para>Resulting abnormal urinary free water retention leads to dilutional hyponatremia (total body sodium levels may be normal or near normal, but the patient 's total body water is increased).
Often secondary to medications but may be associated with an underlying disorder, such as neoplasm, pulmonary disorder, or CNS system disease
Synonym(s): syndrome of inappropriate secretion of ADH
Epidemiology
Incidence
- Often found in the hospital setting, where incidence can be as high as 35%
- Predominant age: elderly
- Predominate sex: females > males
Etiology and Pathophysiology
- Drugs:
Antidepressants (e.g., monoamine oxidase inhibitors [MAOIs], tricyclics, SSRIs)
Oral hypoglycemics (e.g., chlorpropamide, metformin)
Antineoplastic drugs (e.g., vincristine, vinblastine, cisplatin, cyclophosphamide)
Antipsychotic agents (e.g., phenothiazines, thioridazine, haloperidol)
Analgesics (e.g., NSAIDs)
Antiepileptics (e.g., carbamazepine, oxcarbazepine, valproic acid)
Others (e.g., vasopressin, DDAVP, ecstasy, oxytocin,α-interferon)
- Neoplasms (ectopic ADH production):
- Infectious diseases:
- Miscellaneous cardiopulmonary conditions:
Asthma
Atelectasis
Myocardial infarction
Vascular diseases
- Other:
CNS injury
Mechanical ventilation
Multiple sclerosis
Guillain-Barre syndrome
Lupus erythematosus
Porphyria
Hypothyroidism, myxedema
- Idiopathic
Genetics
No known genetic pattern
Risk Factors
- Use of predisposing drugs
- Advanced age
- Postoperative status
- Institutionalization
General Prevention
- Search for cause, if unknown.
- Administration of 0.9% sodium chloride in adults during the perioperative period is recommended (if hypernatremia is not present).
- Monitor electrolytes in postoperative patients to determine if fluid intake needs restriction.
- Reduce/change medications, if drug-induced.
- Lifelong restriction of fluid intake
Commonly Associated Conditions
See "Etiology. "
Diagnosis
History
Early symptoms:
- Fatigue
- Anorexia
- Nausea
- Vomiting
- Diarrhea
- Headaches
- Myalgias
- Increased thirst
Physical Exam
Late/severe hyponatremia (serum Na <100 " 115 mEq/L)
- Altered mental status
- Confusion
- Lethargy
- Seizures
- Psychosis
- Coma
- Death
Differential Diagnosis
- Postoperative complications:
Usually after major abdominal/thoracic surgery
Caused by nonosmotic release of ADH, probably mediated by pain afferents
ADH increased by pain and narcotics
- Postprostatectomy syndrome
- Psychogenic polydipsia
Active therapy rarely is needed.
Diuresis occurs when intake is stopped.
Intake usually >10 L/day
Interaction with other psychotropic drugs
- Acute (usually in children)
- Endocrine
Addison disease
Hypothyroidism
- Spurious hyponatremia: caused by increased serum glucose, cholesterol, or proteins
- Appropriate ADH secretion and hyponatremia with decreased effective arterial blood volume (e.g., congestive heart failure [CHF], nephrotic syndrome, cirrhosis)
- Cerebral salt-wasting syndrome (hyponatremia, extracellular fluid depletion, CNS insult)
Diagnostic Tests & Interpretation
- Serum Na level: low
- Serum osmolality: low
- Urine osmolality: high
- Urinary Na concentration: high (losing sodium, rather than retaining)
- Serum ADH level: high
- Not usually required for diagnosis but to assess for other concerns:
Treatment
General Measures
- Fluid restriction (800 " 1,000 mL/day) is the main form of treatment (1)[C].
- Mildly symptomatic (serum Na >125 mEq/L [>125 mmol/L]): Restrict fluid to 800 " 1,000 mL/day.
- Acute (<48 hours duration) or symptomatic (altered mental status, seizure, coma)
Hypertonic saline (3% normal saline) bolus
Diuresis with loop diuretics
Decrease oral free water to maintenance.
Increase oral salt.
Correct serum Na deficit (mEq Na deficit = [desired Na ’ actual Na] 0.5 body weight [kg]).
Increase serum Na slowly with hypertonic saline by 4 " 6 mEq/L over 4 " 6 hours (not to exceed 9 mEq/L in a 24-hour period) (2,3).
Medication
- Diuretics: furosemide (Lasix) + hourly NaCl and KCl replacement
- IV saline to increase serum Na cautiously (4) [B]:
Goal sodium increase is <9 mEq/L in any 24-period.
