DI, SIADH and Cerebral Salt

Wasting

Mohamad Soud

Similarities – What’s in

common?

Central neurogenic diabetes insipidus (CNDI), syndrome

of inappropriate secretion ofantidiuretic 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.

Antidiuretic hormone (ADH)

Most important

variable is osmotic

pressure of plasma

and ECF. = (2 x serum [Na]) + [glucose,

in mg/dL]/18 + [blood urea nitrogen, in mg/dL]/2.8

Largely a function of the

concentration of Na

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 >> excretion of excessive quantities of very dilute, but otherwise normal urine.

Diabetes Insipidus – Types

Two types:

1. Central DI, a primary deficiency of ADH

2. Nephrogenic DI, caused by an inappropriate renal response to ADH

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%

Cranial surgery - 20%

Head trauma - 16%

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 -

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)

Versus the sweet urine of diabetes mellitus(honey).

Excessive urination, often needing to urinate every hour throughout the day and night.

Central DI - Diagnosis

Central DI – Treatments

Desmopressin is the drug of choice.

IV hypotonic solutions (0.45% saline) to replace urine output.

Syndrome of Inappropriate Antidiuretic

Hormone Secretion (SIADH)

Hyponatremia and hypo-osmolality resulting from inappropriate, continued secretion or action of ADHdespite normal or increased plasma volume, which results in impaired water excretion.

SIADH – Causes

Any CNS disorder, including stroke, hemorrhage (very common in SAH population), infection, trauma, and psychosis can enhance ADH release.

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 selective serotonin reuptake inhibitors.

Pulmonary diseases, particularly pneumonia (viral, bacterial, tuberculous), can lead to the SIADH, although the mechanism by which this occurs is not clear. A similar response may infrequently be seen with asthma, atelectasis, acute respiratory failure, and pneumothorax.

SIADH – Pathophysiology

ADH-induced water retention

Dilutional hyponatremia

Volume expansion >> secondary natriuresis (ANP)

Sodium and water loss

Result: Euvolemic hyponatremia

Reduced serum osmolality

Increased urine osmolality

Increased urine sodium

SIADH – Symptoms

Nausea or vomiting

Cramps or tremors

Depressed mood or memory impairment

Irritability

Personality changes, such as combativeness, confusion, and hallucinations

Seizures

Stupor or coma

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

SIADH – Treatment

Treat the underlying cause, if known 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.

Cerebral Salt Wasting Syndrome

(CSWS)

Cerebral salt-wasting syndrome (CSWS) is a rare endocrine condition featuring a low blood sodiumconcentration and dehydration in response to trauma/injury or the presence of tumors in or surrounding the brain.

CSWS – Causes

Condition leading to CSW include the following:

Head injury

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 reducesserum 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.

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 DI is associated

with HYPERnatremia, whereas

SIADH and CSWS are associated

with 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)