Objective: Data on the incidence, mortality, and causes of death in patients with Cushing's syndrome (CS) are scarce, due to the rarity of CS. The aim of the study was to analyze mortality in a large cohort of patients of all etiologies and to determine the cause of death.Design: This was a retrospective study of patients with CS, treated over a period of 45 years in the main tertiary referral center in Bulgaria.Methods: Three hundred and eighty-six patients with CS of all etiologies were included. The main outcome measures were the standardized mortality ratio (SMR) and the cause of death.Results: Mean (±s.d.) age at diagnosis was 38±13 years; 84% of patients were women; mean follow-up was 85 months (range: 0–494 months). The SMR in the CS cohort was 4.05 (95% CI 2.50–5.80) (P<0.0001). The following subgroups did not have a significantly increased SMR: patients with Cushing's disease SMR – 1.88 (95% CI 0.69–4.08), adrenal adenomas 1.67 (95% CI 0.20–6.02), and ACTH-independent bilateral adrenal hyperplasia 1.14 (95% CI 0.21–6.34). Patients with adrenal carcinomas, ectopic CS, and those with CS of undetermined etiology had significantly increased SMR: 48.00 (95% CI 30.75–71.42), 13.33 (95% CI 0.00–24.59), and 4.00 (95% CI 0.48–14.45) respectively (P<0.0001). The significant predictors for mortality were active disease at death, age, male sex, etiology of the disease, and the overall duration of active disease. The major causes of death were vascular events (40%) – cardiovascular 29%, and cerebrovascular 11% – followed by infections (12%).Conclusions: Patients with CS have increased mortality due to vascular events and infections.

Background: In contrast to cabergoline, evidence-based information about a possible profibrotic effect of bromocriptine in prolactinoma patients is extremely limited.Objective: To assess the prevalence of valvular lesions among patients on long-term bromocriptine or cabergoline therapy.Design: Case–control study.Methods: A transthoracic echocardiographic evaluation was performed in 334 subjects divided into four groups: 103 cabergoline treated, 55 bromocriptine treated, 74 naïve patients, and 102 controls.Results: Clinically relevant valve regurgitations were equally prevalent in all investigated groups whereas subclinical valve fibrosis was significantly more frequent in both bromocriptine- and cabergoline-treated patients (40 vs 43.6 vs 21.6 vs 23.5%; P=0.004). The odds ratio (OR) for developing valvular fibrosis was 2.27 (95% CI 1.17–4.41; P=0.016) for cabergoline and 2.66 (95% CI 1.22–5.78; P=0.014) for bromocriptine groups compared with subjects not exposed to dopamine agonists (DAs). A significantly higher pulmonary arterial pressure corresponding to the longer treatment duration was observed among patients taking bromocriptine compared with cabergoline-treated subjects.Conclusions: Long-term treatment with cabergoline and bromocriptine seems not to be associated with an increased risk of clinically significant valve disease but possible subclinical lesions should be expected. An echocardiographic examination is recommended at the beginning and periodically during therapy with DAs acting as full or partial agonists of 5-hydroxytrytamine 2B receptors (cabergoline and bromocriptine). Bromocriptine seems not to be a safe alternative for patients receiving cabergoline treatment who have preexisting or diagnosed abnormalities suggesting valvular, interstitial myocardial, or pulmonary fibrosis. Further studies are needed to investigate the possible impact of DA treatment on pulmonary arterial pressure.

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.