Leo Sher, M.D.

The hypothalamic-pituitary-adrenal (HPA) axis controls the secretion of corticotropin-releasing hormone (CRH), corticotropin (adrenocorticotropic hormone, ACTH), and cortisol. The dexamethasone suppression test (DST) is the most frequently used test to assess HPA-system function in psychiatric disorders. Dexamethasone is a synthetic steroid that provides negative feedback to the pituitary to suppress the secretion of ACTH. Its potency is about 20-30 times that of hydrocortisone and 4-5 times of prednisone.

Dexamethasone is unable to pass the blood brain barrier which allows this test to assess a specific part of the hypothalamic-pituitary-adrenal axis. Dexamethasone binds to glucocorticoid receptors in the basal medial hypothalamus. Patients who have failed to suppress plasma cortisol secretion, i.e., who escape from the suppressive effect of dexamethasone, have a blunted glucocorticoid receptor response.

After corticotropin-releasing hormone (CRH) became available for clinical studies, the DST was combined with CRH administration. CRH, also called corticotropin-releasing factor (CRF) or corticoliberin, is a 41-amino acid peptide derived from a 191-amino acid preprohormone. CRH is secreted by the paraventricular nucleus of the hypothalamus. CRH is also synthesized in peripheral tissues, such as T lymphocytes. The resulting combined dexamethasone suppression-corticotropin-releasing hormone stimulation (DST–CRH) test proved to be more sensitive in detecting HPA system changes than the DST. There is a growing interest in the use of the DEX-CRH test for psychiatric research (1-4).

References

1. Sher L. Combined dexamethasone suppression-corticotropin-releasing hormone stimulation test in studies of depression, alcoholism, and suicidal behavior. TheScientificWorldJournal, 2006, Vol. 6, pp. 1398-1404.
2. Sher L., Cooper T.B., Mann J.J., Oquendo M.A. Modified dexamethasone suppression – corticotropin-releasing hormone stimulation test: a pilot study of young healthy volunteers and implications for alcoholism research in adolescents and young adults. International Journal of Adolescent Medicine and Health, 2006, Vol. 18, No. 1, pp. 133-137.
3. Sher L., Cooper T.B., Mann J.J., Oquendo M.A. Combined dexamethasone suppression-corticotropin releasing hormone stimulation test in medication free depressed patients and healthy volunteers. In: 63rd Annual Convention of the Society of Biological Psychiatry, Washington, DC, May 1-3, 2008. Biological Psychiatry, 2008, Vol. 63, No. 7, Suppl. 1, p. 112S.
4. Sher L. Combined dexamethasone suppression/corticotropin-releasing hormone stimulation test and antidepressants: different antidepressants may produce different effects. Medical Hypotheses, 2006, Vol. 66, No. 6, pp. 1248-1249.