What is the evaluation for Syndrome of Inappropriate Antidiuretic Hormone (SIADH) secretion?

From the Guidelines

To evaluate Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH), start with a comprehensive assessment including serum sodium, osmolality, urine sodium, and urine osmolality, as this approach has been supported by recent guidelines 1. When evaluating SIADH, it is crucial to consider the patient's clinical presentation, including signs and symptoms such as general weakness, confusion, headache, and nausea, which are determined by the degree of hyponatremia and the acuity of hypoosmolality 1.

Key Diagnostic Criteria

• Hyponatremia (serum sodium < 134 mEq/L)
• Hypoosmolality (plasma osmolality < 275 mosm/kg)
• Inappropriately high urine osmolality (> 500 mosm/kg)
• Inappropriately high urinary sodium concentration (> 20 mEq/L)
• Absence of hypothyroidism or adrenal insufficiency or volume depletion These criteria are essential for diagnosing SIADH, as they distinguish it from other causes of hyponatremia 1.

Additional Tests and Considerations

Additional tests should include:

• Thyroid function tests
• Cortisol levels
• Kidney function tests to rule out other causes of hyponatremia A complete medication review is also essential, as many drugs can cause SIADH, including certain antidepressants, antipsychotics, and chemotherapeutic agents 1. Imaging studies such as chest X-ray or CT scan may be necessary to identify potential underlying causes like malignancies or pulmonary diseases 1.

Underlying Etiologies

Once SIADH is confirmed, it is crucial to investigate for underlying etiologies, including:

• CNS disorders
• Pulmonary diseases
• Malignancies
• Medications Treating the underlying cause is vital for effective management of the syndrome 1. The most recent guidelines recommend a thorough evaluation and treatment of the underlying cause, as well as management of hyponatremia with fluid restriction, demeclocycline, and vasopressin receptor inhibitors as needed 1.

From the FDA Drug Label

Tolvaptan tablets are indicated for the treatment of clinically significant hypervolemic and euvolemic hyponatremia (serum sodium <125 mEq/L or less marked hyponatremia that is symptomatic and has resisted correction with fluid restriction), including patients with heart failure and Syndrome of Inappropriate Antidiuretic Hormone (SIADH) In two double-blind, placebo-controlled, multi-center studies (SALT-1 and SALT-2), a total of 424 patients with euvolemic or hypervolemic hyponatremia (serum sodium <135 mEq/L) resulting from a variety of underlying causes (heart failure, liver cirrhosis, syndrome of inappropriate antidiuretic hormone [SIADH] and others) were treated for 30 days with tolvaptan or placebo, then followed for an additional 7 days after withdrawal.

The evaluation of SIADH can be done by using tolvaptan as it is indicated for the treatment of clinically significant hypervolemic and euvolemic hyponatremia, including patients with SIADH.

• Key points:
  • Tolvaptan is used to treat hyponatremia in patients with SIADH.
  • The usual starting dose for tolvaptan is 15 mg administered once daily without regard to meals.
  • The dose of tolvaptan can be increased at 24-hour intervals to 30 mg once daily, then to 60 mg once daily, until either the maximum dose of 60 mg or normonatremia (serum sodium >135 mEq/L) is reached.
  • Treatment with tolvaptan should be initiated and re-initiated in a hospital where serum sodium can be monitored closely 2, 2, 2.

From the Research

SIADH Evaluation

• The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a common cause of hyponatremia, accounting for approximately one-third of all cases 3.
• Diagnosis of SIADH involves assessing the euvolemic state of extracellular fluid volume, both clinically and by laboratory measurements 3.
• Treatment options for SIADH include fluid restriction, demeclocycline, urea, frusemide, and saline infusion, as well as vasopressin-2 receptor antagonists (vaptans) 3, 4.
• Vaptans have been shown to be effective in treating SIADH, with advantages including no need for fluid restriction and rapid correction of hyponatremia 3, 4.
• However, the use of vaptans is limited by their high cost 4.

Treatment Considerations

• The treatment of SIADH should be individualized based on the patient's symptoms, risks, and benefits of different treatments, as well as psychosocial factors and patient wishes 5.
• Fluid restriction and hypertonic saline are commonly used treatments for SIADH, but may have limitations 3, 6.
• The introduction of vaptans has allowed for more targeted treatment of SIADH, but their efficacy and safety in acute severe symptomatic hyponatremia are still being studied 4.
• Careful monitoring of serum sodium levels is necessary to adjust therapy and prevent overly rapid correction of hyponatremia 3, 6.

Diagnostic Measures

• Laboratory tests are necessary for the diagnosis of SIADH, but may not always be available in a timely manner 5.
• A subgroup of patients with rigorously defined SIADH via measurement of relevant laboratory parameters can be analyzed to determine the efficacy of different treatments 7.
• Appropriate laboratory tests to diagnose SIADH were obtained in less than 50% of patients in one study, highlighting the need for improved diagnostic practices 7.

Outcomes

• Current treatment of hyponatremia in SIADH often uses therapies with limited efficacy, with many patients being discharged from the hospital still hyponatremic 7.
• The use of vaptans has been associated with shorter hospital length of stay in some cases, but outcomes may vary depending on the population and treatment approach 7.
• Overly rapid correction of hyponatremia can occur in some cases, highlighting the need for careful monitoring and adjustment of therapy 3, 7.