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Acute administration of alprazolam, a benzodiazepine activating GABA receptors, inhibits cortisol secretion in patients with subclinical but not overt Cushing’s syndrome

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Abstract

The purpose of this study is to verify whether acute pre-treatment with alprazolam (ALP), a benzodiazepine that inhibits HPA secretion in normal subjects, could better characterize patients with subclinical Cushing’s syndrome (SCS) than the 1-mg dexamethasone test (DST). In 22 patients with SCS, 10 with overt Cushing’s syndrome (CS), 11 with non-functioning adrenal incidentalomas (NF) and 14 normal subjects (NS) we studied the effect of ALP (1 mg, p.o. at 2300 hours) on cortisol levels after 1-mg DST. Cortisol levels (mean ± SEM) after DST were lower (P = 0.012) in SCS (3.9 ± 0.3 μg/dl) than in overt CS (10.4 ± 1.9 μg/dl), while they were higher (P = 0.0005) than in NF (1.1 ± 0.1 μg/dl) and NS (1.5 ± 0.1 μg/dl). After ALP pre-treatment, cortisol levels further decreased (P = 0.004) in SCS (3.0 ± 0.3 μg/dl), but neither in CS (9.3 ± 1.3 μg/dl) nor in NF (1.3 ± 0.1 μg/dl) and in NS (1.3 ± 0.1 μg/dl). In SCS, cortisol levels after ALP + 1-mg DST persisted lower (P = 0.0005) than those in CS, but higher (P = 0.0005) than those in NF and NS. Considering individual cases, ALP pre-treatment reduced cortisol levels <3 and <1.8 μg/dl in 50 and 23 % of SCS patients, respectively. ALP amplifies the cortisol inhibition exerted by 1-mg DST in patients with SCS but not in those with CS. The clinical usefulness of ALP to increase the sensitivity of 1-mg DST to identify true autonomous cortisol release in patients with adrenal incidentalomas as well as to predict different clinical outcomes remains to be clarified.

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Acknowledgments

The present study was supported by University of Turin and the Foundation for the Study of Endocrine and Metabolic Diseases.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy

    Roberta Giordano

  2. Division of Endocrinology, Diabetology and Metabolism, Department of Internal Medicine, University of Turin, San Giovanni Battista Hospital, Turin, Italy

    Rita Berardelli, Ioannis Karamouzis, Valentina D’Angelo, Andreea Picu, Clizia Zichi, Beatrice Fussotto, Ezio Ghigo & Emanuela Arvat

  3. Clinical Biochemistry Laboratory, San Giovanni Battista Hospital, Turin, Italy

    Maria Manzo & Giulio Mengozzi

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  1. Roberta Giordano
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  2. Rita Berardelli
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Correspondence to Roberta Giordano.

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Giordano, R., Berardelli, R., Karamouzis, I. et al. Acute administration of alprazolam, a benzodiazepine activating GABA receptors, inhibits cortisol secretion in patients with subclinical but not overt Cushing’s syndrome. Pituitary 16, 363–369 (2013). https://doi.org/10.1007/s11102-012-0433-5

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