Hypopituitarism (HYPO) is an under-investigated disease in older patients. Symptoms, which may be life-threatening, are aspecific and often attributed to aging and/or related morbidities. We describe here the cases of two elderly patients who were ultimately diagnosed as having HYPO, the clinical presentations and etiologies of which were different. In the first patient, an invasive non-secreting pituitary macroadenoma causing HYPO was detected on brain morphological evaluation for head trauma secondary to falling. Glucocorticoid replacement therapy was started. Thyroid function evaluation showed hyperthyroidism (due to a known toxic multinodular goiter), which was already on treatment with methimazole; ultimately, after withdrawal of the antithyroid drug, secondary hypothyroidism occurred. The patient underwent non-radical pituitary surgery. Cognitive function, gait impairment and falling, which had previously been attributed only to aging, improved markedly after cortisone acetate and L-thyroxine replacement therapy. The second patient was hospitalized one month after the onset of hypotension, edema and pain in the legs, and progressive psychomotor impairment, which ultimately resulted in an intermittent soporous state. She was diagnosed as having global anterior HYPO secondary to empty sella, which caused severe multifaceted clinical and biochemical abnormalities (hyponatremia, pancytopenia, rhabdomyolysis). After treatment with i.v. fluids and hydrocortisone, the patient's clinical condition and biochemical alterations improved, and normalized over time with oral cortisone acetate and Lthyroxine combination therapy. Several protean symptoms that impair the quality of life of elderly patients are usually ascribed to aging. Such symptoms should be investigated with regard to possible HYPO, treatment of which can result in significant clinical benefit.