Publications by authors named "Yves Reznik"

94 Publications

Use of dipeptidyl peptidase-4 inhibitors and prognosis of COVID-19 in hospitalized patients with type 2 diabetes: A propensity score analysis from the CORONADO study.

Diabetes Obes Metab 2021 05 16;23(5):1162-1172. Epub 2021 Feb 16.

Département d'Endocrinologie, Diabétologie et Maladies Métaboliques, CHU de Rouen, Université de Rouen, Rouen, France.

Aim: To investigate the association between routine use of dipeptidyl peptidase-4 (DPP-4) inhibitors and the severity of coronavirus disease 2019 (COVID-19) infection in patient with type 2 diabetes in a large multicentric study.

Materials And Methods: This study was a secondary analysis of the CORONADO study on 2449 patients with type 2 diabetes (T2D) hospitalized for COVID-19 in 68 French centres. The composite primary endpoint combined tracheal intubation for mechanical ventilation and death within 7 days of admission. Stabilized weights were computed for patients based on propensity score (DPP-4 inhibitors users vs. non-users) and were used in multivariable logistic regression models to estimate the average treatment effect in the treated as inverse probability of treatment weighting (IPTW).

Results: Five hundred and ninety-six participants were under DPP-4 inhibitors before admission to hospital (24.3%). The primary outcome occurred at similar rates in users and non-users of DPP-4 inhibitors (27.7% vs. 28.6%; p = .68). In propensity analysis, the IPTW-adjusted models showed no significant association between the use of DPP-4 inhibitors and the primary outcome by Day 7 (OR [95% CI]: 0.95 [0.77-1.17]) or Day 28 (OR [95% CI]: 0.96 [0.78-1.17]). Similar neutral findings were found between use of DPP-4 inhibitors and the risk of tracheal intubation and death.

Conclusions: These data support the safety of DPP-4 inhibitors for diabetes management during the COVID-19 pandemic and they should not be discontinued.
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http://dx.doi.org/10.1111/dom.14324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8013481PMC
May 2021

Closed-loop insulin delivery: understanding when and how it is effective.

Lancet Digit Health 2020 02 3;2(2):e50-e51. Epub 2020 Jan 3.

Department of Endocrinology, University of Caen, Côte de Nacre Regional Hospital Center, Caen, France.

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http://dx.doi.org/10.1016/S2589-7500(19)30219-5DOI Listing
February 2020

Adherence to growth hormone therapy guidelines in a real-world French cohort of adult patients with growth hormone deficiency.

Ann Endocrinol (Paris) 2021 Feb 5;82(1):59-68. Epub 2020 Dec 5.

Novo Nordisk, 100 Esplanade du Général de Gaulle, 92400 Paris, France.

Objective: Using real-world data from patients with growth hormone deficiency (GHD), we evaluated whether clinical practice in France adheres to international guidelines regarding somatropin dose adjustment, and assessed the long-term effectiveness and safety of somatropin.

Methods: Data were obtained from a national prospective systematic longitudinal routine follow-up programme of naive/non-naive adults with childhood-onset (CO) or adult-onset (AO) GHD treated with Norditropin® (Novo Nordisk A/S).

Results: Between 2003 and 2006, 331 treatment-naive and non-naive adults with severe GHD were enrolled and followed for a median duration of approximately 5 years; 328 patients were available for analysis. At baseline, mean patient age was 39.2 years; median standard deviation score (SDS) for insulin-like growth factor-1 (IGF-1) level was -2.2 in naive patients, subsequently fluctuating between -0.1 and +0.3 SDS during the study period. Mean GH doses ranged between 0.25 and 0.51mg/day (naive patients) and 0.39 and 0.46mg/day (non-naive patients). Despite generally receiving a higher somatropin dose, women (naive/non-naive) tended to have lower IGF-1 levels than men. Median somatropin dose was consistently higher in patients with CO-GHD than patients with AO-GHD. Extreme IGF-1 values (<-2 or >+2 SDS) were not systematically accompanied by somatropin dose adjustments. Waist circumference improved in approximately one third of patients, at a mean 3.5 years. Somatropin was well tolerated; there were no cardiovascular or cerebrovascular events during the 5-year analysis period.

Conclusion: Current clinical practice of physicians in France follows international guidelines regarding somatropin dose adjustment in adults with GHD. However, dose adjustments are not always sufficient, notably in women, and treatment effects may have been delayed due to low somatropin dose (Clinical trial registration NCT01580605).
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http://dx.doi.org/10.1016/j.ando.2020.11.007DOI Listing
February 2021

Medical management of adrenocortical carcinoma: Current recommendations, new therapeutic options and future perspectives.

Ann Endocrinol (Paris) 2021 Feb 3;82(1):52-58. Epub 2020 Dec 3.

Aix-Marseille University, Marseille Medical Genetics, INSERM, Department of endocrinology, La Conception Hospital, Marseille, France. Electronic address:

Adrenocortical carcinoma is a rare malignant tumor of poor prognosis, frequently requiring additional treatments after initial surgery. Due to its adrenolytic action, mitotane has become the first-line medical treatment in patients with aggressive adrenocortical carcinoma. Over the last 2years, apart from the classical chemotherapy based on etoposide and platinum salts, several studies reported the use of drugs such as temozolomide, tyrosine kinase inhibitors or immunotherapy, with more or less convincing results. The aim of this review is to give further insights in the use of these drugs, and to describe potential therapeutic perspectives based on recent pangenomic studies, for the future management of these still difficult to treat tumors.
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http://dx.doi.org/10.1016/j.ando.2020.12.003DOI Listing
February 2021

Efficacy and safety of exenatide as add-on therapy for patients with type 2 diabetes with an intensive insulin regimen: A randomized double-blind trial.

Diabetes Obes Metab 2021 Feb 30;23(2):374-381. Epub 2020 Oct 30.

Diabetes Care Unit, Caen University Hospital, Caen, France.

Aim: To assess the safety and efficacy of the short-acting glucagon-like peptide-1 receptor agonist exenatide on a population of patients with type 2 diabetes (T2D) mostly treated with continuous subcutaneous insulin injection (CSII).

Materials And Methods: A phase 2/3, multicentre, randomized, parallel-group, double-blind, placebo-controlled, 6-month trial was conducted. Patients were randomized to receive subcutaneous (SC) injections of exenatide (10 μg BID) or matched placebo.

