Mattia Barbot1, Valentina Guarnotta2, Marialuisa Zilio3, Filippo Ceccato3, Alessandro Ciresi2, Andrea Daniele3, Giuseppe Pizzolanti2, Elena Campello4, Anna Chiara Frigo5, Carla Giordano2, Carla Scaroni3. 1. Endocrinology Unit, Department of Medicine DIMED, University of Padova, Padova, Italy. mattiabarbot@alice.it. 2. Biomedical Department of Internal and Specialist Medicine (DIBIMIS), Section of Endocrinology, University of Palermo, Palermo, Italy. 3. Endocrinology Unit, Department of Medicine DIMED, University of Padova, Padova, Italy. 4. Thrombotic and Hemorrhagic Diseases Unit, Department of Medicine DIMED, University of Padova, Padova, Italy. 5. Department of Cardiac, Thoracic and Vascular Sciences, Section of Biostatistics, Epidemiology and Public Health, University of Padova, Padova, Italy.
Abstract
INTRODUCTION: Cushing's disease (CD) is characterized by procoagulative profile. Treatment with cortisol-reducing medications might normalize the coagulation impairment potentially eliminating the risk of thromboembolic complications. AIM: The aim of this prospective study is to evaluate the effectiveness of 6-12 months of treatment with pasireotide (Signifor®, Novartis) 600 µg twice daily on coagulative factors in 21 patients (16 females, mean age 46 ± 12.2 years) with CD. Biochemical, hormonal (urinary free cortisol, UFC; late night salivary cortisol, LNSC; ACTH) and coagulative parameters as Protrombin time (PT), aPTT, factors VIII, IX and XI, antithrombin III, protein C, protein S, fibrinogen, were evaluated at baseline and during therapy. RESULTS: UFC showed a significant reduction from baseline (3.2 ± 1.8 vs. 1.0 ± 0.8, p < 0.0001) with normalization in 13/21 (61.9%) and in 7/16 (43.8%) at 6 and 12 months, respectively. On the same way LNSC returned to normal in 5/11 at 6 months, showing a trend to reduction (8.6 ± 5 vs. 4.1 ± 2.9), even though without statistical significance (p = 0.07). Throughout the treatment period there was an increase in serum glycaemia (5.5 ± 2.3 vs. 6.8 ± 2.3 mmol/L, p = 0.09), with a concomitant significant increase in HbA1c after 6 months (40.7 ± 8.4 vs. 50.7 ± 12.3 mmol/mol, p = 0.006). Regarding coagulative parameters, no differences were found neither in clotting nor in anticoagulant factors during therapy. No patients developed thrombotic complication during treatment. CONCLUSIONS: Pasireotide resulted an effective treatment in controlling hypercortisolism in more than half of CD patients with partial restoration also of circadian cortisol secretion. No significant improvements were observed on clotting factors; this fact might depend on persistence of typical alteration of CD, such as obesity and hypertension, and reflects also on the worsening in glucide metabolism induced by the drug. Clinical implications of persistent procoagulative impairment while on medical therapy should be considered.
INTRODUCTION:Cushing's disease (CD) is characterized by procoagulative profile. Treatment with cortisol-reducing medications might normalize the coagulation impairment potentially eliminating the risk of thromboembolic complications. AIM: The aim of this prospective study is to evaluate the effectiveness of 6-12 months of treatment with pasireotide (Signifor®, Novartis) 600 µg twice daily on coagulative factors in 21 patients (16 females, mean age 46 ± 12.2 years) with CD. Biochemical, hormonal (urinary free cortisol, UFC; late night salivary cortisol, LNSC; ACTH) and coagulative parameters as Protrombin time (PT), aPTT, factors VIII, IX and XI, antithrombin III, protein C, protein S, fibrinogen, were evaluated at baseline and during therapy. RESULTS: UFC showed a significant reduction from baseline (3.2 ± 1.8 vs. 1.0 ± 0.8, p < 0.0001) with normalization in 13/21 (61.9%) and in 7/16 (43.8%) at 6 and 12 months, respectively. On the same way LNSC returned to normal in 5/11 at 6 months, showing a trend to reduction (8.6 ± 5 vs. 4.1 ± 2.9), even though without statistical significance (p = 0.07). Throughout the treatment period there was an increase in serum glycaemia (5.5 ± 2.3 vs. 6.8 ± 2.3 mmol/L, p = 0.09), with a concomitant significant increase in HbA1c after 6 months (40.7 ± 8.4 vs. 50.7 ± 12.3 mmol/mol, p = 0.006). Regarding coagulative parameters, no differences were found neither in clotting nor in anticoagulant factors during therapy. No patients developed thrombotic complication during treatment. CONCLUSIONS: Pasireotide resulted an effective treatment in controlling hypercortisolism in more than half of CDpatients with partial restoration also of circadian cortisol secretion. No significant improvements were observed on clotting factors; this fact might depend on persistence of typical alteration of CD, such as obesity and hypertension, and reflects also on the worsening in glucide metabolism induced by the drug. Clinical implications of persistent procoagulative impairment while on medical therapy should be considered.
