Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH), Emergency Medicine

Basics

Description

Most common cause of hyponatremia in hospitalized patients (and doubles inpatient mortality in some studies)
A water balance problem more than 1 of sodium (Na) balance
Normal regulation of water balance:
- Antidiuretic hormone (ADH):
  - Integral controller of water balance
  - Increases water permeability of the collecting tubules, resulting in free water reabsorption
  - Synthesized by hypothalamus but secreted by posterior pituitary
- Water deprivation (increased plasma osmolality) stimulates secretion as sensed by:
  - Osmoreceptors/atrial stretch receptors
  - Carotid baroreceptors
  - Aortic arch/pulmonary veins
Hyponatremia:
- Mild: Serum sodium <135 mEq/L
- Moderate: Serum sodium <130 mEq/L
- Severe: Serum sodium <125 mEq/L
- Excess extracellular water relative to Na
- Depletional hyponatremia:
  - Sodium depletion can be caused by diet, GI losses, diuretic use, and renal or adrenal disease.
  - Often accompanied by extracellular fluid volume depletion
  - Hyponatremia associated with clinical signs of hypovolemia
  - Increased Hct, BUN, Cr
  - Urinary sodium excretion <20 mEq/L
- Dilutional hyponatremia:
  - Increased extracellular water in presence of normal or increased total body sodium
  - Can be caused by increased fluid intake (oral, IV), drugs, or medical conditions
  - Euvolemia with edema
  - Normal or decreased Hct, BUN, Cr
  - Urinary sodium excretion >20 mEq/L
  - Inappropriate ADH secretion is a form of dilutional hyponatremia.
Definition of SIADH:
- ADH secretion in absence of hyperosmolality or hypovolemia
Criteria for definition:
- Essential features:
  - Hyponatremia " despite correction for hyperglycemia, hyperproteinemia, or hyperlipidemia
  - Euvolemia " no clinical signs of volume depletion (orthostasis, tachycardia) or volume overload (edema, ascites)
  - Hyposmolality of the plasma " <275 mOsm/kg of water
  - Normal renal, adrenal, and thyroid function
  - No recent diuretic use
  - Urine Osm >100 mOsm/kg of water
- Supplemental features:
  - Plasma uric acid <4 mg/dL
  - BUN <10 mg/dL
  - FENa >1%
  - Failure to correct hyponatremia after an infusion of normal saline (NS) 0.9%
  - Abnormal water load test (inability to excrete ≥90% of a 20 mL/kg water load in 4 hr)

Etiology

Malignant disorders:
- ADH-producing tumors
- Cancer (Small-cell lung, pancreatic, prostate)
- Pituitary tumors
- Thymoma
- Lymphoma
Pulmonary disorders:
- Pneumonia
- TB
- Lung abscess
- COPD
CNS disorders:
- Meningitis/encephalitis
- CVA
- Head injury
Medications:
- Thiazides
- Chlorpropamide
- Vincristine
- Anticonvulsants (carbamazepine)
- Antidepressants (tricyclics, SSRIs)
- Antipsychotics
- NSAIDs
- Ecstasy (MDMA)
- Vasopressin analogs (DDAVP, oxytocin, vasopressin)
Transient:
- Endurance exercise
- General anesthesia
- Pain
- Stress
Other:
- Hereditary
- Positive-pressure ventilation
- HIV/AIDS
- Idiopathic

Cerebral salt-wasting syndrome (CSWS) can mimic SIADH.

Seen in patients with cerebral tumors or subarachnoid hemorrhage and in neurosurgical patients
Etiology unclear
Represents appropriate water resorption in the face of salt wasting (urine Na >30 " 40 mmol/L)
Fluid restriction can help differentiate the 2:
- In SIADH: Hypouricemia will correct
- In CSWS: Hypouricemia will persist
Treatment of CSWS may differ from that of SIADH:
- Infusion of NS
- May benefit from fludrocortisones therapy

Diagnosis

Signs and Symptoms

Serum sodium <135 mEq/L:
- May be asymptomatic
Serum sodium <130 mEq/L:
- Weakness/lethargy
- Weight gain
- Headache
- Anorexia
Sodium serum <120 mEq/L:
- Altered mental status
- Seizure/coma
Chronic hyponatremia: 50% asymptomatic
High mortality in acute hyponatremia

History

Thorough medication history
Course of illness (acute, subacute, or chronic)

Physical Exam

Volume status
Mental status
Stigmata of malignancy

Essential Workup

Diagnosis is 1 of exclusion, need to evaluate for other causes of:
- Depletional or dilutional hyponatremia
Electrolytes, BUN, Cr, glucose, protein, lipids:
- Hyponatremia (serum Na <135 mmol/L)
- Serum hyposmolality (serum Osm <275 mOsm/kg)
Urine osmolality:
- Inability to excrete dilute urine
- Urine osmolality >100 mOsm/kg
Urine sodium:
- Continued urinary excretion of sodium
- Urinary sodium >20 mEq/L

Diagnosis Tests & Interpretation

Lab

Serum protein levels
Lipid levels
Glucose levels
Serum osmolality
LFT and thyroid function test
Morning cortisol level

Imaging
Consider imaging (CXR, CT head) to screen for pathology causing SIADH (tumors/masses)

Differential Diagnosis

Causes of Hyponatremia

See etiologies above
Increased extracellular fluid (dilutional hyponatremia):
- Renal failure/insufficiency
- CHF
- End-stage liver disease
Normal extracellular fluid (dilutional hyponatremia):
- SIADH
- Myxedema
- Sheehan syndrome (postpartum hypopituitarism)
- Reset osmostat syndromes (dilute urine at lower than normal sodium levels)
Decreased extracellular fluid (depletional hyponatremia):
- Increased losses:
  - Excessive sweating (endurance sports)
  - GI losses (vomiting, diarrhea)
- 3rd-space sequestration
- Diuretic use
- Aldosterone deficiency:
  - Addison disease
- Salt-losing nephropathies:
  - Renal tubular acidosis
Pseudohyponatremia (seen in hyperglycemia, hyperproteinemia, hyperlipidemia)

Treatment

Pre-Hospital

In patients with altered mental status, maintenance and protection of the airway are paramount.
When hypovolemia is suspected, appropriate fluid resuscitation should be initiated.
Rapid patient evaluation and transport are essential.

