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.

Design of the Growth hormone deficiency and Efficacy of Treatment (GET) score and non-interventional proof of concept study.

BACKGROUND: The adverse effects of growth hormone (GH) deficiency (GHD) in adults (AGHD) on metabolism and health-related quality of life (HRQoL) can be improved with GH substitution. This investigation aimed to design a score summarising the features of GHD and evaluate its ability to measure the effect of GH substitution in AGHD. METHODS: The Growth hormone deficiency and Efficacy of Treatment (GET) score (0-100 points) assessed (weighting): HRQoL (40%), disease-related days off work (10%), bone mineral density (20%), waist circumference (10%), low-density lipoprotein cholesterol (10%) and body fat mass (10%). A prospective, non-interventional, multicentre proof-of-concept study investigated whether the score could distinguish between untreated and GH-treated patients with AGHD. A 10-point difference in GET score during a 2-year study period was expected based on pre-existing knowledge of the effect of GH substitution in AGHD. RESULTS: Of 106 patients eligible for analysis, 22 were untreated GHD controls (9 females, mean ± SD age 52 ± 17 years; 13 males, 57 ± 13 years) and 84 were GH-treated (31 females, age 45 ± 13 years, GH dose 0.30 ± 0.16 mg/day; 53 males, age 49 ± 15 years, GH dose 0.25 ± 0.10 mg/day). Follow-up was 706 ± 258 days in females and 653 ± 242 days in males. The GET score differed between the untreated control and treated groups with a least squares mean difference of + 10.01 ± 4.01 (p = 0.0145). CONCLUSIONS: The GET score appeared to be a suitable integrative instrument to summarise the clinical features of GHD and measure the effects of GH substitution in adults. Exercise capacity and muscle strength/body muscle mass could be included in the GET score. TRIAL REGISTRATION: NCT number: NCT00934063 . Date of registration: 02 July 2009.

Endoscopic Ultrasound Features of Multiple Endocrine Neoplasia Type 1-Related versus Sporadic Pancreatic Neuroendocrine Tumors: A Single-Center Retrospective Study.

AIM: Pancreatic neuroendocrine tumors (pNETs) can occur in patients with a familial syndrome either as multiple endocrine neoplasia type 1 (MEN-1) or as sporadic tumors. Endoscopic ultrasound (EUS) has become one of the first-line investigations for pNET characterization. The ultrasonographic features of pNETs may differ depending on the familial versus sporadic pathogenesis of the tumor. Therefore, the EUS findings could help and direct the definition of a pNET with an impact on the most appropriate diagnostic and therapeutic patient management. METHODS: In this single-center retrospective study, we reviewed the EUS features of 94 pNETs from 37 MEN-1 patients and 15 pNETs from 11 sporadic disease patients at the time of their first EUS assessment. We analyzed the most relevant morphological and ultrasonographic characteristics of the tumors and compared the findings between the 2 patient groups. RESULTS: Patients with MEN-1 more likely present with multiple pNETs than patients with sporadic disease. Sporadic pNETs are usually much bigger than those due to MEN-1. Moreover, pNETs are more heterogeneous in patients with sporadic disease than in those with MEN-1. No statistical difference with regard to definition of the margins, morphology, and vascularization of the pNETs appears between the 2 groups. CONCLUSIONS: Patients with sporadic disease usually present with bigger and more heterogeneous pNETs than patients with MEN-1, who tend to present with a higher number of lesions. EUS can facilitate the precise characterization of a pNET, and the ultrasonographic features of the lesion can help and distinguish MEN-1-related versus sporadic disease.

Limited Value of Ga-68-DOTATOC-PET-CT in Routine Screening of Patients with Multiple Endocrine Neoplasia Type 1.

