A 44-year-old woman reported several weeks of fatigue, somnolence, pain in the large joints, nausea, and decreased appetite. She had also noted an unintentional 11-kg weight loss over a period of 6 months. She had a remote history of amenorrhea, but she was presently menstruating regularly. She was taking no medications, with the exception of acetaminophen as needed for knee pain. The diagnosis of adrenal insufficiency (AI) was considered. Serum cortisol level after adrenocorticotropin hormone (ACTH) stimulation was abnormal. Because her plasma ACTH level was not increased, a diagnosis of secondary AI (due to deficiency in ACTH) was made. Magnetic resonance imaging of the brain performed to exclude the presence of a sellar or suprasellar mass showed reduction in size of the pituitary gland and an increased cerebrospinal fluid content within the sella, consistent with a partially empty sella. The patient’s symptoms improved rapidly with hydrocortisone therapy but during follow-up, the dose of hydrocortisone was found to be excessive. Important differences exist between primary and secondary AI, and the diagnosis of secondary AI may be challenging. The therapy of AI should be carefully tailored to the requirements of the individual patient.