Farming activity and risk of treated thyroid disorders: Insights from the TRACTOR project, a nationwide cohort study.

BACKGROUND: Epidemiological data regarding thyroid diseases are lacking, in particular for occupationally exposed populations. OBJECTIVES: To compare the risk of hypothyroidism and hyperthyroidism between farming activities within the complete population of French farm managers (FMs). METHODS: Digital health data from retrospective administrative databases, including insurance claims and electronic health/medical records, was employed. This cohort data spanned the entirety of French farm managers (FMs) who had undertaken work at least once from 2002 to 2016. Survival analysis with the time to initial medication reimbursement as timescale was used to examine the association (hazard ratio, HR) between 26 specific farming activities and both treated hypothyroidism and hyperthyroidism. A distinct model was developed for each farming activity, comparing FMs who had never engaged in the specific farming activity between 2002 and 2016 with those who had. All analyses were adjusted for potential confounders (e.g., age), and sensitivity analyses were conducted. RESULTS: Among 1088561 FMs (mean age 46.6 [SD 14.1]; 31% females), there were 31834 hypothyroidism cases (75% females) and 620 hyperthyroidism cases (67% females), respectively. The highest risks were observed for cattle activities for both hyperthyroidism (HR ranging from 1.75 to 2.42) and hypothyroidism (HR ranging from 1.41 to 1.44). For hypothyroidism, higher risks were also observed for several animal farming activities (pig, poultry, and rabbit), as well as fruit arboriculture (HR = 1.22 [1.14-1.31]). The lowest risks were observed for activities involving horses. Sex differences in the risk of hypothyroidism were observed for eight activities, with the risk being higher for males (HR = 1.09 [1.01-1.20]) than females in viticulture (HR = 0.97 [0.93-1.00]). The risk of hyperthyroidism was two times higher for male dairy farmers than females. DISCUSSION: Our findings offer a comprehensive overview of thyroid disease risks within the FM community. Thyroid ailments might not stem from a single cause but likely arise from the combined effects of various causal agents and triggering factors (agricultural exposome). Further investigation into distinct farming activities-especially those involving cattle-is essential to pinpoint potential risk factors that could enhance thyroid disease monitoring in agriculture.

Does prenatal exposure to multiple airborne and tap-water pollutants increase neonatal thyroid-stimulating hormone concentrations? Data from the Picardy region, France.

OBJECTIVE: Systematic screening for congenital hypothyroidism by heel-stick sampling has revealed unexpected heterogeneity in the geographic distribution of newborn thyroid-stimulating hormone concentrations in Picardy, France. We explored a possible relationship with environmental pollutants. METHODS: Zip code geolocation data from mothers of newborns without congenital hypothyroidism born in 2021 were linked to ecological data for a set of airborne (particulate matter with a diameter of 2.5 µm or less [PM2.5] or 10 µm or less [PM10]) and tap-water (nitrate and perchlorate ions and atrazine) pollutants. Statistical associations between mean exposure levels during the third trimester of pregnancy and Thyroid-stimulating hormone (TSH) concentrations in 6249 newborns (51 % male) were investigated using linear regression models. RESULTS: Median neonatal TSH concentration (interquartile range, IQR) was 1.7 (1-2.8) mIU/L. An increase of one IQR in prenatal exposure to perchlorate ions (3.6 µg/L), nitrate ions (19.2 mg/L), PM2.5 (3.7 µg/m3) and PM10 (3.4 µg/m3), were associated with increases in TSH concentrations of 2.30 % (95 % CI: 0.95-3.66), 5.84 % (95 % CI: 2.81-8.87), 13.44 % (95 % CI: 9.65-17.28) and 6.26 % (95 % CI: 3.01-9.56), respectively. CONCLUSIONS: Prenatal exposure to perchlorate and nitrate ions in tap water and to airborne PM over the third trimester of pregnancy was significantly associated with increased neonatal TSH concentrations.

Updates in neuroendocrine neoplasms: From mechanisms to the clinic.

