Dexamethasone

There are two different types of the DST: the low-dose and the high-dose methods, which can be carried out in overnight or multiple day formats.  Traditionally, following administration of the dexamethasone, cortisol levels are measured in blood or urine.  Non-suppressed levels of cortisol following the low-dose DST may indicate the presence of Cushing’s syndrome.  This condition can be caused by the presence of an adrenal tumor that produces too much cortisol, or by tumors in the pituitary gland or elsewhere in the body that secrete too much ACTH.  Excess cortisol production that is not affected by the low-dose DST, but that is suppressed by the high-dose DST, is regarded as evidence of a pituitary tumor. (10) Diagnosis of the exact cause of Cushing’s syndrome can be difficult, however, and the value of the high-dose DST has been questioned.  (11)  The  measurement of late night salivary cortisol in conjunction with the low-dose DST has been proposed as an effective way to discriminate between Cushing’s syndrome and pseudo-Cushing states in obese people. (12)

In blood  dexamethasone does not bind to cortisol-binding globulin (CBG), and the fraction bound to albumin is low (16%).  Like the natural steroid hormones, unbound dexamethasone diffuses readily from blood into saliva via intracellular mechanisms.  Salivary concentrations of dexamethasone show an excellent correlation with those in plasma over a very large concentration range. (13,14)

References

1. Jantz, M.A., Sahn, S.A. (1999).  Corticosteroids in acute respiratory failure.  Am J Respir Crit Care Med, 160(4), 1079-100.
2. Cole, M.A., Kim, P.J., Kalman, B.A., Spencer, R.L. (2000).  Dexamethasone suppression of corticosteroid secretion: Evaluation of the site of action by receptor measures and functional studies.  Psychoneuroendocrinology, 25(2), 151-67.
3. Alexis, M.N., Stylianopoulou, F., Kitraki, E., Sekeris, C.E. (1982).  The distribution and properties of the glucocorticoid receptor from rat brain and pituitary.  J Biol Chem, 258(8), 4710-14.
4. Carroll, T., Raff, H., Findling, J.W. (2009).  Late-night salivary cortisol for the diagnosis of Cushing syndrome: A meta-analysis.  Endocr Pract, 15(4), 335-42.
5. Viardot, A., Huber, P., Puder, J.J., et al. (2005). Reproducibility of nighttime salivary cortisol and its use in the diagnosis of hypercortisolism compared with urinary free cortisol and overnight dexamethasone suppression test.  J Clin Endocrinol Metab, 90(10), 5730-36.
6. Fountoulakis, K.N., Gonda, X., Rihmer, Z., et al. (2008). Revisiting the dexamethasone suppression test in unipolar major depression: An exploratory study.  Ann Gen Psych, 7, 22.
7. Grossman, R., Yehuda, R., New, A., et al (2003). Dexamethasone suppression test findings in subjects with personality disorders: Associations with posttraumatic stress disorder and major depression.  Am J Psychiatry, 160(7), 1291-97.
8. Gaab, J., Hüster, D., Peisen, R., et al. (2002). Low-dose dexamethasone suppression test in chronic fatigue syndrome and  health.  Psychosom Med, 64(2), 311-18.
9. Harbuz, M. (2002). Neuroendocrinology of autoimmunity.  Int Rev Neurobiol, 52, 133-61.
10. U.S. National Library of Medicine, MedlinePlus Medical Encyclopedia, http://www.nlm.nih.gov/medlineplus/ency/article/003694.htm.
11. Aron, D.C., Raff, H., Findling, J.W. (1997).  Effectiveness versus efficacy: The limited value in clinical practice of high dose dexamethasone suppression testing in the differential diagnosis of adrenocorticotropin-dependent Cushing’s syndrome.  J Clin Endocinol Metab, 82(6), 1780-85.
12. Castro, M., Elias, P. C., Quidute, R.P., et al. (1999). Out-patient screening for Cushing’s syndrome: The sensitivity of the combination of circadian rhythm and overnight dexamethasone suppression salivary cortisol tests.  J Clin Endocrinol Metab, 84(3), 878-82.
13. Thijssen, J.H., Gispen-de Wied, C.C., van Heeswijk, G.M., Veeman, W. (1996).  Determination of dexamethasone in saliva.  Clin Chem, 42(8 Pt 1), 1238-42.
14. Vining, R.F., McGinley, R.A., Symons, R.G. (1983).  Hormones in saliva: Mode of entry and consequent implications for clinical interpretation.  Clin Chem, 29(10), 1752-56.