Results: A total of 46 patients with T2D and elevated HbA1c were randomized (42% of the planned sample size): exenatide (n = 28) and placebo (n = 18). CSII treatment was used by 75% and 89% of patients of the exenatide and placebo groups, respectively. At 6 months, the change in HbA1c was -0.62% ± 0.94% and 0.08% ± 0.81% in the exenatide and placebo groups, respectively (difference, -0.70%; 95% CI [-1.24%; -0.15%], P = .014); body weight and body mass index decreased in the exenatide group (-2.55 ± 3.25 kg and -1.00 ± 1.31 kg/m ) and increased in the placebo group (1.29 ± 2.82 kg and 0.46 ± 1.16 kg/m ) (observed difference, -3.85 and -1.45, respectively, both P < .001); the postdinner capillary blood glucose value was lower in the exenatide group compared with the placebo group (162.4 ± 80.5 vs. 259.1 ± 94.4 mg/dL, respectively; observed difference, -96.7, P < .01). Hypoglycaemic risk, quality of life and overall safety were not different between the groups, apart from the expected occurrence of digestive effects in the exenatide group.

Conclusions: Although we failed to reach our planned sample size, the addition of exenatide treatment 10 μg BID SC in T2D patients with uncontrolled HbA1c despite an intensified insulin regimen, resulted in a significant reduction of HbA1c and body weight with a good overall safety profile and acceptance.
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http://dx.doi.org/10.1111/dom.14225DOI Listing
February 2021

DIABEO System Combining a Mobile App Software With and Without Telemonitoring Versus Standard Care: A Randomized Controlled Trial in Diabetes Patients Poorly Controlled with a Basal-Bolus Insulin Regimen.

Diabetes Technol Ther 2020 12 14;22(12):904-911. Epub 2020 Oct 14.

Department of Diabetes, Sud-Francilien Hospital, Corbeil-Essonnes, and Centre d'étude et de Recherche pour l'Intensification du Traitement du Diabète (CERITD), Evry, France.

The DIABEO system (DS) is a telemedicine solution that combines a mobile app for patients with a web portal for health care providers. DS allows real-time monitoring of basal-bolus insulin therapy as well as therapeutic decision-making, integrating both basal and bolus dose calculation. Real-life studies have shown a very low rate of use of mobile health applications by patients. Therefore, we conducted a large randomized controlled trial study to investigate the efficacy of DS in conditions close to real life (TELESAGE study). TELESAGE was a multicenter, randomized, open study with three parallel arms: arm 1 (standard care), arm 2 (DIABEO alone), and arm 3 (DIABEO+telemonitoring by trained nurses). The primary outcome assessed the reduction in HbA levels after a 12-month follow-up. Six hundred sixty-five patients were included in the study. Participants who used DIABEO once or more times a day (DIABEO users) showed a significant and meaningful reduction of HbA versus standard care after a 12-month follow-up: mean difference -0.41% for arm 2-arm 1 ( = 0.001) and -0.51% for arm 3-arm 1 ( ≤ 0.001). DIABEO users included 25.1% of participants in arm 2 and 37.6% in arm 3. In the intention-to-treat population, HbA changes and incidence of hypoglycemia were comparable between arms. A clinical and statistically significant reduction in HbA levels was found in those patients who used DIABEO at least once a day.
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http://dx.doi.org/10.1089/dia.2020.0021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7757616PMC
December 2020

Clinical characteristics of familial hypocalciuric hypercalcaemia type 1: A multicentre study of 77 adult patients.

Clin Endocrinol (Oxf) 2020 09 14;93(3):248-260. Epub 2020 May 14.

Department of Endocrinology, Larrey Hospital, CardioMet Institute, University Hospital Centre of Toulouse, Toulouse, France.

Objective: Familial hypocalciuric hypercalcaemia type 1 (FHH1), related to heterozygous loss-of-function mutations of the calcium-sensing receptor gene, is the main differential diagnosis for primary hyperparathyroidism. The aim of our study was to describe clinical characteristics of adult patients living in France with a genetically confirmed FHH1.

Design And Patients: This observational, retrospective, multicentre study included 77 adults, followed up in 32 clinical departments in France, with a genetic FHH1 diagnosis between 2001 and 2012.

Results: Hypercalcaemia was diagnosed at a median age of 53 years [IQR: 38-61]. The diagnosis was made after clinical manifestations, routine analysis or familial screening in 56, 34 and 10% of cases, respectively, (n = 58; data not available for 19 patients). Chondrocalcinosis was present in 11/51 patients (22%), bone fractures in 8/56 (14%) and renal colic in 6/55 (11%). The median serum calcium was 2.74 mmol/L [IQR: 2.63-2.86 mmol/L], the median plasma parathyroid hormone level was 4.9 pmol/L [3.1-7.1], and the median 24-hour urinary calcium excretion was 2.8 mmol/24 hours [IQR: 1.9-4.0]. Osteoporosis (dual X-ray absorptiometry) or kidney stones (renal ultrasonography) were found in 6/38 patients (16%) and 9/32 patients (28%), respectively. Fourteen patients (18%) underwent parathyroid surgery; parathyroid adenoma was found in three patients (21%) and parathyroid hyperplasia in nine patients (64%). No correlation between genotype and phenotype was established.

Conclusion: This large cohort study demonstrates that FHH1 clinical characteristics can be atypical in 33 patients (43%). Clinicians should be aware of this rare differential diagnosis in order to adopt an appropriate treatment strategy.
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http://dx.doi.org/10.1111/cen.14211DOI Listing
September 2020

[Insulinoma].

Rev Prat 2019 Sep;69(7):e250

Service d'endocrinologie, CHU de Caen, université Caen Normandie, 14032 Caen Cedex, France.

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September 2019

[Hypoglycemia in adults and children].

Rev Prat 2019 May;69(5):e175-e179

Service d'endocrinologie, CHU de Caen, université de Caen Normandie, 14032 Caen Cedex, France.

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May 2019

Efficacy of the Diabeloop closed-loop system to improve glycaemic control in patients with type 1 diabetes exposed to gastronomic dinners or to sustained physical exercise.

Diabetes Obes Metab 2020 03 16;22(3):324-334. Epub 2019 Oct 16.

Department of Endocrinology, University of Caen Côte de Nacre Regional Hospital Centre, Caen, France.

Aims: To compare closed-loop (CL) and open-loop (OL) systems for glycaemic control in patients with type 1 diabetes (T1D) exposed to real-life challenging situations (gastronomic dinners or sustained physical exercise).

Methods: Thirty-eight adult patients with T1D were included in a three-armed randomized pilot trial (Diabeloop WP6.2 trial) comparing glucose control using a CL system with use of an OL device during two crossover 72-hour periods in one of the three following situations: large (gastronomic) dinners; sustained and repeated bouts of physical exercise (with uncontrolled food intake); or control (rest conditions). Outcomes included time in spent in the glucose ranges of 4.4-7.8 mmol/L and 3.9-10.0 mmol/L, and time in hypo- and hyperglycaemia.

