450 http://neuro.psychiatryonline.org J Neuropsychiatry Clin Neurosci 18:4, Fall 2006 SPECIAL ARTICLE The Neuropsychiatric Profile of Addison���s Disease: Revisiting a Forgotten Phenomenon Rebecca E. Anglin, B.Sc., M.D. Patricia I. Rosebush, M.Sc.N., M.D., F.R.C.P.(C.) Michael F. Mazurek, M.D., F.R.C.P.(C.) Received November 2, 2005 revised January 8, 2006 accepted January 19, 2006. Drs. Anglin and Mazurek are affiliated with the Department of Medicine and Department of Psychiatry and Behavioral Neurosci- ences, McMaster University, Hamilton, Ontario, Canada. Dr. Rosebush is affiliated with the Department of Psychiatry and Behavioral Neu- rosciences, McMaster University, Hamilton, Ontario, Canada. Address correspondence to Dr. Rosebush, 3G15, Health Sciences Center, 1200 Main St.W, Hamilton, Ontario, L8Z 3N5, Canada rosebush@hhsc.ca (E-mail). Copyright 2006 American Psychiatric Publishing, Inc. One hundred fifty years since Thomas Addison���s original description of the disease, it is not com- monly appreciated that patients with Addison���s disease may present with psychiatric symptoms. A review of the literature indicates that disturbances in mood, motivation, and behavior are associated with Addison���s disease. Psychosis occurs less fre- quently, but can be the presenting symptom of a life-threatening adrenal crisis. Potential mecha- nisms for the neuropsychiatric symptoms of Addi- son���s disease include electrophysiological, electro- lyte and metabolic abnormalities, glucocorticoid deficiency, increased endorphins, and an associ- ated Hashimoto encephalopathy. Physicians must be aware that Addison���s disease may present solely with psychiatric symptoms and maintain a high index of suspicion for this potentially fatal condition. (The Journal of Neuropsychiatry and Clinical Neurosciences 2006 18:450���459) Aness ddison���s disease is a potentially life-threatening ill- that results from destruction of the adrenal cortex and consequent decreased production of gluco- corticoids and mineralocorticoids. In Thomas Addison���s original description of the disease in 1855, he noted that patients could develop ���attacks of giddiness,��� ���anxiety in the face��� and ���deliri[um].���1 Subsequently, Klippel in- troduced the concept of ���l���encephalopathie addison- ienne��� in 1899,2 noting that neuropsychiatric symptoms are common in adrenal insufficiency. There have been several case reports in the English literature of psycho- logical disturbances associated with Addison���s disease, largely published in the 1940s through 1960s. Four case series published in the 1940s and 1950s found the prev- alence of psychiatric symptoms in Addison���s disease to be between 64% and 84%.3���6 In the recent literature on Addison���s disease, however, the associated psychiatric manifestations have received little or no attention. As a result, many physicians, including psychiatrists, are not aware that Addison���s disease may present with psychi- atric symptoms. We recently diagnosed Addison���s dis- ease in a patient who was referred to psychiatry for

J Neuropsychiatry Clin Neurosci 18:4, Fall 2006 http://neuro.psychiatryonline.org 451 ANGLIN et al. FIGURE 1. Clinical timeline acute onset of psychosis. We present this case, followed by a review of the literature and discussion of the mech- anisms responsible for the observed disturbance in brain function. METHOD A patient presenting with psychotic symptoms was re- ferred to our psychiatry service from the emergency de- partment. We diagnosed her with underlying Addison���s disease. We followed the patient throughout her stay in the hospital for both the psychiatry and neurology ser- vices, and saw the patient in follow-up 2 months after discharge in our outpatient neurology clinic. We accessed the literature on the neuropsychiatric symptoms associated with Addison���s disease using MEDLINE. The search included English-language pub- lications from 1966 through April 2005. Keywords used included Addison���s disease, autoimmune polyendocri- nopathies, glucocorticoids, hydrocortisone, encephalop- athy, neuropsychiatric symptoms, psychotic disorders, mental disorders, depression, and cognition disorders. In addition, we reviewed citations in relevant papers. CASE REPORT A 30-year-old Caucasian married female nurse with no prior psychiatric history was referred to our psychiatry service by the emergency room for agitation, aggression, disinhibition, and delusions that her husband was preg- nant, stealing money, and committing adultery. At times she appeared to respond to auditory and visual hallu- cinations. History of Presenting Illness Two weeks prior to her presentation (Figure 1), the pa- tient had become unwell with fatigue, severe weight loss, nausea, and vomiting. She was assessed at a com- munity hospital and diagnosed with dehydration, food poisoning, and a sinus infection. She was treated with intravenous fluids, amoxicillin, and magnesium supple- ments. Her dose of thyroid medication, which had pre- viously been prescribed for hypothyroidism, was in- creased. One week prior to her presentation, the patient had largely recovered and traveled to a warm climate to attend a friend���s wedding. Three days prior to pre- sentation, while still on vacation, the patient became paranoid about her husband���s fidelity. She was reas- sured and consoled by her husband and behaved nor- mally for the remaining 2 days of the trip. While trav- eling home, however, she became agitated and aggressive. On the plane she began yelling at fellow pas- sengers, accusing them of being pregnant. She again ac- cused her husband of committing adultery, selling their house, and stealing her money. She believed that the TV show she was watching on the plane was a reality show about her life. At one point, she attempted to climb out of the airplane window. When the plane landed, she was taken immediately to the hospital emergency room by her family and referred to psychiatry by the emergency room physician. At presentation, the patient was febrile with a tem- perature of 97.9 F. She was hypotensive with a blood pressure of 76/48 and a pulse of 90 bpm. We were unable to obtain orthostatic blood pressure readings as she be- came very dizzy when standing. She was able to state here name, but was unaware of the date or that she was in a hospital. She was oriented to person but not to place