From the Guidelines
The workup for Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) should begin with laboratory tests to confirm hyponatremia, including serum sodium, serum osmolality, urine osmolality, and urine sodium, as these tests are crucial in diagnosing SIADH and guiding treatment decisions 1.
Initial Evaluation
The diagnosis of SIADH requires hyponatremia (serum sodium <135 mEq/L) with decreased serum osmolality (<280 mOsm/kg), inappropriately concentrated urine (urine osmolality >100 mOsm/kg), elevated urine sodium (>20-30 mEq/L), and euvolemic status.
- Additional tests should include thyroid function tests, morning cortisol, and kidney function tests to rule out other causes of hyponatremia.
- A thorough medication review is essential to identify potential drug-induced SIADH.
Identifying the Underlying Cause
Once the initial criteria are met, further investigation should focus on identifying the underlying cause of SIADH, which commonly includes:
- Malignancies (particularly small cell lung cancer)
- CNS disorders
- Pulmonary diseases
- Medications (such as SSRIs, carbamazepine, and certain chemotherapeutics)
- Post-surgical states Imaging studies like chest X-ray or CT scan may be necessary to identify pulmonary pathology or malignancy, while brain imaging might be indicated if neurological causes are suspected.
Treatment Considerations
The treatment of SIADH often involves the use of vaptans, which selectively inhibit the V2 receptor of vasopressin, an antidiuretic hormone of the principal cell in the collecting duct of the urinary tract, as seen in studies such as 1.
- Vaptans, such as tolvaptan and conivaptan, have been shown to be effective in improving serum sodium concentration in patients with SIADH, heart failure, and liver cirrhosis.
- The use of vaptans should be considered in patients with severe hyponatremia (serum sodium <125 mmol/L) and should be started in a hospital setting with close monitoring of serum sodium levels to avoid rapid correction and potential complications 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) The workup for SIADH is not directly addressed in the provided drug label.
- The label discusses the treatment of hyponatremia, including SIADH, with tolvaptan tablets.
- It emphasizes the importance of initiating and re-initiating therapy in a hospital where serum sodium can be monitored closely.
- However, it does not provide information on the diagnostic workup for SIADH. 2
From the Research
Diagnosis of SIADH
- The diagnosis of SIADH involves assessing the patient's euvolemic state, both clinically and by laboratory measurements 3.
- Laboratory tests, such as urea, uric acid, and urine sodium levels, can help differentiate SIADH from other causes of hyponatremia 4.
- Patients with SIADH typically have low urea and uric acid levels, and high urine sodium levels (>30 mEq/L) 4.
- Measurement of urine osmolality can also be helpful in diagnosing SIADH and guiding treatment decisions 4.
Treatment of SIADH
- The management of SIADH is largely dependent on the symptomatology of the patient 5.
- Treatment options for SIADH include fluid restriction, hypertonic saline, urea, demeclocycline, and vasopressin receptor antagonists (vaptans) 3, 5.
- Vaptans are a specific and direct therapy for SIADH, and have been shown to be effective in correcting hyponatremia without the need for fluid restriction 3.
- However, careful monitoring of serum sodium levels is required to prevent overly rapid correction of hyponatremia, which can lead to osmotic demyelination 3, 5.
Clinical Considerations
- The severity of neurological symptoms and the patient's volemic status should be assessed when diagnosing and treating SIADH 6.
- Laboratory tests are necessary for diagnosis, but treatment should not be delayed in severe, symptomatic cases of hyponatremia 6.
- Treatment decisions should be individualized based on the patient's needs and priorities, taking into account factors such as signs and symptoms, risks and benefits of different treatments, and psychosocial factors 6, 7.