Results: Time spent overnight in the tight range of 4.4 to 7.8 mmol/L was longer with CL (mean values: 63.2% vs 40.9% with OL; P ≤ .0001). Time spent during the day in the range of 3.9 to 10.0 mmol/L was also longer with CL (79.4% vs 64.1% with OL; P ≤ .0001). Participants using the CL system spent less time during the day with hyperglycaemic excursions (glucose >10.0 mmol/L) compared to those using an OL system (17.9% vs 31.9%; P ≤ .0001), and the proportions of time spent during the day with hyperglycaemic excursions of those using the CL system in the gastronomic dinner and physical exercise subgroups were of similar magnitude to those in the control subgroup (18.1 ± 6.3%, 17.2 ± 8.1% and 18.4 ± 12.5%, respectively). Finally, times spent in hypoglycaemia were short and not significantly different among the groups.

Conclusions: The Diabeloop CL system is superior to OL devices in reducing hyperglycaemic excursions in patients with T1D exposed to gastronomic dinners, or exposed to physical exercise followed by uncontrolled food and carbohydrate intake.
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http://dx.doi.org/10.1111/dom.13898DOI Listing
March 2020

Le syndrome des ovaires polykystiques : quelles nouveautés en 2019 ?: Keeping up with PCOS in 2019.

Ann Endocrinol (Paris) 2019 Sep;80 Suppl 1:S29-S37

Endocrinologie et métabolismes, CHU de Caen, Caen, France.

PolyCystic Ovary Syndrome (PCOS) is the first endocrinopathy of women of child-bearing age and the leading cause of anovulatory infertility. The pathophysiology of this syndrome is complex and involves genetic traits highlighted by GWAS and epigenetic traits with DNA methylation modifications. Initially described as an ovarian disease, works carried out over recent years were turned towards neuroendocrine disorder involving GABAergic pathways, KNDy neurons and a possible role of prenatal androgen exposure determined by animal models. Clinically, PCOS leads to many complications including psychological and emotional disorders demonstrated in large populations of PCOS women. © 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.
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http://dx.doi.org/10.1016/S0003-4266(19)30114-3DOI Listing
September 2019

Ga-DOTATOC PET/CT in detecting neuroendocrine tumours responsible for initial or recurrent paraneoplastic Cushing's syndrome.

Endocrine 2020 03 3;67(3):708-717. Epub 2019 Oct 3.

Nuclear Medicine, Hôpital Tenon APHP and Sorbonne University, Paris, France.

Purpose: Paraneoplastic Cushing's syndrome (PCS) is frequently caused by neuroendocrine tumours (NETs). Approximately 20% of tumours are still occult years later. Gallium-68 somatostatin receptor-PET/CT is promising for the detection of the causal primary NET, but its role in case of recurrent PCS is rarely reported. We report our experience with DOTATOC PET/CT in localising the causal NET in cases of initial but also recurrent PCS, and its clinical impact.

Methods: A retrospective review of all DOTATOC PET/CTs performed in consecutive patients referred for PCS to our centre, between January 2011 and June 2017, was done. Nineteen patients underwent 26 PET/CTs, 13 for detection of a primary NET, seven for persistent or recurrent PCS after resection, and six for surveillance after resection of NETs previously detected on a DOTATOC PET/CT in our centre.

Results: Among the 13 PET/CTs performed to search for primary NET, five were positive: four carcinoid lung tumours were confirmed after resection and one lung focus was not confirmed since surgery would have carried a high risk. Clinical impact was 23% (3/13). Among the seven PET/CTs performed for persistent or recurrent PCS, six were true-positive, with confirmation of metastatic lymph nodes after resection. Clinical impact was 57% (4/7). All PET/CTs performed for surveillance were true-negative.

Conclusions: DOTATOC PET/CT seems to be a valuable tool for detection of the NET responsible for persistent or recurrent PCS after surgery. In this context, DOTATOC PET/CT was more effective than for the detection of the causal tumour in initial PCS.
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http://dx.doi.org/10.1007/s12020-019-02098-2DOI Listing
March 2020

Efficacy of two telemonitoring systems to improve glycaemic control during basal insulin initiation in patients with type 2 diabetes: The TeleDiab-2 randomized controlled trial.

Diabetes Obes Metab 2019 10 3;21(10):2327-2332. Epub 2019 Jul 3.

CERITD (Centre for Studies and Research for the Intensification of Diabetes Treatment), Bioparc Genopole Campus, Evry, France.

TeleDiab-2 was a 13-month randomized controlled trial evaluating the efficacy and safety of two telemonitoring systems to optimize basal insulin (BI) initiation in subjects with inadequately controlled type 2 diabetes (HbA1c, 7.5%-10%). A total of 191 participants (mean age 58.7 years, mean HbA1c 8.9%) were randomized into three groups: group 1(G1, standard care, n = 63), group 2 (G2, interactive voice response system, n = 64) and group 3 (G3, Diabeo-BI app software, n = 64). The two telemonitoring systems proposed daily adjustments of BI doses, in order to facilitate the achievement of fasting blood glucose (FBG) values targeted at ~100 mg/dL. At 4 months follow-up, HbA1c reduction was significantly higher in the telemonitoring groups (G2: -1.44% and G3: -1.48% vs. G1: -0.92%; P < 0.002). Moreover, target FBG was reached by twice as many patients in the telemonitoring groups as in the control group, and insulin doses were also titrated to higher levels. No severe hypoglycaemia was observed in the telemonitoring groups and mild hypoglycaemia frequency was similar in all groups. In conclusion, both telemonitoring systems improved glycaemic control to a similar extent, without increasing hypoglycaemic episodes.
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http://dx.doi.org/10.1111/dom.13806DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6771866PMC
October 2019

Liver adenomatosis in patients with hepatocyte nuclear factor-1 alpha maturity onset diabetes of the young (HNF1A-MODY): Clinical, radiological and pathological characteristics in a French series.

J Diabetes 2020 Jan 10;12(1):48-57. Epub 2019 Jul 10.

Department of Endocrinology and Diabetology, Caen University Hospital, Caen, France.

Background: Liver adenomatosis (LA) is a rare disease resulting from biallelic inactivation of the hepatocyte nuclear factor-1 alpha (HNF1A) gene, which induces the proliferation of adenoma cells in liver parenchyma. Liver adenomatosis has only been documented in case reports from patients carrying a HNF1A germline mutation. We have evaluated the frequency of LA among a large cohort of patients with HNF1A-maturity onset diabetes of the young (MODY), previously termed "MODY3," and herein describe its clinical, radiological, and pathological characteristics.

