Background: Whether sleep apnoea syndrome (SAS) subsides after biochemical and clinical remission of acromegaly is controversial.Objective: To assess the presence of SAS in a cohort of acromegalic patients, which included a subgroup with active disease and a subgroup in remission, and to evaluate clinical and biochemical independent predictors of SAS.Design: Cross-sectional and longitudinal study.Setting: Italian university department of internal medicine.Patients: About 36 acromegalic patients: 18 active and 18 controlled.Measurements: Polysomnography was performed in all patients and repeated in six with active acromegaly and SAS after achieving disease control. Echocardiographic parameters were also measured.Results: The prevalence of SAS was 47% in the overall acromegalic population: 56% in the active group and 39% in the controlled one. In a multivariate analysis IGF1, male gender, age, body mass index, and disease duration were associated with SAS. Impaired glucose tolerance or diabetes was more prevalent in patients with SAS, particularly in the severe cases. Among the six patients of the longitudinal study, five showed improvement of SAS, but none recovered. No correlation was found between echocardiographic parameters and severity of SAS.Conclusion: SAS can persist after recovery of acromegaly in several patients. Given the negative prognostic significance of this respiratory disorder, polysomnography should be included as routine procedure in the work-up of the acromegaly, even if in remission, being mandatory in those patients considered at high risk (elderly males, overweight, diabetic). Appropriate intensive treatment should be implemented to minimize the clinical impact of SAS in acromegaly.

Objective: Evidence is limited regarding outcome of patients with ectopic Cushing’s syndrome (ECS) due to neuroendocrine tumors (NETs). Design: We assessed the prognostic factors affecting the survival of patients with NETs and ECS. Methods: Retrospective analysis of clinicopathological features, severity of hormonal syndrome, treatments from a large cohort of patients with NETs and ECS collected from 17 Italian centers. Results: Our series included 110 patients, 58.2% female, with mean (±s.d.) age at diagnosis of 49.5 ± 15.9 years. The main sources of ectopic ACTH were bronchial carcinoids (BC) (40.9%), occult tumors (22.7%) and pancreatic (p)NETs (15.5%). Curative surgery was performed in 56.7% (70.2% of BC, 11% of pNETs). Overall survival was significantly higher in BC compared with pNETs and occult tumors (P = 0.033) and in G1-NETs compared with G2 and G3 (P = 0.007). Negative predictive factors for survival were severity of hypercortisolism (P < 0.02), hypokalemia (P = 0.001), diabetes mellitus (P = 0.0146) and distant metastases (P < 0.001). Improved survival was observed in patients who underwent NET removal (P < 0.001). Adrenalectomy improved short-term survival. Conclusions: Multiple factors affect prognosis of ECS patients: type of NET, grading, distant metastases, severity of hypercortisolism, hypokalemia and diabetes mellitus. BCs have the highest curative surgical rate and better survival compared with occult tumors and pNETs. Hypercortisolism plays a primary role in affecting outcome and quality of life; therefore, prompt and vigorous treatment of hormonal excess by NET surgery and medical therapy should be a key therapeutic goal. In refractory cases, adrenalectomy should be considered as it affects outcome positively at least in the first 2 years.

Introduction: Management of malignant insulinomas is challenging due to the need to control both hypoglycaemic syndrome and tumor growth. Literature data is limited to small series. Aim of the study: To analyze clinico-pathological characteristics, treatments and prognosis of patients with malignant insulinoma. Materials and methods: Multicenter retrospective study on 31 patients (male: 61.3%) diagnosed between 1988 and 2017. Results: The mean age at diagnosis was 48 years. The mean NET diameter was 41 ± 31 mm, and 70.8% of NETs were G2. Metastases were widespread in 38.7%, hepatic in 41.9% and only lymph nodal in 19.4%. In 16.1% of the cases, the hypoglycaemic syndrome occurred after 46 ± 35 months from the diagnosis of originally non-functioning NET, whereas in 83.9% of the cases it led to the diagnosis of NET, of which 42.3% with a mean diagnostic delay of 32.7 ± 39.8 months. Surgical treatment was performed in 67.7% of the cases. The 5-year survival rate was 62%. Overall survival was significantly higher in patients with Ki-67 ≤10% (P = 0.03), insulin level <60 µU/mL (P = 0.015) and in patients who underwent surgery (P = 0.006). Peptide Receptor Radionuclide Therapy (PRRT) was performed in 45.1%, with syndrome control in 93% of patients. Conclusions: Our study includes the largest series of patients with malignant insulinoma reported to date. The hypoglycaemic syndrome may occur after years in initially non-functioning NETs or be misunderstood with delayed diagnosis of NETs. Surgical treatment and Ki67 ≤10% are prognostic factors associated with better survival. PPRT proved to be effective in the control of hypoglycaemia in majority of cases.