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7. Recombinant Cysteine Proteinase B from Leishmania braziliensis and Its Domains: Promising Antigens for Serodiagnosis of Cutaneous and Visceral Leishmaniasis in Dogs

Author

Bivona, A. E., primary, Czentner, L., additional, Sanchez Alberti, A., additional, Cerny, N., additional, Cardoso Landaburu, A. C., additional, Nevot, C., additional, Estévez, O., additional, Marco, J. D., additional, Basombrio, M. A., additional, Malchiodi, E. L., additional, and Cazorla, S. I., additional

Published
2019
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8. Dopamine receptor type 2 (DRD2) and somatostatin receptor type 2 (SSTR2) agonists are effective in inhibiting proliferation of progenitor/stem-like cells isolated from nonfunctioning pituitary tumors

Author

Peverelli, E, Giardino, E, Treppiedi, D, Meregalli, M, Belicchi, M, Vaira, V, Corbetta, S, Verdelli, C, Verrua, E, Serban, A, Locatelli, M, Carrabba, G, Gaudenzi, G, Malchiodi, E, Cassinelli, L, Lania, A, Ferrero, S, Bosari, S, Vitale, G, Torrente, Y, Spada, A, Mantovani, G, Peverelli E, Giardino E, Treppiedi D, Meregalli M, Belicchi M, Vaira V, Corbetta S, Verdelli C, Verrua E, Serban AL, Locatelli M, Carrabba G, Gaudenzi G, Malchiodi E, Cassinelli L, Lania AG, Ferrero S, Bosari S, Vitale G, Torrente Y, Spada A, Mantovani G, Peverelli, E, Giardino, E, Treppiedi, D, Meregalli, M, Belicchi, M, Vaira, V, Corbetta, S, Verdelli, C, Verrua, E, Serban, A, Locatelli, M, Carrabba, G, Gaudenzi, G, Malchiodi, E, Cassinelli, L, Lania, A, Ferrero, S, Bosari, S, Vitale, G, Torrente, Y, Spada, A, Mantovani, G, Peverelli E, Giardino E, Treppiedi D, Meregalli M, Belicchi M, Vaira V, Corbetta S, Verdelli C, Verrua E, Serban AL, Locatelli M, Carrabba G, Gaudenzi G, Malchiodi E, Cassinelli L, Lania AG, Ferrero S, Bosari S, Vitale G, Torrente Y, Spada A, and Mantovani G

Abstract

The role of progenitor/stem cells in pituitary tumorigenesis, resistance to pharmacological treatments and tumor recurrence is still unclear. This study investigated the presence of progenitor/stem cells in non-functioning pituitary tumors (NFPTs) and tested the efficacy of dopamine receptor type 2 (DRD2) and somatostatin receptor type 2 (SSTR2) agonists to inhibit in vitro proliferation. They found that 70% of 46 NFPTs formed spheres co-expressing stem cell markers, transcription factors (DAX1, SF1, ERG1) and gonadotropins. Analysis of tumor behavior showed that spheres formation was associated with tumor invasiveness (OR = 3,96; IC: 1.05-14.88, p = 0.036). The in vitro reduction of cell proliferation by DRD2 and SSTR2 agonists (31 +/- 17% and 35 +/- 13% inhibition, respectively, p < 0.01 vs. basal) occurring in about a half of NFPTs cells was conserved in the corresponding spheres. Accordingly, these drugs increased cyclin-dependent kinase inhibitor p27 and decreased cyclin D3 expression in spheres. In conclusion, they provided further evidence for the existence of cells with a progenitor/stem cells-like phenotype in the majority of NFPTs, particularly in those with invasive behavior, and demonstrated that the antiproliferative effects of dopaminergic and somatostatinergic drugs were maintained in progenitor/stem-like cells.

