Updated: 2/4/2021

Syndrome of Inappropriate ADH (SIADH)

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Snapshot
  • A 44-year-old woman with a recent diagnosis of small cell lung cancer presents to the emergency room with her partner. She had reported some nausea and feelings of malaise yesterday. Today, she continued to feel unwell, and reported feeling lethargic and weak. She is oriented to person and place but not to time. On physical exam, she is noted to have normal skin turgor and no edema. Laboratory testing reveals hyponatremia and decreased serum osmolality.
Introduction
  • Clinical definition
    • syndrome of inappropriate antidiuretic hormone (SIADH) is characterized by excessive free water retention and impaired water excretion, leading to dilutional hyponatremia
  • Epidemiology
    • demographics
      • common in hospitalized patients, particularly those on mechanical ventilation
    • risk factors
      • older age
      • malignancy
      • pulmonary disease
        • pneumonia
        • tuberculosis
    • etiology
      • ectopic production
        • small cell carcinoma of the lung  
      • central nervous system disorders
        • infection
          • e.g., encephalitis and meningitis
        • malignancy
        • stroke
        • trauma
      • drugs
        • cyclophosphamide
        • nonsteroidal anti-inflammatory drugs
        • carbamazepine
        • selective serotonin reuptake inhibitors (SSRIs)
  • Pathogenesis
    • impaired water excretion due to ADH
      • may be due to increased production of ADH
      • may be due to enhanced effects of ADH due to medications
      • may be due to overdose of desmopressin
Presentation
  • Symptoms 
    • depends on level of hyponatremia
    • mild symptoms (sodium usually 125-130 mEq/L)
      • nausea and malaise
    • moderate symptoms (115-125 mEq/L)
      • headaches
      • lethargy
      • weakness
    • severe symptoms (< 120 mEq/L)
      • seizures
      • coma
      • respiratory arrest
  • Physical exam
    • euvolemic fluid status
      • absence of edema
      • normal skin turgor 
Studies
  • Serum labs 
    • serum osmolality (< 275 mOsm/kg)
    • serum sodium (< 135 mEq/L) 
    • serum uric acid (< 4 mg/dL)
    • adrenal and thyroid function are normal
  • Urine studies 
    • urine osmolality > serum osmolality
    • urine osmolality (> 100 mOsm/kg) 
    • urine sodium (40 mEq/L)
Differential
  • Other causes of euvolemic hyponatremia
    • hypothyroidism
    • psychogenic polydipsia 
      • distinguishing factor
        • urine osmolality on water deprivation test
    • thiazide-diuretic use
    • certain diets
      • e.g., "tea and toast" (low solute diet) and beer potomania
Treatment
  • Management approach
    • sodium management is dependent on
      • symptom severity
      • duration of hyponatremia (acute vs chronic)
    • chronic hyponatremia must be corrected slowly to prevent osmotic demyelination syndrome (central pontine myelinolysis)
    • correct underlying cause when possible
  • Medical
    • fluid restriction
      • indication
        • mild or moderate symptoms
        • asymptomatic cases
    • intravenous hypertonic (3%) saline
      • indication
        • chronic hyponatremia
          • severe symptoms
        • acute hyponatremia
          • all cases
    • salt tablets
      • indication
        • adjuvant therapy in patients who are asymptomatic
    • ADH receptor antagonists
      • indication
        • not routinely used
      • medications
        • demeclocycline
        • vaptans (tolvaptan or conivaptan)
Complications
  • Osmotic demyelination syndrome (central pontine myelinolysis)
    • caused by rapid correction of chronic hyponatremia

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Questions (5)
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(M1.EC.15.75) A 57-year-old female presents to the emergency department with complaints of nausea, muscle aches, and confusion that presented and worsened over the past several days. On further probing, she also reports a nagging cough with shortness of breath and a 10-lb. weight loss over the last 3 months. She does not have a primary care doctor and denies having regular check ups. She reports smoking 1 pack of cigarettes per day and denies any alcohol consumption. Her medical history is significant for hypertension, a 30 pack year smoking history, and anxiety. Vital signs are as follows: T 37.2 C, HR 86, BP 137/86, RR 14, and SpO2 96%. Physical examination shows normal skin turgor, moist mucus membranes, and no peripheral edema. A CT scan is performed to investigate the patient's cough in Figure A. Lab work is performed in the ED and the findings are below.
Na: 128 mEq/L
Plasma osmolality: 260 mOsm/kg
Urine osmolality: 300 mOsm/kg
Urine Na: 47 mEq/L

Which of the following is most likely also found in this patient?
Tested Concept

QID: 106822
FIGURES:
1

History of increased consumption of fluids

7%

(3/45)

2

Increased urine glucose

0%

(0/45)

3

Kidney unresponsive to antidiuretic hormone

2%

(1/45)

4

Increased antidiuretic hormone

78%

(35/45)

5

Decreased antidiuretic hormone

13%

(6/45)

M 2 D

Select Answer to see Preferred Response

(M1.EC.13.79) A 48-year-old female presents to the emergency room with mental status changes.
Laboratory analysis of the patient's serum shows:
Na 122 mEq/L
K 3.9 mEq/L
HCO3 24 mEq/L
BUN 21 mg/dL
Cr 0.9 mg/dL
Ca 8.5 mg/dL
Glu 105 mg/dL

Urinalysis shows:
Osmolality 334 mOsm/kg
Na 45 mEq/L
Glu 0 mg/dL

Which of the following is the most likely diagnosis?
Tested Concept

QID: 100380
1

Aspirin overdose

11%

(12/106)

2

Diarrhea

4%

(4/106)

3

Diabetes insipidus

36%

(38/106)

4

Primary polydipsia

17%

(18/106)

5

Lung cancer

26%

(28/106)

M 2 C

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Evidence (2)
EXPERT COMMENTS (24)
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