Spontaneous hypoglycemia: should we mind the gap? Long-term follow-up of healthy people who met Whipple's triad criteria.

CONTEXT: Patients discharged as "healthy" with the symptoms of spontaneous hypoglycemia, commonly known as Whipple's triad, need more attention. OBJECTIVE: Characterization and long-term follow-up of symptom development in patients with spontaneous hypoglycemia discharged as "healthy". The objective was to ascertain whether any conditions related to the symptoms were diagnosed during the follow-up period. METHODS: Retrospective analysis of patient data and evaluation of a specific questionnaire on the development of symptoms of spontaneous hypoglycemia. In addition, patient questionnaires were evaluated and primary care physicians were asked about possible diseases not recorded at baseline that occurred during the follow-up period. SETTING: Center for Endocrinology, Diabetology, and Osteology at the University Hospital Marburg, Inpatient Department, Germany. PATIENTS: All patients who presented to our center for the 72-hour fast between 2005 and 2018 and were discharged without an internal medicine diagnosis were included. INTERVENTIONS: Survey by questionnaire, via telephone interview. MAIN OUTCOME MEASURES: Patient-reported information on current symptoms compared to original symptoms, diagnosis of insulinoma or diabetes mellitus during follow-up, matched with primary care physician data, and metabolic and biometric data such as body mass index (BMI), homeostasis model assessment for insulin resistance (HOMA IR), insulin sensitivity Matsuda Index (ISI-M), and area under the curve. RESULTS: A total of 41 datasets were evaluated at baseline and 38 patients were followed for an average of approximately 10 years. In total, 61% of respondents still reported the same symptoms as at baseline. No insulinoma was missed in these patients. Only two of the 38 patients developed diabetes mellitus. CONCLUSION: The high percentage of patients who are discharged as "healthy" and still have symptoms after many years is disturbing. It is possible that the symptoms are not due to low blood glucose. We urge caution with use of the term "healthy". We advocate a multidisciplinary therapeutic approach after an organic cause of hypoglycemia has been ruled out. Psychosomatic treatment seems to be useful. In addition, more research should be conducted on this topic.

Relevance of Endoscopic Ultrasound in Endocrinology Today: Multiple Endocrine Neoplasia Type 1, Insulinoma, Primary Aldosteronism-An Expert's Perspective Based on Three Decades of Scientific and Clinical Experience.

In endocrinology, endoscopic ultrasound (EUS) may be used to image the adrenals, the endocrine pancreas, and other organs where endocrine neoplasms may occur. During the recent decades, EUS has been established predominantly to assess multiple endocrine neoplasia type 1, to localize insulinomas, and to identify aldosterone-producing adenomas. EUS in endocrinology requires special skills and individual experience in order to provide reliable diagnostic information.

Is the Size of Insulinoma Predictive for its Endocrine Behavior? An Endoscopic Ultrasound Study.

OBJECTIVE: Insulinoma is a rare tumor of the pancreas that can lead to spontaneous hypoglycemia due to excessive insulin secretion. Seventy-two-hour fast is the gold standard for finding the correct diagnosis. Endoscopic ultrasound (EUS) is an established examination method to identify the suspicious lesion. Previous studies correlate the measured size of insulinoma and their endocrine behavior. This study was designed to find a relation between these variables. METHODS: We took the data of patients who had a histologically confirmed insulinoma after receiving an endoscopic ultrasound in our department. Size and echogenicity were correlated with the endpoint of the 72-hour fast and hormone levels. RESULTS: A total of 45 patients were identified. Most insulinomas were small with a volume of<2 cm3 (median 1.15 cm3). There was no correlation between the duration of fasting, hormone levels, and the size of the insulinoma. In addition, in a subgroup analysis, no connection could be established between the size of the insulinoma and the amount of insulin released after oral glucose exposure. We found that homogeneous tumors were significantly smaller and had a lower Ki-67 index. Furthermore, there was a tendency towards a shorter duration for the 72-hour fast for the small tumors. DISCUSSION: This data suggests that the measured size of insulinoma by EUS is not related to the time until termination of the 72-hour fast and measured hormone levels. The echogenicity seems more important, showing that homogenous tumors are an indicator of a higher differentiation, which can result in a shorter duration of the fasting period. The differences in the secretion behavior of the insulinomas could complicate the correlation of size and the 72-hour fast period.