BACKGROUND: Routine screening is recommended for patients with multiple endocrine neoplasia type 1 (MEN1) to enable early detection and treatment of associated neuroendocrine neoplasms (NEN). Gallium68-DOTATOC-Positron emission tomography combined with computed tomography (Ga-68-DOTATOC-PET-CT) is a very sensitive and specific imaging technique for the detection of sporadic neuroendocrine tumors. The present study evaluated the value of Ga-68-DOTATOC-PET-CT in routine screening of patients with MEN1. METHODS: Between January 2014 and March 2016, all MEN1 patients underwent Ga-68-DOTATOC-PET-CT in addition to conventional imaging (computed tomography of the thorax, magnetic resonance imaging of the abdomen and pituitary, endoscopic ultrasonography). The diagnostic yield of conventional imaging and Ga-68-DOTATOC-PET-CT was prospectively documented and compared, and treatment changes caused by the addition of Ga-68-DOTATOC-PET-CT were recorded. RESULTS: Conventional imaging detected 145 NENs, mainly pancreaticoduodenal NENs (n = 117, 81%), in 31 of 33 MEN1 patients. Ga-68-DOTATOC-PET-CT detected 55 NENs in 23 of the 33 patients (p = 0.0001). Ninety (62%) NENs detected by conventional imaging were missed by DOTATOC-PET-CT. The majority of missed lesions were pNEN (n = 68; 74%). The sensitivity of Ga-68-DOTATOC-PET-CT for NENs <5, 5-9, 10-19 and ≥20 mm was 0, 29, 81 and 100%, respectively. However, Ga-68-DOTATOC-PET-CT detected more liver and lymph node metastases in patients with known metastatic disease, which did not lead to a change of patients' management. In one patient (3%), Ga-68-DOTATOC-PET-CT was the only imaging modality that detected a small intestine NEN and led to potentially curative surgery. CONCLUSION: Ga-68-DOTATOC-PET-CT cannot be recommended for routine screening of MEN1 patients. It might provide important additional information in patients with suspected or known metastatic disease.

Bone health of the Ovahimba people of north-western Namibia in the context of urbanization and a change of the sociocultural environment.

The prevalence of osteoporosis in Sub-Saharan African (SSA) countries is low, however, as urbanization takes root, it is predicted that bone health will decrease dramatically. The bone health of the semi-nomadic Ovahimba people of Namibia was investigated in the context of urbanization and changes of the sociocultural environment. Furthermore, data on bone health in SSA countries is scarce; there exists no ethnic-specific reference group for people of black origin. Included in the study were 98 urban and rural living Ovahimba people. Quantitative ultrasound was performed, sunrise/sunset saliva cortisol concentrations was measured and a questionnaire was conducted. There was no significant difference in the QUS parameters, however, after adjustment for confounders, SOS and SI differed significantly. The saliva cortisol concentrations differed significantly. After adjustment for confounders, saliva cortisol was significantly negatively correlated to SOS (r= -0.27, p = 0.021) giving an indication for an association between cortisol concentration and QUS parameters. The urban group furthermore showed a nutritional transition. Even though the bone health of the Ovahimba is very good, first signs of the adverse effects of urbanization were detected. Beside changes of lifestyle, this may be attributed to an increased cortisol exposure of the Ovahimba people living in an urban environment due to an increased psychosocial stress.

Gender-, age- and time-dependent dosing of growth hormone in adults - real-world data from a decade of clinical practice in Germany.

We evaluated treatment patterns and gender-dependent dosing of growth hormone (GH) substitution in adults with GH deficiency (AGHD). Data on GH dose were collected (2003-2013) from 509 GH-treated patients (mean age: 48.9 years; 47% female) enroled in the observational German NordiWin study (NCT01543880). The impact of gender, age, treatment duration and calendar year on GH treatment patterns was evaluated by multiple regression analysis. Mean (SD) baseline GH dose (mg/day) was similar between females (0.25 [0.19] and males (0.24 [0.15]), but increased with treatment duration (at year 10, 0.55 [0.48] and 0.31 [0.09] in females and males, respectively), reflecting patient dose titration. GH dose increased more in females than males during treatment; this was statistically significant in years 2-6 (p < 0.05). Over the 10-year study period, a time trend of an overall estimated GH dose increase by 0.06 mg/day (females) and decrease by 0.07 mg/day (males) was shown; this interaction of gender and calendar year was significant (p < 0.0001). In both genders, overall GH dose decreased with increasing age (p < 0.0001). Our study confirms that females and younger patients require higher GH doses compared with males and older patients.

Adrenal Incidentaloma and Subclinical Cushing's Syndrome: A Longitudinal Follow-Up Study by Endoscopic Ultrasound.

