Chlorpropamide-Induced ADH Release, Hyponatremia and Central Pontine Myelinolysis in Diabetes Mellitus

Chlorpropamide (CPM) has been reported to produce impaired water excretion due to the enhancement of renal vasopressin (ADH) action and/or due to centrally enhanced ADH release, but it is still unknown whether CPM gives rise to ADH release with a subsequent hyponatremia in diabetes mellitus (DM), which, in turn, causes an impairment of the central nervous system. In 3 patients with DM, who developed hyponatremia during the treatment with CPM, an acute water load (WL) was carried out in the presence and absence of the drug, and plasma ADH was determined with plasma and urine osmolalities. Moreover, in 2 cases, MRI scans of the brain were taken. In all the patients, acute WL tests failed to suppress completely ADH release in response to changes in plasma osmolality in the presence of CPM, which, in turn, resulted in the impaired water excretion. In the absence of CPM, an acute WL normally suppressed plasma ADH leading to the diuresis. MRI scans illustrated the presence of central pontine myelinolysis. It is likely that CPM might stimulate ADH release in DM with a subsequent hyponatremia and brain damages.