Two Case Reports of Subacute Thyroiditis after Receiving Vaccine for COVID-19.

The ongoing COVID-19 pandemic, caused by a coronavirus named SARS-CoV-2, has struck the planet with great force. As of December 2019, the virus has made its devasting route across all continents . In January 2022, the World Health Organization (WHO) registered over 5.5 million COVID-19 related deaths. Most of these people had suffered from pneumonia and acute respiratory distress syndrome , and in some cases, extensive damage to all organ systems. To get hold of this pandemic, it was vital to find effective vaccines against it. The two vaccine candidates BNT162b2 (BioNTech/Pfizer) and ChAdOx1 (University of Oxford and AstraZeneca) offer a high level of protection against COVID-19 by providing immunity due to antibody production against the spike protein of SARS-CoV-2. In addition to general side effects, immunological side effects such as subacute thyroiditis can follow the vaccination. This transient inflammatory condition of the thyroid gland is characterized with hyperthyroxinemia, inflammation, pain, and tenderness in the thyroid region, as well as an elevation of serum thyroglobulin concentration. There are only a few reports on the occurrence of this disease after receiving a COVID-19 vaccine. We present two cases of subacute thyroiditis after vaccination with the vaccines BNT162b2 and ChAdOx1 and try to enlighten the problem of immunological phenomena after vaccination. It must be discussed whether cross-reactivity of the spike protein and tissue proteins such as thyroid peroxidase (TPO), an "autoimmune/inflammatory syndrome by adjuvants" (ASIA), or the circulating spike protein itself after vaccination are responsible for the SAT.

Pancreaticoduodenectomy Is the Best Surgical Procedure for Zollinger-Ellison Syndrome Associated with Multiple Endocrine Neoplasia Type 1.

AIM: The aim of this research was to evaluate the long-term outcome of pancreaticoduodenectomy (PD) versus other duodenopancreatic resections (non-PD) for the surgical treatment of the Zollinger-Ellison syndrome (ZES) in patients with multiple endocrine neoplasia type 1 (MEN1). METHODS: Prospectively recorded patients with biochemically confirmed MEN1-ZES who underwent duodenopancreatic surgery were retrospectively analyzed in terms of clinical characteristics, complications, cure rate, and long-term morbidity, including quality of life assessment (EORTC QLQ-C30). RESULTS: 35 patients (16 female, 19 male) with MEN1-ZES due to duodenopancreatic gastrinomas with a median age of 42 (range 30-74) years were included. At the time of diagnosis, 28 (80%) gastrinomas were malignant, but distant metastases were only present in one (3%) patient. Eleven patients (31.4%) underwent pancreatoduodenectomy (PD) as the initial procedure, whereas 24 patients underwent non-PD resections involving duodenotomy with gastrinoma excision, enucleation of the pNEN from the head of the pancreas, and peripancreatic lymphadenectomy, either with or without distal pancreatectomy (i.e., either Thompson procedure, n = 12, or DUODX, n = 12). There was no significant difference in perioperative morbidity and mortality between the two groups (p ≥ 0.05). One (9%) patient of the PD group required reoperation for recurrent or metastatic ZES compared to eight (22.8%) patients of the non-PD resection groups. After a median follow-up time of 134 months (range 6-480) nine of 11 (82%) patients in the PD group, two of 12 (16%) patients in the Thompson procedure group, and three of 12 (25%) patients in the DUODX group had normal serum gastrin levels. In addition, the global health QoLScore was better in the PD group (76.9) compared to the Thompson procedure (57.4) and DUODX (59.5) groups. CONCLUSIONS: Initial PD seems to be the superior surgical procedure for MEN1-ZES, resulting in a long-term cure rate of about 80%, fewer duodenopancreatic reoperations, and an acceptable quality of life.

