CLINICAL BIOCHEMISTRY DEPARTMENT


LOW DOSE (1mg) OVERNIGHT DEXAMETHASONE SUPPRESSION TEST

INTRODUCTION

This test should be used as the first line screening test for all subjects suspected of having Cushing's syndrome. In normal subjects, dexamethasone suppresses ACTH and therefore cortisol secretion. In Cushing's syndrome there is no suppression.

PRECAUTIONS

Please refer to the Trust’s phlebotomy procedure for sample collection precautions.

Patients on enzyme inducing drugs e.g. anticonvulsants and rifampicin, may rapidly metabolise dexamethasone and give a false positive result i.e. no suppression. Women on oestrogen therapy may fail to suppress adequately due to increased cortisol binding globulin. In these instances a higher dose of dexamethasone should be used.

PATIENT PREPARATION

This is an outpatient test and no patient preparation is necessary.

PROTOCOL

Dexamethasone dosage: Adults: 1mg dexamethasone tablet
Children: 15 ug/kg body weight dexamethasone

1.

The patient takes 1mg dexamethasone orally at 23:00 hrs.

2.

The following morning at 9.00 hrs a blood sample is taken for cortisol.

Label the sample with patient details and actual time taken.  Write 'dexamethasone suppression test' on request form and send with sample to the Clinical Biochemistry Department as soon as possible.

INTERPRETATION

Normal response: The 9.00 am cortisol should suppress to < 50 nmol/L.

SENSITIVITY AND SPECIFICITY OF TEST

Plasma cortisol normally falls after 09:00 h and false positive tests may occur if sampling is delayed

Suppression in patients with Cushing's syndrome is rare with this test (2%) and is probably due to slow metabolism of dexamethasone. If suppression occurs in a patient in whom there is strong clinical or biochemical evidence for Cushing's syndrome, a formal low dose (2mg) dexamethasone test should be performed.

Normal subjects rarely (2%) fail to suppress. False positives may occur with depression (30-50%) due to development of a reversible glucocorticoid resistance, and in patients with severe systemic illness (10-20%). Patients with simple obesity do not have an increased rate of false positive results.

Dexamethasone is primarily metabolised by the cytochrome P450 system, by hepatic CYP3A4, an enzyme complex responsible for the metabolism of many xenobiotics. Considerable increases in cytochrome P450 enzymes can be seen in regular smokers and people who drink alcohol regularly. Several drugs such as phenobarbital, primidone, ethosuximide, carbamazepine, and rifampicin induce the activity of CYP3A4, and can lead to false positive dexamethasone suppression tests.

Reviewed by: Tony Everitt, Consultant Biochemist
Last edited 07/08/08