Hypopituitarism (HYPO) is a rare and under-investigated pathology in the elderly. Aim: to review our case records of patients ≥65 yrs with first diagnosis of anterior global hypopituitarism, in order to evaluate presentation symptoms, etiology, biochemical and hormonal pictures, pituitary morphology, and efficacy of therapy. Patients: 15 patients (65-82 yrs) were studied: in 11 (73%) HYPO was secondary to pituitary macroadenoma (nonsecreting in 10 and GH-secreting in 1); in 3 it was associated to empty sella, and in 1 to pituitary hypoplasia. Results: major presenting symptoms were visual-field defects and asthenia (40%) but also memory and/or gait impairment and nausea (30%) and depression (20%) were significantly observed. Dyslipidemia (73%), anemia (20%) and severe hyponatremia (13%) were found. After starting substitutive therapy and clinical improvement, 10 patients with macroadenoma underwent uneventful neurosurgery, which improved visual alterations but not pituitary function. Immunohistochemistry showed positivity for FSH in one patient and for GH in one patient. Six out of the eight patients with a postsurgical tumor remnant required treatment (surgery/radiotherapy/somatostatin analogue treatment in the acromegalic patient). Conclusions: The diagnosis of HYPO is often delayed in the elderly, since symptoms may be ascribed to aging and associated comorbidities. In our series, most of the aspecific symptoms were retrospectively addressed to HYPO since their resolution/improvement with replacement therapy. The prevalent cause of HYPO remains non-functioning pituitary macroadenomas. Hyponatremia can be a life-threatening presenting symptom. Symptoms considered apparently aspecific in the elderly should be investigated in order to possibly diagnose an important treatable disorder as HYPO.