BLOOD SCIENCES
DEPARTMENT OF CLINICAL BIOCHEMISTRY
Title of Document: Investigation of Cushing’s Syndrome
Q Pulse Reference No: BS/CB/DCB/EN/11 Version NO6
Authoriser: Paul Thomas
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INVESTIGATION OF CUSHING'S SYNDROME
Introduction
Cushing’s syndrome is a collective name for a number of endocrine conditions associated
with the overproduction of cortisol by the adrenal gland. Cortisol production is controlled by
the secretion of adrenocorticotrophic hormone (ACTH) from the pituitary and is under
negative feedback control from cortisol. Excess cortisol production can be secondary to an
ACTH secreting pituitary tumour (Cushing’s disease, 70% of cases), ectopic secretion of
ACTH (12% of cases) or an adrenal adenoma/carcinoma (18% of cases).
Indications
Testing for Cushing’s syndrome in adults, after excluding exogenous glucocorticoid use, is
recommended with:
• Multiple and progressive features compatible with the syndrome, particularly those with a
high discriminatory value (e.g. facial plethora, easy bruising, striae, and proximal myopathy)
• Unusual features for age (e.g. osteoporosis, hypertension, and type 2 diabetes);
• Adrenal incidentaloma;
First line screening tests
Random cortisol is not an effective screening tool
Those that may be used are:
1. Overnight dexamethasone suppression test (see BS/CB/DCB/EN/10)
2. At least two 24 hour urinary free cortisol
3. At paired midnight and waking salivary cortisol
In general, these tests have equal accuracy in detecting Cushing’s syndrome but 24 hour urine
free cortisol can be increased by high fluid intake, stress and medications, whilst midnight
salivary cortisol may be affected in shift workers, depression and the critically unwell. There
are also difficulties with collecting saliva and 24 hour urine so the local policy is to
recommend an overnight dexamethasone suppression test which is more appropriate in
morbid obesity, depression, alcohol excess and diabetes.
There are some special circumstances that apply;
• Pregnancy – Advise 24 hour urinary cortisol
• Women on the combined contraceptive should ideally stop 6 weeks prior to dexamethasone
suppression test or use 24 hour urinary free cortisol.
• Enzyme inducing medication, e.g. anticonvulsants, can increase dexamethasone clearance
therefore 24 hour urinary cortisol advised.
• Chronic kidney disease- dexamethasone suppression test should be used rather than 24h
hour urinary cortisol.