Methods: In all, 137 HNF1A-MODY subjects from 74 families were screened by liver ultrasonography in 13 centers, and 15 additional cases of LA were later included in the series. Liver adenomatosis was confirmed by liver computed tomography, magnetic resonance imaging (MRI), and/or histopathology.

Results: Among 137 carriers of an HNF1A mutation, 9 patients (6.5%) from seven families were diagnosed with LA. Diabetes mellitus was present in 87.5% of patients with LA. In 25% of patients, LA was diagnosed due to intra-abdominal or intratumoral bleeding. Liver biochemistry was near normal in all patients. Liver imaging showed adenomas of various sizes and numbers. On MRI, most nodules had the radiological characteristics of steatotic adenomas. Histopathological confirmation of LA was available in 13 cases, and these adenomas were mostly steatotic. Surgery was initially performed in 37.5% of patients, and liver disease progression was observed in 30%. No disease progression was observed in 14 pregnancies.

Conclusions: The frequency of LA in a cohort of screened HNF1A-MODY patients and the high incidence of LA progression and/or hemorrhage warrants systematic screening for liver adenomatosis in HNF1A-MODY families.
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http://dx.doi.org/10.1111/1753-0407.12959DOI Listing
January 2020

Illicit Upregulation of Serotonin Signaling Pathway in Adrenals of Patients With High Plasma or Intra-Adrenal ACTH Levels.

J Clin Endocrinol Metab 2019 11;104(11):4967-4980

Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Normandie University, UNIROUEN, INSERM, U1239, Rouen, France.

Context: In the human adrenal, serotonin (5-HT), released by mast cells stimulates corticosteroid secretion through activation of type 4 serotonin receptors (5-HT4R). In primary pigmented nodular adrenocortical disease cells, activation of the cAMP/protein kinase A (PKA) pathway by PRKAR1A mutations triggers upregulation of the 5-HT synthesizing enzyme tryptophan hydroxylase (TPH) and the 5-HT4, 5-HT6, and 5-HT7 receptors. Because ACTH stimulates cortisol secretion through activation of PKA, adrenocortical tissues exposed to sustained stimulation by ACTH may harbor increased expression of TPH and 5-HT4/6/7 receptors.

Objective: To investigate the effects of long-term ACTH stimulation on the serotonergic pathway in adrenals of patients with high plasma or intra-adrenal ACTH levels.

Methods: Adrenal tissues were obtained from patients with Cushing disease, ectopic secretion of ACTH [paraneoplastic Cushing syndrome; (paraCS)], 21-hydroxylase deficiency (21-OHD), primary bilateral macronodular adrenal hyperplasia with intra-adrenal ACTH presence, or cortisol-producing adenomas. TPH and 5-HT4/6/7 receptor expression was investigated using RT-PCR and immunochemistry in comparison with normal adrenals. Primary cultured adrenocortical cells originating from a patient with paraCS were incubated with 5-HT and 5-HTR agonists/antagonists.

Results: TPH and/or 5-HT4/6/7 receptors were overexpressed in the different types of tissues. In paraCS cultured cells, the cortisol response to 5-HT was exaggerated compared with normal adrenal cells and the stimulatory action of 5-HT was reduced by 5-HT4R antagonist.

Conclusion: Our results indicate that prolonged activation of the cAMP/PKA pathway by ACTH induces an aberrant serotonergic stimulatory loop in the adrenal cortex that likely participates in the pathogenesis of corticosteroid hypersecretion.
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http://dx.doi.org/10.1210/jc.2019-00425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6937520PMC
November 2019

Closed-loop insulin delivery in adults with type 1 diabetes in real-life conditions: a 12-week multicentre, open-label randomised controlled crossover trial.

Lancet Digit Health 2019 05 2;1(1):e17-e25. Epub 2019 May 2.

Center for Study and Research for Improvement of the Treatment of Diabetes, Bioparc-Genopole Evry-Corbeil, Evry, France.

Background: Closed-loop insulin delivery systems are expected to become a standard treatment for patients with type 1 diabetes. We aimed to assess whether the Diabeloop Generation 1 (DBLG1) hybrid closed-loop artificial pancreas system improved glucose control compared with sensor-assisted pump therapy.

Methods: In this multicentre, open-label, randomised, crossover trial, we recruited adults (aged ≥18 years) with at least a 2 year history of type 1 diabetes, who had been treated with external insulin pump therapy for at least 6 months, had glycated haemoglobin (HbA) of 10% or less (86 mmol/mol), and preserved hypoglycaemia awareness. After a 2-week run-in period, patients were randomly assigned (1:1) with a web-based system in randomly permuted blocks of two, to receive insulin via the hybrid closed-loop system (DBLG1; using a machine-learning-based algorithm) or sensor-assisted pump therapy over 12 weeks of free living, followed by an 8-week washout period and then the other intervention for 12 weeks. The primary outcome was the proportion of time that the sensor glucose concentration was within the target range (3·9-10·0 mmol/L) during the 12 week study period. Efficacy analyses were done in the modified intention-to-treat population, which included all randomly assigned patients who completed both 12 week treatment periods. Safety analyses were done in all patients who were exposed to either of the two treatments at least once during the study. This trial is registered with ClinicalTrials.gov, number NCT02987556.

Findings: Between March 3, 2017, and June 19, 2017, 71 patients were screened, and 68 eligible patients were randomly assigned to the DBLG1 group (n=33) or the sensor-assisted pump therapy group (n=35), of whom five dropped out in the washout period (n=1 pregnancy; n=4 withdrew consent). 63 patients completed both 12 week treatment periods and were included in the modified intention-to-treat analysis. The proportion of time that the glucose concentration was within the target range was significantly higher in the DBLG1 group (68·5% [SD 9·4] than the sensor-assisted pump group (59·4% [10·2]; mean difference 9·2% [95% CI 6·4 to 11·9]; p<0·0001). Five severe hypoglycaemic episodes occurred in the DBLG1 group and three episodes occurred in the sensor-assisted pump therapy group, which were associated with hardware malfunctions or human error.

Interpretation: The DBLG1 system improves glucose control compared with sensor-assisted insulin pumps. This finding supports the use of closed-loop technology combined with appropriate health care organisation in adults with type 1 diabetes.

Funding: French Innovation Fund, Diabeloop.
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http://dx.doi.org/10.1016/S2589-7500(19)30003-2DOI Listing
May 2019

Remote Monitoring of Diabetes: A Cloud-Connected Digital System for Individuals With Diabetes and Their Health Care Providers.

J Diabetes Sci Technol 2019 11 12;13(6):1161-1168. Epub 2019 Mar 12.

CERITD (Centre d'étude et de Recherche pour l'Intensification du Traitement du Diabète), Evry, Department of Diabetes, Sud-Francilien Hospital, Corbeil-Essonnes, France.

