, Volume 61, Issue 3, pp 533–541 | Cite as

Epidemiology of acromegaly in Italy: analysis from a large longitudinal primary care database

  • Federico GattoEmail author
  • Gianluca Trifirò
  • Francesco Lapi
  • Francesco Cocchiara
  • Claudia Campana
  • Carlotta Dell’Aquila
  • Carmen Ferrajolo
  • Marica Arvigo
  • Claudio Cricelli
  • Massimo Giusti
  • Diego Ferone
Original Article



Epidemiological data are pivotal for the estimation of disease burden in populations.


Of the study was to estimate the incidence and prevalence of acromegaly in Italy along with the impact of comorbidities and hospitalization rates as compared to the general population.


Retrospective epidemiological study (from 2000 to 2014) and case control-study. Data were extracted from the Health Search Database (HSD). HSD contains patient records from about 1000 general practitioners (GPs) throughout Italy, covering a population of more than 1 million patients. It includes information about patient demographics and medical data including clinical diagnoses and diagnostic tests.


At the end of the study period, 74 acromegaly patients (out of 1,066,871 people) were identified, resulting in a prevalence of 6.9 per 100,000 inhabitants [95% CI 5.4–8.5]. Prevalence was higher in females than men (p = 0.004), and showed a statistically significant trend of increase over time (p < 0.0001). Overall, incidence during the study period was 0.31 per 100,000 person-years. Hypertension and type II diabetes mellitus were the comorbidities more frequently associated with acromegaly (31.3 and 14.6%, respectively) and patients were more likely to undergo a high frequency of yearly hospitalization (≥3 accesses/year, p < 0.001) compared to sex-age matched controls.


This epidemiological study on acromegaly carried out using a large GP-based database, documented a disease prevalence of about 7 cases per 100,000 inhabitants. As expected, acromegaly was associated with a number of comorbidities (mainly hypertension and type II diabetes mellitus) and a high rate of patients’ hospitalization.


Acromegaly Epidemiology Prevalence Incidence Comorbidities 



This research received the unconditional support of Pfizer srl.

Compliance with ethical standards

Conflict of interest

F.G. received fees for lectures and/or participation to advisory boards for Novartis, AMCo, and IONIS Pharmaceuticals. D.F. received grants and fees for lectures and participation to advisory boards for Novartis, Ipsen, and Pfizer. The remaining authors have declare that they have no conflict of interest.