Regional Growth Velocity and Incidence of Pancreatic Neuroendocrine Neoplasias in Multiple Endocrine Neoplasia Type 1.

OBJECTIVES: Pancreatic neuroendocrine neoplasias (pNENs) in multiple endocrine neoplasia type 1 are predominantly found in the dorsal anlage. Whether their growth velocity and incidence might be related to their location in the pancreas has not been investigated yet. METHODS: We studied 117 patients using endoscopic ultrasound. RESULTS: Growth velocity could be calculated for 389 pNENs. Increase of largest tumor diameter (% per month) was 0.67 (standard deviation [SD], 2.04) in the pancreatic tail (n = 138), 1.12 (SD, 3.00) in the pancreatic body (n = 100), 0.58 (SD, 1.19) in the pancreatic head/uncinate process-dorsal anlage (n = 130), and 0.68 (SD, 0.77) in the pancreatic head/uncinate process-ventral anlage (n = 12). Comparing growth velocity of all pNENs in the dorsal (n = 368, 0.76 [SD, 2.13]) versus ventral anlage, no significant difference was detected. Annual tumor incidence rate was 0.21 in the pancreatic tail, 0.13 in the pancreatic body, 0.17 in the pancreatic head/uncinate process-dorsal anlage, 0.51 dorsal anlage together, and 0.02 in the pancreatic head/uncinate process-ventral anlage. CONCLUSIONS: Multiple endocrine neoplasia type 1 pNENs are unequally distributed between ventral (low prevalence and incidence) and dorsal anlage. However, there are no regional differences in growth behavior.

Pheochromocytoma and Adrenocortical Carcinoma: Morphological Characteristics in Endoscopic Ultrasound Imaging.

Purpose Pheochromocytoma (PCC) and adrenocortical carcinoma (ACC) are two rare endocrine diseases. Early diagnosis is crucial to significantly reduce morbidity and mortality. In this study, we used endoscopic ultrasound (EUS) for high-resolution imaging to investigate the endosonographic morphology pattern of PCC and ACC. Materials and Methods This retrospective cohort study included 58 PCC/ACC lesions diagnosed by EUS imaging at two tertiary care centers between 1997 and 2015. The following groups were defined by histology or by the presence of a pheochromocytoma-associated syndrome without histological proof: bPCC (benign PCC), mPCC (malignant PCC), and ACC. Results In our cohort, mPCC tended to be larger at the time of diagnosis (n=5; 39.9±41.9 mm) than bPCC (n=46; 27.3 ±20.8 mm, P=0.548). ACC lesions were significantly larger (n=7; 50.6±14.8 mm) than bPCC and mPCC (n=51; 28.5±23.3 mm, P=0.002). In EUS, bPCC and ACC lesions frequently appeared to have a round shape and nodular structure. bPCC and ACC tended to be more hyperechoic (P=0.112 and P=0.558, respectively) and heterogeneous (P=0.501 and P=0.098, respectively) than mPCC. Compared to PCC, ACC did not show high hyperperfusion (P=0.022). In contrast to adenoma, all tumor entities showed hypo-/anechoic areas within the tumor (P<0.05). Conclusion No significant differences in EUS morphology were found to reliably distinguish benign from malignant PCC and ACC lesions. However, EUS may be a reasonable alternative or complementary method to conventional imaging techniques for the early detection of these tumor entities.

Pancreatic Neuroendocrine Neoplasias in Multiple Endocrine Neoplasia Type 1 Are Predominantly Located in the Dorsal Anlage: An Endoscopic Ultrasound Study.