Benefits of telemedicine have been proven in the field of diabetes. Among a number of technical solutions, Diabeo® has been studied in both type 1 and type 2 diabetes with intensive insulin therapy. This digital therapeutic system contains a self-monitoring glucose logbook and offers automated insulin dose recommendations thanks to a fully customizable algorithm. In addition, the cloud-based dedicated software also has features to facilitate remote monitoring, including a platform for diabetes nurses who perform coaching and treatment adjustment. A detailed description of this telemedicine system is provided, as well as results of completed clinical studies. In particular, TeleDiab 1's positive results on HbA1c in type 1 diabetes are detailed. We conclude with a discussion of the role of this telemedicine system within the landscape of mobile apps for diabetes.
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http://dx.doi.org/10.1177/1932296819834054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6835183PMC
November 2019

Quality of Life but not Cognition is Impacted by Radiotherapy in Patients with Non-Functioning Pituitary Adenoma.

Horm Metab Res 2019 Mar 12;51(3):178-185. Epub 2019 Mar 12.

Department of Endocrinology and Diabetology, University Hospital of Caen, Caen Cedex, France.

Non-functioning pituitary adenomas (NFPA) are benign neoplasms that are first treated by surgery and secondary radiation therapy in case of residual tumor or regrowth. The consequences of surgery and radiotherapy are still debated. The objective of the work was to assess the impact of surgery, radiotherapy (RT) and pituitary deficiencies on long term health-related quality of life (QoL) and cognitive function among NFPA patients. Forty-six NFPA patients were studied after 9.6±7.5 years follow-up using: i) the MoCA questionnaire to detect mild cognitive disabilities, ii) the McNair and Kahn scale to assess perceived cognitive impairment, iii) the HADS questionnaire to score anxiety and depression, and iv) the SF-36 and QLS-H questionnaires to assess QoL. All NFPA patients had surgery and 54% patients had radiation therapy (RT+). The MoCA score was abnormal in 41% NFPA patients. Neither the type of surgery nor radiotherapy influenced the prevalence of cognitive disabilities. The depression score was higher in RT+than RT- patients. Overall, no alteration in SF-36 and QLS-H QoL scales were observed in NFPA patients when compared with the French reference population. Among NFPA patients, mental composite score, general health and vitality scores were altered in RT+compared to RT- patients. The presence of multiple pituitary axis deficiencies worsened general health and vitality scale scoring. Consistent follow-up had a beneficial impact on psycho-emotional dimensions of health. Surgery and radiotherapy had no adverse effects on cognitive functions, however, QoL was altered in RT+patients. These latter alterations may be partly related to pituitary hormone deficiencies.
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http://dx.doi.org/10.1055/a-0850-9448DOI Listing
March 2019

Evaluation of Biochemical Conditions Allowing Bypass of Confirmatory Testing in The Workup of Primary Aldosteronism: A Retrospective Study in a French Hypertensive Population.

Horm Metab Res 2019 Mar 12;51(3):172-177. Epub 2019 Mar 12.

Department of Endocrinology, CHU Côte de Nacre, Caen, France.

The diagnostic workup for primary aldosteronism includes a screening step using the aldosterone-to-renin ratio (ARR) and a confirmatory step based on dynamic testing of aldosterone secretion autonomy. International guidelines suggest that precise clinical and biochemical conditions may allow the bypassing of the confirmatory step, however, data which validate hormone thresholds defining such conditions are lacking. At our tertiary center, we retrospectively examined a cohort of 173 hypertensive patients screened for PA by the ARR, of whom 120 had positive screening and passed a saline infusion test (SIT) or a captopril challenge test (CCT). Fifty-nine had PA, including 34 Conn adenomas and 25 with idiopathic aldosteronism (IA). Using a threshold of 160 pmol/l, post-SIT plasma aldosterone concentration (PAC) identified PA with 86.4% sensitivity, 94.7% specificity, and a negative predictive value of 92.3%. Of those subjects with a high ARR and a PAC above 550 pmol/l, 93% had a positive SIT, while 100% of subjects with a high ARR, but a PAC under 240 pmol/l had a negative SIT. Our results thus validate the biochemical conditions defined in the French and US guidelines for bypassing the confirmatory step in the workup for PA diagnosis.
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http://dx.doi.org/10.1055/a-0857-1620DOI Listing
March 2019

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

J Clin Endocrinol Metab 2019 04;104(4):1109-1118

Assistance Publique, Hôpitaux de Paris, Hôpital Cochin, Service d'Endocrinologie, Centre de Référence Maladies Rares de la Surrénale, Paris, France.

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.
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http://dx.doi.org/10.1210/jc.2018-02411DOI Listing
April 2019

Proton therapy for treatment of intracranial benign tumors in adults: A systematic review.

Cancer Treat Rev 2019 Jan 1;72:56-64. Epub 2018 Dec 1.

Radiation Oncology Department, Centre François Baclesse, Caen, France; Archade, Advanced Resource Center for Hadrontherapy in Europe, Caen, France; Normandy University, Université de Caen Basse Normandie, Caen, France; Laboratoire de Physique Corpusculaire, Caen, France.

Introduction: The depth-dose distribution of a proton beam, materialized by the Bragg peak makes it an attractive radiation modality as it reduces exposure of healthy tissues to radiations, compared with photon therapy Prominent indications, based on a long-standing experience are: intraocular melanomas, low-grade skull-base and spinal canal malignancies. However, many others potential indications are under investigations such as the benign morbid conditions that are compatible with an extended life-expectancy: low grade meningiomas, paragangliomas, pituitary adenomas, neurinomas craniopharyngioma or recurrent pleomorphic adenomas.

Materials: Given the radiation-induced risk of secondary cancer and the potential neurocognitive and functional alteration with photonic radiotherapy, we systematically analyzed the existing clinical literature about the use of proton therapy as an irradiation modality for cervical or intracranial benign tumors. The aim of this review was to report clinical outcomes of adult patients with benign intracranial or cervical tumors treated with proton therapy and to discuss about potential advantages of proton therapy over intensity modulated radiotherapy or radiosurgery.

Results: Twenty-four studies were included. There was no randomized studies. Most studies dealt with low grade meningiomas (n = 9). Studies concerning neurinoma (n = 4), pituitary adenoma (n = 5), paraganglioma (n = 5), or craniopharyngioma (n = 1) were fewer. Whatever the indication, long term local control was systematically higher than 90% and equivalent to series with conventional radiotherapy.

