Cushing's syndrome

Clinical information

The function of the adrenal cortex is to synthesise numerous steroid hormones. These are divided into glucocorticoids (e.g. cortisol), mineralocorticoids (e.g. aldosterone) and sex hormones (e.g. androgens). The amount and timing of the hormone production is primarily regulated by the adrenocorticotropic hormone (ACTH) which is produced by the pituitary gland. ACTH release is controlled in turn by the corticotropin-releasing hormone (CRH).

Cortisol is the main glucocorticoid. Under the control of ACTH stimulation, cortisol secretion follows a diurnal rhythm so that the blood levels of the hormone are highest is the early morning and then decrease during the day.

Cortisol regulates glucose metabolism by enhancing the gluconeogenesis (synthesis of glucose) and by increasing the blood glucose levels. Further, it favours mobilization of fats and it modulates the immune response with an anti-inflammatory action. Lastly, cortisol modulates the response of the vascular system to vasoactive chemicals, including angiotensin II.

Cortisol production in the adrenal cortex can be impaired by different conditions, resulting in an over- or underproduction of the hormone.

Diagnostics

The physiology of cortisol can be altered in two ways: it can be either abnormally increased or abnormally reduced.

The excess of cortisol secretion – or hypercortisolism – is a condition referred to as Cushing’s syndrome (CS). CS is characterized by symptoms that may include weight gain, high blood pressure, spontaneous bruising and a moon-shaped face. When CS is suspected, one or more tests including the measurement of cortisol in blood, saliva or urine are recommended.

If CS is confirmed, the assessment of ACTH allows to differentiate the cause. The hypercortisolism could be driven by high levels of ACTH in the blood as, for instance, in the presence of a pituitary adenoma (Cushing’s disease) or an ectopic ACTH secreting tumour. Alternatively, the hypercortisolism could be caused by an over-secretion inherent to the adrenal gland, for instance due to an adrenal tumour (ACTH-independent CS).