OBJECTIVES: Pancreatic neuroendocrine neoplasias (pNENs) frequently occur in multiple endocrine neoplasia type 1 (MEN1). Their distribution referring to embryology, that is, the pancreatic anlagen, has not been investigated yet. METHODS: In the time between 1998 and 2019, we studied the distribution of pNENs in MEN1 concerning the embryologic origin of the pancreas, that is, the dorsal versus ventral anlage using endoscopic ultrasound in 117 MEN1 patients: 56 women, 61 men; aged 40 years (standard deviation, 14 years) at first endoscopic ultrasound. RESULTS: In 105 patients, a total of 628 pNENs were detected. They were located in the pancreatic tail: 231; pancreatic body: 177; pancreatic head/uncinate process: 220. Of the latter, 22 were located in the ventral anlage, 176 in the dorsal anlage, and 22 remained undefined. In summary, just 3.5% of all detected pNENs were located in the ventral anlage, 93.0% in the dorsal anlage, and 3.5% could not be assigned. CONCLUSIONS: Our study indicates that the vast majority of pNENs in MEN1 is located in the dorsal anlage, whereas the ventral anlage of the pancreas seems to be to a large extend spared from pNENs. Implications for new surgical strategies might be considered.

[Spontaneous Hypoglycemia: A Diagnostic Challenge]. / Spontanhypoglykämien: Eine diagnostische Herausforderung.

HISTORY: A 59-year-old woman presented for an endocrinological evaluation of recurrent spontaneous hypoglycemia. The complaints always regressed after carbohydrate intake. Due to classic congenital adrenal hyperplasia, the patient received substitution therapy with hydrocortisone for decades. FINDINGS AND DIAGNOSIS: The patient was in good general condition and slightly overweight. The blood glucose at the time of admission was 87 mg/dl. The cortisol and adrenocorticotropic hormone (ACTH) under substitution with delayed-release hydrocortisone were unremarkable. The mixed-meal tolerance test (MMTT, standardized breakfast test) showed no reactive hypoglycemia. In the subsequent 72-hour fast, symptomatic hypoglycemia of 46 mg/dl was demonstrated after 36 hours. The insulin secretion was suppressed. The low cortisol as well as the high ACTH indicated an undersupply of hydrocortisone at this time. THERAPY AND COURSE: Initially, the morning dose of delayed-release hydrocortisone was increased. However, this had no effect on blood glucose. Therefore, hydrocortisone was also prescribed at night. CONCLUSION: In addition to endogenous hyperinsulinism, a disturbance of the contrainsulinergic hormones can also be responsible for spontaneous hypoglycemia.The MMTT and the 72-hour fast test should be used for diagnosis. It is important to ensure that hormone analysis is carried out immediately in hypoglycemia. The ratio of insulin, C-peptide and proinsulin to blood glucose and the constellation of counter-regulatory hormones such as cortisol, ACTH, growth hormone, Insulin-like growth factor 1 (IGF-1) and catecholamines can provide information about the etiology of hypoglycemia.

The Effect of Obstructive Sleep Apnea and Continuous Positive Airway Pressure Therapy on Skeletal Muscle Lipid Content in Obese and Nonobese Men.

