Cushing's syndrome

What is Cushing's syndrome?
Statistics on Cushing's syndrome
Risk Factors for Cushing's syndrome
Progression of Cushing's syndrome
How is Cushing's syndrome Diagnosed?
Prognosis of Cushing's syndrome
How is Cushing's syndrome Treated?
Cushing's syndrome References

What is Cushing's syndrome?

Cushing's syndrome refers to the syndrome associated with excessive levels of a type of hormones - glucocorticoids. Glucocorticoids (mainly cortisol) are secreted naturally by the adrenal cortex in response to stimulation from the pituitary gland (ACTH hormone), which in turn responds to CRH secretion from the hypothalamus.Because glucocorticoids like cortisol have such widespread effects on metabolism and the immune system, the symptoms and signs of Cushing's syndrome are wideranging.Cushing's syndrome can result from excess secretion of cortisol from the adrenal gland, or in response to excessive secretion of ACTH from the pituitary gland (e.g. a tumour) or due to adrenocorticotrophic hormone (ACTH) secretion from an ectopic (unusual) site e.g. a lung tumour. Cushing's disease is a term used to describe Cushing's syndrome from excessive production of ACTH by a pituitary tumour. Cushing's syndrome can also result from the administration of corticosteroids for medical reasons (e.g severe asthma, as an immunosuppresant - e.g. kidney transplant recipients).

Statistics on Cushing's syndrome

The prevalence is approximately 40 per million and the incidence is 1-2 cases per million population. As far as the different subgroups:

Cushing's disease accounts for 60% of cases of hypercortisolism. It is more common in women than men (8:1) and rarely occurs in infants and children. In women the main age of presentations is between 20 and 40.

Ectopic ACTH production affects males ten times more often than females.

Adrenal carcinoma is most xommon in the fourth and fifth decades.

Risk Factors for Cushing's syndrome

Cushing's syndrome:

Pituitary disease (Cushing's disease - 60-70)

Ectopic ACTH (5) or CRH (rare) producing tumours

Adrenal adenomas (10-15)/carcinomas (5-10)

Adrenal hyperplasia (rare)Elevated cortisol levels are actually more commonly due to iatrogenic steroids - for the treatment of medical conditions.Pseudo-Cushing's syndrome - a term sometimes used to describe the Cushingoid physical features sometimes seen with alcohol excess.

Progression of Cushing's syndrome

The onset and progression can be gradual of fulminant. Morbidity and mortality result from diabetes and hypertension associated vascular complications, osteoporosis with compression fractures, infection, thromboembolic phenomena and emotional disturbances.

How is Cushing's syndrome Diagnosed?

Full blood count- raised white cell count

Urea and electrolytes - often mild hypokalaemia

In the case of ectopic ACTH there may be marked hyperglycaemia and hypokalaemia with a metabolic alkalosis.

ECG and Chest x-ray - changes of left ventricular hypertrophy.

Lateral chest x-ray - may show osteoporosis (=/-spinal compression fractures).

Prognosis of Cushing's syndrome

Mortality from untreated Cushing's syndrome is almost 50% at 5 years. Mortality and morbididy are reduced with effective treatment.

How is Cushing's syndrome Treated?

Surgical removal - indicated for most pituitary and adrenal tumours. Also for some ectopic ACTH producing tumours.

Drugs that inhibit cortisol synthesis - metyrapone, ketoconazole, aminoglutethimide. Indicated when case is not amenable to surgery.

External beam irraidation of the pituitary - slow response and restricted when surgery unsuccessful, contraindicated or not acceptable to patient.

Cushing's syndrome References

[1] Longmore M, Wilkinson I, Torok E. OXFORD HANDBOOK OF CLINICAL MEDICINE. Oxford Universtiy Press. 2001[2] Kumar P, Clark M. CLINICAL MEDICINE. WB Saunders 2002 Pg 427-430.[3] Hurst JW (Editor-in-chief). Medicine for the practicing physician. 4th edition Appleton and Lange 1996.[4] Braunwald, Fauci, Kasper, Hauser, Longo, Jameson. Harrison's Principles of Internal Medicine. 15th Edition. McGraw-Hill. 2001[5] Cotran, Kumar, Collins 6th edition. Robbins Pathologic Basis of Disease. WB Saunders Company. 1999.