake or hypotonic iv fluid
not provide .
 Hypokalemia , hypomagnesmia ,
hypophosphatemia .

14. Investigation:
 sample of blood & urine, calcium , plasma
elevated , dynamic test .
 Assement of anterior pitutary function &
suprasellar anatomy .
 Mri “ bright spot in the sella “
How to differnate between central &
nephrogenic by plasma AVPlevels afterwater
deprivation orspontaeous development of
mild hypernatremia .

15. Central DI – Treatments
 Desmopressin is the drug of choice.
 Expectant monitoring by water balance , frequency
meusrement of Na , K , Mg , P then
IV hypotonic solutions (0.45% saline) to replace urine output
to avoid dehydration .
 Tretment of tumor if cause

16. Syndrome of Inappropriate Antidiuretic Hormone
Secretion (SIADH(
 Hyponatremia and hypo-osmolality resulting from
inappropriate, excess secretion or action of ADH despite
normal or increased plasma volume, which results in
impaired water excretion.

17. SIADH – Causes
 Any CNS disorder, including stroke,
hemorrhage (very common in SAH population
& subdural hge ), infection, trauma, and
psychosis .
 Ectopic production of ADH by a tumor is
most often due to a small cell carcinoma of
the lung and is rarely seen with other lung
tumors. Less common causes of malignancy-
associated SIADH include head and neck
cancer, olfactory neuroblastoma
(esthesioneuroblastoma), and
extrapulmonary small cell carcinomas.
 Certain drugs can enhance ADH release or
effect, including chlorpropamide,
carbazapine, oxcarbazepine (a derivative of
carbamazepine), high-dose intravenous
cyclophosphamide, and desmopressin .
 Pulmonary diseases, particularly pneumonia
(viral, bacterial, tuberculous) , abscess, can
lead to the SIADH, although the mechanism
by which this occurs is not clear.

18. SIADH – Pathophysiology
 ADH-induced water retention
 Dilutional hyponatremia
 Volume expansion >> secondary natriuresis (ANP)
 Sodium and water loss
 Result: Euvolemic hyponatremia cause acute cerebral edema
 Reduced serum osmolality
 Increased urine osmolality
 Increased urine sodium
 Brain ECF moves into CSF .

19. SIADH – Symptoms
 serum sodium >125 meq/ml : anorexia, Nausea , vomiting , malasie .
 Further decrease : headache , Muscle Cramps or tremors
Depressed mood or memory impairment
Irritability , seizures , coma .
 Personality changes : combativeness, confusion and hallucinations .
 Symptoms from CNS or pulmonary tumors : hemptysis , chronic
headaches .
 Sever or rapid onset hyponatrima : delirim , muscle cramps ,
hyperreflexia , dysarrthia , chyne-stoke respiration .
 No edema , dry mucous membrane , decrease skin turgor .

20. SIADH – Diagnosis
 Euvolemic hyponatremia <134 mEq/L .
 Serum Osm <275 mOsm/kg .
 Urine osmolality >300 mOsm/kg .
 Urine sodium concentration >40 mEq/L with normal dietary
salt intake .
 Radiological image :
1- chest x-ray for pulmonary causes .
2- CT & MRI .

21. SIADH – Treatment
 Treat the underlying cause, if known ( hormonal replacment in adrenal insuffiency ) .
 Water restriction to about 500-1500 mL/d
 Correct Na+ deficit: no more than 10mEq/L in 24 hours, 18mEq/L in 48 hours
 0.9% NaCl
 3% NaCl
 NaCl enteral tablets – 2-3g TID
 Vasopressin receptor antagonists: inhibition of the AVP V2 receptor reduces the number of
aquaporin-2 water channels in the renal collecting duct and decreases the water
permeability of the collecting duct; There are 2 aquaretics that are currently FDA approved:
• Conivaptan (Vaprisol)
• Tolvaptan
 loop diuretic: usually used in conjunction with normal saline to replenish the Na+ excreted
with the diuresis
 Demeclocycline.
 Prolonged therapy in pt with persistent SIADH .

22. Cerebral Salt Wasting Syndrome (CSWS(
 Cerebral salt-wasting syndrome (CSWS) is a rare endocrine
condition featuring a low blood sodium concentration
‘ hyponatremia ‘ and dehydration ‘ hypovolemic ‘ in
response to trauma/injury or the presence of tumors in or
surrounding the brain.
 Hypernatremia is common electrolyte disorder in the
setting of cns disease & CSWS potential cause of
hyponatremia .

23. CSWS – Causes
Condition leading to CSW include the following:
 Head injury
 Hydrocephalous
 Brain tumor
 Intracranial surgery
 Stroke
 Intracerebral hemorrhage
 Tuberculous meningitis

24. CSWS – Pathophysiology
 Sympathetic Nervous System
Hypothesis: loss of adrenergic tone
to nephron >> decrease in renin
secretion by juxtaglomerular cells,
thereby causing decreased levels of
aldosterone and decreased sodium
reabsorption at PCT.
 Natriuretic Peptide Theory: a
release of natriuretic factors,
possibly including brain natriuretic
peptide (C-type natriuretic peptide)
by the injured brain , which
decreases sodium reabsorption and
inhibits renin.

25. CSWS – Symptoms
 As the decline in serum sodium concentration reduces
serum osmolality, a tonicity gradient develops across the
blood-brain barrier that causes cerebral edema.
 Symptoms include lethargy, agitation, headache, altered consciousness, seizures,
and coma.
 Intravascular volume depletion
 thirst, abrupt weight loss, decreasing urinary frequency, and negative fluid balance.

26. Signs::
 Signs of hyponatremia : altered mental status ,
seuziers , coma .
 Signs of volume depltion :
orthostatic hypotension , Increase capillary refil time ,
Dry mucos membrane , skin turgor , sunken anterior
fontanel

27. CSWS – Diagnosis
 Hyponatremia < 135 meq/L with a low plasma osmolality
 An inappropriately elevated urine osmolality >
100 mosmol/kg and > 300 mosmol/kg)
 A urine sodium concentration > 40 meq/L
 A low serum uric acid concentration due to urate wasting in
the urine

28. CSWS – Treatment
 IV hypertonic saline solutions are employed to correct
intravascular volume depletion and hyponatremia and to
replace ongoing urinary sodium loss.
 Mineralocorticoids enhance sodium reabsorption in the
kidney by direct action on distal tubule cells
 Fludrocortisone

29. Summary
CentralCentral DIDI is associated withis associated with HYPERnatremia,HYPERnatremia,
SIADHSIADH andand CSWSCSWS are associated withare associated with HYPOnatremia.HYPOnatremia.

30. Summary – SIADH vs. CSWS

31. Summary – SIADH vs. CSWS vs. DI
SIADH CSWS DI
Serum Na+
Urine Na+
Serum Osm
Urine Osm

32. Summary – SIADH vs. CSWS vs. DI
SIADH CSWS DI
Urine O/P oliguria polyuria polyuria
CVP normal/high low normal/low
Plasma ADH high normal low
Rx Fluid restrict, give
Na+, Conivaptan,
Demeclocycline
Give volume, give
Na+,
Fludrocortisone
Drink to thirst,
45% saline,
DDAVP
(central), HCTZ
(nephrogenic)