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 Cushing's disease (GD) from pseudo-Cushing's states (PGS), i.e. tumoural vs. functional 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 clinical point of view, anorexia nervosa (AN) is associated with CRH-driven hyperactivity 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 healthy 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 subjects had inadequately suppressed plasma cortisol after low-dose dexamethasone suppression test (LDDST) (cortisol 192.8 +/- 63.4 vs.<27 nmol/l, AN vs. controls, respectively). Seven of 19 AN patients had plasma cortisol levels above 50 nmol/l after LDDST, None of the AN patients had CRH-induced increases in plasma ACTH or cortisol (basal cortisol 192.8 +/- 63.4 and peak cortisol 181.7 +/- 59.9 nmol/l). Despite unresponsiveness to CRH and because of the lack of suppression after dexamethasone, using the single plasma cortisol threshold value of 38 nmol/l obtained at 15min during the Dex-CRH test would have been misclassified in half of our AN population (9 of 19). CONCLUSION Since anorexia nervosa represents a model of functional hypercortisolism that shares similar pathophysiological mechanisms to the other causes of pseudo-Cushing's states, we suggest testing all causes of pseudo-Cushing's states using the dexamethasone-CRH approach to (i) describe the actual responses of clinically relevant pseudo-Cushing's states and (ii) to improve our knowledge of the pathophysiological discrepancies between the various causes of pseudo-Cushing's states, Lastly, the evaluation of dexamethasone metabolism (absorption, volume of distribution, clearance) may help to gain more insight into the diagnostic value of the dexamethasone-CRH test.