Conclusion: Proton-therapy for treatment of adult benign intracranial and cervical tumors is safe. Randomized or prospective cohorts with long term cognitive evaluations are needed to assess the real place of proton-therapy in the treatment of adults benign head and neck tumors.
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http://dx.doi.org/10.1016/j.ctrv.2018.11.004DOI Listing
January 2019

MANAGEMENT OF ENDOCRINE DISEASE: The role of confirmatory tests in the diagnosis of primary aldosteronism.

Eur J Endocrinol 2019 Feb;180(2):R45-R58

Department of Endocrinology and Diabetology, Côte de Nacre Regional Hospital Center, Caen, France.

The strategy for diagnosis of primary aldosteronism (PA) in the hypertensive population includes firstly a screening step, based on the measurement of plasma aldosterone-to-renin ratio (ARR), a test which must have high sensitivity, and secondly a confirmatory step based on the demonstration of excessive aldosterone production independent of the renin-angiotensin-aldosterone system (RAAS) activity. The high proportion of false-positive ARR results and conversely of actual PA without a persistent elevation in baseline plasma aldosterone concentration necessitates the addition of a confirmatory step in the work-up of PA diagnosis. The present review focuses on the description of the different dynamic tests available for demonstrating autonomy of aldosterone secretion, on the performance and limitations of confirmatory tests and on possible strategies for PA diagnosis which may either include or avoid the confirmatory step for PA diagnosis. Large prospective studies comparing different strategies with and without dynamic testing are mandatory to delineate clearly the role and limits of confirmatory tests in the work-up of PA.
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http://dx.doi.org/10.1530/EJE-18-0704DOI Listing
February 2019

Contribution of basal and postprandial hyperglycaemia in type 2 diabetes patients treated by an intensified insulin regimen: Impact of pump therapy in the OPT2mise trial.

Diabetes Obes Metab 2018 10 6;20(10):2435-2441. Epub 2018 Jul 6.

Department of Endocrinology and Diabetology, Côte de Nacre Regional Hospital Center, Caen, France.

Aims: The relative contribution of basal hyperglycaemia (BHG) and postprandial hyperglycaemia (PPHG) in type 2 diabetes patients treated with multiple daily injections (MDI) of insulin is poorly documented. In this study, the BHG and PPHG of patients from the OPT2mise study who were initially treated with MDI were assessed before randomization and again after 6 months of continuous subcutaneous insulin infusion (CSII).

Materials And Methods: Blinded continuous glucose monitoring (CGM) data were collected in 259 MDI patients after completion of an 8-week run-in period. The hyperglycaemic area under the curve (AUC) during the 24-hour basal period (AUC-B) and the postprandial period (AUC-P) were compared with analysis of variance based on contribution to total hyperglycaemia in HbA1c groups (Group 1, <8%; Group 2, 8%-8.4%; Group 3, 8.5%-8.9%; Group 4, 9%-9.4%; Group 5, ≥9.5%). Changes in AUC-B and AUC-P were assessed after 6 months of pump therapy in 131 randomized participants with available CGM recordings.

Results: In patients undergoing MDI therapy, AUC-B was 21.6% to 54.8% lower in Group 4 to 1 (P = .0138 and P = .0002, respectively) in comparison to Group 5. In contrast, AUC-P did not differ among HbA1c groups (P = .1009). HbA1c correlated with AUC-B, but not with AUC-P. After switching to CSII, AUC-B and AUC-P decreased by 21% and 17%, respectively. When comparing responders with non-responders to CSII therapy, no between-group differences were observed in AUC-B and AUC-P.

Conclusions: Basal hyperglycaemia is the major determinant of overall exposure to hyperglycaemia in type 2 diabetes with MDI failure.
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http://dx.doi.org/10.1111/dom.13398DOI Listing
October 2018

Optimization of Insulin Regimen and Glucose Outcomes with Short-Term Real-Time Continuous Glucose Monitoring in Adult Type 1 Diabetes Patients with Suboptimal Control on Multiple Daily Injections: The Adult DIACCOR Study.

Diabetes Technol Ther 2018 06 30;20(6):403-412. Epub 2018 May 30.

8 Endocrinology, Diabetology and Nutrition, Brabois Adult Hospital CHRU of Nancy, University of Lorraine , Vandoeuvre Lès Nancy, France .

Background: The impact of a 7-day real-time continuous glucose monitoring (RT-CGM) on type 1 diabetes (T1D) management remains unclear in patients suboptimally controlled by multiple daily injections (MDI). The DIACCOR Study aimed to describe treatment decisions and glucose outcomes after a short-term RT-CGM sequence.

Patients And Methods: This French multicenter longitudinal observational study included T1D patients with HbA1c >7.5% or history of severe hypoglycemia (SH) or recurrent documented hypoglycemia. A sensor was inserted at the inclusion visit, treatment changes were proposed by the investigator within 7-15 days ("INT" = MDI intensification, "CSII" = switch to continuous insulin infusion, or "ER" = educational reinforcement with no change in insulin regimen), and a 4-month follow-up visit (M4) was scheduled.

Results: Four hundred fifty-nine patients were recruited by 155 diabetologists, 17.0% had SH history, and 24.2% had recurrent hypoglycemia. Baseline HbA1c was 8.34% ± 1.21% (>7.5% in 79.6%). Overall, 253 (64.4%), 64 (16.3%), and 76 patients (19.3%) were, respectively, included in the "INT," "CSII," and "ER" subgroups. The number of patients who experienced SH or recurrent hypoglycemia dropped dramatically (7.9% vs. 17.0% and 10.8% vs. 24.2%, respectively). The same trend was observed for ketoacidosis and ketosis (0.3% vs. 3.3% and 2.2% vs. 4.8%). At M4, HbA1c was significantly reduced in the whole cohort to 7.98% ± 1.01% (P < 0.0001). The adjusted differences in HbA1c level in the INT, CSII, and ER subgroups were, respectively, -0.32%, -0.69%, and -0.50% (P < 0.0001 for all).

Conclusion: In real-life setting, a 1-week diagnostic RT-CGM supports appropriate treatment changes in patients with uncontrolled T1D resulting in better glucose control and less hypoglycemia.
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http://dx.doi.org/10.1089/dia.2018.0002DOI Listing
June 2018

DIABEO App Software and Telemedicine Versus Usual Follow-Up in the Treatment of Diabetic Patients: Protocol for the TELESAGE Randomized Controlled Trial.

JMIR Res Protoc 2018 Apr 19;7(4):e66. Epub 2018 Apr 19.

Centre d'Étude et de Recherche pour l'Intensification du Traitement du Diabète, Evry, Department of Diabetes, Sud-Francilien Hospital, University Paris-Sud, Orsay, Corbeil-Essonnes, France.

