Acromegaly is a rare disorder caused by chronic growth hormone (GH) hypersecretion. While diagnostic and therapeutic methods have advanced, little information exists on trends in acromegaly characteristics over time. The Liège Acromegaly Survey (LAS) Database, a relational database, is designed to assess the profile of acromegaly patients at diagnosis and during long-term follow-up at multiple treatment centers. The following results were obtained at diagnosis. The study population consisted of 3173 acromegaly patients from ten countries; 54.5% were female. Males were significantly younger at diagnosis than females (43.5 vs 46.4 years; P < 0.001). The median delay from first symptoms to diagnosis was 2 years longer in females (P = 0.015). Ages at diagnosis and first symptoms increased significantly over time (P < 0.001). Tumors were larger in males than females (P < 0.001); tumor size and invasion were inversely related to patient age (P < 0.001). Random GH at diagnosis correlated with nadir GH levels during OGTT (P < 0.001). GH was inversely related to age in both sexes (P < 0.001). Diabetes mellitus was present in 27.5%, hypertension in 28.8%, sleep apnea syndrome in 25.5% and cardiac hypertrophy in 15.5%. Serious cardiovascular outcomes like stroke, heart failure and myocardial infarction were present in <5% at diagnosis. Erythrocyte levels were increased and correlated with IGF-1 values. Thyroid nodules were frequent (34.0%); 820 patients had colonoscopy at diagnosis and 13% had polyps. Osteoporosis was present at diagnosis in 12.3% and 0.6-4.4% had experienced a fracture. In conclusion, this study of >3100 patients is the largest international acromegaly database and shows clinically relevant trends in the characteristics of acromegaly at diagnosis.

3rd Department of Internal Medicine1st Faculty of Medicine Charles University Prague Czech Republic

APHP Endocrinology and Reproductive DiseasesParis Sud University Le Kremlin Bicêtre France

Clinical Centre of Endocrinology and GerontologyMedical University Sofia Bulgaria

Department of Biotechnological and Applied Clinical SciencesUniversity of L'Aquila L'Aquila Italy and Neuromed IRCCS Pozzilli Italy

Department of EndocrinologyCentre de Référence des Maladies Rares d'Origine Hypophysaire Hôpital de la Timone Marseille France

Department of EndocrinologyCHU de Liège University of Liège Belgium

Department of EndocrinologyCHU de Reims France

Department of EndocrinologyDiabetes and Metabolism Centro Hospitalar S João Faculty of Medicine Instituto de Investigação e Inovação em Saúde University of Porto Porto Portugal

Department of EndocrinologyHospital Universitario de la Ribera Alzira Spain

Department of Internal MedicineEndocrinology and Clinical Chemistry Max Planck Institute of Psychiatry Munich Germany

Department of Internal MedicineEndocrinology Diabetes and Metabolism Unit Centro Hospitalar de Trás os Montes e Alto Douro Portugal

Department of Internal MedicineUniversity of Genoa Genova Italy

Department of Molecular Medicine and SurgeryKarolinska University Hospital Stockholm Sweden

Dipartimento Di Medicina Clinica e ChirurgiaSezione di Endocrinologia University Federico 2 Naples Italy

Section of EndocrinologyDepartment of Medicine Erasmus University Medical Center Rotterdam The Netherlands

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Alexopoulou O, Bex M, Abs R, T’Sjoen G, Velkeniers B, Maiter D. 2008. Divergence between growth hormone and insulin-like growth factor-i concentrations in the follow-up of acromegaly. Journal of Clinical Endocrinology and Metabolism 93 1324–1330. (10.1210/jc.2007-2104) PubMed DOI

Attal P, Chanson P. 2010. Endocrine aspects of obstructive sleep apnea. Journal of Clinical Endocrinology and Metabolism 95 483–495. (10.1210/jc.2009-1912) PubMed DOI

Bajuk Studen K, Barkan A. 2008. Assessment of the magnitude of growth hormone hypersecretion in active acromegaly: reliability of different sampling models. Journal of Clinical Endocrinology and Metabolism 93 491–496. (10.1210/jc.2007-1451) PubMed DOI PMC