Supplementary material

12020_2018_1630_MOESM1_ESM.pdf (357 kb)
Supplementary Information


  1. 1.
    S. Melmed, Medical progress: acromegaly. N. Engl. J. Med. 355(24), 2558–2573 (2006). CrossRefPubMedGoogle Scholar
  2. 2.
    F.G. Davis, V. Kupelian, S. Freels, B. McCarthy, T. Surawicz, Prevalence estimates for primary brain tumors in the United States by behavior and major histology groups. Neuro. Oncol. 3(3), 152–158 (2001)CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    A. Lavrentaki, A. Paluzzi, J.A. Wass, N. Karavitaki, Epidemiology of acromegaly: review of population studies. Pituitary 20(1), 4–9 (2017). CrossRefPubMedGoogle Scholar
  4. 4.
    A. Fernandez, N. Karavitaki, J.A. Wass, Prevalence of pituitary adenomas: a community-based, cross-sectional study in Banbury (Oxfordshire, UK). Clin. Endocrinol. 72(3), 377–382 (2010). CrossRefGoogle Scholar
  5. 5.
    A.F. Daly, M. Rixhon, C. Adam, A. Dempegioti, M.A. Tichomirowa, A. Beckers, High prevalence of pituitary adenomas: a cross-sectional study in the province of Liege, Belgium. J. Clin. Endocrinol. Metab. 91(12), 4769–4775 (2006). CrossRefPubMedGoogle Scholar
  6. 6.
    A. Raappana, J. Koivukangas, T. Ebeling, T. Pirila, Incidence of pituitary adenomas in Northern Finland in 1992-2007. J. Clin. Endocrinol. Metab. 95(9), 4268–4275 (2010). CrossRefPubMedGoogle Scholar
  7. 7.
    T.T. Agustsson, T. Baldvinsdottir, J.G. Jonasson, E. Olafsdottir, V. Steinthorsdottir, G. Sigurdsson, A.V. Thorsson, P.V. Carroll, M. Korbonits, R. Benediktsson, The epidemiology of pituitary adenomas in Iceland, 1955-2012: a nationwide population-based study. Eur. J. Endocrinol. 173(5), 655–664 (2015). CrossRefPubMedGoogle Scholar
  8. 8.
    T. Burton, E. Le Nestour, M. Neary, W.H. Ludlam, Incidence and prevalence of acromegaly in a large US health plan database. Pituitary 19(3), 262–267 (2016). CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    M. Bex, R. Abs, G. T’Sjoen, J. Mockel, B. Velkeniers, K. Muermans, D. Maiter, AcroBel--the Belgian registry on acromegaly: a survey of the ‘real-life’ outcome in 418 acromegalic subjects. Eur. J. Endocrinol. 157(4), 399–409 (2007). CrossRefPubMedGoogle Scholar
  10. 10.
    A. Tjornstrand, K. Gunnarsson, M. Evert, E. Holmberg, O. Ragnarsson, T. Rosen, H. Filipsson Nystrom, The incidence rate of pituitary adenomas in western Sweden for the period 2001-2011. Eur. J. Endocrinol. 171(4), 519–526 (2014). CrossRefPubMedGoogle Scholar
  11. 11.
    J. Dal, U. Feldt-Rasmussen, M. Andersen, L.O. Kristensen, P. Laurberg, L. Pedersen, O.M. Dekkers, H.T. Sorensen, J.O. Jorgensen, Acromegaly incidence, prevalence, complications and long-term prognosis: a nationwide cohort study. Eur. J. Endocrinol. 175(3), 181–190 (2016). CrossRefPubMedGoogle Scholar
  12. 12.
    A. Mestron, S.M. Webb, R. Astorga, P. Benito, M. Catala, S. Gaztambide, J.M. Gomez, I. Halperin, T. Lucas-Morante, B. Moreno, G. Obiols, P. de Pablos, C. Paramo, A. Pico, E. Torres, C. Varela, J.A. Vazquez, J. Zamora, M. Albareda, M. Gilabert, Epidemiology, clinical characteristics, outcome, morbidity and mortality in acromegaly based on the Spanish Acromegaly Registry (Registro Espanol de Acromegalia, REA). Eur. J. Endocrinol. 151(4), 439–446 (2004)CrossRefPubMedGoogle Scholar
  13. 13.
    G.T. Hoskuldsdottir, S.B. Fjalldal, H.A. Sigurjonsdottir, The incidence and prevalence of acromegaly, a nationwide study from 1955 through 2013. Pituitary 18(6), 803–807 (2015). CrossRefPubMedGoogle Scholar
