One hundred years after the discovery of insulin and glucagon:the history of tumors and hyperplasias that hypersecrete these hormones

One century ago, in 1922, Frederick G Banting, Charles H Best, James B Collip and John J R Macleod first published their experiments resulting in the isolation of a hypoglycemic factor, named insulin, from a solution extract from a dog’s pancreas. One year later, in 1923, a hyperglycemic factor named glucagon was isolated by Charles P Kimball and John R Murlin. In the following years, it could be demonstrated that pancreatic islet alpha- and beta-cell neoplasms and hyperplasias could inappropriately secrete excessive amounts of these two hormones. This review is a sequel to the discovery of insulin and glucagon and introduces the history of this fascinating group of neuroendocrine neoplasms and hyperplasias of the pancreas.</p

Medical treatment of neuroendocrine neoplasms

Medical therapy of clinically nonfunctioning (nonsecreting) low grade (grade 1–2) neuroendocrine neoplasms consists of first-line first generation somatostatin analogs and second-line or third-line peptide receptor radiotherapy with radiolabeled beta-emitting somatostatin analogs, Everolimus, Sunitinib, and interferon-α. Second-generation somatostatin analogs like Pasireotide have no proven superiority over first-generation somatostatin analogs. Chemotherapy is usually reserved as second-line therapy in pancreatic neuroendocrine neoplasms and neuroendocrine carcinomas.</p

Peptide receptor radionuclide therapy with 177Lu-DOTATATE for symptomatic control of refractory carcinoid syndrome

Context: Peptide receptor radionuclide therapy (PRRT) with [Lutetium-177-DOTA-Tyr3]octreotate (177Lu-DOTATATE) results in an increase of progression-free survival and quality of life in patients with progressive, well-differentiated neuroendocrine neoplasms (NENs). Objective: To study the effect of 177Lu-DOTATATE in patients with carcinoid syndrome and radiologically stable or newly diagnosed disease treated solely for the purpose of symptom reduction. Design: Retrospective cohort study

Matching-adjusted indirect treatment comparison of [¹⁷⁷Lu]Lu-DOTA-TATE, everolimus and sunitinib in advanced, unresectable gastroenteropancreatic neuroendocrine tumours:Relative effectiveness of [¹⁷⁷Lu]Lu-DOTA-TATE in gastroenteropancreatic neuroendocrine tumours

Head-to-head comparisons of the efficacy of treatments for gastroenteropancreatic neuroendocrine tumours (GEP-NETs) have not yet been reported. This study used a series of matching-adjusted indirect comparisons to indirectly compare the effectiveness of [177Lu]Lu-DOTA-TATE to everolimus, sunitinib and best supportive care (BSC) for extending progression-free survival and overall survival in patients with advanced, unresectable gastrointestinal (GI)-NETs and P-NETs. The results of the main analysis suggest that after accounting for differences in key prognostic variables, the hazard of progression was 62% (hazard ratio [HR], 0.38; confidence interval [CI]95 0.25–0.58) and 65% (HR 0.35 CI95 0.21–0.59) lower in patients with GI-NETs treated with [177Lu]Lu-DOTA-TATE than in those treated with everolimus and BSC, respectively. Similarly, the hazard of progression was 64% (HR 0.36 CI95 0.18–0.70), 54% (HR 0.46 CI95 0.30–0.71) and 79–87% (HR 0.21 CI95 0.13–0.32; HR 0.13 CI95 0.08–0.22) lower in patients with P-NET treated with [177Lu]Lu-DOTA-TATE than in those treated with sunitinib, everolimus and BSC, respectively. The hazard of death was 58% (HR 0.42 CI95 0.25–0.72), 47% (HR 0.53 CI95 0.33–0.87) and 44–64% (HR 0.56 CI95 0.36–0.90; HR 0.34 CI95 0.20–0.57) lower in P-patients with NET treated with [177Lu]Lu-DOTA-TATE than in those treated with sunitinib, everolimus and BSC, respectively. While our results must be interpreted with caution given the non-randomised nature of the comparisons and the potential for residual confounding, the magnitude of the effect sizes we observe and their consistency across comparators suggest that [177Lu]Lu-DOTA-TATE may be a more effective treatment option than everolimus, sunitinib and BSC in advanced, unresectable GEP-NETs

Endoscopic bilateral adrenalectomy in patients with ectopic Cushing’s syndrome

Background: Bilateral adrenalectomy (BLA) is a treatment option to alleviate symptoms in patients with ectopic Cushing's syndrome (ECS) for whom surgical treatment of the responsible nonpituitary tumor is not possible. ECS patients have an increased risk for complications, because of high cortisol levels, poor clinical condition, and metabolic disturbances. This study aims to evaluate the safety and long-term efficacy of endoscopic BLA for ECS. Methods: From 1990 to present, 38 patients were diagnosed and treated for ECS in the Erasmus University Medical Center, a tertiary referral center. Twenty-four patients were treated with BLA (21 endoscopic, 3 open), 9 patients were treated medically, and 5 patients could be cured by complete resection of the adrenocorticotropic hormone (ACTH)-producing tumor. The medical records were retrospectively reviewed and entered into a database. For evaluation of the efficacy of BLA, preoperative biochemical and physical symptoms were assessed and compared with postoperative data. Results: Endoscopic BLA was successfully completed in 20 of the 21 patients; one required conversion to open BLA. Intraoperative complications occurred in two (10%) patients, and postoperative complications occurred in three (14%) patients. Median hospitalization was 9 (2-95) days, and median operating time was 246 (205-347) min. Hypercortisolism was resolved in all patients. Improvements of hypertension, body weight, Cushingoid appearance, impaired muscle strength, and ankle edema were achieved in 87, 90, 65, 61, and 78% of the patients, respectively. Resolution of diabetes, hypokalemia, and metabolic alkalosis was achieved in 33, 89, and 80%, respectively. Conclusion: Endoscopic BLA is a

Evidence that the TRH-like peptide pyroglutamyl-glutamyl-prolineamide in human serum may not be secreted by the pituitary gland

Recent studies have revealed that TRH-like immunoreactivity (TRH-LI) in human serum is predominantly pGlu-Glu-ProNH2 (< EEP-NH2), a peptide previously found in, among others tissues, the pituitary gland of various mammalian species. In the rat pituitary, < EEP-NH2 is present in gonadotrophs and its pituitary content is regulated by gonadal steroids and gonadotrophin-releasing hormone (GnRH). Hence, we reasoned that < EEP-NH2 in human serum may also arise, at least in part, from the pituitary, and that its secretion may correlate with that of gonadotrophins. Therefore, blood was simultaneously sampled from both inferior petrosal sinuses, which are major sites of the venous drainage of the pituitary gland, and a peripheral vein from seven patients with suspected adrenocorticotrophin-secreting pituitary tumours. In addition, in six postmenopausal and six cyclic women, peripheral vein blood was collected at 10-min intervals for 6 h, then a standard 100 micrograms GnRH test was performed. In the sera, TRH-LI was estimated by RIA with antiserum 4319, which binds most tripeptides that share the N- and C-terminal amino acids with TRH (pGlu-His-ProNH2). In addition, LH and FSH were measured in these sera b