Syndrome of Inappropriate Antidiuretic Hormone (SIADH) Clinical Overview
I. The "On-Call" Snapshot
Clinical Significance in Malaysia: Extremely common cause of euvolemic hyponatremia in hospitalized patients, often secondary to pneumonia, CNS insults, or drugs we frequently prescribe.
High-Yield Definition: A disorder of impaired water excretion caused by the inability to suppress the secretion of antidiuretic hormone (ADH), leading to hyponatremia and hypo-osmolality. (Source: UpToDate)
Clinical One-Liner: The patient is retaining too much free water because ADH is being released inappropriately, so their sodium is diluted.
II. Etiology & Risk Factors
Etiology: The underlying principle is non-physiological release of ADH.
CNS Disorders: Stroke, haemorrhage, infection (meningitis, encephalitis), trauma.
Pulmonary Disease: Pneumonia (especially atypical), TB, lung abscess. This is very common here.
Malignancy: Small cell lung cancer (SCLC) is classic for ectopic ADH production.
Drugs: A huge list. The ones you'll see most often are SSRIs, carbamazepine, TCAs, and cyclophosphamide. Always review the patient's medication chart.
Other: Major surgery, severe pain, nausea.
Risk Factors:
Elderly patients
Post-operative state
Ventilated patients
Pre-existing pulmonary or CNS disease
Malignancy
III. Quick Pathophysiology
Excess ADH acts on the V2 receptors in the collecting ducts of the kidneys. This increases the number of aquaporin-2 channels, making the ducts highly permeable to water. The result is massive free water reabsorption back into the circulation, independent of serum osmolality. This dilutes the serum sodium and concentrates the urine. The body tries to compensate by excreting sodium in the urine to maintain euvolemia, which is why urine sodium is paradoxically high.
IV. Classification
SIADH is primarily classified by severity based on symptoms and sodium level, and by acuity.
By Acuity:
Acute: Hyponatremia developing in < 48 hours. Higher risk of cerebral oedema.
Chronic: Hyponatremia present for ≥ 48 hours. Brain has adapted, so rapid correction is dangerous.
By Severity (Symptom-based):
Moderate: Nausea, confusion, headache.
Severe: Vomiting, seizures, coma, cardiorespiratory distress (GCS ≤ 8).
V. Clinical Assessment
Red Flags & Immediate Actions:
GCS < 15 / Seizures / Coma: Action: Alert senior/MO immediately, prepare for airway support (if GCS ≤ 8), and initiate hypertonic saline. Reason: Signs of cerebral oedema; life-threatening neurological emergency.
Serum Sodium < 120 mmol/L: Action: Inform senior, place patient on strict intake/output charting, frequent neurological observation. Reason: High risk for severe neurological complications.
History:
Key Diagnostic Clues: Look for the underlying cause. Ask about new headaches, cough, recent head trauma, or new medications. A history of cancer, especially SCLC, is a major clue.
Symptom Breakdown: Symptoms are primarily neurological and depend on the severity and acuity of the hyponatremia.
Common (>50%): Headache, nausea, anorexia, lethargy. Often non-specific in mild cases.
Less Common (10-50%): Confusion, disorientation, muscle cramps, gait disturbance.
Rare (<10%, Severe Cases): Seizures, coma, respiratory arrest.
Pertinent Negatives: Absence of oedema, ascites, or signs of dehydration (e.g., postural hypotension, dry mucous membranes). The patient should be clinically euvolemic.
Physical Examination (OSCE Approach):
General Inspection: Look for signs of an underlying cause (e.g., cachexia for malignancy, respiratory distress for pneumonia). The patient themselves often looks "normal."
Vitals: Usually normal. No tachycardia or hypotension that would suggest hypovolemia.
Disease-Specific Examination:
Neurological: Full GCS, check for confusion, asterixis (in severe cases), and focal deficits that might point to a CNS cause.
Respiratory: Thorough lung examination for signs of consolidation or effusion.
Hydration Status: This is critical. Check for pitting oedema, raised JVP (suggests hypervolemia). Check skin turgor, mucous membranes, and for postural drop (suggests hypovolemia). In SIADH, these should be normal. The patient is euvolemic.
Examination for Differentials: Check for pigmentation (Addison's), goitre (hypothyroidism).
Clinical Pearl: If you see a patient with hyponatremia but their skin turgor is good and they have no oedema, SIADH should be at the top of your list. The diagnosis is made by blood and urine tests, but your clinical assessment of volume status is what points you in the right direction.
VI. Diagnostic Workflow
Differential Diagnosis: (For Euvolemic Hyponatremia)
Hypothyroidism:
Points For: Lethargy, non-specific symptoms.
Points Against: Presence of other signs like bradycardia, goitre, delayed reflexes.
How to Differentiate: Thyroid function test (TSH, Free T4).
Adrenal Insufficiency (Secondary/Tertiary):
Points For: Non-specific weakness, fatigue.
Points Against: Absence of hyperkalemia and hypotension which are typical in primary adrenal insufficiency.
How to Differentiate: Serum cortisol (8 AM sample).
Psychogenic Polydipsia:
Points For: Hyponatremia. Often have psychiatric history.
Points Against: Urine osmolality will be very low (<100 mOsm/kg) as kidneys are appropriately trying to excrete vast amounts of water.
How to Differentiate: Check urine osmolality.
Investigations Plan:
Bedside / Initial (First 15 Mins):
Capillary Blood Glucose: Rule out hyperglycemia causing pseudohyponatremia.
First-Line Labs & Imaging (The "SIADH Panel"):
Serum Electrolytes & Osmolality: Confirms true hyponatremia (Na+ < 135 mmol/L) and low serum osmolality (< 275 mOsm/kg).
