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Dexamethasone suppression tests

INTRODUCTION

Dexamethasone suppression tests are used to assess the status of the hypothalamic-pituitary-adrenal (HPA) axis and for the differential diagnosis of adrenal hyperfunction. The low-dose dexamethasone suppression tests are used to assess nonsuppressible cortisol production by adrenal incidentalomas and to differentiate patients with Cushing's syndrome of any cause from patients who do not have Cushing's syndrome. The high-dose dexamethasone suppression tests help to distinguish patients with Cushing's disease (Cushing's syndrome caused by pituitary hypersecretion of corticotropin [ACTH]) from most patients with the ectopic ACTH syndrome (Cushing's syndrome caused by nonpituitary ACTH-secreting tumors).

This topic will review the basic principles of the dexamethasone suppression tests. Additional information on their role in determining the diagnosis and the cause of subclinical and clinical Cushing's syndrome is discussed separately. (See "The adrenal incidentaloma" and "Establishing the diagnosis of Cushing's syndrome" and "Establishing the cause of Cushing's syndrome".)

DEXAMETHASONE SUPPRESSION TESTS

The dexamethasone suppression tests assess the pituitary corticotroph cell response to glucocorticoid negative feedback inhibition of corticotropin (ACTH) secretion. Dexamethasone is a potent glucocorticoid, about 30 to 40 times more potent than cortisol. Thus, the average daily maintenance dose of dexamethasone for a patient with adrenal insufficiency is 0.5 mg, versus 20 mg for hydrocortisone.

Dexamethasone and steroid measurements — Measurements of serum, salivary, and urinary cortisol by current assays are unaffected by the presence of dexamethasone. Antibodies used in current cortisol immunoassays are directed toward the D ring of the molecule and react very poorly with dexamethasone, which has a 16-alpha-methyl modification of the D ring. Structurally-based assays such as mass spectrometry or high pressure liquid chromatography fully discriminate the two steroids.

Low-dose dexamethasone suppression tests — The binding of dexamethasone to glucocorticoid receptors in corticotroph cells inhibits pituitary ACTH secretion. Dexamethasone directly inhibits steroidogenesis in rat adrenals [1], but in humans, dexamethasone has no inhibitory effect on steroid production when exogenous ACTH is infused [2].

            

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Literature review current through: Oct 2014. | This topic last updated: Mar 4, 2014.
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