Scientific advances constantly improve our understanding of the mechanisms underlying tumorigenesis, allowing us now to analyze cancer in a more precise manner and to identify at an earlier stage the tumors that have greater risk of aggressive behavior. Understanding neuroendocrine neoplasms at molecular level has enabled increasingly targeted treatments, with safety and efficacy validated in large randomized trials. Moreover, the first studies of targeted therapies after molecular profiling of neuroendocrine neoplasms have shown encouraging results, allowing us to foresee ever more personalized medical treatments in the future. This literature review aims to summarize recent advances in the study of neuroendocrine neoplasms and to show how identification of new mechanisms underlying tumorigenesis can be of benefit in clinical practice.

Thyrotropin Levels in Patients with Coronavirus Disease 2019: Assessment during Hospitalization and in the Medium Term after Discharge.

BACKGROUND: The objectives of this study were (1) to compare TSH levels between inpatients with critical versus non-critical coronavirus disease 19 (COVID-19), and (2) to describe the status of TSH levels three months after hospitalization. METHODS: We collected data on adult patients hospitalized with COVID-19 at Amiens University Hospital. We compared TSH levels between inpatients with critical (intensive care unit admission and/or death) versus non-critical COVID-19. Thereafter, survivors were invited to return for a three-month post-discharge visit where thyroid function tests were performed, regardless of the availability of TSH measurement during hospitalization. RESULTS: Among 448 inpatients with COVID-19, TSH assay data during hospitalization were available for 139 patients without prior thyroid disease. Patients with critical and non-critical forms of COVID-19 did not differ significantly with regard to the median (interquartile range) TSH level (0.96 (0.68-1.71) vs. 1.27 mIU/L (0.75-1.79), p = 0.40). Abnormal TSH level was encountered in 17 patients (12.2%); most of them had subclinical thyroid disease. TSH assay data at the three-month post-discharge visit were available for 151 patients without prior thyroid disease. Only seven of them (4.6%) had abnormal TSH levels. Median TSH level at the post-discharge visit was significantly higher than median TSH level during hospitalization. CONCLUSIONS: Our findings suggest that COVID-19 is associated with a transient suppression of TSH in a minority of patients regardless of the clinical form. The higher TSH levels three months after COVID-19 might suggest recovery from non-thyroidal illness syndrome.

Pituitary apoplexy in the aftermath of a SARS-CoV-2 infection: a case series from Amiens University Hospital.

Objective: Since the outbreak of the COVID-19 pandemic, several cases of pituitary apoplexy (PA) following a SARS-CoV-2 infection have been described in several countries. Here, we describe a case series of PA occurring in the aftermath of a SARS-CoV-2 infection to alert physicians about possible neuro-endocrinological damage caused by the virus that can lead to visual sequelae and hypopituitarism. Design and methods: We retrospectively identified all the adult patients treated at Amiens University Hospital between March 2020 and May 2021 for PA confirmed by cerebral imaging and following an RT-PCR-confirmed SARS-CoV-2 infection. Results: Eight cases (six women, two men) occurred between March 2020 and May 2021 and were reviewed in this study. The mean age at diagnosis was 67.5 ± 9.8 years. Only one patient had a 'known' non-functional pituitary macroadenoma. The most common symptom of PA was a sudden headache. Brain imaging was typical in all cases. Only two patients required decompression surgery, whereas the others were managed conservatively. The clinical outcome was favorable for all patients but without recovery of their pituitary deficiencies. There was no diabetes insipidus. Conclusion: This case series, the largest in the literature, reinforces the strength, consistency, and coherence of the association between SARS-CoV-2 infection and PA. Our study provides support for the hypothesis that SARS-CoV-2 may be a new precipitating factor for PA. It is essential that practitioners be alerted about possible pituitary disease due to the virus so that such patients are recognized and appropriately managed, hence improving their prognosis.

Impact of diabetes on COVID-19 prognosis beyond comorbidity burden: the CORONADO initiative.