Bergamaschi S, Giavoli C, Ferrante E, Lania A, Rusconi R, Spada A, Beck-Peccoz P. 2006. Growth hormone replacement therapy in growth hormone deficient children and adults: effects on hemochrome. Journal of Endocrinological Investigation 29 399–404. (10.1007/BF03344122) PubMed DOI

Bernabeu I, Pico A, Venegas E, Aller J, Alvarez-Escolá C, García-Arnés JA, Marazuela M, Jonsson P, Mir N, García Vargas M, et al. 2016. Safety of long-term treatment with Pegvisomant: analysis of Spanish patients included in global ACROSTUDY. Pituitary 19 127–137. (10.1007/s11102-015-0691-0) PubMed DOI

Bex M, Abs R, T’Sjoen G, Mockel J, Velkeniers B, Muermans K, Maiter D. 2007. AcroBel--the Belgian registry on acromegaly: a survey of the ‘real-life’ outcome in 418 acromegalic subjects. European Journal of Endocrinology 157 399–409. (10.1530/EJE-07-0358) PubMed DOI

Burton T, Le Nestour E, Neary M, Ludlam WH. 2016. Incidence and prevalence of acromegaly in a large US health plan database. Pituitary 19 262–267. (10.1007/s11102-015-0701-2) PubMed DOI PMC

Butz LB, Sullivan SE, Chandler WF, Barkan AL. 2016. ‘Micromegaly’: an update on the prevalence of acromegaly with apparently normal GH secretion in the modern era. Pituitary 19 547–551. (10.1007/s11102-016-0735-0) PubMed DOI

Christ ER, Cummings MH, Westwood NB, Sawyer BM, Pearson TC, Sönksen PH, Russell-Jones DL. 1997. The importance of growth hormone in the regulation of erythropoiesis, red cell mass, and plasma volume in adults with growth hormone deficiency. Journal of Clinical Endocrinology and Metabolism 82 2985–2990. (10.1210/jcem.82.9.4199) PubMed DOI

Daly AF, Rixhon M, Adam C, Dempegioti A, Tichomirowa MA, Beckers A. 2006. High prevalence of pituitary adenomas: a cross-sectional study in the province of Liège, Belgium. Journal of Clinical Endocrinology and Metabolism 91 4769–4775. (10.1210/jc.2006-1668) PubMed DOI

Daly AF, Tichomirowa MA, Petrossians P, Heliövaara E, Jaffrain-Rea M-L, Barlier A, Naves LA, Ebeling T, Karhu A, Raappana A, et al. 2010. Clinical characteristics and therapeutic responses in patients with germ-line AIP mutations and pituitary adenomas: an international collaborative study. Journal of Clinical Endocrinology and Metabolism 95 E373–E383. (10.1210/jc.2009-2556) PubMed DOI

De P, Foucault DRG. 2014. What the mind knows but the eyes may still miss: reducing the ‘Acromegalic Window’. Case Reports 2014 bcr2013202622–bcr2013202622. (10.1136/bcr-2013-202622) PubMed DOI PMC

Dekkers OM, Biermasz NR, Pereira AM, Romijn JA, Vandenbroucke JP. 2008. Mortality in acromegaly: a metaanalysis. Journal of Clinical Endocrinology and Metabolism 93 61–67. (10.1210/jc.2007-1191) PubMed DOI

Dimaraki EV, Jaffe CA, DeMott-Friberg R, Chandler WF, Barkan AL. 2002. Acromegaly with apparently normal GH secretion: implications for diagnosis and follow-up. Journal of Clinical Endocrinology and Metabolism 87 3537–3542. (10.1210/jcem.87.8.8658) PubMed DOI

Esposito A, Capalbo D, De Martino L, Rezzuto M, Di Mase R, Pignata C, Salerno M. 2016. Long-term effects of growth hormone (GH) replacement therapy on hematopoiesis in a large cohort of children with GH deficiency. Endocrine 53 192–198. (10.1007/s12020-015-0781-9) PubMed DOI

Fernandez A, Karavitaki N, Wass JA. 2010. Prevalence of pituitary adenomas: a community-based, cross-sectional study in Banbury (Oxfordshire, UK). Clinical Endocrinology 72 377–382. (10.1111/j.1365-2265.2009.03667.x) PubMed DOI

