5th April 2024

Diagnosis

Numerous other conditions can present similarly to Cushing’s syndrome and it is important to exclude differentials such as metabolic syndrome; alcohol excess, pregnancy and physiological stress, before making a diagnosis. Medication history is important as chronic steroid use makes a diagnosis of Cushing’s syndrome more likely. Blood glucose should be monitored as Cushing’s syndrome can lead to glucose intolerance and diabetes.

Initial investigations include measurement of cortisol levels. This has diurnal variation with a morning peak and nadir at midnight. Measurements are checked at night when levels are lowest and the sample can be from saliva or a blood test.

Dexamethasone suppression tests are performed to confirm the diagnosis. This involves giving the patient 1mg of dexamethasone at 11pm and then testing their cortisol level at 8am the following morning. In a person without Cushing’s syndrome, the dexamethasone should inhibit further cortisol release due to the negative feedback loop on the hypothalamus-pituitary-adrenal axis, but this feedback loop is suppressed in Cushing’s syndrome. A positive result is indicated by a morning cortisol of >50 nanomols/L (it is worth noting that in some causes of Cushing’s syndrome, such as Cushing’s disease, a drop in cortisol is seen in response to high doses of dexamethasone).  Following confirmation of Cushing’s syndrome, checking ACTH levels can differentiate between ACTH-dependent and ACTH-independent causes. High ACTH levels indicate ACTH dependent causes of Cushing’s syndrome. This includes pituitary tumour (Cushing’s disease) and ectopic ACTH producing tumours. In ACTH independent causes (adrenal adenoma/bilateral adrenal hyperplasia), ACTH levels will be low.

If exogenous steroids are excluded as a cause but initial investigations still suggest Cushing’s syndrome then imaging including CT TAP and pituitary MRI are required to try and find the source of a possible ACTH or cortisol secreting tumour.