Cushing syndrome

Published on 02/04/2015 by admin

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Last modified 22/04/2025

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145 Cushing syndrome

Instruction

Examine this patient.

Look at this patient’s face.

Salient features

Examination

• Moon-like facies (Fig. 145.1), acne, hirsutism and plethora (from 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 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 he or she has back pain and then examine the spine, looking for evidence of osteoporosis and collapse of vertebra, kyphoscoliosis.

• Measure the BP.

• 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.

• Comment on signs of asthma, rheumatoid arthritis, SLE, fibrosing alveolitis (as these are conditions that are treated with long-term steroids).

Fig. 145.1 Typical findings in Cushing syndrome.

Note: Hirsutism is not common in Cushing syndrome caused by exogenous steroids because they suppress adrenal androgen secretion.

Diagnosis

This patient has moon-like facies, acne and supraclavicular pads of fat (lesions), which are features of Cushing syndrome caused by long-term steroid therapy (aetiology) for asthma. The patient is now steroid dependent and is disabled by proximal myopathy and kyphoscoliosis because of osteoporosis (functional status).

Questions

Mention some causes of Cushing syndrome

• Steroids, including ACTH

• Pituitary adenoma (Cushing’s disease)

• Adrenal adenoma

• Adrenal carcinoma

• Ectopic ACTH (usually by small cell carcinoma of the lung): the presence of hyperpigmentation or hypokalaemic alkalosis suggests that the Cushing syndrome results from ectopic ACTH secretion.

What is the difference between Cushing’s disease and Cushing syndrome?

Cushing’s disease is increased production by the adrenals secondary to excess pituitary ACTH, whereas Cushing syndrome is caused by excess steroid from any cause.

How would you investigate such a patient?

Tests to confirm the diagnosis of hypercortisolism:

• Urinary free cortisol as 24-h collection: this is the most direct and reliable practical index of cortisol secretion. The reason is that plasma concentrations of ACTH and cortisol fall and rise episodically, in normal subjects, in Cushing syndrome and in ectopic ACTH syndrome

• Measurement of midnight salivary cortisol levels

• Overnight dexamethasone test

• Plasma cortisol.

Tests to determine the site of hormone production:

• 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 every 6 h for 2 days) suppresses at least 50% of urinary steroid secretion

• Chest radiography 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: >10 pg per mL (2 pmol per L) suggests ACTH dependency; a level below 5 p/l (1 pmol/l) suggests an adrenal source

• radiography of pituitary

• MRI gadolinium enhancement: MRI can identify pituitary tumours approximately 60% of the time once ACTH dependency is established

• bilateral measurement of ACTH in the inferior petrosal sinus; Cushing’s disease is the most likely diagnosis if the sinus-to-peripheral-vein ratio of plasma ACTH is at least 2:1 before or at least 3:1 after injection of ACTH-releasing hormone (corticotrophin-releasing hormone (CRH)) during sampling from the inferior petrosal sinus

• CRH test (helpful in distinguishing pituitary-led Cushing’s disease from ectopic ACTH 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.

(See J Clin Endocrinol Metab 1999;84:440–8.)

How would you manage Cushing syndrome?

• 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.

Advanced-level questions

What is pseudo-Cushing syndrome?

In chronic alcoholics and patients with depression, there may be increased urinary excretion of steroids, absent diurnal variation of plasma steroids and a positive overnight dexamethasone test. All these investigations return to normal on discontinuation of alcohol or improvement of emotional status.

What do you know about Nelson syndrome?

It is a syndrome that occurs after bilateral adrenalectomy and is characterized by 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 Osler (Cushing H. The basophil adenomas of the pituitary body and their clinical manifestation. Bull Johns Hopkins Hosp 1932;1:137).

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