Endocrine Abstracts

Background: Hyponatremia due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a very common electrolyte disorder in older patients leading often to hospital admissions. Symptoms can vary between mild disabilities (e.g. nausea, dizziness, attention deficits, gait disturbance) to severe life-threatening conditions (e.g. seizures, coma). Treatment of SIADH is challenging in particular when fluid restriction is limited or even not effective in restoring normal sodium levels. Therefore, selective vasopressin receptor antagonists rising serum sodium levels by increasing the output of electrolyte-free water have become important treatment options. Tolvaptan, a selective vasopressin 2 receptor antagonist is approved for the treatment of patients with hyponatremia or autosomal dominant polycystic kidney disease. However, poor data is available especially concerning long-term treatment of elderly patients with tolvaptan and idiopathic SIADH.

Methods: Case report.

Results: We report three patients (mean age: 83 years) with refractory hypo-osmolar hyponatremia due to idiopathic SIADH. Two of them needed repeated treatment with hypertonic saline in the intensive-care unit because of severe symptomatic hyponatremia with confusion and seizures (serum sodium below 110 mmol/l in both cases). After initial stabilization of serum sodium levels subsequent treatment with tolvaptan (15 mg per day) was begun in all patients leading to a quick recovery and stabilization of serum sodium without any additional measures. Dosing interval then was extended stepwise and under close monitoring to an administration every second then every third day, thereby achieving persistent normal serum sodium values. Drug tolerance was excellent in all patients without any side effects (e.g. hepatotoxicity). After a mean follow-up of 28 months all patients treated with tolvaptan demonstrate persistent normal natremia and no need for re-hospitalization.

Conclusions: Tolvaptan should be recognized as a very effective, easy to handle, well-tolerated and probably cost-effective therapy in old patients with severe forms of chronic refractory SIADH. On a long term basis extended dosing regimens (e.g. every second/third day) under close monitoring are feasible.