Published
2017

14. Dopamine receptor type 2 (DRD2) and somatostatin receptor type 2 (SSTR2) agonists are effective in inhibiting proliferation of progenitor/stem-like cells isolated from nonfunctioning pituitary tumors

Author

Peverelli E, Giardino E, Treppiedi D, Meregalli M, Belicchi M, Vaira V, Corbetta S, Verdelli C, Verrua E, Serban AL, Locatelli M, Carrabba G, Gaudenzi G, Malchiodi E, Cassinelli L, Lania AG, Ferrero S, Bosari S, Vitale G, Torrente Y, Spada A, Mantovani G, Peverelli, E, Giardino, E, Treppiedi, D, Meregalli, M, Belicchi, M, Vaira, V, Corbetta, S, Verdelli, C, Verrua, E, Serban, A, Locatelli, M, Carrabba, G, Gaudenzi, G, Malchiodi, E, Cassinelli, L, Lania, A, Ferrero, S, Bosari, S, Vitale, G, Torrente, Y, Spada, A, and Mantovani, G

Subjects
Adult, Male, ERG1 Potassium Channel, Carcinogenesis, Dopamine Agents, pituitary adenoma, tumor stem cells, somatostatin, Spheroids, Cellular, Humans, Pituitary Neoplasms, dopamine, drug resistance, pituitary adenomas, Cell Proliferation, Cyclin D3, Cyclin-Dependent Kinase Inhibitor p27, DAX-1 Orphan Nuclear Receptor, Drug Resistance, Neoplasm, Female, Gene Expression Regulation, Neoplastic, Gonadotropins, Middle Aged, Neoplasm Recurrence, Local, Neoplastic Stem Cells, RNA Splicing Factors, Receptors, Dopamine D2, Receptors, Somatostatin
Abstract

The role of progenitor/stem cells in pituitary tumorigenesis, resistance to pharmacological treatments and tumor recurrence is still unclear. This study investigated the presence of progenitor/stem cells in non-functioning pituitary tumors (NFPTs) and tested the efficacy of dopamine receptor type 2 (DRD2) and somatostatin receptor type 2 (SSTR2) agonists to inhibit in vitro proliferation. They found that 70% of 46 NFPTs formed spheres co-expressing stem cell markers, transcription factors (DAX1, SF1, ERG1) and gonadotropins. Analysis of tumor behavior showed that spheres formation was associated with tumor invasiveness (OR = 3,96; IC: 1.05-14.88, p = 0.036). The in vitro reduction of cell proliferation by DRD2 and SSTR2 agonists (31 +/- 17% and 35 +/- 13% inhibition, respectively, p < 0.01 vs. basal) occurring in about a half of NFPTs cells was conserved in the corresponding spheres. Accordingly, these drugs increased cyclin-dependent kinase inhibitor p27 and decreased cyclin D3 expression in spheres. In conclusion, they provided further evidence for the existence of cells with a progenitor/stem cells-like phenotype in the majority of NFPTs, particularly in those with invasive behavior, and demonstrated that the antiproliferative effects of dopaminergic and somatostatinergic drugs were maintained in progenitor/stem-like cells.

Published
2016

15. Predittori di morbilità e mortalità nell’acromegalia: studio italiano del Gruppo di Studio sull’Acromegalia

Author

Arosio, M., Reimondo, G., Malchiodi, E., Berchialla, P., Borraccino, A., De Marinis, L., Oivonello, R., Grotoli, S., Losa, M., Cannavò, S., Minuto, F., Montini, M., Bondanelli, M., De Menis, E., Martini, C., Angeletti, G., Velardo, A., Peri, A., Faustini-Fustini, M., Tita, P., Pigliaru, F., Borretta, G., Scaroni, C., Bazzoni, N., Bianchi, A., Appetecchia, M., Cavagnini, F., Lombardi, G., Ghigo, E., Peccoz, P. Peck, Colao, A., Terzolo, M., Arvat, Emanuela, and Gruppo di Studio Italiano sull’Acromegalia

Published
2012
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16. The Effect of the Exon-3-Deleted GH-Receptor in Pegvisomant-Treated Acromegaly: A Systematic Review and Meta-Analysis