AIMS/HYPOTHESIS: Diabetes has been recognised as a pejorative prognostic factor in coronavirus disease 2019 (COVID-19). Since diabetes is typically a disease of advanced age, it remains unclear whether diabetes remains a COVID-19 risk factor beyond advanced age and associated comorbidities. We designed a cohort study that considered age and comorbidities to address this question. METHODS: The Coronavirus SARS-CoV-2 and Diabetes Outcomes (CORONADO) initiative is a French, multicentric, cohort study of individuals with (exposed) and without diabetes (non-exposed) admitted to hospital with COVID-19, with a 1:1 matching on sex, age (±5 years), centre and admission date (10 March 2020 to 10 April 2020). Comorbidity burden was assessed by calculating the updated Charlson comorbidity index (uCCi). A predefined composite primary endpoint combining death and/or invasive mechanical ventilation (IMV), as well as these two components separately, was assessed within 7 and 28 days following hospital admission. We performed multivariable analyses to compare clinical outcomes between patients with and without diabetes. RESULTS: A total of 2210 pairs of participants (diabetes/no-diabetes) were matched on age (mean±SD 69.4±13.2/69.5±13.2 years) and sex (36.3% women). The uCCi was higher in individuals with diabetes. In unadjusted analysis, the primary composite endpoint occurred more frequently in the diabetes group by day 7 (29.0% vs 21.6% in the no-diabetes group; HR 1.43 [95% CI 1.19, 1.72], p<0.001). After multiple adjustments for age, BMI, uCCi, clinical (time between onset of COVID-19 symptoms and dyspnoea) and biological variables (eGFR, aspartate aminotransferase, white cell count, platelet count, C-reactive protein) on admission to hospital, diabetes remained associated with a higher risk of primary composite endpoint within 7 days (adjusted HR 1.42 [95% CI 1.17, 1.72], p<0.001) and 28 days (adjusted HR 1.30 [95% CI 1.09, 1.55], p=0.003), compared with individuals without diabetes. Using the same adjustment model, diabetes was associated with the risk of IMV, but not with risk of death, within 28 days of admission to hospital. CONCLUSIONS/INTERPRETATION: Our results demonstrate that diabetes status was associated with a deleterious COVID-19 prognosis irrespective of age and comorbidity status. TRIAL REGISTRATION: ClinicalTrials.gov NCT04324736.

Follicular GH and IGF1 Levels Are Associated With Oocyte Cohort Quality: A Pilot Study.

Introduction: Oocyte quality contributes to the development of an optimal embryo and thus a successful pregnancy. The objective of this study was to analyse the association between oocyte cohort quality and the follicular levels of growth hormone (GH), insulin-like growth factor 1 (IGF1), 25-hydroxy vitamin D (25OHD), thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4) and antithyroid antibodies, as a function of intracytoplasmic sperm injection (ICSI) outcomes. Material and methods: We conducted a prospective comparative pilot study from January 2013 to December 2017. 59 ICSI cycles constituted an abnormal oocyte cohort (n=34 cycles, in which more than 50% of oocytes presented at least one morphological abnormality) and a normal oocyte cohort (n=25 cycles, in which 50% or less of the oocytes presented at least one morphological abnormality). GH, IGF1, 25OHD, TSH, fT3, fT4 and antithyroid antibodies were measured in follicular fluid. Results: The fertilisation rate was lower in the abnormal oocyte cohort (65.5% vs. 80%, respectively, p=0.012). Oocytes' proportion with at least one abnormality was 79.4% in the abnormal oocyte cohort and 29.0% in the normal oocyte cohort. The mean number of morphological abnormalities per oocyte was significantly higher in the abnormal oocyte cohort. The follicular levels of GH (4.98 vs. 2.75 mIU/L, respectively; p <0.01) and IGF1 (72.1 vs. 54.2 ng/mL, respectively; p=0.05) were higher in the normal oocyte cohort. There was no association with follicular levels of TSH, fT3, fT4, antithyroid antibodies, or 25OHD. Conclusion: Oocyte cohort quality appears to be associated with follicular levels of GH and IGF1.

Pegvisomant treatment in acromegaly in clinical practice: Final results of the French ACROSTUDY (312 patients).

