Incidence: 5-6 New Cases per million per year

Cushing's disease

Cushing's disease ((i.e., an ACTH-secreting pituitary adenoma) is the most common cause of spontaneous Cushing's syndrome; other causes are an adrenal tumour or an ectopic tumour secreting ACTH.  Spontaneous Cushing's syndrome is caused by excessive circulating Cortisol; it is rare but it is associated with a significant increase in morbidity and mortality, even if treated.  Cushing's syndrome may also be the unavoidable result of steroid treatment for allergy, asthma, arthritis or other life-threatening condition. Diagnosis and differential diagnosis of Cushing's syndrome is complex and referral to a specialist centre is recommended in all cases in whom the condition is suspected.  The recommended route of referral is through an Endocrinologist rather than neurosurgeon or others.  Please see 'Who and When to Refer' (factsheet 14).

Presenting symptoms

• moon face - particularly filling in of the temporal fossa
• weight gain - central obesity
• muscle wasting and proximal myopathy (patients have difficulty standing from a seated position without use of arms)
• thin skin  - tendency to bruise
• hirsutism (caused by androgen excess)
• violaceous striae
• hypertension
• diabetes
• osteoporsis and fractures
• psychiatric disturbance (often characterised by amplification of previous personality traits)

Investigations

Overnight dexamethasone suppression test and/or 24 hour urinary cortisol measurements. If this indicates Cushing's syndrome further tests to confirm the diagnosis and to determine the source of excessive cortisol will be required.  Normal screening tests do not always exclude the diagnosis - if clinical suspecion is high then specialist referral may still be necessary.

During diagnosis and differential diagnosis further dynamic endocrine tests, chest X-ray and pituitary, adrenal and lung/abdomen MRI or CT scans may be required.

Treatment possibilities

Transsphenoidal surgery is usually the recommended treatment if the condition is due to a Pituitary tumour. In cases where surgery is contra-indicated or fails to reduce cortisol levels, Adrenalectomy and/or pituitary Radiotherapy may be necessary.

Patient management

Post-operative

Patients in remission normally undergo substantial changes immediately after surgery which, apart from welcome changes in physical appearance and resolution of other symptoms and signs, may initially involve depression. This is the result of the profound change in steroid status. No further treatment may be required except monitoring for recurrence of Cushing's and regrowth of the tumour. However most patients will require Hydrocortisone therapy, some on a long-term basis. If the patient needs hydrocortisone for more than one year post-operatively, the outlook for long-term remission is excellent. If surgery results in hypopituitarism, long-term hormone replacement therapy will be required (factsheet 11).

Long-term

Patients require close follow up on a long-term basis. Pituitary hormone therapy will be required after surgery in some cases, and requires careful specialist monitoring. Advice should be given regarding the dose of steroid to be taken during intercurrent illness (factsheet 11).

Long-term effects of radiotherapy may also include the development of partial or complete hypopituitarism. Patients may need help to follow a suitable diet and encouragement to take regular exercise to control weight gain.

Watchpoints

Urgent - refer to hospital

• Deterioration of vision
• Clear fluid dripping down the back of the throat or through the nose soon after surgery (CSF leak - factsheet 9)

Non-urgent (but still very important)

• If the patient is on hydrocortisone, ensure that replacement therapy is increased when seriously ill or under major physical or psychological stress
• Patients may have major mood swings after successful treatment to lower circulating corticosteroids. This can last for many months, so reassurance and treatment for depression may be necessary
• Obesity is often the aspect of Cushing's disease that female patients find most distressing. Weight reduction following successful treatment is often slow
• Patients will need exercises to restore muscle strength and possibly further treatment for Osteoporosis

Resources for patients

Please go to the Resource Library of this website to access resources for patients.  Our library includes literuature, newsletters and articles available from The Pituitary Foundation as well as the contact information for other organisations who provide support and information.  All of our patient leaflets are available to read as well as downloadable in PDF format from this website. 

Resources for GPs

Endotext.org 'Your Endocrine Source'
www.endotext.org  (www.endotext.org/neuroendo/index.htm)

Management of Pituitary Tumors: The Clinician's Practical Guide (2003) (Second Edition), Editors and authors Michael P. Powell, Stafford L. Lightman and Edward R. Laws. Humana Press, Totowa, New Jersey

Pituitary Tumours. Recommendations for service provision and guidelines for management of patients. Consensus statement of a working party (1997) RN Clayton & JAH Wass (Eds) London: Royal College of Physicians

The Epidemiology, Pathogenesis and Management of Pituitary Tumours (1998) Webb SM (Ed) Bristol, UK: BioScientifica

Oxford Textbook of Endocrinology OUP (2002) JAH Wass & S Shalet (Eds)