clinico pathological features treatments and survival of malignant insulinomas a multicenter study

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

Lymphnode metastasis of thyroid cancer misinterpreted as lateral aberrant thyroid 40 years before identification of primary tumor. Case report and review of the literature

The differential diagnosis between lateral ectopic thyroid tissue with orthotopic normal gland and metastatic thyroid carcinoma is challenging. Lateral cervical site is a very rare location for ectopic tissue since only a few cases have been reported. The peculiarity of this clinical case is the finding of a thyroid carcinoma forty years after surgical resection of the ectopic thyroid lesion. This asynchronous association, never reported in literature, raises the question of the differential diagnosis between a true ectopic aberrant thyroid and an early lymph node metastasis from an occult thyroid carcinoma, evident in the primitive site many years later. Several elements, which will be matter of discussion, seem to favour the latter hypothesis

Presentation, diagnostic features and glucose handling in a monocentric series of insulinomas

New aspects have emerged in the clinical and diagnostic scenarios of insulinoma: current guidelines have lowered the diagnostic insulin threshold to 3 \u3bcU/ml in the presence of hypoglycemia (<55 mg/dl); post-prandial hypoglycemia has been reported as the only presenting symptom; preexisting diabetes mellitus (DM) was recognized in some patients

Presentation and Outcome of Pancreaticoduodenal Endocrine Tumors in Multiple Endocrine Neoplasia Type 1 Syndrome

Aim: To assess presentation and outcome of pancreaticoduodenal endocrine tumors (PDETs) in a single center series of multiple endocrine neoplasia type 1 (MEN1) patients. Methods: Retrospective analysis of prospectively collected data of MEN1 patients observed at the University of Verona. Results: Thirty-one MEN1 patients had PDETs, including 16 nonfunctioning (NF), 6 insulinomas and 9 Zollinger-Ellison syndrome (ZES). In 16 of these patients (52%), PDET was the manifestation which led to the diagnosis of MEN1; among this group, 15 patients (94%) previously had unidentified primary hyperparathyroidism (PHPT), which was asymptomatic in 9 cases (60%). Of the 31 patients, 19 (61%) underwent curativesurgery and 13 (68%, 7 NF-PDETs, 4 insulinomas and 2 ZES) were disease-free after a median follow-up of 3 years (range: 0.5-15). One patient had debulking surgery with stable disease after 2 years of follow-up. Eight patients with NF-PDETs 6420 mm and 2 with ZES, treated with a conservative approach, showed stable disease. One patient with insulinoma was lost to follow-up. Conclusions: PDET may be the manifestation that leads to MEN1 diagnosis since the almost constant presence of PHPT is very often unrecognized or considered sporadic. Conversely, the presence of PDETs should be looked for in all patients presenting PHPT, even if asymptomatic, particularly before age 50. Surgery may be curative in the majority of insulinomas and can prolong disease-free survival in NF-PDET, but is not proven to be effective in ZES. A conservative approach can be safely reserved for patients with NF-PDETs 6420 mm

Hyperinsulinaemic hypoglycemia associated with ectopic Cushing syndromes due to a pancreatic endocrine tumor in a type 2 diabetes mellitus patient: clinical implications of a rare association.

Background: The coexistence of insulin and ACTH hypersecretion in the same patient is extremely rare. A diabetic patient with a pancreatic endocrine tumor (PET) co-secreting insulin and ACTH is still more rare and has never been described. The combination of these two endocrine syndromes results in a peculiar clinical picture. Aim: To determine the cause of glycemic variations in a patient with previously stable diabetes mellitus. Subjects and Methods: This is a clinical case report from the Endocrinology Unit of Aosta Hospital and Internal Medicine and Surgical Unit of Verona University. A 69 year-old diabetic patient was hospitalized for recurrent severe hypoglycemic events persistent after withdrawal of anti-diabetic drugs. The causes of hypoglycemia and subsequent resumption of hyperglycemia were investigated. Results: An insulin secreting PET was diagnosed. Diazoxide and octreotide therapy initially was able to control hypoglycemic symptoms, then, a Cushing's syndrome occurred resulting in worsening of diabetes control. ACTH was found to be released by the PET previously diagnosed as an insulin secreting tumor. The tumor was removed and the histology was consistent with a well differentiated endocrine carcinoma. After surgery, adrenal function was normal and insulin therapy was newly necessary to control diabetes. Conclusions: A single PET may be responsible for both a hyperinsulinaemic and a Cushing's syndrome. When this rare association occurs, each of the two syndromes may affect the other resulting in a peculiar clinical course. Finally, an insulin secreting PET has to be kept in mind as a rare cause of hypoglycemia in diabetic patients

