Case Report and Literature Review of Insulinoma in the Geriatric Population: An 86-Year-Old Female with Syncope of Unknown Origin

Insulinomas are extremely rare pancreatic endocrine tumors. The tumor is characterized by endogenous hypersecretion of insulin and ensuing development of symptoms of neuroglycopenia and the catecholaminergic response. Symptoms may not always be present, particularly in patients compensating appropriately with increased appetites and caloric intake due to low glucose levels. Early localization of the disease is essential to prevent lethal hypoglycemia and timely treatment. This case report and literature review depict the case of a pancreatic insulinoma in an 86-year-old female, an exceptionally rare presentation based on age and absence of clinical symptoms for one or more years prior to hospitalization. Despite its rarity, similar presentations have been reported in the literature and are further outlined with characteristics and treatment plans. This case highlights a unique presentation of insulinoma and suggests the need for clinical vigilance and further study. It also discusses diagnosis, localization, and management of this uncommon disease in patients above the age of seventy-five.

SUN-907 Dual Ectopic Gastrin and ACTH Secretion Leading to Combined Zollinger-Ellison Syndrome and Cushing’s Syndrome in a Patient with Metastatic Neuroendocrine Pancreatic Tumor

Background: Zollinger-Ellison Syndrome (ZES) is caused by ectopic secretion of gastrin from a gastrinoma. The annual incidence of gastrinomas is 0.5 to 2 per million population1. Although 17-30% of gastrinomas will stain positive for both gastrin and ACTH, the clinical manifestation of both ZES and Cushing’s syndrome is rare. In a study by Maton et al., 3 of 59 patients (5%) with sporadic ZES (not MEN1) had Cushing’s syndrome as well2. Clinical Case: A 63yo woman with DM2 presented with persistent diarrhea for 2 years, and was diagnosed with ZES with a gastrin level of 1359 pg/mL (<100 pg/mL). A CT A/P showed a 3.8 cm pancreatic tail mass with multiple liver lesions. These lesions showed positive uptake on octreoscan, and a biopsy was positive a pancreatic neuroendocrine (NE) tumor. Her diarrhea was controlled with a PPI and no other intervention was made. 7 months later, she experienced severe worsening of her DM control despite aggressive medication titration. Due to new confusion and lethargy, she presented acutely to the ED. Labs showed metabolic alkalosis and profound hypokalemia with a CO2 38 mmol/L (22 - 31 mmol/L), venous pH 7.58 (7.32 - 7.42) and K 2.1 mmol/L (3.5 – 5.0 mmol/L). Her skin was diffusely hyperpigmented, and she had numerous cushingoid features on exam including supraclavicular fat pads, round face, thin skin and thin extremities. A subsequent cortisol level was found to be 125 mcg/dL (AM [6-10 am] 4.8 – 19.5 mcg/dL) with an ACTH of 1081 pg/mL (6-50 pg/mL). She was not an optimal candidate for adrenalectomy given previous abdominal surgeries. After an octreotide drip (total 1475 mcg in 24 hrs) failed to reduce cortisol levels, metyrapone 250 mg q6h was started which led to an immediate and significant reduction in cortisol (209 to 38 mcg/dL), improved quality of life and significant reduction in her insulin and K supplementation requirement. Conclusion: We present a rare case of a dual gastrin and ACTH-secreting metastatic pancreatic NE cancer, in which overt ZES preceded the relatively abrupt onset of clinical Cushing’s syndrome. Similar to Babu et al., the initial presentation was dominated by worsening DM control3. Despite the octreoscan positivity, cortisol production was not appreciably blocked by octreotide but was well controlled by metyrapone. As seen in other cases, we again highlight the pluripotency of NE tumors and the ability to change hormone production. We also present the unique circumstance this patient faced for treatment options as she was not an optimal candidate for surgery. Reference: 1. Oberg K. Pancreatic endocrine tumors. Semin Oncol. 2010 Dec;37(6):594-618. 2. Maton PN, Gardner JD, Jensen RT. Cushing’s syndrome in patients with the Zollinger-Ellison syndrome. N Engl J Med. 1986 Jul 3;315(1):1-5. 3. Babu AR, Dwarakanathan AA. Cushing’s syndrome from ectopic production of corticotropin by a metastatic gastrinoma. Endocr Pract. 2003 May-Jun;9(3):229-32.

TREATMENT OF PATIENTS WITH PANCREATIC NEUROENDOCRINE TUMOURS DEPENDING ON THE DIFFERENTIATION GRADE

The incidence of neuroendocrine tumors has significantly increased over the last years.The purpose of the study was to analyze treatment outcomes in patients with pancreatic endocrine tumors (PETs) with regard to histopathologic diagnosis.Material and Methods. The clinical records of 1077 patients with pancreatic tumors were retrospectively analyzed. Fifty patients were diagnosed with PET. Treatment outcomes were assessed with regard to tumor differentiation grade, tumor stage, extent of surgery and drug therapy.Results. The most common histological grade was G1. Patients with G1 tumors had the best 1-and 3-year survival rates regardless of tumor stage. Factors influencing prognosis in patients with PETs were: radical surgery, Ki67 expression level, histological grade (G1–3), tumor stage at diagnosis.