Franck SE, Korevaar T, Petrossians P, Daly AF, Chanson P, Jaffrian-Rea M, Brue T, Stalla GK, Carvalho D, Colao AAL, et al. 2017. A multivariable prediction model for pegvisomant dosing: monotherapy and in combination with long-acting somatostatin analogues. European Journal of Endocrinology 176 421–430. (10.1530/EJE-16-0956) PubMed DOI

Freda PU, Gordon MB, Kelepouris N, Jonsson P, Koltowska-Haggstrom M, van der Lely AJ. 2015. Long-term treatment with pegvisomant as monotherapy in patients with acromegaly: experience from ACROSTUDY. Endocrine Practice 21 264–274. (10.4158/EP14330.OR) PubMed DOI PMC

Giustina A, Chanson P, Bronstein MD, Klibanski A, Lamberts S, Casanueva FF, Trainer P, Ghigo E, Ho K, Melmed S. 2010. A consensus on criteria for cure of acromegaly. Journal of Clinical Endocrinology and Metabolism 95 3141–3148. (10.1210/jc.2009-2670) PubMed DOI

Grellier P, Chanson P, Casadevall N, Abboud S, Schaison G. 1996. Remission of polycythemia vera after surgical cure of acromegaly. Annals of Internal Medicine 124 495–496. (10.7326/0003-4819-124-5-199603010-00006) PubMed DOI

Hannon AM, Thompson CJ, Sherlock M. 2017. Diabetes in patients with acromegaly. Current Diabetes Reports 17 8 (10.1007/s11892-017-0838-7) PubMed DOI

Holdaway IM, Bolland MJ, Gamble GD. 2008. A meta-analysis of the effect of lowering serum levels of GH and IGF-I on mortality in acromegaly. European Journal of Endocrinology 159 89–95. (10.1530/EJE-08-0267) PubMed DOI

Jenkins D, O’Brien I, Johnson A, Shakespear R, Sheppard MC, Stewart PM. 1995. The Birmingham pituitary database: auditing the outcome of the treatment of acromegaly. Clinical Endocrinology 43 517–522. (10.1111/j.1365-2265.1995.tb02913.x) PubMed DOI

Katznelson L, Laws ER, Melmed S, Molitch ME, Murad MH, Utz A, Wass JAH, Endocrine Society 2014. Acromegaly: an endocrine society clinical practice guideline. Journal of Clinical Endocrinology and Metabolism 99 3933–3951. (10.1210/jc.2014-2700) PubMed DOI

Lavrentaki A, Paluzzi A, Wass JAH, Karavitaki N. 2017. Epidemiology of acromegaly: review of population studies. Pituitary 20 4–9. (10.1007/s11102-016-0754-x) PubMed DOI PMC

Lesén E, Granfeldt D, Houchard A, Dinet J, Berthon A, Olsson DS, Björholt I, Johannsson G. 2017. Comorbidities, treatment patterns and cost-of-illness of acromegaly in Sweden: a register-linkage population-based study. European Journal of Endocrinology 176 203–212. (10.1530/EJE-16-0623) PubMed DOI

Lutz JM, Francisci S, Mugno E, Usel M, Pompe-Kirn V, Coebergh J-W, Bieslka-Lasota M. & EUROPREVAL Working Group 2003. Cancer prevalence in Central Europe: the EUROPREVAL study. Annals of Oncology 14 313–322. PubMed

Maione L, Brue T, Beckers A, Delemer B, Petrossians P, Borson-Chazot F, Chabre O, François P, Bertherat J, Cortet-Rudelli C, et al. 2017. Changes in the management and comorbidities of acromegaly over three decades: the French Acromegaly Registry. European Journal of Endocrinology 176 645–655. (10.1530/EJE-16-1064) PubMed DOI

Melmed S. 2016. Pituitary medicine from discovery to patient-focused outcomes. Journal of Clinical Endocrinology and Metabolism 101 769–777. (10.1210/jc.2015-3653) PubMed DOI PMC

Melmed S. 2017. Acromegaly. In The Pituitary, ch 15, pp 423–466. Cambridge, MA, USA: Academic Press: (10.1016/B978-0-12-804169-7.00015-5) DOI

