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A relatively simple, standardized 6 1/2 hour water deprivation test is described which adequately differentiates disorders of the neurohypophyseal-hypothalamic system from primary polydipsia. Normal subjects are characterized by an initial serum osmolality between 273 and 293 milliosmoles (mOsm) per kilogram by remarkable constancy of the serum osmolality throughout the 6 1/2 hours and by a urine-to-serum osmolality ratio of 1.9 or greater. Individuals with diabetes insipidus show loss of this homeostatic mechanism to a variable degree. All patients with diabetes insipidus demonstrate defective urinary concentrating capacity. Those patients with diabetes insipidus severe enough to require vasopressin therapy invariably show serum osmolar concentrations of 300 mOsm/kg or greater by the end of the test. Individuals with primary polydipsia demonstrate stability of serum osmolality at normal or slightly below normal levels, while urinary osmolality at the end of the test period is within normal limits.

PITUITARY ABLATION by stereotactic transnasal Yttrium Y 90 implantation has been carried out at this institution in a number of patients with advanced metastatic mammary carcinoma.1 The occurrence of subsequent water intoxication and the ultimate degree of diabetes insipidus varied from case to case, indicating that the interruption of the hypothalamico-hypophyseal system was frequently incomplete.2 The question is: Are these disturbances determined by the degree of pituitary damage or by the degree of retrograde loss of hypohyponeurons, or both?In the present study an attempt was made to correlate diabetes insipidus with hypothalamic damage by assessing the degree of nuclear and neuronal atrophy occurring in the supraoptic (SON) and paraventricular (PVN) nuclei of five patients who died from 5 to 20 months following Yttrium Y 90 hypophysectomy and in whom both anterior and posterior pituitary function had been studied preoperatively and postoperatively. Estimates of degree of