DI, SIADH AND CSWS

Amro al tarawneh

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.

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.

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

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

Antidiuretic hormone (ADH(

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.

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

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

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

Diabetes Insipidus - SymptomsCharacterized 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 “

Central DI - Diagnosis

Complication Hypernatremia , hyperosmolarity , dehydration

if sufficient water intake or hypotonic iv fluid not provide .

Hypokalemia , hypomagnesmia , hypophosphatemia .

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 AVP levels after water deprivation or spontaeous development of mild hypernatremia .

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

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.

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.

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 .

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 .

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 .

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 .

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 .

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

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.

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.

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

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

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 

Summary

Central Central DIDI is associated with is associated with HYPERnatremia, HYPERnatremia,

SIADHSIADH and and CSWSCSWS are associated with are associated with HYPOnatremia.HYPOnatremia.

Summary – SIADH vs. CSWS

Summary – SIADH vs. CSWS vs. DI

SIADH CSWS DI

Serum Na+

Urine Na+

Serum Osm

Urine Osm

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)