Essential hypernatraemia, antidiuretic hormone and neurophysin secretion: response to chlorpropamide

An adolescent boy with essential hypernatremia, absent corpus callosum, mental retardation, hypodipsia, and partial diabetes insipidus with "inappropriate" ADH regulation and secretion was studied regarding factors controlling ADH and neurophysin release. Persistent hyperosmolality was noted while on 100 mEq sodium intake daily. Endogenous vasopressin activity was demonstrated after prolonged water deprivation. Hypertonic saline infusion produced increased volumes but dilute urine. Aqueous pitressin increased urinary osmolality, decreased serum osmolality, urine flow rate, and free water clearance. Stable water diuresis was induced by water loading and on normal saline infusion. Nicotine-stimulated neurophysin remained unexpectedly low and below the level of detectability when sampled during the physiologic studies, whereas oestrogen-stimulated neurophysin was elevated during oestrogen stimulation, water loading, and orthostasis procedures. Plasma vasopressin was suppressed with water loading but remained suppressed 90 min after tilt table testing. These data indicate impairment of the osmoreceptor mechanism: however, since the patient had a normal response of oestrogen-stimulated neurophysin, that part of the neurohypophysis appears intact. Chlorpropamide was effective in alleviating the hyperosmolar state acutely and maintained normal osmolar concentrations during two years of therapy.