Background: Self-management of diabetes minimizes the risk of macrovascular and microvascular complications, but understanding and/or adherence to self-management recommendations is often suboptimal. DIABEO is a smartphone app (downloaded via the internet) used to calculate bolus insulin doses. A previous study (TELEDIAB 1) showed that the use of DIABEO was associated with a significant improvement in glycemic control in patients with poorly controlled type 1 diabetes mellitus, particularly when combined with teleconsultations with physicians.

Objective: Here, we present the protocol for a new study (Suivi A Grande Echelle d'une cohorte de diabétiques de type 1 et de type 2 sous schéma insulinique basal bolus par la TELEmédecine; abbreviated TELESAGE), conducted in a larger population of diabetic patients with poorly controlled basal-bolus insulin levels.

Methods: TELESAGE is a multicenter, double-randomized, open-label, three parallel-arms study, conducted in approximately 100 centers in France. The study will compare a control group (arm 1: usual follow-up) with two DIABEO telemedicine systems: (1) physician-assisted telemedicine (arm 2), and (2) nurse-assisted telemonitoring and teleconsultations by a diabetologist's task delegation (arm 3). Initial randomization will allocate the study arms in 12 French regions. A second randomization will assign patients in the groups allocated to each studied region. The primary objective of TELESAGE will be to investigate the effect of the DIABEO telemedicine system versus usual follow-up, with respect to improvements in the glycated hemoglobin levels of approximately 696 diabetic patients with poorly controlled basal-bolus insulin levels.

Results: The TELESAGE study is sponsored by Sanofi (Gentilly, France). A primary completion date is expected in June 2018, and publication of results is expected within 6 months of work completion.

Conclusions: The TELESAGE study is expected to confirm the previous results of the TELEDIAB 1 study using a larger sample of diabetic patients. It is also expected to evaluate a nurse-assisted telemonitoring system. We will assess the potential of the DIABEO telemedicine service in terms of its utility and explore whether it can become an integral part of diabetes care for patients.

Trial Registration: ClinicalTrials.gov NCT02287532; https://clinicaltrials.gov/ct2/show/NCT02287532 (Archived by WebCite at http://www.webcitation.org/6ykajhJKd).
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http://dx.doi.org/10.2196/resprot.9154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5934533PMC
April 2018

Arterial stiffness evaluated by pulse wave velocity is not predictive of the improvement in hypertension after adrenal surgery for primary aldosteronism: A multicentre study from the French European Society of Hypertension Excellence Centres.

Arch Cardiovasc Dis 2018 Oct 16;111(10):564-572. Epub 2018 Mar 16.

Department of Therapeutics and Hypertension, Rangueil University Hospital, 31059 Toulouse, France.

Background: Predictive factors associated with normal blood pressure (BP) after unilateral adrenalectomy for primary aldosteronism (PA) are not clearly identified.

Aims: To evaluate the predictive value of arterial stiffness before surgery on BP after surgery.

Methods: During 2009-2013, 96 patients with PA due to unilateral adrenal adenoma who underwent surgery were enrolled in a multicentre open-label, prospective study. Aortic pulse wave velocity (PWV) was assessed before surgery. Patients underwent ambulatory blood pressure monitoring (ABPM) before surgery and 6 and 12months after surgery. Twenty-four h SBP/DBP values were compared in subjects with PWV
Results: BP and PWV were available for 82 patients (mean age 49±12years). Mean 24-hour systolic/diastolic BP (SBP/DBP) values decreased from 144±15/91±9 before surgery to 131±15/84±11mmHg 6months after surgery. At 6months, mean 24-hour SBP did not differ significantly between high versus low PWV groups (SBP-0.8mmHg, 95% confidence interval-6.9 to 5.2, P=0.79). A total of 42.3% of women versus 20.0% of men had 24-hour SBP/DBP<130/80mmHg at 6months (P=0.07) and 57.9% vs. 23.8% at 12months (P=0.03). Higher SBP/DBP was recorded for men versus women after 6months (P=0.01/0.001) and 1year (P=0.04/0.05).

Conclusion: Preoperative arterial stiffness does not predict a beneficial effect of adrenalectomy on BP values.
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http://dx.doi.org/10.1016/j.acvd.2018.01.004DOI Listing
October 2018

SFE/SFEDP adrenal insufficiency French consensus: Introduction and handbook.

Ann Endocrinol (Paris) 2018 Feb 12;79(1):1-22. Epub 2018 Jan 12.

Service d'endocrinologie diabétologie pédiatrique, hôpital Robert-Debré, centre de référence des maladies endocriniennes rares de la croissance et du développement, université Paris Diderot, Assistance publique-Hôpitaux de Paris, 48, boulevard Sérurier, 75019 Paris, France.

The French endocrinology society (SFE) and the French pediatric endocrinology society (DFSDP) have drawn up recommendations for the management of primary and secondary adrenal insufficiency in the adult and child, based on an analysis of the literature by 19 experts in 6 work-groups. A diagnosis of adrenal insufficiency should be suspected in the presence of a number of non-specific symptoms except hyperpigmentation which is observed in primary adrenal insufficiency. Diagnosis rely on plasma cortisol and ACTH measurement at 8am and/or the cortisol increase after synacthen administration. When there is a persistant doubt of secondary adrenal insufficiency, insulin hypoglycemia test should be carried out in adults, adolescents and children older than 2 years. For determining the cause of primary adrenal insufficiency, measurement of anti-21-hydroxylase antibodies is the initial testing. An adrenal CT scan should be performed if auto-antibody tests are negative, then assay for very long chain fatty acids is recommended in young males. In children, a genetic anomaly is generally found, most often congenital adrenal hyperplasia. In the case of isolated corticotropin (ACTH) insufficiency, it is recommended to first eliminate corticosteroid-induced adrenal insufficiency, then perform an hypothalamic-pituitary MRI. Acute adrenal insufficiency is a serious condition, a gastrointestinal infection being the most frequently reported initiating factor. After blood sampling for cortisol and ACTH assay, treatment should be commenced by parenteral hydrocortisone hemisuccinate together with the correction of hypoglycemia and hypovolemia. Prevention of acute adrenal crisis requires an education of the patient and/or parent in the case of pediatric patients and the development of educational programs. Treatment of adrenal insufficiency is based on the use of hydrocortisone given at the lowest possible dose, administered several times per day. Mineralocorticoid replacement is often necessary for primary adrenal insufficiency but not for corticotroph deficiency. Androgen replacement by DHEA may be offered in certain conditions. Monitoring is based on the detection of signs of under- and over-dosage and on the diagnosis of associated auto-immune disorders.
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http://dx.doi.org/10.1016/j.ando.2017.12.001DOI Listing
February 2018

F18-choline PET/CT guided surgery in primary hyperparathyroidism when ultrasound and MIBI SPECT/CT are negative or inconclusive: the APACH1 study.

