Objective: Metyrapone has been approved for the treatment of patients with Cushing’s syndrome (CS), but only few retrospective clinical studies are available. The aim of our study was the prospective assessment of metyrapone as pre-operative treatment. Design and methods: Before adrenalectomy, seven patients with ACTH-independent CS due to adrenal adenoma were prospectively treated with metyrapone for 3 months in three tertiary academic centers, with endocrine work-up and clinical evaluation at screening and at predefined evaluation time points (Days 14, 31, 48, 65, 82). Results: In all patients, UFC levels decreased up to normal range from baseline to Day 82 (609 (188–1476) vs 69 (28–152) nmol/24 h, P < 0.02), with a reduction of serum and salivary cortisol levels, and no significant increase of plasma ACTH and serum DHEAS levels. Clinical improvement was reported on quality of life (+16.7 (+4.2; +52.00) points, P < 0.04) and pressure control (systolic pressure, −25 (−52; −10) mmHg, P < 0.01; diastolic pressure, −16 (−50; +2 mmHg), P < 0.03). No significant change in weight, electrolytes, glycemic and lipid profile was reported. Although in women a significant increase of testosterone and androstenedione was reported, no worsening of clinical hyperandrogenism was observed. All drug-related adverse events (nausea, fatigue, low grade fever, edema of lower limbs and facial rash) were grade 1 or 2 and generally transient. Conclusions: This prospective pilot study demonstrated that metyrapone is effective in normalizing biochemical and clinical parameters in patients with CS due to adrenal adenoma before surgical intervention, with minimal side effects.

Preoperative treatment with metyrapone in patients with cushing’s syndrome due to adrenal adenoma. a pilot prospective study / Puglisi, S.; Perotti, P.; Barbot, M.; Cosio, P.; Scaroni, C.; Stigliano, A.; Lardo, P.; Morelli, V.; Polledri, E.; Chiodini, I.; Reimondo, G.; Pia, A.; Terzolo, M.. - In: ENDOCRINE CONNECTIONS. - ISSN 2049-3614. - 7:11(2018), pp. 1227-1235. [10.1530/EC-18-0400]

Preoperative treatment with metyrapone in patients with cushing’s syndrome due to adrenal adenoma. a pilot prospective study

Barbot M.;Scaroni C.;Stigliano A.;Chiodini I.;
2018

Abstract

Objective: Metyrapone has been approved for the treatment of patients with Cushing’s syndrome (CS), but only few retrospective clinical studies are available. The aim of our study was the prospective assessment of metyrapone as pre-operative treatment. Design and methods: Before adrenalectomy, seven patients with ACTH-independent CS due to adrenal adenoma were prospectively treated with metyrapone for 3 months in three tertiary academic centers, with endocrine work-up and clinical evaluation at screening and at predefined evaluation time points (Days 14, 31, 48, 65, 82). Results: In all patients, UFC levels decreased up to normal range from baseline to Day 82 (609 (188–1476) vs 69 (28–152) nmol/24 h, P < 0.02), with a reduction of serum and salivary cortisol levels, and no significant increase of plasma ACTH and serum DHEAS levels. Clinical improvement was reported on quality of life (+16.7 (+4.2; +52.00) points, P < 0.04) and pressure control (systolic pressure, −25 (−52; −10) mmHg, P < 0.01; diastolic pressure, −16 (−50; +2 mmHg), P < 0.03). No significant change in weight, electrolytes, glycemic and lipid profile was reported. Although in women a significant increase of testosterone and androstenedione was reported, no worsening of clinical hyperandrogenism was observed. All drug-related adverse events (nausea, fatigue, low grade fever, edema of lower limbs and facial rash) were grade 1 or 2 and generally transient. Conclusions: This prospective pilot study demonstrated that metyrapone is effective in normalizing biochemical and clinical parameters in patients with CS due to adrenal adenoma before surgical intervention, with minimal side effects.
2018
cortisol; cushing’s syndrome; medical treatment; metyrapone
01 Pubblicazione su rivista::01a Articolo in rivista
Preoperative treatment with metyrapone in patients with cushing’s syndrome due to adrenal adenoma. a pilot prospective study / Puglisi, S.; Perotti, P.; Barbot, M.; Cosio, P.; Scaroni, C.; Stigliano, A.; Lardo, P.; Morelli, V.; Polledri, E.; Chiodini, I.; Reimondo, G.; Pia, A.; Terzolo, M.. - In: ENDOCRINE CONNECTIONS. - ISSN 2049-3614. - 7:11(2018), pp. 1227-1235. [10.1530/EC-18-0400]
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