Obstructive sleep apnea (OSA), independently of obesity (OBS), predisposes to insulin resistance (IR) for largely unknown reasons. Because OSA-related intermittent hypoxia triggers lipolysis, overnight increases in circulating free fatty acids (FFAs) including palmitic acid (PA) may lead to ectopic intramuscular lipid accumulation potentially contributing to IR. Using 3-T-1H-magnetic resonance spectroscopy, we therefore compared intramyocellular and extramyocellular lipid (IMCL and EMCL) in the vastus lateralis muscle at approximately 7 am between 26 male patients with moderate-to-severe OSA (17 obese, 9 nonobese) and 23 healthy male controls (12 obese, 11 nonobese). Fiber type composition was evaluated by muscle biopsies. Moreover, we measured fasted FFAs including PA, glycated hemoglobin A1c, thigh subcutaneous fat volume (ScFAT, 1.5-T magnetic resonance tomography), and maximal oxygen uptake (VO2max). Fourteen patients were reassessed after continuous positive airway pressure (CPAP) therapy. Total FFAs and PA were significantly (by 178% and 166%) higher in OSA patients vs controls and correlated with the apnea-hypopnea index (AHI) (r ≥ 0.45, P < .01). Moreover, IMCL and EMCL were 55% (P < .05) and 40% (P < .05) higher in OSA patients, that is, 114% and 103% in nonobese, 24.4% and 8.4% in obese participants (with higher control levels). Overall, PA, FFAs (minus PA), and ScFAT significantly contributed to IMCL (multiple r = 0.568, P = .002). CPAP significantly decreased EMCL (-26%) and, by trend only, IMCL, total FFAs, and PA. Muscle fiber composition was unaffected by OSA or CPAP. Increases in IMCL and EMCL are detectable at approximately 7 am in OSA patients and are partly attributable to overnight FFA excesses and high ScFAT or body mass index. CPAP decreases FFAs and IMCL by trend but significantly reduces EMCL.

Adult Proinsulinomatosis Associated With a MAFA Germline Mutation as a Rare Cause of Recurrent Hypoglycemia.

ABSTRACT: Sporadic adult insulinomatosis is an extremely rare clinical condition. Adult proinsulinomatosis has not yet been described. We report the case of a 48-year-old female patient with recurrent hypoglycemia caused by benign proinsulin-secreting pancreatic neuroendocrine neoplasias (pNENs) with no history of multiple endocrine neoplasia type 1. Initial workup revealed elevated serum proinsulin levels and a positive fasting test. Magnetic resonance imaging and endosonography visualized 2 pNENs in the pancreatic body and tail that were treated by robotic-assisted enucleation. After initial biochemical cure, the patient's hypoglycemia recurred 3 months after surgery. Imaging showed a new lesion in the pancreatic body, so that now a spleen-preserving subtotal distal pancreatectomy was performed. The pathological examination revealed 17 neuroendocrine microadenomas and 1 well-differentiated pNEN (Ki-67% 1%-2%) of 22-mm size as well as more than 200 (pro)insulin-producing ß-cell precursor lesions, confirming the diagnosis of adult proinsulinomatosis. Mutation analysis of the germline DNA identified the in-frame deletion mutation (p.His207del) in the MAFA gene on chromosome 8. The patient was biochemically cured 16 months after the last surgical resection. Similarly to adult insulinomatosis, the presence of proinsulin-secreting tumors causes recurrent hypoglycemia and might be associated with germline mutations in the MAFA gene.

Gender Differences in Multiple Endocrine Neoplasia Type 1: Implications for Screening?

BACKGROUND: Some gender-related differences have been reported in multiple endocrine neoplasia type 1 (MEN1), although not all reports are conclusive. This systematic review with analysis of the own MEN1 cohort evaluates gender differences and potential consequences for screening. METHODS: A systematic review of the literature between 1990 and 2019 with the search terms "MEN1" or "multiple endocrine neoplasia type 1" and "gender" or "sex" was performed. In addition, the prospectively collected data of a genetically confirmed MEN1 cohort of the Philipps University Marburg were retrospectively analyzed. RESULTS: Review of the literature identified five retrospective case series with original data of 1,057 MEN1 patients. One series suggested a higher frequency of pancreatic neuroendocrine neoplasms (NEN), especially gastrinomas, in men (61 vs. 54%) and a higher frequency of pituitary tumors in women (47 vs. 30%), but others did not. Only thymic NEN occurred predominantly in men throughout all studies. Women with MEN1 were found to have an increased risk of breast cancer. In the own series consisting of 116 MEN1 patients (male = 58, female = 58), thymic lesions were also more frequently detected in male patients (male = 5, female = 1). No gender difference was found with regard to the other manifestations. CONCLUSION: Regarding the typical MEN1 tumor manifestations, gender-adapted diagnostic and therapeutic approaches cannot be recommended. Female MEN1 patients should be encouraged to participate in breast cancer screening programs.

