Syndrome of Inappropriate Antidiuretic Hormone (SIADH)

Syndrome of Inappropriate Antidiuretic Hormone secretion, commonly known as SIADH, is a disorder of water balance caused by excessive release or action of antidiuretic hormone (ADH). This condition leads to dilution of blood sodium levels, resulting in hyponatremia, which can range from mild and asymptomatic to severe and life-threatening. Early diagnosis and appropriate management are crucial to prevent serious neurological complications.

What Is Antidiuretic Hormone (ADH)?

Antidiuretic hormone, also called vasopressin, is produced in the hypothalamus and released by the posterior pituitary gland. Its primary function is to regulate water balance by controlling how much water the kidneys reabsorb.

Under normal circumstances:

• ADH is released when the body is dehydrated

• It helps conserve water by concentrating urine

• It maintains normal blood osmolality and sodium levels

In SIADH, ADH is released inappropriately, even when the body does not need to conserve water.

What Is Syndrome of Inappropriate Antidiuretic Hormone (SIADH)?

SIADH is a condition characterized by:

• Excessive ADH secretion

• Increased water retention

• Dilutional hyponatremia

• Low serum osmolality

• Inappropriately concentrated urine

Despite excess water retention, patients often appear euvolemic, meaning they do not show obvious signs of fluid overload like edema.

Pathophysiology of Syndrome of Inappropriate Antidiuretic Hormone (SIADH)

The underlying mechanism of SIADH involves:

• Persistent ADH action on the kidneys

• Increased water reabsorption in the collecting ducts

• Dilution of sodium in the blood

• Suppression of aldosterone and increased natriuresis (sodium loss in urine)

This combination leads to low sodium levels without significant fluid accumulation in tissues.

Causes of Syndrome of Inappropriate Antidiuretic Hormone (SIADH)

SIADH can be triggered by a wide range of medical conditions and external factors.

1. Central Nervous System Disorders

• Stroke

• Head injury

• Meningitis

• Encephalitis

• Brain tumors

2. Malignancies

• Small cell lung carcinoma (most common)

• Pancreatic cancer

• Prostate cancer

• Lymphoma

Certain tumors can produce ADH ectopically.

3. Pulmonary Conditions

• Pneumonia

• Tuberculosis

• Acute respiratory failure

• Mechanical ventilation

4. Medications

• Antidepressants (SSRIs, TCAs)

• Antipsychotics

• Antiepileptics (carbamazepine)

• Chemotherapy drugs

• NSAIDs

5. Post-operative States

• Major surgery

• Pain and stress response

• Anesthesia-related ADH release

6. Infections

• HIV

• CNS infections

• Severe systemic infections

7. Genetic and Idiopathic Causes

In some patients, no clear cause is identified.

Risk Factors for Syndrome of Inappropriate Antidiuretic Hormone (SIADH)

Individuals at higher risk include:

• Elderly patients

• Cancer patients

• Patients on long-term psychotropic medications

• Those with recent brain or lung disease

• Hospitalized or critically ill patients

Signs and symptoms of Syndrome of Inappropriate Antidiuretic Hormone (SIADH)

Symptoms depend largely on:

• Severity of hyponatremia

• Speed of sodium decline

Mild Symptoms

• Nausea

• Headache

• Fatigue

• Dizziness

Moderate Symptoms

• Confusion

• Muscle cramps

• Weakness

• Restlessness

Severe Symptoms

• Vomiting

• Seizures

• Decreased consciousness

• Respiratory arrest

• Coma

Rapid onset hyponatremia is particularly dangerous due to cerebral edema.

Complications of Untreated Syndrome of Inappropriate Antidiuretic Hormone (SIADH)

If not treated promptly, SIADH can lead to:

• Brain swelling

• Permanent neurological damage

• Seizures

• Respiratory failure

• Death

Overcorrection of sodium can also cause osmotic demyelination syndrome, a serious neurological condition.

Diagnosis of Syndrome of Inappropriate Antidiuretic Hormone (SIADH)

Diagnosing SIADH involves a combination of clinical evaluation and laboratory testing.

Key Diagnostic Criteria

• Serum sodium <135 mmol/L

• Low plasma osmolality

• Inappropriately high urine osmolality

• Elevated urine sodium

• Normal renal, adrenal, and thyroid function

• Clinical euvolemia

Additional Tests

• Serum cortisol

• Thyroid function tests

• Chest imaging

• Brain imaging if CNS cause suspected

Early and accurate diagnosis is essential for safe management.

Differential Diagnosis

Conditions that may mimic SIADH include:

• Hypothyroidism

• Adrenal insufficiency

• Congestive heart failure

• Liver cirrhosis

• Nephrotic syndrome

• Polydipsia

These must be ruled out before confirming SIADH.

Management and Treatment of Syndrome of Inappropriate Antidiuretic Hormone (SIADH)

Treatment depends on:

• Severity of symptoms

• Sodium levels

• Underlying cause

1. Fluid Restriction

• First-line therapy in most cases

• Typically 800–1000 mL/day

2. Treat Underlying Cause

• Stop offending medications

• Treat infections or tumors

• Manage CNS or pulmonary disease

3. Hypertonic Saline

• Used in severe or symptomatic hyponatremia

• Administered carefully under monitoring

4. ADH Antagonists (Vaptans)

• Block ADH receptors

• Increase free water excretion

• Used in resistant cases

5. Oral Salt or Urea

• Helps increase serum sodium in chronic cases

Monitoring During Treatment

Careful monitoring is critical to prevent complications:

• Frequent sodium level checks

• Strict fluid balance monitoring

• Neurological assessment

Sodium correction should not exceed 8–10 mmol/L per 24 hours.

Prognosis of Syndrome of Inappropriate Antidiuretic Hormone (SIADH)

The outcome depends on:

• Speed of diagnosis

• Severity of hyponatremia

• Underlying cause

With appropriate treatment:

• Most patients recover well

• Chronic cases require long-term monitoring

• Prognosis is poorer when associated with malignancy

Prevention and Patient Awareness

While SIADH cannot always be prevented, risk can be reduced by:

• Regular monitoring in high-risk patients

• Medication review

• Early evaluation of neurological or respiratory symptoms

• Prompt laboratory testing for unexplained symptoms

Frequently Asked Questions (FAQs)

What is the most common cause of SIADH?

Malignancy, particularly small cell lung cancer, is one of the most common causes.

Is SIADH a life-threatening condition?

Yes, severe or rapidly developing hyponatremia can be life-threatening if untreated.

Can SIADH be cured?

SIADH is often reversible if the underlying cause is treated successfully.

What sodium level is dangerous in SIADH?

Levels below 120 mmol/L are considered severe and require urgent medical care.

How is SIADH different from dehydration?

SIADH involves excess water retention, while dehydration involves fluid loss.

Can SIADH recur?

Yes, especially if the underlying cause persists or recurs.

Is fluid restriction always required?

In most cases, yes, but treatment is individualized.

Which tests confirm SIADH?

Blood sodium, serum osmolality, urine osmolality, and urine sodium tests.

Syndrome of Inappropriate Antidiuretic Hormone is a complex but treatable condition that requires timely recognition and careful management. Understanding its causes, symptoms, and diagnostic criteria helps prevent serious complications. With modern diagnostic tools and targeted therapies, patients with SIADH can achieve excellent outcomes when treated promptly and appropriately.

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