Examine this patient.

Look at this patient's face.

Moon-like facies , acne, hirsutism and plethora (due to telangiectasia).

· Examine the following:

-The mouth for superimposed thrush.

-The interscapular area for 'buffalo hump'.

-Increased fat pads and bulge above supraclavicular fossae (more specific for

Cushing's syndrome).

-The abdomen for thinning of skin and purple striae (also seen over the shoulders

and thighs) - said to be present on almost all patients.

-The limbs for bruising, wasting of the limbs, weakness of the muscles of the

shoulders and hips - get the patient to squat (proximal myopathy).

-Ask the patient whether she has back pain and then examine the spine, looking for

evidence of osteoporosis and collapse of vertebra, kyphoscoliosis.

-Measure the blood pressure. · Tell the examiner you would like to:

-Test the urine for glucose.

-Check visual fields (for pituitary tumour).

-Examine the fundus for optic atrophy, papilloedema, signs of hypertensive or

diabetic retinopathy.

Note. Hirsutism is not common in Cushing's syndrome caused by exogenous steroids

because they suppress adrenal androgen secretion.

Also comment on signs of asthma, rheumatoid arthritis, SLE, fibrosing alveolitis (as

these are conditions that are treated with long-term steroids).

This patient has moon-like facies, acne and supraclavicular pads of fat (lesions),

which are features of Cushing's syndrome caused by long-term steroid therapy

(aetiology) for asthma. The patient is now steroid dependent and is disabled by

proximal myopathy and kyphoscoliosis due to osteoporosis (functional status).

· Steroids, including adrenocorticotrophic hormone (ACTH).

· Pituitary adenoma (Cushing's disease).

· Adrenal adenoma.

· Adrenal carcinoma.

· Ectopic ACTH (usually by small cell carcinoma of the lung).

Cushing's disease is increased production by the adrenals secondary to excess

pituitary ACTH, whereas Cushing's syndrome is caused by excess steroid from

any cause.

· 24-hour urinary free cortisol: this is the most direct and reliable practical index of

cortisol secretion. The reason is that plasma concentrations of corticotrophins and

cortisol fall and rise episodically, in normal subjects, in Cushing's syndrome and in

ectopic ACTH syndrome.

· Overnight dexamethasone test.

· Plasma cortisol.

· Low- and high-dose dexamethasone test: low-dose dexamethasone fails to

suppress urinary steroid secretion in Cushing's disease whereas high-dose

dexamethasone (2 mg q6h for 2 days) suppresses at least 50% of urinary steroid

secretion.

· CXR for carcinoma of the bronchus.

· Plain radiograph of the abdomen for adrenal calcification.

· Ultrasonography of the abdomen for adrenal tumours.

· If Cushing's disease is suspected:

-Plasma ACTH, radiography of pituitary, MRI gadolinium enhancement, and

bilateral measurement of corticotrophin in the inferior petrosal sinus.

-Corticotrophin-releasing hormone (CRH) test (helpful in distinguishing

pituitary-led Cushing's disease from ectopic corticotrophin secretion).

· Inferior petrosal sinus sampling is used to distinguish primary and ectopic sources

of ACTH when the source of the ACTH is not obvious based on clinical

circumstances, biochemical evaluation and imaging studies.

· Cushing's disease: trans-sphenoidal microadenomectomy, pituitary irradiation,

total bilateral adrenalectomy.

· Adrenal tumour: surgical resection, mitotane therapy, resection of recurrent

tumour.

· Ectopic ACTH: surgical resection of tumour.

· Taper corticosteroid therapy.

In chronic alcoholics and patients with depression there may be increased urinary

excretion of steroids, absent diurnal variation of plasma steroids and a positive

over-night dexamethasone test. All these investigations return to normal on

discon-tinuation of alcohol or improvement of emotional status.

It is a syndrome that occurs after bilateral adrenalectomy and is characterized by a

rapidly growing pituitary adenoma, very high ACTH levels and hyperpigmentation.

As the incidence may be as high as 50%, patients with Cushing's disease who

have undergone adrenalectomy should be followed by regular plasma ACTH levels

and imaging for pituitary tumours.

Harvey Williams Cushing (1869-1939) was Professor of Surgery at Harvard. He was

awarded the Pulitzer Prize for his biography of Osier (Cushing H 1932 The

basophil adenomas of the pituitary body and their clinical manifestation. Bull Johns

Hopkins Hosp 1: 137).

Christopher Edwards, contemporary Principal, Imperial College, London; his chief

interest is metabolism of steroids.