Single Centre Experience in Patients with Primary Hyperparathyroidism: Sporadic, Lithium-associated and in Multiple Endocrine Neoplasia.

PURPOSE: It is assumed that primary hyperparathyroidism (pHPT) in Multiple Endocrine Neoplasia (MEN) and lithium-associated pHPT (LIHPT) are associated with multiple gland disease (MGD), persistence and recurrence. The studies purpose was to determine frequencies, clinical presentation and outcome of sporadic pHPT (spHPT), LIHPT and pHPT in MEN. Additional main outcome measures were the rates of MGD and persistence/recurrence. METHODS: Retrospective analysis of medical records of 682 patients with pHPT who had attended the University Hospital of Marburg between 01-01-2004 and 30-06-2013. All patients were sent a questionnaire asking about their history of lithium medication. RESULTS: Out of 682 patients, 557 underwent primary surgery (532 spHPT, 5 LIHPT, 20 MEN), 38 redo-surgery (31 spHPT, 7 MEN), 55 were in follow-up due to previous surgery (16 spHPT, 1 LIHPT, 38 MEN) and 37 were not operated (33 spHPT, 1 LIHPT, 3 MEN). Primary surgeries were successful in 97.4%, revealed singular adenomas in 92.4%, double adenomas in 2.9% and MGD in 3.4% of the cases. Rates of MGD in MEN1 (82.35%) were significantly higher than in spHPT (3.8%), while there was no significant difference between LIHPT (20%) and spHPT. Rates of persistence/recurrence did not significantly differ due to type of surgery (bilateral/unilateral) or type of HPT (spHPT/LIHPT/MEN). CONCLUSIONS: History of lithium medication is rare among pHPT patients. While MGD is common in MEN1, rates of MGD, persistence or recurrence in LIHPT were not significantly higher than in spHPT.

Risk and Relevance of Insulin Pump Therapy in the Aetiology of Ketoacidosis in People with Type 1 Diabetes.

OBJECTIVE: The aim of this systematic data analysis was to determine the prevalence of diabetic ketoacidosis (DKA) as well as hypoglycemic and hyperglycemic disorders during insulin pump therapy (CSII) in patients with type 1 diabetes. The main focus was to investigate whether CSII patients have more DKA than the general type 1 diabetes population. SUBJECTS AND METHODS: This retrospective study with patients who were treated in our treatment center from 2003 to 2016 includes data from 229 patients (52.4% male, 47.6% female, 37.2±16.3 years; DKA: 93, hypoglycemia: 66, hyperglycemia: 70). RESULTS: Intensified insulin therapy was the most common treatment regimen in the study cohort (73.4%), followed by CSII (24%). However, 32.3% of the patients with DKA were on CSII. This number of DKA cases among the insulin pump users in our study cohort was higher than the prevalence reported in a previously published study by Reichel et al. (2013; p<0.05) and in a customer database (p<0.005). Most common causes of DKA in our study cohort were patient errors (43.3%) or insulin resistance induced by an underlying infection (29.8%). Device malfunction caused 13.5% of all DKA cases with an overwhelming majority on insulin pump treatment (93%). Overall, patient errors caused more DKA cases than device malfunctions. CONCLUSIONS: Our findings suggest that despite development of more sophisticated insulin pump devices, DKA is still more frequent with CSII than with other kinds of insulin treatment.

Cardivascular Risk Profile in Patients with Diabetes and Acromegaly or Cushing's Disease - Analysis from the DPV Database.

