Updated: 12/12/2020

Syndrome of Inappropriate ADH (SIADH)

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Snapshot
  • A 79-year-old woman is brought to the emergency department from home for altered mental status. Her family reports that she is normally alert and oriented to person, place, and time, and very conversational. On exam, she is confused, alert only to person, and appears anxious. She has moist mucous membranes and normal skin turgor. Pulmonary auscultation reveals localized crackles. Laboratory tests are significant for serum sodium of 126 mEq/L.
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)
          • citalopram 
  • 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
  • Diagnostic testing
    • studies
      • serum studies
        • 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
  • First-line
    • fluid restriction
      • indication
        • mild or moderate symptoms
        • asymptomatic cases
    • intravenous hypertonic (3%) saline
      • indication
        • chronic hyponatremia
          • severe symptoms
        • acute hyponatremia
          • all cases
  • Second-line
    • salt tablets
      • indication
        • adjuvant therapy in patients who are asymptomatic
  • Other medications
    • demeclocycline (ADH receptor antagonist)
    • vaptans (ADH receptor antagonist)
Complications
  • Osmotic demyelination syndrome (central pontine myelinolysis)
    • caused by rapid correction of chronic hyponatremia

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(M2.EC.17.4770) A 69-year-old male presents to the emergency department for slurred speech and an inability to use his right arm which occurred while he was eating dinner. The patient arrived at the emergency department within one hour. A CT scan was performed of the head and did not reveal any signs of hemorrhage. The patient is given thrombolytics and is then managed on the neurology floor. Three days later, the patient is recovering and is stable. He seems depressed but is doing well with his symptoms gradually improving as compared to his initial presentation. The patient complains of neck pain that has worsened slowly over the past few days for which he is being given ibuprofen. Laboratory values are ordered and return as indicated below:

Serum:
Na+: 130 mEq/L
K+: 3.7 mEq/L
Cl-: 100 mEq/L
HCO3-: 24 mEq/L
Urea nitrogen: 7 mg/dL
Glucose: 70 mg/dL
Creatinine: 0.9 mg/dL
Ca2+: 9.7 mg/dL

Urine:
Appearance: dark
Glucose: negative
WBC: 0/hpf
Bacterial: none
Na+: 320 mEq/L/24 hours

His temperature is 99.5°F (37.5°C), pulse is 95/min, blood pressure is 129/70 mmHg, respirations are 10/min, and oxygen saturation is 98% on room air. Which of the following is the best next step in management?

QID: 109096
1

Fluid restriction

59%

(16/27)

2

Oral salt tablets

11%

(3/27)

3

Demeclocycline

4%

(1/27)

4

Conivaptan

7%

(2/27)

5

Continue conservative management

11%

(3/27)

M 6 C

Select Answer to see Preferred Response

(M2.EC.15.46) A 39-year-old female presents with confusion. Her husband reports that she doesn't know where she is and cannot remember the date. She was recently diagnosed with small cell lung cancer. Vital signs are T 37C, HR 80, BP 120/80 mmHg, RR 14, and O2 sat 99% on room air. She is not orthostatic. Physical examination reveals moist mucous membranes and normal capillary refill. A basic metabolic profile reveals that serum sodium is 129. Regarding this patient's illness, which of the following is true?

QID: 104320
1

Urinary osmolarity will be > 100, and this illness will not correct with saline infusion

39%

(35/90)

2

Urinary osmolarity will be < 100, and another potential cause of this disorder is excessive water drinking

12%

(11/90)

3

Urinary sodium will be > 20 and fractional excretion of sodium will be >1%

37%

(33/90)

4

Urinary sodium will be < 10, and fractional excretion of sodium will be <1%

10%

(9/90)

5

Urinary sodium will be > 20 and another potential cause of this disorder is renal failure

1%

(1/90)

M 6 E

Select Answer to see Preferred Response

Evidence (1)
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