Initial Stabilization/Therapy

Severe symptomatic hyponatremia with CNS manifestations
Endotracheal intubation for patients in need of airway protection
Identify/treat other causes of altered mental status
Treat seizures with benzodiazepines
Proceed to hyponatremia treatment

Ed Treatment/Procedures

Most effective treatment of SIADH is successful eradication of the underlying cause.
Initial treatment of hyponatremia caused by SIADH is the same for all causes of euvolemic/hypervolemic hyponatremia.

Mildly Symptomatic Hyponatremia, Chronic Hyponatremia with Minimal Symptoms, Asymptomatic Hyponatremia

Serum sodium usually >125 mEq/L
Fluid restriction 800 " 1,000 mL/day alone or in conjunction with:
- 0.9% NS infusion and/or IV furosemide
Correct serum sodium by no more than 0.5 mEq/L/hr (5 " 6 mEq/day):
- Too rapid correction of serum sodium levels can induce central pontine myelinolysis, associated with development of bulbar palsy, quadriplegia, seizures, coma, and death.

Severe Hyponatremia

Symptomatic patient, serum sodium <125 mEq/L
Increase serum sodium by no more than 12 mEq/L in 1st 24 hr at a rate of 1 mEq/L/hr (8 " 12 mEq/day when serum sodium below 125 mEq/L and slow to 5 " 6 mEq/day when serum sodium rises to 125 mEq/L).
Target level: 125 mEq/L
Treat patients with significant neurologic symptoms with 3% saline solution.
Serum sodium lab testing every 1 " 2 hr

Acute Life-threatening Hyponatremia

Serum sodium usually <120 mEq/L
Associated with seizures or coma
Clinical goal: Stop seizure and improve neurologic status
Therapeutic goal: Same as for severe hyponatremia
Administer hypertonic saline solution (3%)
Stop hypertonic saline when symptoms (i.e., seizures) resolve and transition to NS.
IV furosemide to promote diuresis and induce a negative fluid balance.
Once serum sodium = 125 mEq/L, further IV fluid should be in the form of 0.9% saline solution.
Restoration of serum sodium to normal levels should take place over ≥48 hr.
Drugs that inhibit the secretion/effects of ADH:
- Indicated when SIADH not self-limited and cause cannot be removed
- Demeclocycline (blocks effect of ADH)

Medication

Conivaptan 20 mg IV over 30 min (for severe hyponatremia in concert with admitting physician)
Demeclocycline: 300 mg PO BID " QID
Hypertonic saline solution (3% NaCl): 250 " 500 mL (max. initial dose 5 mL/kg):
- 25 " 100 mL/hr
- Limit rate in rise of serum sodium to 0.5 " 1 mEq/L/h.
- Discontinue when seizure resolves or serum sodium of 125 mEq/L is reached.
- Rise in serum sodium by 4 " 6 mEq/L is usually sufficient to stop seizures.
0.9% NS: Maintenance rates
Lasix: 1 mg/kg up to 20 " 40 mg IV

Follow-Up

Disposition

Admission Criteria

Severe life-threatening hyponatremia
Symptomatic hyponatremia
Serum sodium <125 mEq/L regardless of symptoms
New-onset SIADH in which underlying cause or complications must be diagnosed and treated
Patients compliance an issue

Discharge Criteria

Asymptomatic chronic hyponatremia
Serum sodium >125 mEq/L
No unstable comorbid factors
Known diagnosis of SIADH

Followup Recommendations

All patients with hyponatremia that meet discharge criteria still require follow-up to check for resolution, monitoring, and/or diagnosis of the underlying cause of the SIADH/hyponatremia.

Pearls and Pitfalls

SIADH is a diagnosis of exclusion.
Must evaluate for other causes as well as renal, thyroid, adrenal, cardiac, and hepatic dysfunction.
Take a thorough medication history.

Additional Reading

Balasubramanian A, Flareau B, Sourberr J. Syndrome of inappropriate antidiuretic hormone secretion. Hospital Physician. 2007;39:33 " 36.
Brimioulle S, Orellana-Jimenez C, Aminian A, et al. Hyponatremia in neurological patients: Cerebral salt wasting versus inappropriate antidiuretic hormone secretion. Intensive Care Med. 2008;34:125 " 131.
Ellison DH, Berl T. Clinical practice. The syndrome of inappropriate antidiuresis. N Engl J Med. 2007;356(20):2064 " 2072.
Gross P. Clinical management of SIADH. Ther Adv Endocrinol Metab. 2012;3(2):61 " 73.
Verbalis JG. Managing hyponatremia in patients with syndrome of inappropriate antidiuretic hormone secretion. J Hosp Med. 2010;5(suppl 3):S18 " S26.

Codes

ICD9

253.6 Other disorders of neurohypophysis
276.1 Hyposmolality and/or hyponatremia

ICD10

E22.2 Syndrome of inappropriate secretion of antidiuretic hormone
E87.1 Hypo-osmolality and hyponatremia

SNOMED

55004003 Syndrome of inappropriate vasopressin secretion (disorder)
89627008 Hyponatremia (disorder)

Home

Erectile Dysfunction

Doctor123.org