OBJECTIVE: We report the final analysis of the French ACROSTUDY, using data revised and enriched since the 2013 interim analysis. Our objective was to validate the use of pegvisomant (PEGV) in the treatment of acromegaly and to determine efficacy and safety. PATIENTS AND METHODS: Patients with acromegaly treated with PEGV and followed up for at least 5 years were included. Eighty-eight investigators from 62 clinical centers in France included patients from April 2007 to April 2014. PEGV dose and administration frequency were determined by the physicians, based on their clinical evaluation and local habits. No additional examinations beyond those performed in normal follow-up were required. Minimum recommended follow-up included check-ups at treatment initiation, 6 months, 12 months and then annually. RESULTS: In total, 312 patients were enrolled. Mean age was 46.1±14.3 years at introduction of PEGV. Median PEGV treatment duration was 6.3 years and median follow-up was 5.6 years. Median dose at initiation was 10mg/day. The percentages of patients with IGF-1 ≤ ULN (upper limit of normal) were 10% (n=300) at baseline, 54% at 6 months (n=278), and 61.7% (n=253) at 2 years, then stabilizing at 64.4% (n=180) at 5 years. Mean PEGV dose was 17.4±11.7mg in patients with controlled disease versus 21.1±17.3mg in those without control at 5 years. At 5 years, 21.8% of patients (54/248) were receiving >30mg PEGV per day. In patients with at least one pituitary imaging procedure during the 5-year follow-up (n=292), the most recent image showed stable tumor volume in 212 subjects (72.6%), increased volume in 13 (4.5%), and decreased volume in 30 (10.3%). No PEGV treatments were permanently discontinued due to transaminase elevation. There were no cases of liver failure. CONCLUSION: The French ACROSTUDY showed normalization of IGF-1 levels in 64.4% of a real-life cohort of patients, mostly with uncontrolled disease despite multiple prior therapies. Long-term follow-up showed a sustained effectiveness and good long-term safety.

Growth hormone replacement improved oocyte quality in a patient with hypopituitarism: A study of follicular fluid.

BACKGROUND: Growth hormone (GH) is known to be involved in ovarian folliculogenesis and oocyte maturation. In patients with poor ovarian response without growth hormone deficiency (GHD), adjuvant GH treatment improves in-vitro fertilization (IVF) results. Improvement of oocyte quality in IVF by GH replacement was reported in only a few patients with GHD. We report on a new case with study of follicular fluid. METHODS: A 29-year-old patient with hypopituitarism was referred to our infertility center. She was undergoing hormonal replacement for hypogonadotropic hypogonadism and diabetes insipidus, and did not consider at first GH replacement. Four IVF procedures were performed between 2011 and 2014. Growth hormone replacement (somatotropin 1.1mg/day) was initiated before the fourth IVF procedure and unmasked central hypothyroidism; levothyroxine (75mg/day) was introduced. It took 10 months to reach the treatment objectives for insulin-like growth factor 1 (IGF1), free triiodothyronine (fT3) and free thyroxine (fT4). GH, IGF1 and thyroid hormones were measured in the blood and follicular fluid before and after GH and thyroid hormone replacement. Oocyte and embryo quality were also compared. RESULTS: The first 3 IVF procedures were performed without GH replacement. 62% to 100% of mature oocytes presented one or more morphologic abnormalities: diffuse cytoplasmic granularity, large perivitelline space with fragments, fragmentation of the first polar body, ovoid shape, or difficult denudation. Embryo quality was moderate to poor (grade B to D), and no pregnancy was obtained after embryo transfer. After GH replacement, hormones levels increased in follicular fluid: GH [7.68 vs. 1.39 mIU/L], IGF1 [109 vs. <25ng/mL], fT3 [3.7 vs. 2.5pmol/L] and fT4 [1.45 vs. 0.84ng/mL]. Concomitantly, there was dramatic improvement in oocyte quality (no abnormal morphologies) and embryo quality (grade A), allowing an embryo transfer with successful pregnancy. CONCLUSIONS: This is the first report illustrating changes in hormonal levels in follicular fluid and the beneficial effect of GH replacement on oocyte and embryo quality during an IVF procedure in a patient with hypopituitarism. These results suggest that GH replacement is beneficial for oocyte quality in patients with GHD.