Purpose Adrenal incidentaloma (AI) and adrenal masses in cases of subclinical Cushing's syndrome (SCS) initially require follow-up imaging. In this study we used endoscopic ultrasound (EUS) as a method for high-resolution imaging. The aim was to evaluate the growth rate of AI and SCS by EUS. Materials and Methods This retrospective analysis included 93 out of 229 patients with AI or SCS who were investigated longitudinally by EUS in our university hospital between 1997 and 2013. The longitudinal follow-up required at least two investigations by EUS and evaluation of endocrine function. Plasma renin, serum aldosterone, 24 h urinary catecholamines and 2 mg dexamethasone suppression test were performed. EUS was performed at baseline and during follow-up. Each time, the maximum diameter was measured. Three groups were defined: non-functioning adenomas (NFA), non-functioning nodular hyperplasias (NFH) and SCS. Results 86 patients had non-functioning masses [NFM] (59 NFA, 48 NFH) and 7 patients had SCS (10 masses). At baseline the mean diameter was 19.4 (±â€Š9.3) mm (NFM) and 19.6 (±â€Š9.2) mm (SCS). The mean follow-up period was 31.6 ±â€Š28.7 months. The estimated mean growth rates per year were low: They were 0.35 mm/yr [NFA], 0.02 mm/yr [NFH] and 0.53 mm/yr [SCS]. Furthermore, there was no malignant progression of any mass. Conclusion The growth rate as determined by EUS was low for all tumor entities observed in this study. There was no difference in tumor growth between the groups.

Effect of adjuvant endocrine therapy on hormonal levels in premenopausal women with breast cancer: the ProBONE II study.

Endocrine therapy (ET) is a key treatment modality in hormone receptor positive (HR+) early breast cancer (BC) patients. Although the anticancer activity of adjuvant ET + zoledronic acid (ZOL) has been investigated, the potential effects of ET ± ZOL on endocrine hormones in premenopausal women with HR+ early BC are not well understood. ProBONE II was prospective, double-blind, randomized controlled trial. Premenopausal patients with histologically confirmed invasive BC with no evidence of metastases and a T score >-2.5 received ET ± ZOL 4 mg every 3 months for 2 years. Serum levels of estradiol (E2), follicle-stimulating hormone, anti-muellerian hormone (AMH), inhibins A and B, sex hormone-binding globulin, parathyroid hormone, total testosterone, and vitamin D were evaluated at baseline and at every scheduled visit. Of 71 women enrolled, 70 were evaluable (n = 34, ZOL; n = 36, placebo). No statistically significant differences were observed in hormone levels, except E2 and AMH, which showed minor differences. These included decreases in serum E2 levels, which reached a nadir after 3 and 9 months in placebo and ZOL groups, respectively, and decrease in serum AMH levels throughout the study with ZOL, but remained constant with placebo after 6 months. Adverse events in ZOL-treated group were influenza-like illness (32.4 %), bone pain (32.4 %), chills (20.6 %), and nausea (23.5 %). ET ± ZOL was well tolerated. This study showed no influence of ZOL on hormonal level changes that accompany ET, supporting inclusion of ZOL in adjuvant therapy for premenopausal women with HR + BC.

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.

Partial pancreaticoduodenectomy can provide cure for duodenal gastrinoma associated with multiple endocrine neoplasia type 1.

OBJECTIVE: To evaluate the outcome of pancreaticoduodenectomy (PD) versus non-PD resections for the treatment of gastrinoma in multiple endocrine neoplasia type 1. BACKGROUND: Gastrinoma in MEN1 is considered a rarely curable disease and its management is highly controversial both for timing and extent of surgery. METHODS: Clinical characteristics, complications and outcomes of 27 prospectively collected MEN1 patients with biochemically proven gastrinoma, who underwent surgery, were analyzed with special regard to the gastrinoma type and the initial operative procedure. RESULTS: Twenty-two (81%) patients with gastrinoma in MEN1 had duodenal gastrinomas and 5 patients (19%) had pancreatic gastrinomas. At the time of diagnosis, 21 (77%) gastrinomas were malignant (18 duodenal, 3 pancreatic), but distant metastases were only present in 4 (15%) patients. Patients with pancreatic gastrinomas underwent either distal pancreatic resections or gastrinoma enucleation with lymphadenectomy, 2 patients also had synchronous resections of liver metastases. One of these patients was biochemically cured after a median of 136 (77-312) months. Thirteen patients with duodenal gastrinomas underwent PD resections (group 1, partial PD [n = 11], total PD [n = 2]), whereas 9 patients had no-PD resections (group 2) as initial operative procedure. Perioperative morbidity and mortality, including postoperative diabetes, differed not significantly between groups (P > 0.5). All patients of group 1 and 5 of 9 (55%) patients of group 2 had a negative secretin test at hospital discharge. However, after a median follow-up of 136 (3-276) months, 12 (92%) patients of group 1 were still normogastrinemic compared to only 3 of 9 (33%) patients of group 2 (P = 0.023). Three (33%) patients of group 2 had to undergo up to 3 reoperations for recurrent or metastatic disease compared to none of group 1. CONCLUSIONS: Duodenal gastrinoma in MEN1 should be considered a surgically curable disease. PD seems to be the adequate approach to this disease, providing a high cure rate and acceptable morbidity compared to non-PD resections.

