Cushing's Disease

 

Definition and Presentation

A disease caused by overproduction of cortisone. The overproduction is stimulated by an excess of the pituitary hormone ACTH that regulates adrenal gland production of cortisone. In Cushing's disease the ACTH overproduction usually comes from a benign tumour in, or very close to the pituitary gland. In Cushing's syndrome the clinical features are the same as in Cushing's disease but the ACTH regulatory hormone emanates from a tumour in another location or by a condition in the adrenal gland itself. A Cushing syndrome can also be produced by medication with cortisone or cortisone derivatives.

 

A patient with pronounced Cushing's disease may present with the classic features of moon-face, redistribution of fat to abdomen and upper back, thin skin with bruising and hypertension. There may also be emotional disorders, back pain from decalcification from the skeleton and generalised muscular weakness. In more than 50% of the patients only a milder form of the characteristic symptoms are found. Due to hypertension, hypercholesterolemia and impaired immune function, patients with an active untreated disease run a risk of death from cardiovascular and infectious complications.

 

Diagnosis

The ultimate diagnosis rests on an assessment of cortisol and ACTH hormone levels in the blood. Only 60% of ACTH producing pituitary tumours can be visualised by MRI. Cushing's disease is established when it can be shown that the increased level of cortisol in the blood is caused by an excessive ACTH production from the pituitary gland. Sometimes blood sampling from veins draining the pituitary area as well as from peripheral blood is required.

 

Treatment

Many pituitary tumours producing excessive ACTH (or so-called microadenomas) are less than 5mm in diameter and some are not visible on MRI scans. However, most of them can be identified during transphenoidal surgery. This is therefore the treatment of choice when diagnosis has been established. The success rate is 65-85%. The risk of recurring disease is 10-20%. It has been shown that Gamma Knife surgery up-front can be equally effective but due to the frequent problems of visualisation of the small tumour it is still not considered the primary choice. This may change with improving imaging techniques. Cortisol production and the manifestations of the disease can also be suppressed by certain drugs (e.g. ketoconazole). Drug treatment is currently recommended only as a temporary solution when the patient is awaiting definitive treatment.