Pegvisomant in combination or pegvisomant alone after failure of somatostatin analogs in acromegaly patients: an observational French ACROSTUDY cohort study.

OBJECTIVE: After surgery, when somatostatin analogs (SAs) do not normalise IGF-I, pegvisomant (PEG) is indicated. Our aim was to define the medical reasons for the treatment of patients with PEG as monotherapy (M) or combined with SA, either as primary bitherapy, PB (PEG is secondarily introduced after SA) or as secondary bitherapy, SB (SAs secondarily introduced after PEG). METHODS: We retrospectively analysed French data from ACROSTUDY. RESULTS: 167, 88 and 57 patients were treated with M, PB or SB, respectively, during a median time of 80, 42 and 70 months. The median PEG dose was respectively 15, 10 and 20 mg. Before PEG, the mean IGF-I level did not differ between M and PB but the proportion of patients with suprasellar tumour extension was higher in PB group (67.5% vs. 44.4%, P = 0.022). SB regimen was used preferentially in patients with tumour increase and IGF-I level difficult to normalise under PEG. In both secondary regimens, the decrease of the frequency of PEG's injections, compared to monotherapy was confirmed. However, the mean weekly dose of PEG between M and PB remained the same. CONCLUSIONS: The medical rationale for continuing SAs rather than switching to PEG alone in patients who do not normalise IGF-I under SAs was a tumour concern with suprasellar extension and tumour shrinkage under SA. A potential explanation for introducing SA in association with PEG appears to be a tumour enlargement and difficulties to normalise IGF-I levels under PEG given alone. In both regimens, the prospect of lowering PEG injection frequency favoured the choice.

Characteristics and outcomes of COVID-19 in hospitalized patients with and without diabetes.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a rapidly progressing pandemic, with four million confirmed cases and 280 000 deaths at the time of writing. Some studies have suggested that diabetes is associated with a greater risk of developing severe forms of COVID-19. The primary objective of the present study was to compare the clinical features and outcomes in hospitalized COVID-19 patients with vs without diabetes. METHODS: All consecutive adult patients admitted to Amiens University Hospital (Amiens, France) with confirmed COVID-19 up until April 21st, 2020, were included. The composite primary endpoint comprised admission to the intensive care unit (ICU) and death. Both components were also analysed separately in a logistic regression analysis and a Cox proportional hazards model. RESULTS: A total of 433 patients (median age: 72; 238 (55%) men; diabetes: 115 (26.6%)) were included. Most of the deaths occurred in non-ICU units and among older adults. Multivariate analyses showed that diabetes was associated neither with the primary endpoint (odds ratio (OR): 1.12; 95% confidence interval (CI): 0.66-1.90) nor with mortality (hazard ratio: 0.73; 95%CI: 0.40-1.34) but was associated with ICU admission (OR: 2.06; 95%CI 1.09-3.92, P = .027) and a longer length of hospital stay. Age was negatively associated with ICU admission and positively associated with death. CONCLUSIONS: Diabetes was prevalent in a quarter of the patients hospitalized with COVID-19; it was associated with a greater risk of ICU admission but not with a significant elevation in mortality. Further investigation of the relationship between COVID-19 severity and diabetes is warranted.

Non-classical effects of vitamin D: Non-bone effects of vitamin D.

Our understanding of vitamin D has improved considerably in recent years. The role of vitamin D in preventing osteoporotic fractures is now well-established. However, an important controversy has emerged in the last decade concerning the effects of the active form of vitamin D (1,25-dihydroxy-vitamin D) on tissues other than bone (non-classical effects). The demonstration that the vitamin D receptor (VDR) is ubiquitously, expressed combined with increasing observational data supporting a relationship between the level of 25-hydroxy-vitamin D in the serum and chronic metabolic disorders, cardiovascular disease and neoplasms, have led to its redefinition as a steroid hormone and the proposal of its use in preventing and/or treating those diseases. This article is an update on the different non-bone or non-classical effects of "vitamin-hormone D", and its potential preventive or therapeutic role in certain diseases, however, this review is not exhaustive. The different modalities of substitution or supplementation proposed in France by the Groupe de Recherche et d'Information sur les Ostéoporoses (GRIO) are also summarised.