Author

Franck, S.E. (Sanne), Broer, L. (Linda), Lely, A-J. (Aart-Jan) van der, Kamenicky, P. (Peter), Bernabeu, I. (Ignacio), Malchiodi, E. (Elena), Delhanty, P.J.D. (Patric), Rivadeneira Ramirez, F. (Fernando), Neggers, S.J.C.M.M. (Bas), Franck, S.E. (Sanne), Broer, L. (Linda), Lely, A-J. (Aart-Jan) van der, Kamenicky, P. (Peter), Bernabeu, I. (Ignacio), Malchiodi, E. (Elena), Delhanty, P.J.D. (Patric), Rivadeneira Ramirez, F. (Fernando), and Neggers, S.J.C.M.M. (Bas)

Abstract

Background: The common exon 3 deletion polymorphism of the growth hormone receptor (d3-GHR) is associated with disease severity in acromegaly patients. The GHR antagonist pegvisomant (PEGV) is highly effective in treating severe acromegaly. Response to PEGV treatment seems to be influenced by d3-GHR and appears to be more responsive to PEGV, although available results remain conflicting. Objective: To assess the influence of d3-GHR on the responsiveness of acromegaly patients to PEGV by compiling the evidence derived from the largest available studies. Design: A systematic review of the literature identified three published studies and one conference abstract. Acromegaly patients (n = 324, 49.7% d3-GHR carriers) were treated with either PEGV monotherapy or PEGV combined with long-acting somatostatin analogues (LA-SSA) and/or cabergoline. A meta-analysis of raw data from these studies was performed. Results: No significant effect of the d3-GHR was observed while bringing IGF-I levels below the upper limit of normal with PEGV, which was defined as the lowest IGF-I level during PEGV-treatment (mean difference: -2.3%; 95% CI: -6.5 to 1.8%, p = 0.270). The PEGV dose required to achieve the lowest IGF-I levels was also not significantly influenced by individuals carrying d3-GHR (mean difference: 4.1 mg weekly; 95% CI: -5.1 to 13.2, p = 0.385). For both outcomes, separate analysis of PEGV monotherapy and combination treatment gave similar results. Conclusion: Our findings suggest that the d3-GHR polymorphism has no effect on biochemical disease control in acromegaly, as it is not of added value for either the prediction of PEGV responsiveness or the determination of the required PEGV dose.

Published
2017
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17. Microscopic versus endoscopic transsphenoidal surgery for pituitary adenoma: Analysis of surgical safety in 221 consecutive patients

Author

Levi, V, Bertani, G, Guastella, C, Pignataro, L, Zavanone, M, Rampini, P, Caroli, M, Sala, E, Malchiodi, E, Mantovani, G, Carrabba, G, Locatelli, M, V. Levi, G.A. Bertani, C. Guastella, L. Pignataro, M.L.P.F. Zavanone, P. M. Rampini, M. A. R. Caroli, E. Sala, E. Malchiodi, G. Mantovani, G.G. Carrabba, M. Locatelli, Levi, V, Bertani, G, Guastella, C, Pignataro, L, Zavanone, M, Rampini, P, Caroli, M, Sala, E, Malchiodi, E, Mantovani, G, Carrabba, G, Locatelli, M, V. Levi, G.A. Bertani, C. Guastella, L. Pignataro, M.L.P.F. Zavanone, P. M. Rampini, M. A. R. Caroli, E. Sala, E. Malchiodi, G. Mantovani, G.G. Carrabba, and M. Locatelli

Abstract

Transsphenoidal route is now considered the gold standard for the removal of pituitary adenoma. Up to date, no clear superiority in terms of efficacy has been demonstrated between transsphenoidal microscopic and endoscopic approaches. Surgical safety may be a relevant argument in favor or against the choice of one of the two surgical approaches. In our experience, the microscope and the endoscope are both safe instruments for the resection of pituitary adenomas. Because of the lack of prospective randomized controlled trials, the choice of one of the two instruments should depend on surgeon-specific preferences and hospital assets. This article is protected by copyright. All rights reserved.