Eur J Nucl Med Mol Imaging 2018 04 22;45(4):658-666. Epub 2017 Dec 22.

Department of Nuclear Medicine and Thyroid Unit, François Baclesse Cancer Centre, Caen, France.

Purpose: To evaluate the sensitivity of F18-choline (FCH) PET/CT for parathyroid adenoma detection prior to surgery in patients with primary hyperparathyroidism and negative or inconclusive cervical ultrasound and Tc99m-sestaMIBI SPECT/CT.

Methods: We conducted a prospective bicentric study (NCT02432599). All patients underwent FCH PET/CT. The result was scored positive, inconclusive or negative. The number of uptakes and their sites were recorded. The FCH PET/CT result guided the surgical procedure (minimally invasive parathyroidectomy, bilateral cervical exploration, or other in case of multiple or ectopic foci). FCH PET/CT results were compared to the surgical and pathological findings and the follow-up.

Results: Twenty-five patients were included. Mean calcium and PTH levels prior to surgery were 2.76 ± 0.17 mmol/l and 94.8 ± 37.4 ng/l. Nineteen (76%) FCH PET/CTs were scored positive, 3 (12%) inconclusive and 3 (12%) negative, showing 21 cases of uniglandular disease, including 1 ectopic localization and 1 case of multiglandular (3 foci) disease. Mean lesion size was 13.1 ± 8.6 mm. Twenty-four patients underwent surgery. FCH PET/CT guided surgery in 22 (88%) patients, allowing for 17 minimally invasive parathyroidectomies, 1 bilateral cervical exploration for multifocality and 4 other surgical procedures. Two patients with negative FCH-PET/CT underwent bilateral cervical exploration. When dichotomizing the FCH PET/CT results, thereby classifying the inconclusive FCH PET/CT results as positive, the per lesion and per patient sensitivities were 91.3% (95%CI: 72.0-98.9) and 90.5% (95%CI: 69.6-98.8) and the corresponding positive predictive values were 87.5% (95%CI: 67.6-97.3) and 86.4% (95%CI: 65.1-97.1), respectively. Twenty-one (88%) patients were considered cured after surgery. Their mean calcium level after surgery was 2.36 ± 0.17 mmol/l.

Conclusions: Preoperative FCH PET/CT has a high sensitivity and positive predictive value for parathyroid adenoma detection in patients with primary hyperparathyroidism and negative or inconclusive conventional imaging results. Bilateral cervical exploration could be avoided in the majority (75%) of patients.
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http://dx.doi.org/10.1007/s00259-017-3911-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5829113PMC
April 2018

Group 6. Modalities and frequency of monitoring of patients with adrenal insufficiency. Patient education.

Ann Endocrinol (Paris) 2017 Dec 1;78(6):544-558. Epub 2017 Dec 1.

Service d'endocrinologie diabétologie pédiatrique, hôpital Robert-Debré, université Paris-Diderot, centre de référence des maladies endocriniennes rares de la croissance et du développement, Assistance publique-hôpitaux de Paris, 48, boulevard Sérurier, 75019 Paris, France.

Patients with adrenal insufficiency require regular, specialised monitoring in order to optimise their replacement therapy, to detect signs of under- and over-dosage, and to examine for possible associated disorders (auto-immune disorders in the case of auto-immune primary adrenal insufficiency either isolated or as part of auto-immune polyendocrinopathy syndrome type 1; illnesses with underlying monogenic causes). The transition period between adolescence and adulthood represents an added risk of a breakdown in monitoring which requires particular attention from medical teams and coordination between adult and pediatric medical teams. It is essential to encourage patient autonomy in the management of their illness, notably their participation in treatment education programs, in particular programs that target avoidance of, or early treatment of acute adrenal insufficiency. The principal educational objectives for patients in such programs are: to be in possession of, and carry the necessary tools for their treatment in an emergency; to be able to identify situations of increased risk and the early signs of adrenal crisis; to know how to adjust their oral glucocorticoid treatment; to be capable of administering hydrocortisone by subcutaneous injection; to be able to predict and therefore adjust treatment to different situations (heat, physical exercise, travel) and to be able to correctly use the appropriate resources of the healthcare services. Other programs could also be developed to respond to needs and expectations of patients, notably concerning the adjustment of hydrocortisone dosage to avoid overdose in the context of chronic fatigue syndrome.
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http://dx.doi.org/10.1016/j.ando.2017.10.009DOI Listing
December 2017

Group 2: Adrenal insufficiency: screening methods and confirmation of diagnosis.

Ann Endocrinol (Paris) 2017 Dec 23;78(6):495-511. Epub 2017 Nov 23.

Service d'endocrinologie et nutrition, CHU Ambroise-Paré, AP-HP, 9, avenue Charles-de-Gaulle, Boulogne-Billancourt, France; Inserm U1173, université Versailles-Saint-Quentin, Montigny-Le-Bretonneux, France. Electronic address:

A diagnosis of adrenal insufficiency should be suspected in the presence of a number of non-specific symptoms (fatigue, anorexia, weight loss, hypotension, hyponatremia and hyperkalemia amongst adrenal causes of insufficiency). The diagnosis should be considered in case of pituitary disease or a state of shock. Treatment should be commenced immediately without waiting for confirmation from biochemical tests, which rely on cortisol level at 8am (expected to be low) and on ACTH level (expected to be high in the case of primary adrenal insufficiency). If these tests are inconclusive, a Synacthen test should be carried out. The threshold limits are provided as a guide. Low plasma cortisol and normal to low plasma ACTH indicates a pituitary origin for the deficiency. In this situation, the Synacthen test can give a false normal result, and if this adrenal insufficiency is strongly suspected, an insulin hypoglycemia test or metyrapone (Metopirone) test should be carried out. In children younger than 2yr, hypoglycemia, dehydration and convulsions are frequently observed and in young girls, virilization is suspect of congenital adrenal hyperplasia . The circadian rhythm of cortisol is not present until after 4months of age and the Synacthen test is the only one that is feasible. In children older than 2yrs, the signs and diagnostic methods are the same as in the adult. Cessation of corticosteroid treatment is a frequent circumstance however there is little published data and no evidence for definitive guidelines. After ceasing a short period of corticosteroid treatment, patient education is all that is required. After longer treatment, consensus leaves the choice up to the physician, between educating the patient and prescribing hydrocortisone in case of stress, or prescribing low daily dose hydrocortisone and evaluating the ACTH axis over time until normal function is recovered.
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http://dx.doi.org/10.1016/j.ando.2017.10.005DOI Listing
December 2017