Melmed S, Casanueva FF, Klibanski A, Bronstein MD, Chanson P, Lamberts SW, Strasburger CJ, Wass JAH, Giustina A. 2013. A consensus on the diagnosis and treatment of acromegaly complications. Pituitary 16 294–302. (10.1007/s11102-012-0420-x) PubMed DOI PMC

Mestron A, Webb SM, Astorga R, Benito P, Catala M, Gaztambide S, Gomez JM, Halperin I, Lucas-Morante T, Moreno B, et al. 2004. Epidemiology, clinical characteristics, outcome, morbidity and mortality in acromegaly based on the Spanish Acromegaly Registry (Registro Espanol de Acromegalia, REA). European Journal of Endocrinology 151 439–446. (10.1530/eje.0.1510439) PubMed DOI

Petrossians P, Tichomirowa MA, Stevenaert A, Martin D, Daly AF, Beckers A. 2012. The Liege Acromegaly Survey (LAS): a new software tool for the study of acromegaly. Annales D’endocrinologie 73 190–201. (10.1016/j.ando.2012.05.001) PubMed DOI

Pivonello R, Auriemma RS, Grasso LFS, Pivonello C, Simeoli C, Patalano R, Galdiero M, Colao A. 2017. Complications of acromegaly: cardiovascular, respiratory and metabolic comorbidities. Pituitary 20 46–62. (10.1007/s11102-017-0797-7) PubMed DOI

Portocarrero-Ortiz LA, Vergara-Lopez, Vidrio-Velazquez M, Uribe-Diaz AM, García-Dominguez A, Reza-Albarrán AA, Cuevas-Ramos D, Melgar V, Talavera J, Rivera-Hernandez A de J, et al. 2016. The Mexican Acromegaly Registry: clinical and biochemical characteristics at diagnosis and therapeutic outcomes. Journal of Clinical Endocrinology and Metabolism 101 3997–4004. (10.1210/jc.2016-1937) PubMed DOI

Potorac I, Petrossians P, Daly AF, Schillo F, Ben Slama C, Nagi S, Sahnoun M, Brue T, Girard N, Chanson P, et al. 2015. Pituitary MRI characteristics in 297 acromegaly patients based on T2-weighted sequences. Endocrine-Related Cancer 22 169–177. (10.1530/ERC-14-0305) PubMed DOI

Potorac I, Petrossians P, Daly AF, Alexopoulou O, Borot S, Sahnoun-Fathallah M, Castinetti F, Devuyst F, Jaffrain-Rea ML, Briet C, et al. 2016. T2-weighted MRI signal predicts hormone and tumor responses to somatostatin analogs in acromegaly. Endocrine-Related Cancer 23 871–881. (10.1530/ERC-16-0356) PubMed DOI

Ramos-Leví AM, Marazuela M. 2017. Cardiovascular comorbidities in acromegaly: an update on their diagnosis and management. Endocrine 55 346– 359 (10.1007/s12020-016-1191-3) PubMed DOI

Reid TJ, Post KD, Bruce JN, Nabi Kanibir M, Reyes-Vidal CM, Freda PU. 2010. Features at diagnosis of 324 patients with acromegaly did not change from 1981 to 2006: acromegaly remains under-recognized and under-diagnosed. Clinical Endocrinology 72 203–208. (10.1111/j.1365-2265.2009.03626.x) PubMed DOI PMC

Reincke M, Petersenn S, Buchfelder M, Gerbert B, Skrobek-Engel G, Franz H, Lohmann R, Quabbe H-J. 2006. The German Acromegaly Registry: description of the database and initial results. Experimental and Clinical Endocrinology and Diabetes 114 498–505. (10.1055/s-2006-948313) PubMed DOI

Ritvonen E, Löyttyniemi E, Jaatinen P, Ebeling T, Moilanen L, Nuutila P, Kauppinen-Mäkelin R, Schalin-Jäntti C. 2015. Mortality in acromegaly: a 20-year follow-up study. Endocrine-Related Cancer 23 469–480. (10.1530/ERC-16-0106) PubMed DOI

Sesmilo G, Gaztambide S, Venegas E, Pico A, Del Pozo C, Blanco C, Torres E, Alvarez-Escola C, Fajardo C, Garcia R, et al. 2013. Changes in acromegaly treatment over four decades in Spain: analysis of the Spanish Acromegaly Registry (REA). Pituitary 16 115–121. (10.1007/s11102-012-0384-x) PubMed DOI