  14. 14.
    S. Ezzat, S.L. Asa, W.T. Couldwell, C.E. Barr, W.E. Dodge, M.L. Vance, I.E. McCutcheon, The prevalence of pituitary adenomas: a systematic review. Cancer 101(3), 613–619 (2004). CrossRefPubMedGoogle Scholar
  15. 15.
    A. Colao, D. Ferone, P. Marzullo, G. Lombardi, Systemic complications of acromegaly: epidemiology, pathogenesis, and management. Endocr. Rev. 25(1), 102–152 (2004). CrossRefPubMedGoogle Scholar
  16. 16.
    L. Katznelson, E.R. Laws Jr., S. Melmed, M.E. Molitch, M.H. Murad, A. Utz, J.A. Wass, S. Endocrine, Acromegaly: an endocrine society clinical practice guideline. J. Clin. Endocrinol. Metab. 99(11), 3933–3951 (2014). CrossRefPubMedGoogle Scholar
  17. 17.
    S.M. Webb, X. Badia, Quality of Life in Acromegaly. Neuroendocrinology 103(1), 106–111 (2016). CrossRefPubMedGoogle Scholar
  18. 18.
    T. Brue, F. Castinetti, The risks of overlooking the diagnosis of secreting pituitary adenomas. Orphanet. J. Rare. Dis. 11(1), 135 (2016). CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    I.M. Holdaway, R.C. Rajasoorya, G.D. Gamble, Factors influencing mortality in acromegaly. J. Clin. Endocrinol. Metab. 89(2), 667–674 (2004). CrossRefPubMedGoogle Scholar
  20. 20.
    R. Kauppinen-Makelin, T. Sane, A. Reunanen, M.J. Valimaki, L. Niskanen, H. Markkanen, E. Loyttyniemi, T. Ebeling, P. Jaatinen, H. Laine, P. Nuutila, P. Salmela, J. Salmi, U.H. Stenman, J. Viikari, E. Voutilainen, A nationwide survey of mortality in acromegaly. J. Clin. Endocrinol. Metab. 90(7), 4081–4086 (2005). CrossRefPubMedGoogle Scholar
  21. 21.
    I.M. Holdaway, M.J. Bolland, G.D. Gamble, A meta-analysis of the effect of lowering serum levels of GH and IGF-I on mortality in acromegaly. Eur. J. Endocrinol. 159(2), 89–95 (2008). CrossRefPubMedGoogle Scholar
  22. 22.
    M. Arosio, G. Reimondo, E. Malchiodi, P. Berchialla, A. Borraccino, L. De Marinis, R. Pivonello, S. Grottoli, M. Losa, S. Cannavo, 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; Italian Study Group of, A., Predictors of morbidity and mortality in acromegaly: an Italian survey. Eur. J. Endocrinol. 167(2), 189–198 (2012). PubMedCrossRefGoogle Scholar
  23. 23.
    L. Maione, T. Brue, A. Beckers, B. Delemer, P. Petrossians, F. Borson-Chazot, O. Chabre, P. Francois, J. Bertherat, C. Cortet-Rudelli, P. Chanson; French Acromegaly Registry, G., Changes in the management and comorbidities of acromegaly over three decades: the French Acromegaly Registry. Eur. J. Endocrinol. 176(5), 645–655 (2017). CrossRefPubMedGoogle Scholar
  24. 24.
    A. Giustina, P. Chanson, D. Kleinberg, M.D. Bronstein, D.R. Clemmons, A. Klibanski, A.J. van der Lely, C.J. Strasburger, S.W. Lamberts, K.K. Ho, F.F. Casanueva, S. Melmed; Acromegaly Consensus, G., Expert consensus document: a consensus on the medical treatment of acromegaly. Nature reviews. Endocrinology 10(4), 243–248 (2014). PubMedCrossRefGoogle Scholar
  25. 25.
    E. Lesen, D. Granfeldt, A. Houchard, J. Dinet, A. Berthon, D.S. Olsson, I. Bjorholt, G. Johannsson, Comorbidities, treatment patterns and cost-of-illness of acromegaly in Sweden: a register-linkage population-based study. Eur. J. Endocrinol. 176(2), 203–212 (2017). CrossRefPubMedGoogle Scholar
  26. 26.
