Effects of the opiate agonist loperamide on pituitary-adrenal function in patients with suspected hypercortisolism

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Abstract
In the present work the possible use of loperamide, an opiate agonist, in the dynamic evaluation of patients with suspected hypercortisolism was investigated. The effects of loperamide on plasma ACTH and Cortisol levels were evaluated in normal subjects and in 58 patients with suspected Cushing’s syndrome. The results were compared to those obtained after the overnight dexamethasone suppression test. In normal subjects plasma ACTH and Cortisol levels were significantly (p < 0.005) suppressed by both loperamide (16 mg po) and dexamethasone (1 mg po). In 17 patients, in whom the diagnosis of Cushing’s syndrome was confirmed by subsequent investigations, neither loperamide or dexamethasone inhibited Cortisol (from a baseline of 606 ± 55 nmol/L) to a nadir of 502 ± 43 nmol/L and 539 ± 50 nmol/L, respectively) and ACTH concentration (from a basal level of 70.1 +11.8 pg/ml to a nadir of 46.0 ± 8.6 pg/ml and 54.3 ± 7.5 pg/ml, respectively). In 34 patients, in whom the suspect of hypercortisolism was ruled out, either loperamide or dexamethasone suppressed the pituitary-adrenal axis: Cortisol and ACTH levels significantly fell from 417 ± 24 nmol/L and 28.3 ± 3.5 pg/ml to 60 ± 6 nmol/L and 14.4 ± 1.4 pg/ml after loperamide and to 26 ± 4 nmol and 16.4 ± 1.7 pg/ml after dexamethasone. In 7 patients discordant responses were observed. In 3 patients treated with antiepileptic drugs ACTH and Cortisol levels were inhibited by loperamide, but not by dexamethasone. In 4 other patients a normal suppression was induced by dexamethasone, but not by loperamide: in 2 cases the suspected hypercortisolism was definitely ruled out while in the other two no definitive diagnosis could be established. In these series of patients, the loperamide test equals the 1 mg dexamethasone suppression test in terms of sensitivity, specificity, diagnostic accuracy and predictive value. In conclusion: i) Loperamide administration is practical and reliable in testing the pituitary-adrenal function; ii) The procedure needs only three and half h to be completed and thus it is suitable and compliant to outpatients; iii) Loperamide might be useful in patients in some conditions (drug interference), in which the low-dose dexamethasone test has some limitations.