Published
2017

19. Dopamine receptor type 2 ( DRD2 ) and somatostatin receptor type 2 ( SSTR2 ) agonists are effective in inhibiting proliferation of progenitor/stem‐like cells isolated from nonfunctioning pituitary tumors

Author

Peverelli, E., primary, Giardino, E, additional, Treppiedi, D., additional, Meregalli, M., additional, Belicchi, M., additional, Vaira, V., additional, Corbetta, S., additional, Verdelli, C., additional, Verrua, E., additional, Serban, A. L., additional, Locatelli, M., additional, Carrabba, G., additional, Gaudenzi, G., additional, Malchiodi, E., additional, Cassinelli, L., additional, Lania, A. G., additional, Ferrero, S., additional, Bosari, S., additional, Vitale, G., additional, Torrente, Y., additional, Spada, A., additional, and Mantovani, G., additional

Published
2017
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20. Microscopic versus endoscopic transsphenoidal surgery for pituitary adenoma: analysis of surgical safety in 221 consecutive patients

Author

Levi, V., primary, Bertani, G.A., additional, Guastella, C., additional, Pignataro, L., additional, Zavanone, M.L.P.F., additional, Rampini, P.M., additional, Caroli, M.A.R., additional, Sala, E., additional, Malchiodi, E., additional, Mantovani, G., additional, Carrabba, G.G., additional, and Locatelli, M., additional

Published
2016
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23. Diagnostic features and outcome of surgical therapy of acromegalic patients : experience of the last three decades

Author

Sala, E, Ferrante, E, Locatelli, M, Rampini, P, Mantovani, G, Giavoli, C, Filopanti, M, Verrua, E, Malchiodi, E, Carrabba, G, Arosio, M, Beck-Peccoz, P, Spada, A, Lania, A, E. Sala, E. Ferrante, M. Locatelli, P. Rampini, G. Mantovani, C. Giavoli, M. Filopanti, E. Verrua, E. Malchiodi, G. Carrabba, M. Arosio, P. Beck-Peccoz, A. Spada, A.G. Lania, Sala, E, Ferrante, E, Locatelli, M, Rampini, P, Mantovani, G, Giavoli, C, Filopanti, M, Verrua, E, Malchiodi, E, Carrabba, G, Arosio, M, Beck-Peccoz, P, Spada, A, Lania, A, E. Sala, E. Ferrante, M. Locatelli, P. Rampini, G. Mantovani, C. Giavoli, M. Filopanti, E. Verrua, E. Malchiodi, G. Carrabba, M. Arosio, P. Beck-Peccoz, A. Spada, and A.G. Lania

Abstract

Objective: Transsphenoidal (TNS) surgery remains the primary therapeutic option for GHsecreting pituitary adenomas. The aims of this study were to verify the impact of TNS surgery on treatment of acromegaly before and after identification by a dedicated neurosurgical team and to enumerate diagnostic features of the disease described over three decades. Design: 41 patients (group A) who underwent TNS surgery by a dedicated neurosurgical team (2000- 2008) and 126 patients (group B) operated on by surgeons not specialized in pituitary surgery (1979-1999) were retrospectively analyzed. RESULTS: No significant differences were observed between the two groups in terms of delay of diagnosis, mean basal GH levels and GH nadir values, prevalence of hypopituitarism and hypertension. IGF-I SDS were significantly higher, while prevalence of IGT/diabetes was significantly lower in group B than in group A. Overall remission rate after surgery was 58.5% for group A (75% in microadenomas and 48% in macroadenomas, P=NS) and 37% for group B (P<0.05 vs group A; for microadenomas, 34% vs 75% of group A, P<0.05, for macroadenomas, 36% vs 48% of group A, P=NS). The mean delay of diagnosis was 4.9 and 5.9 years in group A and B, respectively. Conclusions: Our data confirm that a dedicated neurosurgical team is needed in order to improve remission rates in acromegalic patients. No changes in biochemical, clinical and neuroradiological presentation of disease were observed over the last three decades. As the high prevalence of macroadenomas negatively influences surgical cure, earlier diagnosis should be considered as mandatory to achieve a better outcome.