Urine Electrolytes & Osmolality: This is key. Expect high urine osmolality (> 100 mOsm/kg, usually > 300) and high urine sodium (> 30 mmol/L).
Renal Profile, LFTs
Thyroid Function Test (TSH, fT4)
Serum Cortisol (8 AM)
Chest X-Ray: Look for pulmonary causes (pneumonia, malignancy).
Confirmatory / Gold Standard: There is no single "gold standard" test. The diagnosis is based on meeting the Bartter-Schwartz criteria:
Serum osmolality < 275 mOsm/kg
Urine osmolality > 100 mOsm/kg
Clinical euvolemia
Urine sodium > 30 mmol/L with normal salt and water intake
Absence of adrenal, thyroid, pituitary, or renal insufficiency and no recent diuretic use.
VII. Staging & Severity Assessment
Severity is clinical. Don't just treat the number.
Mild: Na+ 130-134 mmol/L. Often asymptomatic.
Moderate: Na+ 125-129 mmol/L. Nausea, confusion.
Profound: Na+ < 125 mmol/L. High risk for severe symptoms.
The presence of severe symptoms (seizures, coma) overrides any sodium value and mandates immediate, aggressive treatment.
VIII. Management Plan
A. Principle of Management:
Treat the underlying cause.
Correct the serum sodium at a safe rate to prevent neurological complications.
Manage symptoms of hyponatremia.
B. Immediate Stabilisation (The ABCDE Plan for Severe, Symptomatic Hyponatremia):
This is a medical emergency.
A, B, C: Secure airway, give oxygen, establish IV access.
D: Control seizures with benzodiazepines. The definitive treatment is hypertonic saline.
Give 100-150 mL of IV Hypertonic Saline (3% NaCl) over 20 minutes.
Goal: Raise serum sodium by 4-6 mmol/L in the first few hours to alleviate cerebral oedema. Re-check serum sodium after the bolus.
Do not delay. This can be life-saving.
C. Definitive Treatment (The Ward Round Plan):
Safety Limits for Correction:
Target: ≤ 8-10 mmol/L in the first 24 hours and ≤ 18 mmol/L in the first 48 hours.
Why? Overly rapid correction causes Osmotic Demyelination Syndrome (ODS), which is irreversible.
First-Line (Asymptomatic/Mild-Moderate):
Fluid Restriction: This is the cornerstone. Typically 800mL - 1L per day. Be strict. You must write it in the fluid chart and explain it to the patient and nurses.
Treat the cause: Start antibiotics for pneumonia, review and stop offending drugs, etc.
Second-Line (If fluid restriction fails or is not tolerated):
Oral Salt Tablets: NaCl tablets can be used, often with a loop diuretic like furosemide to increase free water clearance.
Urea: Oral urea sachets can induce osmotic diuresis. It's effective but tastes terrible.
Vaptans (e.g., Tolvaptan): V2 receptor antagonists. Highly effective but expensive and specialist-use only in our setting. Usually initiated by nephrology or endocrinology.
D. Long-Term & Discharge Plan:
Ensure underlying cause is resolved.
Educate patient on symptoms of hyponatremia.
Gradually liberalise fluid restriction upon discharge, monitoring sodium levels.
IX. Complications
From the Disease (Hyponatremia):
Immediate: Cerebral oedema, seizures, coma, death.
Long-Term (Chronic): Gait instability, falls, osteoporosis.
From the Treatment:
Immediate/Short-Term: Osmotic Demyelination Syndrome (ODS) from over-correction. Presents with dysarthria, dysphagia, quadriparesis days after the "successful" correction. This is a nightmare scenario you must avoid.
X. Prognosis
Prognosis depends entirely on the underlying cause. SIADH from a reversible cause like pneumonia has an excellent prognosis.
If caused by an untreatable malignancy like SCLC, the prognosis is poor and tied to the cancer itself.
Key Prognostic Factor: The severity of the underlying condition and the presence of severe neurological symptoms on admission.
XI. How to Present to Your Senior
"Selamat pagi/petang Dr, I'm calling about Patient
, IC number
, in Ward
, Bed
.
Situation: The patient is a
-year-old
admitted for
. I am concerned about his/her hyponatremia. He/she is currently confused with a GCS of 13.
Background: His baseline sodium is unknown. On admission, sodium was 128. The latest result at
is now 119. He is clinically euvolemic, with no oedema and good skin turgor.
Assessment: My impression is severe, symptomatic hyponatremia, likely due to SIADH secondary to his pneumonia. He has no history of renal, thyroid, or adrenal disease.
Recommendation: I think we should give a stat bolus of 150mL IV 3% hypertonic saline over 20 minutes to manage his confusion. I have also sent off a "SIADH panel" including serum/urine osmolality and will implement a strict 1L/day fluid restriction. Could you come and review the patient?"
XII. Summary & Further Reading
Top 3 Takeaways:
Suspect SIADH in any euvolemic hyponatremic patient.
Diagnosis requires paired serum and urine tests: expect low serum osmolality with inappropriately high urine osmolality.
Correct sodium slowly (max 8-10 mmol/L per 24h) unless the patient is having severe neurological symptoms (seizures/coma), in which case a rapid initial bolus of hypertonic saline is life-saving.
Key Resources:
Guidelines: There isn't a specific Malaysian CPG just for SIADH, it's covered under Hyponatremia in general medical and nephrology texts. Refer to the European Society guidelines as a robust reference. (https://www.european-renal-best-practice.org/guidelines-navigator/)
UpToDate: "Pathophysiology and etiology of the syndrome of inappropriate antidiuretic hormone secretion (SIADH)" and "Treatment of hyponatremia