Unimpaired postprandial pancreatic polypeptide secretion in Parkinson's disease and REM sleep behavior disorder.

BACKGROUND: Pancreatic polypeptide is released immediately after food ingestion. The release is operated by vagal-abdominal projections and has therefore been suggested as a test for vagal nerve integrity. Pathoanatomical and clinical studies indicate vagal dysfunction in early Parkinson's disease (PD). METHODS: We assessed the postprandial secretion of pancreatic polypeptide and motilin in healthy controls (n = 18) and patients with idiopathic rapid-eye-movement sleep behavior disorder (iRBD, n = 10), a potential premotor stage of PD, as well as in drug-naive (n = 19) and treated (n = 19) PD patients. RESULTS: The postprandial pancreatic polypeptide secretion showed a physiological pattern in all groups and even an enhanced response in drug-naive PD and iRBD. Motilin concentrations correlated with pancreatic polypeptide concentrations. CONCLUSIONS: Postprandial pancreatic polypeptide secretion is not a suitable test for vagal nerve integrity in PD. The unimpaired pancreatic polypeptide response in iRBD and PD might be explained by partially intact vagal-abdominal projections or compensatory mechanisms substituting a defective neuronal brain-gut axis.

Enucleation and limited pancreatic resection provide long-term cure for insulinoma in multiple endocrine neoplasia type 1.

AIM: To assess the characteristics and long-term outcome after surgery in patients with multiple endocrine neoplasia type 1 (MEN1)-associated insulinoma. METHODS: Retrospective analysis of prospectively collected data of MEN1 patients with organic hyperinsulinism at a tertiary referral center. RESULTS: Thirteen (17%) of 74 patients with MEN1 had organic hyperinsulinism. The median age at diagnosis was 27 (range 9-48) years. In 7 patients insulinoma was the first manifestation of the syndrome. All patients had at least one pancreatic neuroendocrine neoplasm (pNEN) upon imaging, including CT, MRI or endoscopic ultrasonography. Seven patients had solitary lesions upon imaging, 4 patients had one dominant tumor with coexisting multiple small pNENs, and 2 patients had multiple lesions without dominance. Eight patients had limited resections (1 segmental resection, 7 enucleations), 4 subtotal distal pancreatectomies, and 1 patient a partial duodenopancreatectomy. There was no postoperative mortality. Six patients experienced complications, including pancreatic fistula in 5 patients. Pathological examination revealed median three (range 1-14) macro-pNENs sized between 6 and 40 mm, and a total of 14 potentially benign insulinomas were detected in the 13 patients. After median follow-up of 156 months, only 1 patient developed recurrent hyperinsulinism after initial enucleation. Twelve patients developed new pNENs in the pancreatic remnant and 4 patients underwent reoperations (3 for metastatic ZES, 1 for recurrent hyperinsulinism). One of 5 patients with an initial extended pancreatic resection developed insulin-dependent diabetes mellitus. CONCLUSION: Enucleation and limited resection provide long-term cure for MEN1 insulinoma in patients with solitary or dominant tumors. Subtotal distal pancreatectomy should thus be preserved for patients with multiple pNENs without dominance given the risk of exocrine and endocrine pancreas insufficiency in the mostly young patients.

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.

Relation between bone quality values from ultrasound transmission velocity and implant stability parameters--an ex vivo study.