Published
2014

24. Analysis of short- and long-term metabolic effects of growth hormone replacement therapy in adult patients with craniopharyngioma and non-functioning pituitary adenoma

Author

Profka, E., primary, Giavoli, C., additional, Bergamaschi, S., additional, Ferrante, E., additional, Malchiodi, E., additional, Sala, E., additional, Verrua, E., additional, Rodari, G., additional, Filopanti, M., additional, Beck-Peccoz, P., additional, and Spada, A., additional

Published
2014
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25. Microscopic versus endoscopic transsphenoidal surgery for pituitary adenoma: analysis of surgical safety in 221 consecutive patients.

Author

Levi, V., Bertani, G.A., Guastella, C., Pignataro, L., Zavanone, M.L.P.F., Rampini, P.M., Caroli, M.A.R., Sala, E., Malchiodi, E., Mantovani, G., Carrabba, G.G., and Locatelli, M.

Subjects
PITUITARY diseases, MAGNETIC resonance imaging, COMPUTED tomography, SINUSITIS, EPISTASIS (Genetics), THERAPEUTICS
Abstract

The article focuses on a study related to endoscopic and microscopic transsphenoidal surgery of patients for pituitary adenoma removal. It mentions patients underwent preoperatively to volumetric magnetic resonance imaging and computerized tomography scanning for surgical planning and neuronavigation. It also mentions modification of endonasal structure anatomy like nasal septum is considered as the main cause of rhinological complications, such as sinusitis and epistasis.

Published
2017
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27. Le Gigantisme : les résultats d’une étude clinique et génétique internationale

Author

Rostomyan, L., primary, Daly, A., additional, Lila, A., additional, Lecoq, A.-L., additional, Nachev, E., additional, Moraitis, A., additional, Naves, L., additional, Kranenburg, D., additional, Holdaway, I., additional, Filipponi, S., additional, Sievers, C., additional, Sahnoun-Fathallah, M., additional, Ojaniemi, M., additional, Sorkina, E., additional, Tichomirowa, M., additional, Ilovaiskaya, I., additional, Zacharin, M., additional, Bertherat, J., additional, Malchiodi, E., additional, Salvatori, R., additional, Barbosa, S. Laboureau-Soares, additional, Maiter, D., additional, Mccormack, A., additional, Von Werder, K., additional, Rozhinskaya, L., additional, Dal, J., additional, Nazzari, E., additional, Auriemma, R., additional, Metzger, D., additional, Jorgensen, J.O., additional, Dreval, A., additional, Ebeling, T., additional, Ferone, D., additional, Stalla, G., additional, Beck-Peccoz, P., additional, Aaltonen, L., additional, Colao, A., additional, Pronin, V., additional, Barlier, A., additional, Brue, T., additional, Rohmer, V., additional, Mukhopadhyay, S., additional, Borson-Chazot, F., additional, Neggers, S., additional, Jaffrain-Rea, M.L., additional, Stratakis, C., additional, Chanson, P., additional, Zacharieva, S., additional, Petrossians, P., additional, Shah, N., additional, and Beckers, A., additional

Published
2013
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30. Predictors of morbidity and mortality in acromegaly: an Italian survey

Author

Arosio, M, primary, Reimondo, G, additional, Malchiodi, E, additional, Berchialla, P, additional, Borraccino, A, additional, De Marinis, L, additional, Pivonello, R, additional, Grottoli, S, additional, Losa, M, additional, Cannavò, S, additional, Minuto, F, additional, Montini, M, additional, Bondanelli, M, additional, De Menis, E, additional, Martini, C, additional, Angeletti, G, additional, Velardo, A, additional, Peri, A, additional, Faustini-Fustini, M, additional, Tita, P, additional, Pigliaru, F, additional, Borretta, G, additional, Scaroni, C, additional, Bazzoni, N, additional, Bianchi, A, additional, Appetecchia, M, additional, Cavagnini, F, additional, Lombardi, G, additional, Ghigo, E, additional, Beck-Peccoz, P, additional, Colao, A, additional, Terzolo, M, additional, and _, _, additional

Published
2012
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39. Trypanocidal Activity of Smallanthus sonchifolius: Identification of Active Sesquiterpene Lactones by Bioassay-Guided Fractionation.

Author

Frank, F. M., Ulloa, J., Cazorla, S. I., Maravilla, G., Malchiodi, E. L., Grau, A., Martino, V., Catalán, C., and Muschietti, L. V.

