Hypercortisolism is associated with mood disorders such as depression and bipolar disorder. A 75-year-old female patient who had been diagnosed with bipolar disorder forty years ago was admitted to our hospital with a severe, therapy-resistant mania. Careful diagnostic considerations, resulted in the patient being diagnosed with Cushing’s syndrome. Treatment with metyrapone led to a swift improvement of the patient’s symptoms. Could Cushing’s syndrome underlie this patient’s psychiatric history? Or are two co-existing, intertwining causes responsible for the psychiatric symptoms? The case illustrates that even if a patient has a long history of psychiatric problems that have been plausibly diagnosed over time, clinicians and psychiatrists should always consider the possibility that there may be an underlying somatic cause for the patient’s psychiatric symptoms.