Sherlock M, Aragon Alonso A, Reulen RC, Ayuk J, Clayton RN, Holder G, Sheppard MC, Bates A, Stewart PM. 2009. Monitoring disease activity using GH and IGF-I in the follow-up of 501 patients with acromegaly. Clinical Endocrinology 71 74–81. (10.1111/j.1365-2265.2008.03461.x) PubMed DOI

Sherlock M, Ayuk J, Tomlinson JW, Toogood AA, Aragon-Alonso A, Sheppard MC, Bates AS, Stewart PM. 2010. Mortality in patients with pituitary disease. Endocrine Reviews 31 301–342. (10.1210/er.2009-0033) PubMed DOI

Stewart PM. 2004. Acromegaly databases – time for European unification. European Journal of Endocrinology 151 431–432. (10.1530/eje.0.1510431) PubMed DOI

Stewart PM, Sherlock M. 2012. Mortality and pituitary disease. Annals of Endocrinology 73 81–82. (10.1016/j.ando.2012.03.026) PubMed DOI

Surchi H, Jafar-Mohammadi B, Pal A, Cudlip S, Grossman AB. 2017. Local optometrists are a major source of referrals to a pituitary tumour clinic. Endocrine-Related Cancer 24 L33–L34. (10.1530/ERC-17-0034) PubMed DOI

Teramoto S, Ouchi V. 1997. Polycythemia vera in acromegaly. Annals of Internal Medicine 126 87 (10.7326/0003-4819-126-1-199701010-00017) PubMed DOI

Theodoropoulou M, Tichomirowa MA, Sievers C, Yassouridis A, Arzberger T, Hougrand O, Deprez M, Daly AF, Petrossians P, Pagotto U, et al. 2009. Tumor ZAC1 expression is associated with the response to somatostatin analog therapy in patients with acromegaly. International Journal of Cancer 125 2122–2126. (10.1002/ijc.24602) PubMed DOI

Trainer PJ. 2009. ACROSTUDY: the first 5 years. European Journal of Endocrinology 161 S19–S24. (10.1530/EJE-09-0322) PubMed DOI

Tritos NA, Johannsson G, Korbonits M, Miller KK, Feldt-Rasmussen U, Yuen KCJ, King D, Mattsson AF, Jonsson PJ, Koltowska-Haggstrom M, et al. 2014. Effects of long-term growth hormone replacement in adults with growth hormone deficiency following cure of acromegaly: a KIMS analysis. Journal of Clinical Endocrinology and Metabolism 99 2018–2029. (10.1210/jc.2014-1013) PubMed DOI

Valerio G, Di Maio S, Salerno M, Argenziano A, Badolato R, Tenore A. 1997. Assessment of red blood cell indices in growth-hormone-treated children. Hormone Research 47 62–66. (10.1159/000185433) PubMed DOI

van der Lely AJ, Harris AG, Lamberts SW. 1992. The sensitivity of growth hormone secretion to medical treatment in acromegalic patients: influence of age and sex. Clinical Endocrinology 37 181–185. (10.1111/j.1365-2265.1992.tb02304.x) PubMed DOI

van der Lely AJ, Biller BM, Brue T, Buchfelder M, Ghigo E, Gomez R, Hey-Hadavi J, Lundgren F, Rajicic N, Strasburger CJ, et al. 2012. Long-term safety of pegvisomant in patients with acromegaly: comprehensive review of 1288 subjects in ACROSTUDY. Journal of Clinical Endocrinology and Metabolism 97 1589–1597. (10.1210/jc.2011-2508) PubMed DOI

Zoppoli G, Bianchi F, Bruzzone A, Calvia A, Oneto C, Passalia C, Balleari E, Bedognetti D, Ponomareva E, Nazzari E, et al. 2011. Polycythemia as rare secondary direct manifestation of acromegaly: management and single-centre epidemiological data. Pituitary 15 209–214. (10.1007/s11102-011-0311-6) PubMed DOI

Acromegaly: Clinical Care in Central and Eastern Europe, Israel, and Kazakhstan