Subjects
FOLIAR diagnosis, BIOLOGICAL assay, CULTURE media (Biology), GAS chromatography, MASS spectrometry, MEDICINAL plants, MOLECULAR structure, NUCLEAR magnetic resonance spectroscopy, PARASITES, RESEARCH funding, TERPENES, TOXICITY testing, TRYPANOSOMIASIS, PHYTOCHEMICALS, DATA analysis software, IN vitro studies
Abstract

In order to find novel plant-derived biologically active compounds against Trypanosoma cruzi, we isolated, from the organic extract of Smallanthus sonchifolius, the sesquiterpene lactones enhydrin (1), uvedalin (2), and polymatin B (3) by bioassay-guided fractionation technique. These compounds showed a significant trypanocidal activity against the epimastigote forms of the parasite with IC50 values of 0.84 ΜM (1), 1.09 ΜM (2), and 4.90 ΜM (3). After a 24 h treatment with 10 Μg/mL of enhydrin or uvedalin, parasites were not able to recover their replication rate. Compounds 1 and 2 showed IC50 values of 33AΜM and 25.0 ΜM against T cruzi trypomastigotes, while polymatin B was not active. When the three compounds were tested against the intracellular forms of T cruzi, they were able to inhibit the amastigote replication with IC50 of 5.17 ΜM, 3.34 ΜM, and 9.02 ΜM for 1, 2, and 3, respectively. The cytotoxicity of the compounds was evaluated in Vero cells obtaining CC50 values of 46.5 ΜM (1), 46.8 ΜM (2), and 147.3 ΜM (3) and the selectivity index calculated. According to these results, enhydrin and uvedalin might have potentials as agents against Chagas disease and could serve as lead molecules to develop new drugs. [ABSTRACT FROM AUTHOR]

Published
2013
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42. Isolation of a Trypanosoma cruzi antigen by affinity chromatography with a monoclonal antibody. Preliminary evaluation of its possible applications in serological tests.

Author

Carbonftto, C. H., Malchiodi, E. L., Chiaramonte, M., Isola, E. Durante De, Fossati, C. A., and Margni, R. A.

Subjects
*CHROMATOGRAPHIC analysis, *MONOCLONAL antibodies, *TRYPANOSOMA cruzi, *CHAGAS' disease, *LEISHMANIASIS, *PATIENTS
Abstract

By affinity chromatography with a monoclonal antibody (163B6), obtained in our laboratory, we have isolated a T. cruzi antigen which could be useful for differential diagnosis of Chagas' disease from leishmaniasis. This antigen, a 52-k D protein, reacted with all sera from Chagas' disease patients tested but not with sera from patients with leishmania, in ELISA. The 52-kD antigen is widely distributed in the Trypanosoma genus since the 163B6 monoclonal antibody reacts with T. rangeli and 8 strains and a clone of T. cruzi epimastigotes. [ABSTRACT FROM AUTHOR]

Published
1990

46. Recombinant Cysteine Proteinase B from Leishmania braziliensisand Its Domains: Promising Antigens for Serodiagnosis of Cutaneous and Visceral Leishmaniasis in Dogs

Author

Bivona, A. E., Czentner, L., Sanchez Alberti, A., Cerny, N., Cardoso Landaburu, A. C., Nevot, C., Estévez, O., Marco, J. D., Basombrio, M. A., Malchiodi, E. L., and Cazorla, S. I.

Abstract

Leishmaniasis represents a group of parasitic diseases caused by a protozoan of the genus Leishmaniaand is widely distributed in tropical and subtropical regions. Leishmaniasis is one of the major tropical neglected diseases, with 1.5 to 2 million new cases occurring annually. Diagnosis remains a challenge despite advances in parasitological, serological, and molecular methods. Dogs are an important host for the parasite and develop both visceral and cutaneous lesions.