Metformin use is associated with a reduced risk of mortality in patients with diabetes hospitalised for COVID-19.

AIMS: Metformin exerts anti-inflammatory and immunosuppressive effects. We addressed the impact of prior metformin use on prognosis in patients with type 2 diabetes hospitalised for COVID-19. METHODS: CORONADO is a nationwide observational study that included patients with diabetes hospitalised for COVID-19 between March 10 and April 10, 2020 in 68 French centres. The primary outcome combined tracheal intubation and/or death within 7 days of admission. A Kaplan-Meier survival curve was reported for death up to day 28. The association between metformin use and outcomes was then estimated in a logistic regression analysis after applying a propensity score inverse probability of treatment weighting approach. RESULTS: Among the 2449 patients included, 1496 were metformin users and 953 were not. Compared with non-users, metformin users were younger with a lower prevalence of diabetic complications, but had more severe features of COVID-19 on admission. The primary endpoint occurred in 28.0% of metformin users (vs 29.0% in non-users, P = 0.6134) on day 7 and in 32.6% (vs 38.7%, P = 0.0023) on day 28. The mortality rate was lower in metformin users on day 7 (8.2 vs 16.1%, P < 0.0001) and on day 28 (16.0 vs 28.6%, P < 0.0001). After propensity score weighting was applied, the odds ratios for primary outcome and death (OR [95%CI], metformin users vs non-users) were 0.838 [0.649-1.082] and 0.688 [0.470-1.007] on day 7, then 0.783 [0.615-0.996] and 0.710 [0.537-0.938] on day 28, respectively. CONCLUSION: Metformin use appeared to be associated with a lower risk of death in patients with diabetes hospitalised for COVID-19.

The association between body mass index class and coronavirus disease 2019 outcomes.

BACKGROUND/OBJECTIVES: A growing body of data suggests that obesity influences coronavirus disease 2019 (COVID-19). Our study's primary objective was to assess the association between body mass index (BMI) categories and critical forms of COVID-19. SUBJECTS/METHODS: Data on consecutive adult patients hospitalized with laboratory-confirmed COVID-19 at Amiens University Hospital (Amiens, France) were extracted retrospectively. The association between BMI categories and the composite primary endpoint (admission to the intensive care unit or death) was probed in a logistic regression analysis. RESULTS: In total, 433 patients were included, and BMI data were available for 329: 20 were underweight (6.1%), 95 have a normal weight (28.9%), 90 were overweight (27.4%), and 124 were obese (37.7%). The BMI category was associated with the primary endpoint in the fully adjusted model; the odds ratio (OR) [95% confidence interval (CI)] for overweight and obesity were respectively 1.58 [0.77-3.24] and 2.58 [1.28-5.31]. The ORs [95% CI] for ICU admission were similar for overweight (3.16 [1.29-8.06]) and obesity (3.05 [1.25-7.82]) in the fully adjusted model. The unadjusted ORs for death were similar in all BMI categories while obesity only was associated with higher risk after adjustment. CONCLUSIONS: Our results suggest that overweight (and not only obesity) is associated with ICU admission, but overweight is not associated with death.

The impact of endocrine disruptor chemicals on oocyte/embryo and clinical outcomes in IVF.

The negative impact of endocrine-disrupting pesticides on human fertility is now a key issue in reproductive health. There are much fewer literature data about the impact of pesticide exposure on women than on men and very few studies of women participating in an in vitro fertilization (IVF) programme. In the present review, we found that (1) various pesticides with an endocrine-disrupting action are associated with poor oocyte maturation and competency, embryonic defects and poor IVF outcomes, and (2) some pesticide compounds are linked to specific causes of female infertility, such as premature ovarian insufficiency, polycystic ovarian syndrome, and endometriosis. IVF participants living in agricultural regions should be informed about the fertility decline, low ongoing pregnancy rates, and elevated risk of miscarriage associated with exposure to high doses of pesticides.