BACKGROUND: Although diabetes is a common complication of acromegaly or Cushing´s disease, there are only few detailed studies with a focus on cardiovascular risk, metabolic control or diabetes therapy. Here, we provide a comprehensive characterization from the longitudinal DPV (Diabetes Patienten Verlaufsdokumentation) registry. METHODS: Patients from the registry≥18 years of age with diabetes and acromegaly or Cushing´s disease were compared to patients with type 1 diabetes or type 2 diabetes using the statistical software SAS 9.4. RESULTS: Patients with diabetes and acromegaly (n=52) or Cushing's disease (n=15) were significantly younger at diabetes onset (median age 50.1 and 45.0 vs. 59.0 years in type 2 diabetes; both p<0.05). Dyslipidemia was common in both diseases (71.0% and 88.9% vs. 71.8% in type 2 diabetes; n.s.), while hypertension was most frequent in acromegaly (56.8% vs. 20.9% in type 1 diabetes, p<0.00001). 36.5% of patients with acromegaly and 46.7% with Cushing´s disease receive insulin, compared to 50.4% with type 2 diabetes. Oral antidiabetic drugs were used in 36.5% of patients with acromegaly and 40% with Cushing´s disease, with a predominance of biguanides and dipeptidyl peptidase-4 inhibitors. HbA1c was well controlled in both groups (median 7.0% and 6.5%; vs. 7.2% in type 2 diabetes). CONCLUSION: Patients with acromegaly are at a high risk for cardiovascular disease, reflected by dyslipidemia and hypertension. A high proportion of patients with diabetes in acromegaly or Cushing´s disease receives insulin. Based on a multicenter register, a sufficient number of patients with rare forms of diabetes can be analyzed.

The effects of prolonged single night session of videogaming on sleep and declarative memory.

Use of electronic media is widespread among adolescents. Many male adolescents spend a major part of their evenings playing video games. The increased exposure to artificial light as well as the exciting nature of this pastime is under suspicion to impair sleep. Sleep is considered to be important for memory consolidation, so there is also a potential risk for memory impairment due to video gaming. As learning and gaining knowledge is a very important part of adolescence, we decided to study the effects of prolonged video gaming on sleep and memory. The study was structured in a repeated measures design. Eighteen male participants played either the violent video game "Counter Strike: Global Offensive" or the board game "Monopoly" for five hours each on two Saturday nights. The game evenings were followed by sleep studies. Memory testing and vigilance evaluation was performed the next morning. During the course of the study, saliva samples were taken to determine melatonin and cortisol levels. The results of this crossover study showed slightly reduced sleep efficiency after "Counter Strike: Global Offensive" (-3.5%, p = .017) and impaired declarative memory recall (p = .005) compared to "Monopoly". Melatonin levels at bedtime were lower after "Counter Strike: Global Offensive" (p = .005), cortisol levels were elevated while playing the video game (p = .031). Negative effects on sleep were not strong but consistent with more wake after sleep onset (+12 min) and a higher arousal index after "Counter Strike: Global Offensive". We conclude that excessive video gaming in the evening can contribute to worsened sleep and impaired memory in male adolescents.

Surgical Management, Preoperative Tumor Localization, and Histopathology of 80 Patients Operated on for Insulinoma.

