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Establishing the cause of Cushing's syndrome

Author
Lynnette K Nieman, MD
Section Editor
André Lacroix, MD
Deputy Editor
Kathryn A Martin, MD

INTRODUCTION

After the diagnosis of hypercortisolism is established, its cause must be determined (table 1). The tests listed in the figure do not differentiate Cushing's syndrome from non-Cushing's syndrome because the response of normal corticotropes is most often similar to that of corticotrope adenomas. Thus, testing for the cause of Cushing's syndrome should be performed only if the normal corticotrope responses are suppressed by ongoing hypercortisolism (algorithm 1). This precaution will avoid erroneous diagnosis of Cushing's disease in a normal individual or a patient with another cause of Cushing's syndrome.

Both laboratory and patient errors can cause misleading results. One way to minimize these errors is to make certain that the results of different tests are internally consistent. (See "Basic principles in the laboratory evaluation of adrenocortical function".)

The approach to establishing the cause of Cushing's syndrome will be reviewed here. The causes, pathophysiology, and diagnosis of Cushing's syndrome are discussed separately. (See "Causes and pathophysiology of Cushing's syndrome" and "Establishing the diagnosis of Cushing's syndrome".)

INITIAL EVALUATION

Primary adrenal disease versus ACTH-secreting tumor — The first step in the evaluation is to determine whether the hypercortisolism is adrenocorticotropic hormone (ACTH)-dependent (ie, due to a pituitary or nonpituitary ACTH-secreting tumor), or ACTH-independent (ie, due to an adrenal source) by measuring plasma ACTH (algorithm 1). This test is now best performed using a two-site immunoradiometric assay (IRMA) [1]. (See "Measurement of ACTH, CRH, and other hypothalamic and pituitary peptides".)

Plasma ACTH — Plasma ACTH concentrations are normally between 20 and 80 pg/mL (4.5 and 18 pmol/L) at 8 AM. The values fall during the waking hours and are usually less than 20 pg/mL (4.5 pmol/L) at 4 PM and less than 10 pg/mL (2.2 pmol/L), usually less than 5 pg/mL (1.1 pmol/L), within one hour after the usual time of falling sleep.

                    

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Literature review current through: Nov 2016. | This topic last updated: Tue Nov 26 00:00:00 GMT+00:00 2013.
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