Syndrome of recurrent increased secretion of antidiuretic hormone following multiple doses of vincristine

Abstract

The syndrome of inappropriate antidiuretic hormone secretion (SIADH) has been recognized to occur following treatment with vincristine. None of the reports have provided information regarding its potential for recurrence on further challenge with vincristine (VCR), an agent generally required for repeated use in patients with malignancies. Symptomatic hyponatremia and SIADH that occurred 8 days following administration of VCR in a child with acute lymphatic leukemia was documented with specific radioimmunoassay of urinary ADH levels. The further occurrence of recurrent elevations in ADH excretion 8–10 days following repeated treatment with VCR was also observed. However, SIADH was prevented by prophylactic rigorous fluid restriction. The occurrence of SIADH following VCR therefore does not preclude the further safe usage of this drug.

Potentiation of vincristine toxicity by itraconazole in children with lymphoid malignancies

“…Side effects are varied and mainly neurotoxic, including abdominal pain, constipation, sensory and motor dysfunction, and convulsions. Hypertension may also occur with SIADH an infrequent complication (12). Itraconazole, which exerts its antifungal effect by interfering with cytochrome P450 dependent synthesis of ergosterol, the principal sterol in fungal cell membrane (13), is postulated to enhance vincristine neurotoxicity by modulating cytochrome P450 pathways via the same mechanism in hepatic microsomes (14).…”

Electrolyte Abnormalities in Lymphosarcoma After Chemotherapy

“…On the other hand, both vincristine and cyclophosphamide have the same effect on the hypothalamus and/or the hypothalamic-pituitary pathway, causing ab-normal secretion of ADH, which continues to act paradoxically since hyponatremia would be expected to suppress ADH secretion. Cases have been recorded in which ADH was found at high levels by radioimmunoassay (7). Unfortunately ADH was not measured in our patient.…”

The Syndrome of Inappropriate ADH Secretion Secondary to Vinblastine-Bleomycin Therapy

“…It is clear from the above case histories that the patients developed inappropriate ADH secretion as evidenced by low serum sodium, low serum osmolality, high urine sodium, and inappropriately high urine osmolality in the presence of normal renal and adrenal functions and hemodynamic stability. This syndrome can be brought about by drugs, and among the chemotherapeutic agents, vincristine and high-dose cytoxan are well known to produce inappropriate ADH secretion [6,11]. To our knowledge there are only three previous reports of vinblastine causing this syndrome [1,4,13].…”