What are the criteria for diagnosing Hyponatremia (low sodium levels in the blood) related to Syndrome of Inappropriate Antidiuretic Hormone (SIADH) secretion?

From the Guidelines

Hyponatremia related to SIADH is diagnosed when specific criteria are met, including hyponatremia (serum sodium < 134 mEq/L), hypoosmolality (plasma osmolality < 275 mosm/kg), inappropriately high urine osmolality (> 500 mosm/kg), and inappropriately high urinary sodium concentration (> 20 mEq/L) in the absence of diuretic treatment, adrenal insufficiency, heart failure, cirrhosis, and hypothyroidism 1.

Diagnosis of SIADH

The diagnosis of SIADH is based on the following 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

Management of SIADH

The management of SIADH typically begins with fluid restriction (< 1 L/d) for asymptomatic mild cases, and pharmacologic options such as demeclocycline, lithium, and vasopressin 2 receptor antagonists (conivaptan, lixivaptan, tolvaptan, and satavaptan) may also be used to correct hyponatremia 1. For severe symptomatic hyponatremia (serum sodium < 120 mEq/L with neurological symptoms), more aggressive treatment with hypertonic (3%) saline is required, aiming for sodium correction of 4-6 mEq/L in the first 24 hours to prevent osmotic demyelination syndrome.

Underlying Cause of SIADH

The underlying cause of SIADH, such as malignancy, CNS disorders, pulmonary disease, or medications, should be identified and addressed whenever possible 1. It is worth noting that other evidence, such as the 2013 ACCF/AHA guideline for the management of heart failure 1 and the 2022 AHA/ACC/HFSA guideline for the management of heart failure 1, may not be directly relevant to the diagnosis and management of SIADH, and therefore should not influence the management of this condition.

From the Research

Hyponatremia Related to SIADH Criteria

• Hyponatremia is the most frequent electrolyte disorder, and the syndrome of inappropriate antidiuretic hormone secretion (SIADH) accounts for approximately one-third of all cases 2.
• In the diagnosis of SIADH, it is essential to ascertain the euvolemic state of extracellular fluid volume, both clinically and by laboratory measurements 2.
• The clinical management of SIADH involves treating the condition to cure symptoms, with therapeutic modalities including nonspecific measures such as fluid restriction, hypertonic saline, urea, and demeclocycline 2.

Treatment Options for SIADH

• Vasopressin receptor antagonists, called vaptans, have been introduced as specific and direct therapy for SIADH, offering advantages such as no need for fluid restriction and rapid correction of hyponatremia 2, 3.
• Tolvaptan, a selective vasopressin V2-receptor antagonist, is approved for the treatment of SIADH-related hyponatremia, with studies showing its efficacy and safety in long-term treatment 4, 5.
• The use of vaptans, including tolvaptan, has been shown to be effective in treating mild to moderate hyponatremia in patients with SIADH, with a good safety profile 3, 5, 6.

Important Considerations in SIADH Treatment

• It is crucial to limit the daily increase of serum sodium to less than 8-10 mmol/liter to prevent osmotic demyelination 2.
• Monitoring of serum sodium levels is essential, particularly during the first 24 hours of treatment with vaptans, to prevent overly rapid correction of hyponatremia 2.
• Discontinuation of vaptan therapy should be monitored to prevent hyponatremic relapse, and tapering of the vaptan dose or restricting fluid intake may be necessary 2.