Objective: Insulinomas are rare functional pancreatic neuroendocrine tumours. As previous data on the long-term prognosis of insulinoma patients are scarce, we studied the morbidity and mortality in the Finnish insulinoma cohort. Design: Retrospective cohort study. Methods: Incidence of endocrine, cardiovascular, gastrointestinal and psychiatric disorders, and cancers was compared in all the patients diagnosed with an insulinoma in Finland during 1980–2010 (n = 79, including two patients with multiple endocrine neoplasia type 1 syndrome), vs 316 matched controls, using the Mantel–Haenszel method. Overall survival was analysed with Kaplan–Meier and Cox regression analyses. Results: The median length of follow-up was 10.7 years for the patients and 12.2 years for the controls. The long-term incidence of atrial fibrillation (rate ratio (RR): 2.07 (95% CI: 1.02–4.22)), intestinal obstruction (18.65 (2.09–166.86)), and possibly breast (4.46 (1.29–15.39) and kidney cancers (RR not applicable) was increased among insulinoma patients vs controls, P < 0.05 for all comparisons. Endocrine disorders and pancreatic diseases were more frequent in the patients during the first year after insulinoma diagnosis, but not later on. The survival of patients with a non-metastatic insulinoma (n = 70) was similar to that of controls, but for patients with distant metastases (n = 9), the survival was significantly impaired (median 3.4 years). Conclusions: The long-term prognosis of patients with a non-metastatic insulinoma is similar to the general population, except for an increased incidence of atrial fibrillation, intestinal obstruction, and possibly breast and kidney cancers. These results need to be confirmed in future studies. Metastatic insulinomas entail a markedly decreased survival.

Insulinomas are rare pancreatic neuroendocrine tumours. Most patients can be cured with surgery, but patients with a metastatic disease show impaired survival. The aim of this study was to evaluate somatostatin receptor (SSTR) 1-5 expression in insulinomas and to correlate the expression profile with clinicopathological variables and with patient outcome. This retrospective study involved 52 insulinoma patients. After histological re-evaluation, formalin-fixed paraffin-embedded tissue samples were processed into tissue microarrays and stained immunohistochemically with monoclonal SSTR1-5 antibodies. All the 52 tumours (49 non-metastatic, 3 metastatic) expressed at least one SSTR subtype. SSTR2 was expressed most frequently (71%), followed by SSTR3 (33%), SSTR1 (27%), SSTR5 (6%) and SSTR4 (0%). SSTR3 expression was associated with a larger tumour size (median diameter 19 mm vs. 13 mm, p = 0.043), and SSTR3 and SSTR5 expression were associated with impaired overall survival [HR 3.532 (95% CI 1.106-11,277), p = 0.033, and HR 6.805 (95% CI 1.364-33.955), p = 0.019 respectively]. Most insulinomas express SSTR2, which may be utilized in diagnostic imaging, and in planning individualized treatment strategies for insulinoma patients. Further studies are needed to clarify the association between SSTR profile and overall survival.

Insulinomas are rare functional pancreatic neuroendocrine tumours, which metastasize in 10% of cases. As predicting the prognosis can be challenging, there is a need for the determination of clinicopathological factors associated with metastatic potential. The aim of this study is to evaluate the glucagon-like peptide-1 receptor (GLP-1R) expression in insulinomas and to analyse its association with clinicopathological features and patient outcome. This retrospective study involves pancreatic tumour tissue samples from fifty-two insulinoma patients. After histological re-evaluation, formalin-fixed paraffin-embedded tissue samples were processed into tissue microarrays and stained immunohistochemically with a monoclonal GLP-1R antibody. Forty-eight of the forty-nine (98%) non-metastatic tumours expressed GLP-1R, while one non-metastatic, multiple endocrine neoplasia type 1 (MEN1)-related tumour and all three of the metastatic tumours lacked GLP-1R expression. The lack of GLP-1R expression was associated with impaired overall survival, larger tumour diameter, higher Ki-67 PI and weaker insulin staining. Somatostatin receptor 1–5 expression did not differ between GLP-1R-positive and GLP-1R-negative insulinomas. In conclusion, the lack of GLP-1R expression is associated with metastatic disease and impaired survival in insulinoma patients. Thus, GLP-1R expression could be a useful biomarker in estimating the metastatic potential of the tumour and the prognosis of surgically treated patients.

Objective: Insulinomas are rare pancreatic neoplasms, which can usually be cured by surgery. As the diagnostic delay is often long and the prolonged hyperinsulinemia may have long‐term effects on health and the quality of life, we studied the long‐term health‐related quality of life (HRQoL) in insulinoma patients.Design, patients and measurements: The HRQoL of adults diagnosed with an insulinoma in Finland in 1980‐2010 was studied with the 15D instrument, and the results were compared to those of an age‐ and gender‐matched sample of the general population. The minimum clinically important difference in the total 15D score has been defined as ±0.015. The clinical characteristics, details of insulinoma diagnosis and treatment, and the current health status of the subjects were examined to specify the possible determinants of long‐term HRQoL.Results: Thirty‐eight insulinoma patients participated in the HRQoL survey (response rate 75%). All had undergone surgery with a curative aim, a median of 13 (min 7, max 34) years before the survey. The insulinoma patients had a clinically importantly and statistically significantly better mean 15D score compared with the controls (0.930 ± 0.072 vs 0.903 ± 0.039, P = .046) and were significantly better off regarding mobility, usual activities and eating. Among the insulinoma patients, younger age at the time of survey, higher level of education and smaller number of chronic diseases were associated with better overall HRQoL.Conclusions: In the long term, the overall HRQoL of insulinoma patients is slightly better than that of the general population.

Objective: Acromegaly has been associated with increased cardiovascular morbidity, but it is unclear to what extent this holds true in contemporary acromegaly cohorts and when the cardiovascular diseases (CVDs) evolve in relation to the time of diagnosis. Design: Retrospective cohort study. Methods: Cardiovascular morbidity was studied in the Finnish acromegaly cohort (n = 565) and 5629 controls using Kaplan–Meier analysis from 10 years before the diagnosis of acromegaly and continuing up to >30 years after the diagnosis. Hazard ratios for CVD-related hospital visits were calculated with Cox regression analyses in the post-diagnosis period. The effects of received treatments, hypopituitarism, and biochemical control of acromegaly were studied with multivariable analyses among the patients. Results: Cardiovascular morbidity increased years before the diagnosis of acromegaly and remained elevated compared to controls [hazard ratio (HR) 1.59 (95% CI 1.42–1.78)] throughout the follow-up (median 17.2 years, IQR 8.7–26.5 years). The highest increase was observed in diseases of pulmonary arteries [HR 2.74 (1.87-4.02)], valvular diseases and cardiomyopathies [HR 2.68 (2.09-3.44)], and hypertension [HR 2.11 (1.85-2.42)]. Radiotherapy, hypopituitarism, and post-treatment Insulin-Like Growth Factor-1 (IGF-1) above or below the reference range were associated with increased cardiovascular morbidity. Even patients who achieved biochemical remission and normal pituitary function after surgery suffered from increased morbidity compared to controls. Conclusions: Patients with acromegaly are still characterized by increased morbidity across a wide range of CVDs. Cardiovascular morbidity is already present before diagnosis and persists despite acromegaly-specific therapy. This underlines the importance of early diagnostics and CVD prevention for these patients.