SUMMARY: Pituitary metastasis (PM) is a rare complication of an advanced malignancy. Albeit rare, PM can be more detected and achieve a longer survival rate through frequent neuroimaging and newer oncology therapies. Lung cancer is the most frequent primary site, followed by breast and kidney cancers. Patients with lung cancer generally present with respiratory symptoms and are commonly diagnosed at an advanced stage already. Nevertheless, physicians should be mindful of other systemic manifestations as well as signs and symptoms related to metastatic spread and paraneoplastic syndromes. Herein, we report the case of a 53-year-old woman who presented with PM as the first sign of an undiagnosed lung cancer. Initially, her condition was a challenging diagnosis and was even complicated with diabetes insipidus (DI), which can present as severe hyponatremia when coexisting with adrenal insufficiency. This case also highlights that treating DI with antidiuretic hormone (ADH) replacement was complicated by extreme difficulties in attaining satisfactory sodium and water balance during the clinical course, with the possibility of coexistent DI and syndrome of inappropriate ADH secretion because of the underlying lung cancer.LEARNING POINTS: When patients present with pituitary mass and diabetes insipidus (DI), pituitary metastasis should be considered as an initial differential diagnosis. DI caused by pituitary adenoma is rare and is typically a late finding.DI can present as severe hyponatremia when coexisting with adrenal insufficiency.Cortisol can directly inhibit endogenous antidiuretic hormone (ADH) secretion. Patients with adrenocorticotropic hormone deficiency will have increased tonic ADH activity and subsequently reduced capacity for free-water excretion. However, when on steroid therapy, patients should be monitored for possible DI because steroids can restore free-water excretion.A substantial change in serum sodium after desmopressin treatment should eliminate the possibility of desmopressin overdose or coexistence of DI and syndrome of inappropriate ADH secretion in patients with lung cancer. Therefore, frequent monitoring of serum sodium concentrations is crucial.