Can Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) develop suddenly in an adult with a longstanding large meningioma?

Can SIADH Develop Suddenly After Longstanding Large Meningioma?

Yes, SIADH can develop suddenly in patients with longstanding large meningiomas, as CNS space-occupying lesions are well-established causes of SIADH through disruption of hypothalamic-pituitary function. 1

Mechanism and Pathophysiology

CNS tumors, including meningiomas, can cause SIADH by disrupting the normal hypothalamic-pituitary axis, leading to inappropriate ADH secretion despite hyponatremia and low plasma osmolality. 1 The mechanism involves:

• Direct compression or infiltration of the hypothalamus or posterior pituitary by the tumor mass 1
• Damage to the pituitary stalk causing non-osmotic hypersecretion of ADH 2
• Nonosmotic stimuli such as increased intracranial pressure, which can override normal osmotic regulation 1

Large meningiomas are particularly prone to causing SIADH because they frequently present with significant mass effect, edema (occurring in 40-80% of cases), and symptoms of raised intracranial pressure. 3

Why Sudden Onset Can Occur

Several factors explain why SIADH may develop suddenly in a longstanding meningioma:

• Acute tumor expansion or hemorrhage into the tumor can rapidly increase mass effect 3
• Progressive peritumoral edema accumulation, which is common in large meningiomas, can acutely worsen 3
• Development of acute intracranial hypertension from the tumor's mass effect 3
• Proximity to critical structures: Meningiomas near the pituitary gland or hypothalamus pose particular risk for hormonal dysfunction 3

Diagnostic Confirmation

When SIADH is suspected in a patient with a known meningioma, confirm the diagnosis by simultaneously checking: 1

• Serum sodium <134 mEq/L with plasma osmolality <275 mosm/kg 1
• Urine osmolality >500 mosm/kg (inappropriately concentrated despite low plasma osmolality) 1
• Urine sodium >20 mEq/L (continued natriuresis) 1
• Clinical euvolemia (no orthostatic hypotension, tachycardia, edema, or ascites) 1
• Normal thyroid and adrenal function (TSH and cortisol) to exclude other causes 1

Serum uric acid <4 mg/dL has a 73-100% positive predictive value for SIADH and can help confirm the diagnosis. 4

Critical Clinical Pitfall: Distinguishing SIADH from Cerebral Salt Wasting

The most important diagnostic challenge is differentiating SIADH from cerebral salt wasting (CSW), as they require opposite treatments—SIADH requires fluid restriction while CSW requires volume and sodium replacement. 1, 4 This distinction is critical because:

• Both conditions present with hyponatremia in neurosurgical patients 1
• SIADH patients are euvolemic (CVP 6-10 cm H₂O), while CSW patients are hypovolemic (CVP <6 cm H₂O) 4
• Physical examination alone has poor accuracy for volume assessment; CVP measurement should be used when available 1
• Incorrect treatment (fluid restriction in CSW) can worsen outcomes 4

Management Algorithm

For Severe Symptomatic Hyponatremia (Sodium <120 mEq/L with neurological symptoms):

• Transfer to ICU for close monitoring 4
• Administer 3% hypertonic saline with goal to correct 6 mmol/L over 6 hours or until severe symptoms resolve 4
• Monitor serum sodium every 2 hours initially 4
• Never exceed 8 mmol/L correction in 24 hours to prevent osmotic demyelination syndrome 4
• For patients with malnutrition, alcoholism, or advanced liver disease, use more cautious correction rates of 4-6 mmol/L per day 4

For Mild-Moderate Symptomatic or Asymptomatic Hyponatremia (Sodium 120-134 mEq/L):

• Fluid restriction to 1 L/day as first-line treatment 4
• Monitor serum sodium levels regularly during treatment 4
• Consider demeclocycline as second-line therapy if fluid restriction is ineffective or poorly tolerated 4, 2

Special Consideration for Meningioma Patients:

If the patient is being considered for surgical resection or has acute intracranial hypertension, corticosteroids may be prescribed for management of mass effect, which could potentially help with SIADH as well. 3 However, the definitive treatment is addressing the underlying tumor through surgical resection when feasible 3, 5

Monitoring for Hormone Dysfunction

Baseline evaluation and monitoring of pituitary hormone levels should be considered in patients with meningiomas in close proximity to the pituitary gland, as hormonal dysfunction can develop. 3 This is particularly important for:

• Large skull base meningiomas 3
• Tumors with documented proximity to hypothalamic-pituitary structures on imaging 3
• Patients developing new endocrine symptoms 3

Long-term Considerations

SIADH following CNS lesions like meningiomas can be chronic and persistent, sometimes lasting years if the underlying tumor is not treated. 2 In cases where:

• Surgical resection is not feasible due to tumor location or patient factors 3
• The tumor is being observed rather than treated 3
• Residual tumor remains after incomplete resection 3

Long-term management with fluid restriction or demeclocycline may be necessary, as adherence to permanent fluid restriction is challenging and demeclocycline has proven effective and well-tolerated for chronic SIADH 2