    M.S. Broder, M.P. Neary, E. Chang, D. Cherepanov, L. Katznelson, Treatments, complications, and healthcare utilization associated with acromegaly: a study in two large United States databases. Pituitary 17(4), 333–341 (2014). CrossRefPubMedGoogle Scholar
  27. 27.
    C. Cricelli, G. Mazzaglia, F. Samani, M. Marchi, A. Sabatini, R. Nardi, G. Ventriglia, A.P. Caputi, Prevalence estimates for chronic diseases in Italy: exploring the differences between self-report and primary care databases. J. Public Health Med. 25(3), 254–257 (2003)CrossRefPubMedGoogle Scholar
  28. 28.
    G. Trifiro, P. Morabito, L. Cavagna, C. Ferrajolo, S. Pecchioli, M. Simonetti, E. Bianchini, G. Medea, C. Cricelli, A.P. Caputi, G. Mazzaglia, Epidemiology of gout and hyperuricaemia in Italy during the years 2005-2009: a nationwide population-based study. Ann. Rheum. Dis. 72(5), 694–700 (2013). CrossRefPubMedGoogle Scholar
  29. 29.
    G. Mazzaglia, E. Ambrosioni, M. Alacqua, A. Filippi, E. Sessa, V. Immordino, C. Borghi, O. Brignoli, A.P. Caputi, C. Cricelli, L.G. Mantovani, Adherence to antihypertensive medications and cardiovascular morbidity among newly diagnosed hypertensive patients. Circulation 120(16), 1598–1605 (2009). CrossRefPubMedGoogle Scholar
  30. 30.
    J. Etxabe, S. Gaztambide, P. Latorre, J.A. Vazquez, Acromegaly: an epidemiological study. J. Endocrinol. Invest. 16(3), 181–187 (1993). CrossRefPubMedGoogle Scholar
  31. 31.
    I.M. Holdaway, C. Rajasoorya, Epidemiology of acromegaly. Pituitary 2(1), 29–41 (1999)CrossRefPubMedGoogle Scholar
  32. 32.
    L.A. Naves, L.B. Porto, J.W. Rosa, L.A. Casulari, J.W. Rosa, Geographical information system (GIS) as a new tool to evaluate epidemiology based on spatial analysis and clinical outcomes in acromegaly. Pituitary 18(1), 8–15 (2015). CrossRefPubMedGoogle Scholar
  33. 33.
    S. Cannavo, F. Ferrau, M. Ragonese, L. Curto, M.L. Torre, M. Magistri, A. Marchese, A. Alibrandi, F. Trimarchi, Increased prevalence of acromegaly in a highly polluted area. Eur. J. Endocrinol. 163(4), 509–513 (2010). CrossRefPubMedGoogle Scholar
  34. 34.
    M. Gruppetta, C. Mercieca, J. Vassallo, Prevalence and incidence of pituitary adenomas: a population based study in Malta. Pituitary 16(4), 545–553 (2013). CrossRefPubMedGoogle Scholar
  35. 35.
    J. Dal, N. Skou, E.H. Nielsen, J.O. Jorgensen, L. Pedersen, Acromegaly according to the Danish National Registry of Patients: how valid are ICD diagnoses and how do patterns of registration affect the accuracy of registry data? Clin. Epidemiol. 6, 295–299 (2014). CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    S. Fieffe, I. Morange, P. Petrossians, P. Chanson, V. Rohmer, C. Cortet, F. Borson-Chazot, T. Brue, B. Delemer; French Acromegaly, R., Diabetes in acromegaly, prevalence, risk factors, and evolution: data from the French Acromegaly Registry. Eur. J. Endocrinol. 164(6), 877–884 (2011). CrossRefPubMedGoogle Scholar
  37. 37.
    S. Petersenn, M. Buchfelder, M. Reincke, C.M. Strasburger, H. Franz, R. Lohmann, H.J. Quabbe, U. Plockinger, Participants of the German Acromegaly, R.: Results of surgical and somatostatin analog therapies and their combination in acromegaly: a retrospective analysis of the German Acromegaly Register. Eur. J. Endocrinol. 159(5), 525–532 (2008). CrossRefPubMedGoogle Scholar
  38. 38.