La néoplasie endocrinienne multiple de type 1 : mise au point après le congrès de l'ENETS 2019: Multiple Endocrine Neoplasia Type 1: Development after the ENETS 2019 Congress.

Multiple Endocrine Neoplasia Type 1 (NEM1) is related to mutations of the menin gene. It is an autosomal dominant disease. Its prevalence is about 1/30 000 with a hugh penetrance. There is no genotype-phenotype correlation. This hereditary syndrome is characterized by the presence of tumors of the endocrine system (parathyroid, endocrine pancreas, pituitary and adrenal gland). Other disorders have also been described (bronchial and thymic carcinoid tumor, breast cancer, skin lesions). Management must take into account the specificities of these pathologies in NEM1 compared to sporadic forms (young age at diagnosis, multiple lesions within the same gland, multi-focal disease). © 2019 Published by Elsevier Masson SAS. All rights reserved. Cet article fait partie du numéro supplément Les Must de l'Endocrinologie 2019 réalisé avec le soutien institutionnel de Ipsen-Pharma.

Impact of coxsackievirus-B4E2 combined with a single low dose of streptozotocin on pancreas of outbred mice: investigation of viral load, pathology and inflammation.

Coxsackieviruses B (CV-B) belong to the EV-B species. CV-B and particularly CV-B4 are thought to be involved in the development of chronic diseases like type 1 diabetes (T1D). The mechanisms of the enteroviral pathogenesis of T1D are not well known, yet. The in vitro studies are rich with information but in vivo infection models are needed to investigate the impact of viruses onto organs. Our objective was to study the impact of CV-B4E2 combined with a single sub-diabetogenic dose of streptozotocin (STZ) on the pancreas of mice. The infection with CV-B4E2 of CD1 outbred mice treated with a sub-diabetogenic dose of STZ induced hyperglycemia and hypoinsulinemia. Along with the chemokine IP-10, viral RNA and infectious particles were detected in the pancreas. The pancreas of these animals was also marked with insulitis and other histological alterations. The model combining STZ and CV-B4E2 opens the door to new perspectives to better understand the interactions between virus and host, and the role of environmental factors capable, like STZ, to predispose the host to the diabetogenic effects of enteroviruses.

Positive Impact of Genetic Test on the Management and Outcome of Patients With Paraganglioma and/or Pheochromocytoma.

CONTEXT: Pheochromocytomas and paragangliomas (PPGLs) are characterized by a strong genetic component, with up to 40% of patients carrying a germline mutation in a PPGL susceptibility gene. International guidelines recommend that genetic screening be proposed to all patients with PPGL. OBJECTIVE: Our objective was to evaluate how a positive genetic test impacts the management and outcome of patients with SDHx or VHL-related PPGL. DESIGN: We performed a multicentric retrospective study involving 221 propositi carrying an SDHB, SDHD, SDHC, or VHL germline mutation. Patients were divided into two groups: genetic patients, who were informed of their genetic status within the year following the first PPGL diagnosis, and historic patients, who only benefited from the genetic test several years after initial PPGL diagnosis. RESULTS: Genetic patients had better follow-up than historic patients, with a greater number of examinations and a reduced number of patients lost to follow-up (9.6% vs 72%, respectively). During follow-up, smaller (18.7 vs 27.6 mm; P = 0.0128) new PPGLs and metastases as well as lower metastatic spread were observed in genetic patients. Of note, these differences were reversed in the historic cohort after genetic testing. Genetic patients who developed metachronous metastases had a better 5-year survival rate than historic patients (P = 0.0127). CONCLUSION: Altogether, our data suggest that early knowledge of genetic status had a positive impact on the management and clinical outcome of patients with a germline SDHx or VHL mutation.