Stressful life events in the pathogenesis of Cushing's syndrome.

Some clinical observations suggested that stressful life events may play an aetiological role in Cushing's syndrome. However, there are no controlled investigations using standardized methods of life events assessment to substantiate this hypothesis. Events in the year before the first signs of disease onset were investigated in 30 consecutive patients with Cushing's syndrome (26 with a pituitary-dependent form, three with an adrenal adenoma, and one with an adrenal carcinoma) and 30 control subjects matched for sociodemographic variables by means of Paykel's Interview for Recent Life Events. Patients with Cushing's syndrome reported significantly more stressful life events than a normal control group (P less than 0.001) and had significantly more of the following: exits (P less than 0.05), undesirable (P less than 0.01) and uncontrolled (P less than 0.01) events. More events that had an objective negative impact (P less than 0.001) and more independent events (unlikely to be a consequence of the illness; P less than 0.001) were also reported. Such ratings were carried out by an independent rater unaware whether the event had occurred in patients or controls. The results are suggestive of a causal relationship between stressful life events and Cushing's syndrome. Such relationship largely pertains to the hypothalamic-pituitary forms of the illness. This is in agreement with a multifactorial model of pathogenesis in Cushing's disease and with current understanding of the complex interdependence of neurophysiological, biochemical and behavioural factors.