AIM: The objective of this study was to determine the relationship between bone qualities measured by ultrasound transmission velocity (UTV) and primary implant stability parameters measured by radiofrequency analysis (RFA) and push-out test (POT) in an ex-vivo model. MATERIALS AND METHODS: Three blocks of fresh porcine bone samples were obtained from different anatomic regions, correlating to cortical, mixed and cancellous bone. Mechanical bone qualities of these samples were measured using UTV (expressed in m/s) prior to implantation. Three similar implants (4.1 × 11 mm, AstraTech OS) were inserted into each of the procured bone blocks. The evaluation of implant-bone interface stability was evaluated by RFA expressed as implant stability quotient (ISQ), and POT measured in Newton (N). RESULTS: For cortical, mixed and cancellous bone samples UTV values showed a mean of 2049.33, 1728.67 and 1427.67 m/s, respectively. For the implants inserted into cortical, mixed and cancellous bone samples the mean RFA (ISQ) values were 94.33, 81.33 and 63.11, whereas the POT values were >2000, 680 and 290 N, respectively. There was a strong correlation between UTV values and implant stability parameters that was shown descriptively by scatter box plots. CONCLUSION: The bone quality measurements obtained by UTV values significantly correlated to primary implant stability values measured by RFA and push-out test. Moreover, UTV was able to significantly differentiate between the different bone types. This suggested that UTV may be considered as a reasonable instrument to measure bone quality preoperatively and would help clinicians predict primary implant stability before implant insertion.

Embalmed and fresh frozen human bones in orthopedic cadaveric studies: which bone is authentic and feasible?

BACKGROUND AND PURPOSE: The most frequently used bones for mechanical testing of orthopedic and trauma devices are fresh frozen cadaveric bones, embalmed cadaveric bones, and artificial composite bones. Even today, the comparability of these different bone types has not been established. METHODS: We tested fresh frozen and embalmed cadaveric femora that were similar concerning age, sex, bone mineral density, and stiffness. Artificial composite femora were used as a reference group. Testing parameters were pullout forces of cortex and cancellous screws, maximum load until failure, and type of fracture generated. RESULTS: Stiffness and type of fracture generated (Pauwels III) were similar for all 3 bone types (fresh frozen: 969 N/mm, 95% confidence interval (CI): 897-1,039; embalmed: 999 N/mm, CI: 875-1,121; composite: 946 N/mm, CI: 852-1,040). Furthermore, no significant differences were found between fresh frozen and embalmed femora concerning pullout forces of cancellous screws (fresh frozen: 654 N, CI: 471-836; embalmed: 595 N, CI: 365-823) and cortex screws (fresh frozen: 1,152 N, CI: 894-1,408; embalmed: 1,461 N, CI: 880-2,042), and axial load until failure (fresh frozen: 3,427 N, CI: 2,564-4290; embalmed: 3,603 N, CI: 2,898-4,306). The reference group showed statistically significantly different results for pullout forces of cancellous screws (2,344 N, CI: 2,068-2,620) and cortex screws (5,536 N, CI: 5,203-5,867) and for the axial load until failure (> 7,952 N). INTERPRETATION: Embalmed femur bones and fresh frozen bones had similar characteristics by mechanical testing. Thus, we suggest that embalmed human cadaveric bone is a good and safe option for mechanical testing of orthopedic and trauma devices.

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.

Effects of growth hormone replacement within the KIMS survey on estimated cardiovascular risk and predictors of risk reduction in patients with growth hormone deficiency.

OBJECTIVE: There is growing evidence for an increased cardiovascular (CV) risk in untreated growth hormone deficiency of adults (GHD). We aimed at estimating CV risk with established algorithms before and during GH replacement in GHD and in healthy controls and at identifying predictors of risk reduction. DESIGN: A prospective, nested case-control study. PATIENTS: We included 344 patients (44·7 ± 14·9 years) from the German Pfizer (formerly Kabi) International Metabolic Database (KIMS) cohort and included a healthy sex- and age-matched control group from a primary care cohort. MEASUREMENTS: We calculated Framingham, Prospective Cardiovascular Münster Heart Study (PROCAM) and European Society of Cardiology (ESC) Score algorithms at all time points. In multivariate analyses, we analysed potential predictors of 2-year reduction in CV risk, defined as a higher than median reduction in risk. RESULTS: In KIMS, the estimated 10-year risks of CV events or CV mortality calculated with Framingham, PROCAM and ESC Score algorithms at baseline were 4·6%, 6·0% and 2·3%, respectively. These dropped to 2·4%, 4·8% and 0·8%, respectively, after 2 years of GH replacement (all P < 0·001 vs baseline) and returned to baseline levels after four years of GH replacement. In controls, the Framingham risk estimates were lower than in KIMS at baseline. All risk estimates increased during follow-up and were significantly higher than in KIMS after four years (all P < 0·01). In backward-selection models, high total cholesterol, low high-density lipoprotein (HDL) cholesterol and male sex were significant predictors of response in most scores. CONCLUSION: Two years of GH replacement decreased CV risk estimates approximately by half. Male sex, high total and low HDL cholesterol levels are potential predictors of good response.