Assessment of cortisol and ACTH responses to the desmopressin test in patients with Cushing's syndrome and simple obesity

OBJECTIVE The desmopressin test has recently been introduced in clinical pr actice as an adjunctive tool in the differential diagnosis of ACTH-dependen t Cushing's syndrome (CS), It has been reported that the majority of patien ts with pituitary-dependent CS (Cushing's disease, CD) respond to desmopres sin, while no such response is usually observed in other forms of this synd rome. In the present study, the responsiveness of the HPA axis to desmopres sin was studied in a group of obese subjects. In addition, the ability of d esmopressin administration to differentiate between patients with obesity a nd the various forms of Gushing's syndrome was investigated. DESIGN AND SUBJECTS Cortisol and ACTH responses to the administration of de smopressin (10 pg bolus i.v.) were examined in 20 consecutive patients with obesity (14 women and six men; BMI range: 34.5-66.7 kg/m(2)). Obese subjec ts had no clinical stigmata of GS, In all obese patients, either an overnig ht (dex 1 mg at 2300 h) (n = 8) or a formal low-dose (dex 0.5 mg 6-hourly f or 2 days) (n=12) dexamethasone suppression test was performed for the excl usion of Gushing's syndrome, Three of eight subjects showed failure of cort isol suppression (i.e. F>28nmol/l) to the overnight dexamethasone suppressi on test, but they had undetectable cortisol levels (< 28 nmol/l) on further testing with the formal P-day test, All but two of the remaining subjects had undetectable cortisol levels (< 28 nmol/l) following the formal 2-day, low-dose, dexamethasone suppression test. For comparison, desmopressin resp onses were also tested in 33 patients with GS of varied aetiologies (25 pat ients with pituitary-dependent GS, three patients with occult ectopic ACTH secretion and five patients with primary adrenal GS). A positive response w as considered to be an increment greater than 20% and 50% from baseline lev els of cortisol and ACTH, respectively. RESULTS Mean cortisol (F) and ACTH levels did not differ from the baseline at any time point following desmopressin administration in the obese group (basal F: 417 +/- 41, peak F: 389 +/- 32 nmol/l, P > 0.05; basal ACTH: 33.5 +/- 4.3, peak ACTH: 50.6 +/- 16.6 ng/l, P > 0.05), or in patients with occ ult ectopic or primary adrenal GS, In contrast, in the group of patients wi th CD, there was a significant rise in the mean ACTH and F levels from base line (basal F: 725 +/- 50, peak F: 1010 +/- 64 nmol/l, P < 0.01; basal ACTH : 88.6 +/- 11.8, peak ACTH: 351 +/- 64 ng/l, P < 0.01). Cortisol responses greater than 20% from baseline were observed in 21/25 (84%) patients with G D, but in only 3/20 (15%) of the obese patients, With regard to ACTH, incre ments greater than 50% over baseline were observed in 23/25 (92%) of patien ts with GD, and in only 3/20 (15%) of the obese patients. As previously rep orted, none of the patients with occult ectopic AGTH secretion or primary a drenal GS had a positive response. CONCLUSIONS The prevalence of subjects who met the criteria adopted to defi ne positive cortisol and AGTH responses to the desmopressin test was signif icantly higher in the group of patients with Cushing's disease than in the group of patients with obesity, It is therefore suggested that this test ma y be occasionally useful in the differentiation between simple obesity and the pituitary-dependent form (but not other forms) of Gushing's syndrome.