Hyperinsulinemic hypoglycemia associated with ectopic Cushing's syndrome due to a pancreatic endocrine tumor in a Type 2 diabetes mellitus patient: clinical implications of a rare association.

BACKGROUND: The coexistence of insulin and ACTH hypersecretion in the same patient is extremely rare. A diabetic patient with a pancreatic endocrine tumor (PET) co-secreting insulin and ACTH is even rarer and has never been described. The combination of these two endocrine syndromes results in a peculiar clinical picture. AIM: To determine the cause of glycemic variations in a patient with previously stable diabetes mellitus. SUBJECTS AND METHODS: This is a clinical case report from the Endocrinology Unit of Aosta Hospital and Internal Medicine and Surgical Unit of Verona University. A 69-yr-old diabetic patient was hospitalized for recurrent severe hypoglycemic events persistent after withdrawal of anti-diabetic drugs. The causes of hypoglycemia and subsequent resumption of hyperglycemia were investigated. RESULTS: An insulin-secreting PET was diagnosed. Diazoxide and octreotide therapy initially was able to control hypoglycemic symptoms, then, a Cushing's syndrome occurred resulting in worsening of diabetes control. ACTH was found to be released by the PET previously diagnosed as an insulin-secreting tumor. The tumor was removed and the histology was consistent with a well differentiated endocrine carcinoma. After surgery, adrenal function was normal and insulin therapy was again necessary to control diabetes. CONCLUSIONS: A single PET may be responsible for both a hyperinsulinemic and a Cushing's syndrome. When this rare association occurs, each of the two syndromes may affect the other resulting in a peculiar clinical course. Finally, an insulin-secreting PET has to be kept in mind as a rare cause of hypoglycemia in diabetic patients

Hyperinsulinemic hypoglycemia associated with ectopic Cushing's syndrome due to a pancreatic endocrine tumor in a Type 2 diabetes mellitus patient: Clinical implications of a rare association.

The coexistence of insulin and ACTH hypersecretion in the same patient is extremely rare. A diabetic patient with a pancreatic endocrine tumor (PET) co-secreting insulin and ACTH is even rarer and has never been described. The combination of these two endocrine syndromes results in a peculiar clinical picture.To determine the cause of glycemic variations in a patient with previously stable diabetes mellitus.This is a clinical case report from the Endocrinology Unit of Aosta Hospital and Internal Medicine and Surgical Unit of Verona University. A 69-yr-old diabetic patient was hospitalized for recurrent severe hypoglycemic events persistent after withdrawal of anti-diabetic drugs. The causes of hypoglycemia and subsequent resumption of hyperglycemia were investigated.An insulin-secreting PET was diagnosed. Diazoxide and octreotide therapy initially was able to control hypoglycemic symptoms, then, a Cushing's syndrome occurred resulting in worsening of diabetes control. ACTH was found to be released by the PET previously diagnosed as an insulin-secreting tumor. The tumor was removed and the histology was consistent with a well differentiated endocrine carcinoma. After surgery, adrenal function was normal and insulin therapy was again necessary to control diabetes.A single PET may be responsible for both a hyperinsulinemic and a Cushing's syndrome. When this rare association occurs, each of the two syndromes may affect the other resulting in a peculiar clinical course. Finally, an insulin-secreting PET has to be kept in mind as a rare cause of hypoglycemia in diabetic patients