Syndrome of Inappropriate Secretion of Anti-Diuretic Hormone in Children with Acute Lymphoblastic Leukemia.

Background: The syndrome of inappropriate secretion of anti diuretic hormone (SIADH) is a well known complication of vincristine. Available literature on SIADH in pediatric acute lymphoblastic leukemia (ALL) focuses on patients with severe manifestations. We performed this study to determine the clinical consequences of SIADH that occurred during ALL therapy.

Patients and Methods: We studied all episodes of hyponatremia in patients with ALL diagnosed from December 1991 to October 2002 at St Jude Children’s Research Hospital who had not relapsed or undergone stem cell transplantation. SIADH was defined as sodium ≤ 130 meq/L in a euvolemic patient with increased urinary sodium excretion, decreased serum osmolarity and increased urine osmolarity with creatinine normal for sex and age. For each episode, we reviewed demographic features, treatment phase, predisposing factors, presenting features, duration, severity, treatment and outcome.

Results: Of 605 patients studied, 68 patients had 79 episodes of SIADH. Fifty-nine patients (87%) had only 1 episode while 9 patients (13%) had recurrences. The mean lowest serum sodium was 128.3 mEq/L (range, 121–130 mEq/L) and the mean duration of hyponatremia was 1.9 days (range, 1–14 days). Ninety-six percent of episodes were associated with the administration of 1 (n=29) or 2 (n=43) doses of vincristine in the preceding 2 weeks. Episodes were associated with infection in 51 cases and central nervous system pathology in 3 cases. Only 6 (8 %) patients had serum sodium 125 mEq/L or lower; 50% of these had altered mental status, compared to 7% whose sodium never fell below 125 mEq/L. Treatment included fluid restriction (46%), change or cessation of intravenous fluids (6%), diuretics (2%), or observation (46%). All symptomatic patients had complete neurological recovery.

Conclusions: SIADH is common during treatment for ALL but is rarely severe or symptomatic. The risk is greatest within 14 days of vincristine administration. Most episodes are self limited and need neither extensive investigation nor aggressive therapy.