If serum Na <120 mEq/L or severe neurologic symptoms; consider use of hypertonic saline to increase serum Na by 4 " 6 mEq/L over the first 4 " 6 hours.
- Contraindications: Avoid fluids in CHF, nephrotic syndrome, or cirrhosis.
- Precautions: Overly rapid correction (>9 " 10 mEq/L/day) can increase risk for the following:
CHF
Subdural and intracerebral hemorrhage
Permanent CNS damage, especially with serum Na <120 mEq/L (<120 mmol/L)
Demyelination syndrome
- Vasopressin-2 receptor antagonist (the vaptans: tolvaptan, conivaptan) (4),(5)[C]
- Demeclocycline (second line) (6)[C]
Blocks ADH at renal tubule; produces nephrogenic diabetes insipidus
Dosage for long-term management: 300 " 600 mg PO BID
Onset of action within 1 week; therefore, not best for acute management.
Alert
Increase Na levels slowly, no more than 9 mEq/L/24 hr, to prevent complications such as central pontine myelinosis (CPM) (7)[C].
Ongoing Care
Follow-up Recommendations
Patient Monitoring
- Careful continuous clinical and laboratory monitoring of hyponatremic state during acute phase:
- Chronic management: Monitor underlying cause, as needed.
Diet
May need increased salt/decreased water intake, depending on cause
Patient Education
Diet and fluid restrictions
Prognosis
- Depends on underlying cause; in general, higher morbidity and mortality in hospitalized patients with hyponatremia
- If symptomatic (seizure, coma): high mortality due to cerebral edema if serum Na <120 mEq/L (<120 mmol/L)
Complications
- Osmotic demyelination: central pontine and extrapontine irreversible myelinolysis (2,7)
- Chronic hyponatremia: usually <120 mEq/L (<120 mmol/L)
- Complications of overly rapid correction (see "Treatment, " precautions)
- Chronic hyponatremia is associated with osteoporosis (8)[C].
References
1.Ellison DH, Berl T. Clinical practice. The syndrome of inappropriate antidiuresis. N Engl J Med. 2007;356(20):2064 " 2072. [View Abstract]2.Adrogue HJ, Madias NE. The challenge of hyponatremia. J Am Soc Nephrol. 2012;23(7):1140 " 1148. [View Abstract]3.Sterns RH, Nigwekar SU, Hix JK. The treatment of hyponatremia. Semin Nephrol. 2009;29(3):282 " 299. [View Abstract]4.Esposito P, Piotti G, Bianzina S, et al. The syndrome of inappropriate antidiuresis: pathophysiology, clinical management and new therapeutic options. Nephron Clin Pract. 2011;119(1):c62 " c73. [View Abstract]5.Friedman B, Cirulli J. Hyponatremia in critical care patients: frequency, outcome, characteristics, and treatment with the vasopressin V(2)-receptor antagonist tolvaptan. J Crit Care. 2013;28(2):219.e1 " e12. [View Abstract]6.Sherlock M, Thompson CJ. The syndrome of inappropriate antidiuretic hormone: current and future management options. Eur J Endocrinol. 2010;162(Suppl 1):S13 " S18. [View Abstract]7.Fleming JD, Babu S. Images in clinical medicine. Central pontine myelinolysis. N Engl J Med. 2008;359(23):e29. [View Abstract]8.Verbalis JG, Barsony J, Sugimura Y, et al. Hyponatremia-induced osteoporosis. J Bone Miner Res. 2010;25(3):554 " 563. [View Abstract]
Additional Reading
See Also
Hyponatremia
Codes
ICD10
- E22.2 Syndrome of inappropriate secretion of antidiuretic hormone
ICD09
- 253.6 Other disorders of neurohypophysis
SNOMED
- 55004003 Syndrome of inappropriate vasopressin secretion (disorder)
Clinical Pearls
- Fluid restriction to 600 " 800 mL/day 2 " 3 days will result in weight loss and correction of hyponatremia and salt wasting in SIADH. Fluid restriction fails to correct hyponatremia and Na wasting in salt-losing renal disease.
- Cerebral salt wasting is a controversial disease entity and is similar to SIADH. However, patients with SIADH are euvolemic, whereas patients with cerebral salt wasting are hypovolemic. The only real way to establish the diagnosis is through fluid restriction. Serum urate and fractional excretion of urate will be corrected with fluid restriction in SIADH, but will not correct in cerebral salt wasting.
- CPM is a cerebral demyelination syndrome that causes quadriplegia, pseudobulbar palsy, seizures, coma, and death. It is caused by an overly rapid rate of Na correction.
- Safe correction of hyponatremia is important. Online calculators are available: www.medcalc.com/sodium.html.