The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is defined by the hyponatremia and hypo-osmolality resulting from inappropriate, continued secretion or action of the antidiuretic hormone arginine vasopressin (AVP) despite normal or increased plasma volume, which results in impaired water excretion. [1]The key to understanding the pathophysiology, signs, symptoms, and treatment of SIADH is the awareness that the hyponatremia results from an excess of water rather than a deficiency of sodium.
Signs and symptoms
Depending on the magnitude and rate of development, hyponatremia may or may not cause symptoms. The history should take into account the following considerations:
- In general, slowly progressive hyponatremia is associated with fewer symptoms than is a rapid drop of serum sodium to the same value
- Signs and symptoms of acute hyponatremia do not precisely correlate with the severity or the acuity of the hyponatremia
- Patients may have symptoms that suggest increased secretion of AVP, such as chronic pain, symptoms from central nervous system or pulmonary tumors or head injury, or drug use
- Sources of excessive fluid intake should be evaluated
- The chronicity of the condition should be considered
After the identification of hyponatremia, the approach to the patient depends on the clinically assessed volume status. Prominent physical findings may be seen only in severe or rapid-onset hyponatremia and can include the following:
- Confusion, disorientation, delirium
- Generalized muscle weakness, myoclonus, tremor, asterixis, hyporeflexia, ataxia, dysarthria, Cheyne-Stokes respiration, pathologic reflexes
- Generalized seizures, coma
See Presentation for more detail.
Diagnosis
In the absence of a single laboratory test to confirm the diagnosis, SIADH is best defined by the classic Bartter-Schwartz criteria, which can be summarized as follows[2] :
- Hyponatremia with corresponding hypo-osmolality
- Continued renal excretion of sodium
- Urine less than maximally dilute
- Absence of clinical evidence of volume depletion
- Absence of other causes of hyponatremia
- Correction of hyponatremia by fluid restriction
The following laboratory tests may be helpful in the diagnosis of SIADH:
- Serum sodium, potassium, chloride, and bicarbonate
- Plasma osmolality
- Serum creatinine
- Blood urea nitrogen
- Blood glucose
- Urine osmolality
- Serum uric acid
- Serum cortisol
- Thyroid-stimulating hormone
- Plasma AVP level
The patient’s volume should be assessed clinically to help rule out the presence of hypovolemia.
Imaging studies that may be considered include the following:
- Chest radiography (for detection of an underlying pulmonary cause of SIADH)
- Computed tomography or magnetic resonance imaging of the head (for detection of cerebral edema occurring as a complication of SIADH, for identification of a CNS disorder responsible for SIADH, or for helping to rule out other potential causes of a change in neurologic status)
See Workup for more detail.
Management
Treatment of SIADH and the rapidity of correction of hyponatremia depend on the following:
- Degree of hyponatremia
- Whether the patient is symptomatic
- Whether the syndrome is acute (<48 hours) or chronic
- Urine osmolality and creatinine clearance
If the duration of hyponatremia is unknown and the patient is asymptomatic, it is reasonable to presume chronic SIADH. Diagnosis and treatment of the underlying cause of SIADH are also important.
In an emergency setting, aggressive treatment of hyponatremia should always be weighed against the risk of inducing central pontine myelinolysis (CMP). Such treatment is warranted as follows:
- Indicated in patients who have severe symptoms (eg, seizures, stupor, coma, and respiratory arrest), regardless of the degree of hyponatremia
- Strongly considered for those who have moderate-to-severe hyponatremia with a documented duration of less than 48 hours
The goal is to correct hyponatremia at a rate that does not cause neurologic complications, as follows:
- Raise serum sodium by 0.5-1 mEq/hr, and not more than 10-12 mEq in the first 24 hours
- Aim at maximum serum sodium of 125-130 mEq/L
In an acute setting (<48 hours since onset) where moderate symptoms are noted, treatment options for hyponatremia include the following:
- 3% hypertonic saline (513 mEq/L)
- Loop diuretics with saline
- Vasopressin-2 receptor antagonists (aquaretics, such as conivaptan or tolvaptan)
- Water restriction
In a chronic asymptomatic setting, the principal options are as follows:
- Fluid restriction
- Vassopressin-2 receptor antagonists
- If vasopressin-2 receptor antagonists are unavailable or if local experience with them is limited, other agents to be considered include loop diuretics with increased salt intake, urea, mannitol, and demeclocycline
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