Syndrome of Inappropriate Antidiuretic Hormone (SIADH)

The following findings suggest SIADH:
A low serum osmolality
An inappropriately elevated urine osmolality
A urine sodium concentration usually above 40 meq/L
Low blood urea nitrogen and serum uric acid concentration
A relatively normal serum creatinine concentration
Normal acid-base and potassium balance
Normal adrenal and thyroid function
The most uncertainty lies in excluding hypovolemia as a cause of hyponatremia vs SIADH.
In this case, some recommend a slow infusion of .9%NS (2L over 24-48h) as hyponatremia should improve with volume contraction and worsen with SIADH. Measuring ADH is not recommended.

SIADH Treatment:
Acute symptomatic hyponatremia should be treated with 3% NS with goal of 1-2 mmol/L inc in Na hourly
Most recommend correcting by 8-10 mmol/L Na over 24 hrs and 18-25 for first 48 hrs. A goal of symptom improvement is safer than normalization of sodium, which is not recommended.

Correction of chronic SIADH is associated with a documented risk of osmotic demyelination if Na is corrected more than 12mmol/L in 24 hrs. Unlike acute SIADH, there is no urgency in correcting Na, and one should slowly increase it ie) 8mmol Na per 24 hrs. Monitoring bmp every 2-3 hrs is key.
Free water restriction is the cornerstone. Pharmacotherapy includes Demeclocycline, which reduces urinary osmolality and raises serum sodium but may cause nephrotoxicity. Lithium is no longer used. Again, a goal of symptom improvement is safer than normalization of sodium.

Calculating Initial Saline Bolus:
There are many complex formulas to guide 3% NS dose and rate
A simple strategy is to start 3% NS at 1-2mL/kg/hr
2-4mL/kg/hr may be used briefly in seizure and/or coma due to hyponatremia
.5-1mL/kg/hr may be used for milder symptoms
Again, check sodium q 2-3 hrs and shoot for an increase of 1-2mmol/L Na per hour

Conivaptan, a vasopressin-receptor antagonist, is FDA approved for IV treatment of euvolemic and hypervolemic hyponatremia. It is a nonselective antagonist and also blocks V1 receptor causing some vasodilation, which in theory could cause HypoTension. Other side effects are infusion site reactions and drug interactions (metab by cytochrome p450)

Tolvaptan, an oral V2 selective antagonist, was FDA approved in 2009 for euvolemic and hypervolemic hyponatremia due to CHF, cirrhosis or SIADH. It should be initiated in the hospital withOUT fluid restriction and WITH frequent Na monitoring out of concern for demyelination with rapid correction.

Ellison and Berl. Syndrome of Inappropriate ADH. NEJM 356;20 www.nejm.org may 17, 2007

(Ellen Eaton MD, 4/12/11)