INTRODUCTION: Diagnosis and pathological classification of insulinomas are challenging. AIM: To characterize localization of tumors, surgery outcomes, and histopathology in patients with insulinoma. METHODS: Patients with surgically resected sporadic insulinoma were included. RESULTS: Eighty patients were included. Seven had a malignant tumor. A total of 312 diagnostic examinations were performed: endoscopic ultrasonography (EUS; n = 59; sensitivity, 70%), MRI (n = 33; sensitivity, 58%), CT (n = 55; sensitivity, 47%), transabdominal ultrasonography (US; n = 45; sensitivity, 40%), somatostatin receptor imaging (n = 17; sensitivity, 29%), 18F-fluorodeoxyglucose positron emission tomography/CT (n = 1; negative), percutaneous transhepatic venous sampling (n = 10; sensitivity, 90%), arterial stimulation venous sampling (n = 20; sensitivity, 65%), and intraoperative US (n = 72; sensitivity, 89%). Fourteen tumors could not be visualized. Invasive methods were used in 7 of these 14 patients and localized the tumor in all cases. Median tumor size was 15 mm (range, 7 to 80 mm). Tumors with malignant vs benign behavior showed less staining for insulin (3 of 7 vs 66 of 73; P = 0.015) and for proinsulin (3 of 6 vs 58 of 59; P < 0.001). Staining for glucagon was seen in 2 of 6 malignant tumors and in no benign tumors (P < 0.001). Forty-three insulinomas stained negative for somatostatin receptor subtype 2a. CONCLUSION: Localization of insulinomas requires many different diagnostic procedures. Most tumors can be localized by conventional imaging, including EUS. For nonvisible tumors, invasive methods may be a useful diagnostic tool. Malignant tumors showed reduced staining for insulin and proinsulin and increased staining for glucagon.

Is endoscopic ultrasonography more sensitive than magnetic resonance imaging in detecting and localizing pancreatic neuroendocrine tumors?

To compare endoscopic ultrasonography (EUS) and magnetic resonance imaging (MRI) in terms of their sensitivities to localize pancreatic neuroendocrine tumors (pNET) preoperatively. Systematic analysis of the literature; sensitivity of EUS and MRI in insulinomas and pancreaticoduodenal NETs in multiple endocrine neoplasia type 1 (MEN1) in series of at least 20 subjects referring to tumors confirmed by surgery and histopathology. Other imaging methods reported were also assessed. Eighteen publications on insulinomas (782 cases) could be analyzed, no study in MEN1 fulfilled the inclusion criteria and compared EUS to MRI. Data quality was moderate: all publications referred to case series. Mean correct detection / localization rates (sensitivity) were calculated: EUS 80%, MRI 66%, computed tomography 63%, angiography 52%, somatostatin receptor scintigraphy 42%, ultrasonography 23%; arterial calcium stimulation with hepatic venous sampling regionalized correctly in 80%. EUS seems to be more sensitive than MRI in localizing pancreatic neuroendocrine tumors. If a specialized endosonographist is available, EUS is the preferable imaging procedure. Otherwise, MRI is a suitable alternative.

Prevention of breast cancer treatment-induced bone loss in premenopausal women treated with zoledronic acid: Final 5-year results from the randomized, double-blind, placebo-controlled ProBONE II trial.

PURPOSE: Premenopausal women receiving chemotherapy or endocrine treatment for early breast cancer are at increased risk for cancer treatment induced bone loss (CTIBL). The aim of the randomized, double-blind ProBONE II trial was to investigate whether a 2-year adjuvant treatment with 4 mg intravenous zoledronic acid (ZOL) every 3 months versus placebo would prevent CTIBL after a five-year period. METHODS: Thirty-one of the 34 participants in the ZOL arm and thirty-four of the 36 participants in the placebo arm were followed-up to the 5-year visit and completed the study as planned. The changes in Bone Mass Density (BMD) were assessed at baseline and each visit after treatment initiation. RESULTS: After 24 months, BMD at the lumbar spine showed a 2.9% increase in patients treated with ZOL vs. a 7.1% decrease in placebo-treated participants compared to baseline (p < 0.001). Over the 60-month study period, we found a decrease of 2.2% vs. 7.3% in the BMD at the lumbar spine in patients receiving ZOL and placebo respectively (p < 0.001). Over the 60-month study period, BMD in the placebo arm showed a continuous decrease at all sites (p < 0001), whereas patients treated with ZOL reached baseline BMD-values at the femoral neck and total hip. CONCLUSIONS: In ProBone II, a 2-year treatment with ZOL 4 mg intravenous every 3 months prevented cancer treatment induced bone loss in premenopausal women with breast cancer and maintained the BMD up to 3 years post-treatment.