A 48-year-old man presented with long-standing symptoms of major depression in the absence of markedly abnormal neurological findings or structural brain alterations. Antidepressive treatment, including medication and psychotherapy, had not led to significant improvement. The EEG, cerebrospinal fluid (CSF) analysis, fluorodeoxyglucose-positron emission tomography and neuropsychological testing showed pathological findings. An epileptic state provided further evidence for an organic encephalopathy. Extensively elevated thyroid-antibodies in the serum and CSF, as well as the rapid and sustained recovery after intravenous treatment with prednisolone, pointed to the diagnosis of a primarily psychiatric manifestation of a steroid responsive encephalopathy associated with autoimmune thyroiditis (SREAT).