    L.A. Portocarrero-Ortiz, A. Vergara-Lopez, M. Vidrio-Velazquez, A.M. Uribe-Diaz, A. Garcia-Dominguez, A.A. Reza-Albarran, D. Cuevas-Ramos, V. Melgar, J. Talavera, A.J. Rivera-Hernandez, C.V. Valencia-Mendez, M. Mercado, Mexican Acromegaly Registry, G.: The Mexican Acromegaly Registry: Clinical and Biochemical Characteristics at Diagnosis and Therapeutic Outcomes. J. Clin. Endocrinol. Metab. 101(11), 3997–4004 (2016). CrossRefPubMedGoogle Scholar
  39. 39.
    P. Petrossians, A.F. Daly, E. Natchev, L. Maione, K. Blijdorp, M. Sahnoun-Fathallah, R. Auriemma, A.M. Diallo, A.L. Hulting, D. Ferone, V. Hana Jr., S. Filipponi, C. Sievers, C. Nogueira, C. Fajardo-Montanana, D. Carvalho, V. Hana, G.K. Stalla, M.L. Jaffrain-Rea, B. Delemer, A. Colao, T. Brue, S. Neggers, S. Zacharieva, P. Chanson, A. Beckers, Acromegaly at diagnosis in 3173 patients from the Liege Acromegaly Survey (LAS) Database. Endocr.-Relat. Cancer 24(10), 505–518 (2017). CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    O. Kwon, Y.D. Song, S.Y. Kim, E.J. Lee; Rare Disease Study Group, S., Research Committee, K.E.S., Nationwide survey of acromegaly in South Korea. Clin. Endocrinol. 78(4), 577–585 (2013). CrossRefGoogle Scholar
  41. 41.
    M. Bondanelli, M.R. Ambrosio, E.C. degli Uberti, Pathogenesis and prevalence of hypertension in acromegaly. Pituitary 4(4), 239–249 (2001)CrossRefPubMedGoogle Scholar
  42. 42.
    R. Gini, M.J. Schuemie, G. Mazzaglia, F. Lapi, P. Francesconi, A. Pasqua, E. Bianchini, C. Montalbano, G. Roberto, V. Barletta, I. Cricelli, C. Cricelli, G. Dal Co, M. Bellentani, M. Sturkenboom, N. Klazinga, Automatic identification of type 2 diabetes, hypertension, ischaemic heart disease, heart failure and their levels of severity from Italian General Practitioners’ electronic medical records: a validation study. BMJ Open 6(12), e012413 (2016). CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    T.J. Reid, K.D. Post, J.N. Bruce, M. Nabi Kanibir, C.M. Reyes-Vidal, P.U. Freda, Features at diagnosis of 324 patients with acromegaly did not change from 1981 to 2006: acromegaly remains under-recognized and under-diagnosed. Clin. Endocrinol. 72(2), 203–208 (2010). CrossRefGoogle Scholar
  44. 44.
    T. Burton, E. Le Nestour, T. Bancroft, M. Neary, Real-world comorbidities and treatment patterns of patients with acromegaly in two large US health plan databases. Pituitary 16(3), 354–362 (2013). CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Federico Gatto
    • 1
    • 2
    Email author
  • Gianluca Trifirò
    • 3
  • Francesco Lapi
    • 4
  • Francesco Cocchiara
    • 1
  • Claudia Campana
    • 1
  • Carlotta Dell’Aquila
    • 1
  • Carmen Ferrajolo
    • 5
  • Marica Arvigo
    • 1
    • 2
  • Claudio Cricelli
    • 6
  • Massimo Giusti
    • 1
  • Diego Ferone
    • 1
    • 2
  1. 1.Endocrinology, Department of Internal Medicine and Medical Specialties (DIMI)University of GenoaGenoaItaly
  2. 2.Center of Excellence for Biomedical Research (CEBR), Policlinico San MartinoUniversity of GenoaGenoaItaly
  3. 3.Department of Biomedical and Dental Sciences and Morphofunctional ImagingUniversity of MessinaMessinaItaly
  4. 4.Health SearchItalian College of General Practitioners and Primary CareFlorenceItaly
  5. 5.Department of Experimental Medicine, Pharmacology Section, Campania Regional Centre of Pharmacovigilance and PharmacoepidemiologyUniversity of CampaniaNaplesItaly
  6. 6.Italian College of General Practitioners and Primary CareFlorenceItaly

Personalised recommendations