Gamma Emitters in Pancreatic Endocrine Tumors Imaging in the PET Era: Is there a Clinical Space for 99mTc-peptides?

Background: Pancreatic Neuroendocrine Tumors (PNETs) are rare neoplasms, sporadic or familial, even being part of a syndrome. Their diagnosis is based on symptoms, hormonal disorders or may be fortuitous. The role of Nuclear Medicine is important, mainly because of the possibility of a theranostic strategy. This approach is allowed by the availability of biochemical agents, which may be labeled with radionuclides suitable for diagnostic or therapeutic purposes, showing almost identical pharmacokinetics. The major role for radiopharmaceuticals is connected with radiolabeled Somatostatin Analogues (SSA), since somatostatin receptors are highly expressed on some of the neoplastic cell types. Discussion: Nowadays, in the category of radiolabeled SSA, although 111In-pentetreotide, firstly commercially proposed, is still used, the best choice for diagnosis is related to the so called DOTAPET radiotracers labeled with 68-Gallium (Ga), such as 68Ga-DOTATATE, 68Ga-DOTANOC, and 68Ga-DOTATOC. More recently, labeling with 64-Copper (Cu) (64Cu-DOTATATE) has also been proposed. In this review, we discuss the clinical interest of a SAA (Tektrotyd©) radiolabeled with 99mTc, a gamma emitter with better characteristics, with respect to 111Indium, radiolabeling Octreoscan ©. By comparing both pharmacokinetics and pharmacodynamics of Octreoscan©, Tektrotyd© and PET DOTA-peptides, on the basis of literature data and of our own experience, we tried to highlight these topics to stimulate further studies, individuating actual clinical indications for all of these radiotracers. Conclusion: In our opinion, Tektrotyd© could already find its applicative dimension in the daily practice of NETs, either pancreatic or not, at least in centers without a PET/CT or a 68Ga generator. Because of wider availability, a lower cost, and a longer decay, compared with respect to peptides labeled with 68Ga, it could be also proposed, in a theranostic context, for a dosimetry evaluation of patients undergoing Peptide Receptor Radionuclide Therapy (PRRT), and for non-oncologic indications of radiolabelled SSA. In this direction, and for a more rigorous cost/effective evaluation, more precisely individuating its clinical role, further studies are needed.

Comparison of the diagnostic accuracy of the current guidelines for detecting insulinoma

Objective Insulinomas are rare pancreatic endocrine tumors characterized by hypoglycemia. Guidelines by the Endocrine Society (ES), the European (ENETS) and the North American (NANETS) Neuroendocrine Tumor Societies provide divergent diagnostic criteria. This study compared the diagnostic accuracy of these different criteria during the 72-h fasting test. Design Retrospective cohort study. Methods From 2000 to 2014, 64 patients with a suspected insulinoma underwent a 72-h fasting test and were included in the analysis. This study assessed the diagnostic sensitivity, specificity and accuracy based on venous blood glucose and corresponding insulin levels measured by electrochemiluminescence immunoassay (ECLIA). Results Based on 64 individuals (18 with, 46 without insulinoma), the ES criteria provided a diagnostic sensitivity of 0.94 (0.73–1.00), specificity of 0.89 (0.76–0.96) and accuracy of 0.91 (0.81–0.96). ENETS/NANETS criteria reached a diagnostic sensitivity of 0.78 (0.52–0.94), specificity of 1.00 (0.92–1.00) and accuracy of 0.94 (0.85–0.98). Conclusions These results point to a higher diagnostic sensitivity with less specificity for diagnosing insulinoma using ES criteria and a higher specificity at lower sensitivity by using ENETS/NANETS criteria. Before considering these results when applying the different criteria in clinical practice, the results should be confirmed in further studies comprising larger cohorts.

One Case of Interventional Chemoembolization Treatment of Small Cell Neuroendocrine Cervical Cancer

Small cell neuroendocrine cervical cancer (SCNEC) is some kind of rare malignant cancer of the cervix area. In 1997, according to the research of International Cancer Institute and the American Association of Pathology, the pancreatic endocrine tumors can be sorted into four types by the morphological similarity compared with tumors of the same type in the lung: typical carcinoid, non-typical carcinoid, large cell neuroendocrine cancer, and small cell neuroendocrine cancer, in which the last one is the most previaling. The SCNEC recurs much more often and its distant metastasis is more common in the lungs, brain and liver[1][2]. It characterizes low incidence and few cases, and a retrospective study is commonly used. Without clinical experience, there have been no fair treatment so far. A patient diagnosed as SCNEC A2 period was treated in our hospital, and uterine artery embolization chemotherapy, a new treatment, was taken to her. Consequently, the treatment worked, creating significant surgical conditions for her. Moreover, postoperative examination showed obvious effect of this treatment. The case report is as follows: