• Inappropriate antidiuretic hormone (ADH) or ADH-like peptide secretion in the presence of low serum sodium, low serum osmolality, and high urine osmolality, but in the absence of renal or adrenal pathology

• Idiopathic
• CNS pathology, causing increased secretion of ADH or ADH-like peptides: meningitis, head trauma, neurosurgical procedures, encephalitis, Guillain-Barré syndrome, brain tumor, brain abscess, hydrocephalus, hypoxia, subarachnoid hemorrhage, cerebral venous thrombosis
• Non-CNS tumor with independent secretion of ADH or ADH-like peptides: bronchogenic carcinoma, pancreatic carcinoma
• Pulmonary disease (leading to secondary elevation in ADH secretion or ADH-like peptides): tuberculosis, pneumonia, asthma, cystic fibrosis, positive-pressure ventilation
• Drugs (which mimic ADH or stimulate its release): vincristine, cyclophosphamide, carbamazepine, chlorpropamide, phenothiazines, clofibrate, nicotine, fluoxetine, sertraline

• ADH is synthesized within neurons of the hypothalamus and stored in the posterior pituitary.
• ADH acts on the renal collecting ducts.
• Interaction of ADH with its receptors forms intracellular cyclic AMP (cAMP).
• cAMP increases water permeability through aquaporins (water channels) of the ducts and consequently reabsorption of free water.

• Direct stimulation of the posterior pituitary (e.g., CNS disorders)
• Independent production of ADH or ADH-like substances from ectopic sources (e.g., oat-cell carcinoma, tuberculosis)
• Decreased venous return that stimulates atrial volume receptors and thereby leads to ADH release (e.g., pulmonary and intrathoracic diseases)

• Based on the primary cause

• Hyponatremic dehydration
• Congestive heart failure
• Adrenal insufficiency
• Cirrhosis
• Nephrotic syndrome
• Renal failure
• Severe potassium depletion
• Water intoxication
• Cerebral salt wasting (CSW): excess production or effects of atrial and/or brain natriuretic peptide hormones
• Hypothyroidism
• Reset hypothalamic osmostat
• Rocky Mountain spotted fever

• Unusual water intake
• Review of intake and output for inpatients
• Changes in urine output
• Anorexia, lethargy
• Weight gain or weight loss
• Renal disease
• Vomiting
• Diarrhea
• Use of diuretics
• Burns
• Heart disease
• Liver disease
• Brain injury: trauma, surgery, hypoxia, toxin

• No signs of dehydration
• Signs of fluid overload
• Lack of edema
• Due to hyponatremia, the patient may be lethargic or irritable with muscle cramps. In severe cases, patients may lose deep tendon reflexes, seize, or be comatose.

• Failure to distinguish SIADH from various forms of salt wasting

• Urinary osmolality and sodium with simultaneous serum osmolality, sodium, and uric acid
• Typically, serum sodium is less than 125 mEq/L, serum osmolality is less than 260 mOsm/L, and serum uric acid is less than 2.4 mg/dL, while simultaneous urinary osmolality is greater than 100 mOsm/L.
• Plasma ADH concentration: diagnostic but not helpful for rapid diagnosis

• Fractional renal excretion of sodium: Net sodium loss is normal or elevated.
• Urinary specific gravity

• Head MRI if indicated

• Fluid restriction

• For emergency use only: hypertonic saline (1.5%–3% NaCl).
• Diuretics should be avoided because they worsen hyponatremia.
• ADH antagonists: Available only through research trials now but expected to soon become standard of care
• Demeclocycline

• Varies with different etiologies and between patients

• Use of other medications that require a large volume for administration

• Slowly, but usually during the first 48 to 72 hours

• Changes in neurologic status

Q: Is the use of diuretics beneficial?
A: No. Although diuretics may relieve the effects of volume overloading, they also worsen hyponatremia. Overall, diuretics usually cause more detriment than benefit.

Q: What distinguishes SIADH from hyponatremic dehydration?
A: The history of dehydrated patients reveals excessive water loss (e.g., vomiting and diarrhea). Dehydrated patients are thirsty and have lost weight. Patients with SIADH have a history of underlying disease and weight gain. On physical examination, patients with dehydration have signs of hypovolemia in contrast to patients with SIADH who do not. Dehydrated patients have elevated blood urea nitrogen (BUN) and serum creatinine, whereas patients with SIADH have low BUN, creatinine, and albumin.

Q: What distinguishes SIADH from cerebral salt wasting (CSW)?
A: Salt wasters appear dehydrated due to decreased plasma volume, but SIADH patients do not. CSW is associated with very high urine output in contrast to SIADH, which has low urine output. Net sodium loss is very high in CSW, but SIADH has normal to slightly elevated net sodium loss. Distinguishing laboratory features of CSW include suppressed plasma aldosterone concentration, suppressed plasma ADH concentration, and normal serum uric acid concentration. Note that plasma ADH concentration is high in both SIADH and CSW.

Q: Why is it important to distinguish SIADH from CSW (and other causes of hyponatremic dehydration)?
A: Therapies differ dramatically for these conditions. Unlike the water restriction used to treat SIADH, treatment of dehydration, such as that seen in CSW, requires replacement of ongoing salt and water losses.

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