Case Presentation: We present a rare manifestation of adrenal insufficiency with initial symptoms limited to psychosis. A 51 y.o male, with hypothyroidism, but no prior psychiatric history presented with acute behavioral changes. Approximately 14 days prior to presentation he was diagnosed with sinus infection, treated with antibiotics and oral hydration. He consumed excessive fluids and was admitted to an outside institution with hyponatremia (Na: 119).  His sodium was corrected and he was discharged, 4 days later Na was 134, K: 4.6, Cl:95, Cr: 0.8. He then developed racing thoughts, irritable, argumentative mood, insomnia with memory deficit. He was taken to the ER for neuropsychiatry evaluation.  His laboratory evaluation revealed stable Na: 134, Cl: 94, normal glucose, K and Cr and no metabolic acidosis. He had negative Urine Toxin Screen and UA, normal CBC, LFTs, NH3, B12 and TSH. Brain MRI was unremarkable.  Examination revealed dark nipples, tangential, rapid speech, agitation, perseveration, disorganized thought process with attachment to details, poor judgment, concentration and memory. The constellation of symptoms was consistent with acute psychosis.  His vital signs were normal, he had no tachycardia, fever or hypotension.  Primary adrenal insufficiency was diagnosed based on low AM cortisol at 1.7mcg/dl,  high plasma ACTH at 441 pg/ml, and subnormal response to ACTH stimulation (cortisol 30 min: 1.5mcg/dl, cortisol 60 min: 1.6  mcg/dl). Initially IV, then oral hydrocortisone supplementation was initiated leading to complete psychiatric recovery. 

Discussion: Primary adrenal insufficiency (Addison’s disease) is a potentially life threatening condition, characterized by impaired production or action of glucocorticoids, and/or mineralocorticoids and adrenal androgens.   The signs and symptoms of chronic primary adrenal insufficiency are nonspecific like fatigue, weight loss, nausea, hyperpigmentation, myalgia/arthralgia, salt craving, postural hypotension, anemia, hyponatremia, hyperkalemia and hyperchloremic metabolic acidosis.  The disease may remain undetected until infection or stressors precipitate an adrenal crisis (manifested by shock, hypotension, fever, electrolyte disturbance, confusion and delirium).  Neuropsychiatric symptoms, like impaired memory, depression, anxiety are commonly seen with chronic untreated adrenal insufficiency, and can progress to psychosis, mania and delirium. Neuropsychiatric disturbance may predate the usual biochemical and clinical manifestations of Addison’s disease and can manifest as psychosis without associated features of Addison’s crisis.  The etiology of neuropsychiatric symptoms in Addison’s disease is not well understood. The brain, especially the hippocampus has glucocorticoid receptors. Glucocorticoid deficiency can result to frontal circuit dysfunction, and can alter the reasoning, thinking, and executive function. Low cortisol stimulates proopiomelanocortin synthesis resulting in increased endorphin production. Higher endorphins are correlated with hallucinations and psychosis.  

Conclusions: Addison’s disease can present solely with psychiatric symptoms.  Maintaining a high index of suspicion for this potentially life threatening condition is crucial to avoid misdiagnosis and delay of curative therapy.  Diagnostic testing, like AM Cortisol, plasma ACTH, and ACTH stimulation are readily available. Corticosteroid supplementation is expected to lead to full recovery.