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The Value of the Low-Dose Dexamethasone Suppression Test in the Differential Diagnosis of Hyperandrogenism in Women

Sections of Pediatric Endocrinology (R.L.R.) and Endocrinology (D.A.E.), The University of Chicago Hospitals, Chicago, Illinois 60637; Division of Reproductive Endocrinology (R.B.B.), Northwestern University Medical School, Chicago, Illinois 60611; and Center for Statistical Sciences (A.Y.T.), Brown University, Providence, Rhode Island 02912

Address correspondence to: Robert Rosenfield, M.D., University of Chicago/Pritzker School of Medicine, Department of Pediatric Endocrinology, 5841 South Maryland (M/C 5053), Chicago, Illinois 60637-1470. E-mail: robros{at}peds.bsd.uchicago.edu.

To the editor:

Kaltsas et al. (1) recently provided data that demonstrate that the evaluation of androgens as an end-point of the "low-dose" (2 mg daily) dexamethasone androgen-suppression test (DAST) permits the reliable distinction of adrenal tumors from other forms of androgen excess in women (1). This study, as well as other data that they and others have published, also indicates that their dexamethasone test protocol identifies Cushing’s syndrome patients, as well, when the final dexamethasone dose is given 2 h before blood sampling (2).

As valuable as it is to diagnose tumors and Cushing’s syndrome, the DAST potentially has the greatest diagnostic utility in distinguishing nonclassic congenital adrenal hyperplasia from the most frequent cause of androgen excess, polycystic ovary syndrome (3). To determine which patients with androgen excess require an ACTH test for a definitive diagnosis of nonclassic congenital adrenal hyperplasia, a single blood sample for assay of a few steroid levels is a simple, cost-effective method of screening. For this purpose, we have established that the plasma free testosterone (fT) is the most sensitive end-point for the DAST, which we perform as a 4-d test because it ordinarily takes this long to suppress blood levels of the major adrenal androgen dehydroepiandrosterone sulfate below the normal range of healthy controls. Under these conditions, the absolute level of fT normally falls below 8 pg/ml in our studies (4). A normal level of fT in a hyperandrogenic woman after a 4-d DAST indicates an ACTH-dependent adrenal source for the androgen excess. Unfortunately, this test has not been widely used, perhaps because the assay of fT, and consequently, dexamethasone-suppressed norms, is method-dependent.

Recently, we have retrospectively analyzed our collected data on DASTs performed in conjunction with GnRH agonist (nafarelin) tests. Receiver-operating characteristic curve analysis showed that measurement of 17-hydroxyprogesterone (17PROG) after a 4-d DAST provided optimal discrimination between hyperandrogenic women with and without ovarian hyperandrogenism, as defined by nafarelin testing: a 17PROG value of 50 ng/dl (1.5 nmol/liter) or more provided a sensitivity of 0.85 and specificity of 0.96. This is comparable to the sensitivity of fT as the DAST end-point, although 17PROG cannot be used as a marker in luteal phase women. Thus, a 17PROG level less than 50 ng/dl after DAST indicates that the androgen excess is ACTH-dependent, and so is an indication for ACTH testing.

Therefore, it would be of interest to know whether Kaltsas and co-workers can provide additional data on the outcome of DAST, as well as on the outcome of their series on more complete adrenal androgen suppression testing using 1 month of prednisone. In particular, clinically useful information would be plasma 17PROG, dehydroepiandrosterone sulfate, and fT, as well as the responses of normal controls to each of these forms of adrenocortical suppression testing.

Received August 4, 2003.

References

1. Kaltsas GA, Isidori AM, Kola BP, Skelly RH, Chew SL, Jenkins PJ, Monson JP, Grossman AB, Besser GM 2003 The value of the low-dose dexamethasone suppression test in the differential diagnosis of hyperandrogenism in women. J Clin Endocrinol Metab 88:2634–2643[Abstract/Free Full Text]
2. Newell-Price J, Trainer P, Besser M, Grossman A 1998 The diagnosis and differential diagnosis of Cushing’s syndrome and pseudo-Cushing’s states. Endocr Rev 19:647–672[Abstract/Free Full Text]
3. Ehrmann D, Rosenfield R 1990 An endocrinologic approach to the patient with hirsutism. J Clin Endocrinol Metab 71:1–4[Medline]
4. Ehrmann DA, Rosenfield RL, Barnes RB, Brigell DF, Sheikh Z 1992 Detection of functional ovarian hyperandrogenism in women with androgen excess. N Engl J Med 327:157–162[Abstract]

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