Authors: R van der Pas; C de Bruin; F W G Leebeek; M P M de Maat; D C Rijken; A M Pereira; J A Romijn; R T Netea-Maier; A R Hermus; P M J Zelissen; F H de Jong; A J van der Lely; W W de Herder; S W J Lamberts; L J Hofland; R A Feelders Journal: J Clin Endocrinol Metab Date: 2012-01-25 Impact factor: 5.958
Authors: Susan M Webb; John E Ware; Anna Forsythe; Min Yang; Xavier Badia; Lauren M Nelson; James E Signorovitch; Lori McLeod; Mario Maldonado; Wojciech Zgliczynski; Christophe de Block; Lesly Portocarrero-Ortiz; Monica Gadelha Journal: Eur J Endocrinol Date: 2014-04-23 Impact factor: 6.664
Authors: Lynnette K Nieman; Beverly M K Biller; James W Findling; M Hassan Murad; John Newell-Price; Martin O Savage; Antoine Tabarin Journal: J Clin Endocrinol Metab Date: 2015-07-29 Impact factor: 5.958
Authors: L Trementino; G Michetti; A Angeletti; G Marcelli; C Concettoni; C Cardinaletti; B Polenta; M Boscaro; G Arnaldi Journal: Horm Metab Res Date: 2016-04-29 Impact factor: 2.936
Authors: Rosario Pivonello; Stephan Petersenn; John Newell-Price; James W Findling; Feng Gu; Mario Maldonado; Andrew Trovato; Gareth Hughes; Luiz R Salgado; André Lacroix; Jochen Schopohl; Beverly M K Biller Journal: Clin Endocrinol (Oxf) Date: 2014-03-27 Impact factor: 3.478
Authors: Maria Fleseriu; Richard Auchus; Irina Bancos; Anat Ben-Shlomo; Jerome Bertherat; Nienke R Biermasz; Cesar L Boguszewski; Marcello D Bronstein; Michael Buchfelder; John D Carmichael; Felipe F Casanueva; Frederic Castinetti; Philippe Chanson; James Findling; Mônica Gadelha; Eliza B Geer; Andrea Giustina; Ashley Grossman; Mark Gurnell; Ken Ho; Adriana G Ioachimescu; Ursula B Kaiser; Niki Karavitaki; Laurence Katznelson; Daniel F Kelly; André Lacroix; Ann McCormack; Shlomo Melmed; Mark Molitch; Pietro Mortini; John Newell-Price; Lynnette Nieman; Alberto M Pereira; Stephan Petersenn; Rosario Pivonello; Hershel Raff; Martin Reincke; Roberto Salvatori; Carla Scaroni; Ilan Shimon; Constantine A Stratakis; Brooke Swearingen; Antoine Tabarin; Yutaka Takahashi; Marily Theodoropoulou; Stylianos Tsagarakis; Elena Valassi; Elena V Varlamov; Greisa Vila; John Wass; Susan M Webb; Maria C Zatelli; Beverly M K Biller Journal: Lancet Diabetes Endocrinol Date: 2021-10-20 Impact factor: 32.069