The dexamethasone-suppressed corticotrophin-releasing hormone stimulation test in anorexia nervosa

OBJECTIVE The dexamethasone-CRH test (combination of dexamethasone-induced suppression of HPA axis function and subsequent stimulation with oCRH) (Dex -CRH test) has been proposed to fully distinguish ACTH-dependent Gushing's disease (GD) from pseudo-Gushing's states (PGS), i.e. tumoural vs. function al hypercortisolism. A plasma cortisol concentration greater than 38 nmol/l 15 min after CRH injection has been demonstrated to identify all cases of CD and to exclude all cases of PCS, Although obviously not a PGS from a cli nical point of view, anorexia nervosa (AN) is associated with CRH-driven hy peractivity of the HPA axis. This study reports the response of AN patients , a model of functional biological hypercortisolism, to the Dex-CRH test. PATIENTS AND METHODS Nineteen women affected with anorexia nervosa and 6 he althy sex-matched controls were studied. RESULTS Three of 19 AN patients had an abnormal 24-h urinary free cortisol excretion (UFC), whereas 1 of 19 AN had increased overnight UFC, AN subject s had inadequately suppressed plasma cortisol after low-dose dexamethasone suppression test (LDDST) (cortisol 192.8 +/- 63.4 vs.<27 nmol/l, AN vs. con trols, respectively). Seven of 19 AN patients had plasma cortisol levels ab ove 50 nmol/l after LDDST, None of the AN patients had CRH-induced increase s in plasma ACTH or cortisol (basal cortisol 192.8 +/- 63.4 and peak cortis ol 181.7 +/- 59.9 nmol/l). Despite unresponsiveness to CRH and because of t he lack of suppression after dexamethasone, using the single plasma cortiso l threshold value of 38 nmol/l obtained at 15min during the Dex-CRH test wo uld have been misclassified in half of our AN population (9 of 19). CONCLUSION Since anorexia nervosa represents a model of functional hypercor tisolism that shares similar pathophysiological mechanisms to the other cau ses of pseudo-Gushing's states, we suggest testing all causes of pseudo-Cus hing's states using the dexamethasone-CRH approach to (i) describe the actu al responses of clinically relevant pseudo-Gushing's states and (ii) to imp rove our knowledge of the pathophysiological discrepancies between the vari ous causes of pseudo-Gushing's states, Lastly, the evaluation of dexamethas one metabolism (absorption, volume of distribution, clearance) may help to gain more insight into the diagnostic value of the dexamethasone-CRH test.