This study investigated the pathophysiology of preoperative hyponatremia in elderly patients with a large pituitary tumor. The tumor size, initial symptoms, and preoperative pituitary hormonal function were analyzed in 96 patients, consisting of 82 younger than 70 years old (mean age 49.7 years) and 14 older than 70 years old (mean age 72.0 years). There was no difference in tumor size between the two age groups. The initial symptom of all younger patients was visual disturbance. Preoperative hormonal evaluations revealed subclinical panhypopituitarism in four patients (4.9%). Five of the 14 older patients had severe hyponatremia (107-117 mEq/l) based on panhypopituitarism, and four of these five patients showed consciousness disturbance as the initial symptom, initiated by physical and/or psychological stress, or occurrence of intratumoral hemorrhage. Preoperative subclinical panhypopituitarism was found in another patient. The overall occurrence rate of preoperative panhypopituitarism in the older patients was 42.9%. The difference in the frequency of preoperative panhypopituitarism was statistically significant between the two groups. Preoperative severe hyponatremia associated with a large pituitary tumor is characteristic of elderly patients. The number of receptors for adrenocorticotropic hormone in the adrenal cortex decreases during the aging process. Additional physical and/or psychological stress prompts pituitary dysfunction in such patients, causing the manifestation of acute symptoms of adrenal insufficiency based on panhypopituitarism. Primary care using high dose hydrocortisone and electrolyte fluid is critical.