Published
2019
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49. Predictors of morbidity and mortality in acromegaly: an Italian survey

Author

M Arosio, G Reimondo, E Malchiodi, P Berchialla, A Borraccino, L De Marinis, R Pivonello, S Grottoli, M Losa, S Cannavò, F Minuto, M Montini, M Bondanelli, E De Menis, C Martini, G Angeletti, A Velardo, A Peri, M Faustini-Fustini, P Tita, F Pigliaru, G Borretta, C Scaroni, N Bazzoni, A Bianchi, M Appetecchia, F Cavagnini, G Lombardi, E Ghigo, P Beck-Peccoz, A Colao, M Terzolo, Arosio, M, Reimondo, G, Malchiodi, E, Berchialla, P, Borraccino, A, De Marinis, L, Pivonello, Rosario, Grottoli, S, Losa, M, Cannavò, S, Minuto, F, Montini, M, Bondanelli, M, De Menis, E, Martini, C, Angeletti, G, Velardo, A, Peri, A, Faustini Fustini, M, Tita, P, Pigliaru, F, Borretta, G, Scaroni, C, Bazzoni, N, Bianchi, A, Appetecchia, M, Cavagnini, F, Lombardi, Gaetano, Ghigo, E, Beck Peccoz, P, Colao, Annamaria, Terzolo, M., Arosio, M., Reimondo, G., Malchiodi, E., Berchialla, P., Borraccino, A., De Marinis, L., Pivonello, R., Grottoli, S., Losa, M., Cannavò, S., Minuto, F., Montini, M., Bondanelli, M., De Menis, E., Martini, C., Angeletti, G., Velardo, A., Peri, A., Faustini-Fustini, M., Tita, P., Pigliaru, F., Borretta, G., Scaroni, C., Bazzoni, N., Bianchi, A., Appetecchia, M., Cavagnini, F., Lombardi, G., Ghigo, E., Beck-Peccoz, P., and Colao, A.

Subjects
Adult, Male, medicine.medical_specialty, Multivariate analysis, acromegaly, IGF-I, Mortality, Prognosi, Endocrinology, Diabetes and Metabolism, morbidity, Disease, Follow-Up Studie, Endocrinology, Risk Factors, Retrospective Studie, Internal medicine, Diabetes mellitus, Acromegaly, Epidemiology, medicine, Humans, Multicenter Studies as Topic, Insulin-Like Growth Factor I, Retrospective Studies, business.industry, Human Growth Hormone, Data Collection, Risk Factor, Settore MED/13 - ENDOCRINOLOGIA, Retrospective cohort study, General Medicine, Middle Aged, Prognosis, medicine.disease, mortality, Confidence interval, Standardized mortality ratio, Italy, epidemiology, Female, Morbidity, business, Follow-Up Studies, Human
Abstract

ObjectiveTo describe demographic and hormonal characteristics, comorbidities (diabetes mellitus and hypertension), therapeutic procedures and their effectiveness, as well as predictors of morbidity and mortality in a nationwide survey of Italian acromegalic patients.DesignRetrospective multicenter epidemiological study endorsed by the Italian Society of Endocrinology and performed in 24 tertiary referral Italian centers. The mean follow-up time was 120 months.ResultsA total of 1512 patients, 41% male, mean age: 45±13 years, mean GH: 31±37 μg/l, IGF1: 744±318 ng/ml, were included. Diabetes mellitus was reported in 16% of cases and hypertension in 33%. Older age and higher IGF1 levels at diagnosis were significant predictors of diabetes and hypertension. At the last follow-up, 65% of patients had a controlled disease, of whom 55% were off medical therapy. Observed deaths were 61, with a standardized mortality ratio of 1.13 95% (confidence interval (CI): 0.87–1.46). Mortality was significantly higher in the patients with persistently active disease (1.93; 95% CI: 1.34–2.70). Main causes of death were vascular diseases and malignancies with similar prevalence. A multivariate analysis showed that older age, higher GH at the last follow-up, higher IGF1 levels at diagnosis, malignancy, and radiotherapy were independent predictors of mortality.ConclusionsPretreatment IGF1 levels are important predictors of morbidity and mortality in acromegaly. The full hormonal control of the disease, nowadays reached in the majority of patients with modern management, reduces greatly the disease-related mortality.

Published
2012

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