title: Could different treatment approaches in acromegaly influence life expectancy? A comparative study between Bulgaria and Campania (Italy).
abstract: BACKGROUND
  Mortality in acromegaly strictly depends on optimal control of GH and IGF1 levels. Modern medical therapy with somatostatin analogs (SSAs) and GH receptor antagonists (GHRAs) is not available in many countries due to funding restrictions. This retrospective, comparative, cohort study investigated the impact of different treatment modalities on disease control (GH and IGF1) and mortality in acromegaly patients.
  
  
  METHODS
  Two cohorts of patients with acromegaly from Bulgaria (n=407) and Campania, Italy (n=220), were compared, and mortality rates were evaluated during a 10-year period (1999-2008).
  
  
  RESULTS
  The major difference in treatment approach between cohorts was the higher utilization of SSAs and GHRAs in Italy, leading to a decreased requirement for radiotherapy. Significantly more Italian than Bulgarian patients had achieved disease control (50.1 vs 39.1%, P=0.005) at the last follow-up. Compared with the general population, the Bulgarian cohort had a decreased life expectancy with a standardized mortality ratio (SMR) of 2.0 (95% CI 1.54-2.47) that was restored to normal in patients with disease control - SMR 1.25 (95% CI 0.68-1.81). Irradiated patients had a higher cerebrovascular mortality - SMR 7.15 (95% CI 2.92-11.37). Internal analysis revealed an independent role of age at diagnosis and last GH value on all-cause mortality and radiotherapy on cerebrovascular mortality. Normal survival rates were observed in the Italian cohort: SMR 0.66 (95% CI 0.27-1.36).
  
  
  CONCLUSIONS
  Suboptimal biochemical control was associated with a higher mortality in the Bulgarian cohort. Modern treatment options that induce a strict biochemical control and reduce the necessity of radiotherapy might influence the life expectancy. Other factors, possibly management of comorbidities, could contribute to survival rates.
authors.affiliation: Dipartimento di Medicina Clinica e ChirurgiaSezione di Endocrinologia, Università Federico II di Napoli, via S. Pansini 5, 80131 Naples, ItalyClinical Center of Endocrinology and Gerontology 'Akad. Ivan Pentchev' Medical University Sofia2 Zdrave Street, 1431 Sofia, BulgariaNew Bulgarian University21 Montevideo Street, 1618 Sofia, Bulgaria colao@unina.it.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Colao
authors.affiliation: Dipartimento di Medicina Clinica e ChirurgiaSezione di Endocrinologia, Università Federico II di Napoli, via S. Pansini 5, 80131 Naples, ItalyClinical Center of Endocrinology and Gerontology 'Akad. Ivan Pentchev' Medical University Sofia2 Zdrave Street, 1431 Sofia, BulgariaNew Bulgarian University21 Montevideo Street, 1618 Sofia, Bulgaria.
authors.forename: Silvia
authors.initials: S
authors.lastname: Vandeva
authors.affiliation: Dipartimento di Medicina Clinica e ChirurgiaSezione di Endocrinologia, Università Federico II di Napoli, via S. Pansini 5, 80131 Naples, ItalyClinical Center of Endocrinology and Gerontology 'Akad. Ivan Pentchev' Medical University Sofia2 Zdrave Street, 1431 Sofia, BulgariaNew Bulgarian University21 Montevideo Street, 1618 Sofia, Bulgaria.
authors.forename: Rosario
authors.initials: R
authors.lastname: Pivonello
authors.affiliation: Dipartimento di Medicina Clinica e ChirurgiaSezione di Endocrinologia, Università Federico II di Napoli, via S. Pansini 5, 80131 Naples, ItalyClinical Center of Endocrinology and Gerontology 'Akad. Ivan Pentchev' Medical University Sofia2 Zdrave Street, 1431 Sofia, BulgariaNew Bulgarian University21 Montevideo Street, 1618 Sofia, Bulgaria.
authors.forename: Ludovica Francesca Stella
authors.initials: LF
authors.lastname: Grasso
authors.affiliation: Dipartimento di Medicina Clinica e ChirurgiaSezione di Endocrinologia, Università Federico II di Napoli, via S. Pansini 5, 80131 Naples, ItalyClinical Center of Endocrinology and Gerontology 'Akad. Ivan Pentchev' Medical University Sofia2 Zdrave Street, 1431 Sofia, BulgariaNew Bulgarian University21 Montevideo Street, 1618 Sofia, Bulgaria.
authors.forename: Emil
authors.initials: E
authors.lastname: Nachev
authors.affiliation: Dipartimento di Medicina Clinica e ChirurgiaSezione di Endocrinologia, Università Federico II di Napoli, via S. Pansini 5, 80131 Naples, ItalyClinical Center of Endocrinology and Gerontology 'Akad. Ivan Pentchev' Medical University Sofia2 Zdrave Street, 1431 Sofia, BulgariaNew Bulgarian University21 Montevideo Street, 1618 Sofia, Bulgaria.
authors.forename: Renata S
authors.initials: RS
authors.lastname: Auriemma
authors.affiliation: Dipartimento di Medicina Clinica e ChirurgiaSezione di Endocrinologia, Università Federico II di Napoli, via S. Pansini 5, 80131 Naples, ItalyClinical Center of Endocrinology and Gerontology 'Akad. Ivan Pentchev' Medical University Sofia2 Zdrave Street, 1431 Sofia, BulgariaNew Bulgarian University21 Montevideo Street, 1618 Sofia, Bulgaria.
authors.forename: Krasimir
authors.initials: K
authors.lastname: Kalinov
authors.affiliation: Dipartimento di Medicina Clinica e ChirurgiaSezione di Endocrinologia, Università Federico II di Napoli, via S. Pansini 5, 80131 Naples, ItalyClinical Center of Endocrinology and Gerontology 'Akad. Ivan Pentchev' Medical University Sofia2 Zdrave Street, 1431 Sofia, BulgariaNew Bulgarian University21 Montevideo Street, 1618 Sofia, Bulgaria.
authors.forename: Sabina
authors.initials: S
authors.lastname: Zacharieva
mesh_terms: D000172:Acromegaly / Q000188:drug therapy / Q000401:mortality* / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D000328:Adult; D002031:Bulgaria / Q000453:epidemiology; D015331:Cohort Studies; D015897:Comorbidity; D018491:Dopamine Agonists / Q000627:therapeutic use; D005260:Female; D019382:Human Growth Hormone / Q000627:therapeutic use; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007558:Italy / Q000453:epidemiology; D008017:Life Expectancy; D008297:Male; D008875:Middle Aged; D011986:Receptors, Somatotropin / Q000037:antagonists & inhibitors / Q000627:therapeutic use; D012189:Retrospective Studies; D013004:Somatostatin / Q000031:analogs & derivatives / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D018491:Dopamine Agonists; D011986:Receptors, Somatotropin; D019382:Human Growth Hormone; D013004:Somatostatin; D007334:Insulin-Like Growth Factor I