Management of Graves' ophthalmopathy by radiotherapy: A literature review.

Orbital radiotherapy for Graves' ophthalmopathy is an example of non-oncological radiotherapy. First introduced in the 1930s, this treatment has become widely used since the 1980s with several studies showing proof of both effectiveness and safety: a decrease of soft tissue involvement in 70 to 80% of patients and an improvement of ocular mobility in 30 to 80% of patients. Nowadays, it's one of the second line treatment options recognized by the European Group on Graves' orbitopathy in the management of a moderate to severe and active disease after failure of glucocorticoids. In that setting, orbital radiotherapy should be combined with glucocorticoids. To our knowledge, there are no practical recommendations on how orbital radiotherapy should be planned and conducted for Graves' ophthalmopathy. Optimal dose is not defined however the most frequent regimen consists of 20Gy in ten fractions of 2Gy, though other options may yield better results. Lastly, the use of modern technique of radiotherapy such as intensity-modulated radiation therapy may allow a better sparing of organs at risk compared to three-dimensional radiotherapy using lateral opposing fields.

Whole-exome sequencing identifies the first French MODY 6 family with a new mutation in the NEUROD1 gene.

AIM: The aim of the present study was to identify the affected gene in a French family with maturity-onset diabetes of the young (MODY) using whole-exome sequencing (WES). METHODS: WES was performed in one patient with MODY, and candidate variants were confirmed in members of the immediate family by Sanger sequencing. RESULTS: In the proband, a new heterozygous missense mutation (c.340A>C) was identified in the NEUROD1 gene by WES analysis and confirmed by Sanger sequencing. Additional Sanger sequencing of the proband's sister and mother revealed the same heterozygous mutation. The proband and his sister displayed typical clinical characteristics of MODY, while their mother had the same typical MODY features except for later onset. When clinical and biological profiles were established for all three patients, the severity of diabetes-related complications varied substantially from one family member to another. CONCLUSION: A novel missense mutation found in NEUROD1 was associated with MODY 6 features in a single French family.

[Thyroiditis: What's new in 2019?] / Thyroïdites : où en est-on en 2019 ?

Thyroiditis is a frequent and mostly benign disease that can sometimes disrupt the thyroid balance. Their diagnosis, as well as their aetiology, is a necessary step in the management of the patients. Painful thyroiditis includes acute thyroiditis of infectious origin and subacute thyroiditis. The first one can be treated by antibiotics or antifungals depending on the germ found. The second one will be treated with non-steroidal anti-inflammatory drugs or corticosteroids. In cases of Hashimoto's thyroiditis with overt hypothyroidism, replacement therapy with L-thyroxine will be adapted to the TSH level. As amiodarone treatment provides dysthyroidism, the thyroid status should be monitored regularly. Hypothyroidism will be treated using thyroid replacement therapy. Hyperthyroidism imposes a stop of amiodarone when it is possible. Treatment with synthetic antithyroid drugs (propyl-thio-uracil) or corticosteroids could be used whether there is an underlying thyroid disease or not. Immunotherapies with anti-PD-1/PDL1 or anti-CTLA-4 can also provide dysthyroidism. A monitoring of the thyroid assessment needs to be done in these patients, even if there are no clinical signs, which are not very specific in this context. The treatment of hypothyroidism will be based on thyroid replacement therapy according to the TSH level and the presence or absence of anti-TPO antibodies. Treatment of symptomatic hyperthyroidism may involve a prescription of beta-blockers, or synthetic antithyroid drugs in case of positive anti-TSH receptor antibodies. In all cases, it is desirable to contact an endocrinologist to confirm the diagnosis hypothesis and to decide on a suitable treatment.

[Intake of high dose biotin: A cause of artificial hyperthyroidism]. / La prise de biotine à fortes doses : une cause d'hyperthyroïdie biologique factice.

INTRODUCTION: Many hormone immunoassays use the biotin streptavidin interaction to immobilize immune complexes. The intake of high dose biotin can interfere with immunoassays using the biotin streptavidin interaction. The biotin-immunoassay interference generates falsely low or falsely high tests of hormones according to the type of immunoassay used. CASE REPORT: A 70-year-old patient, with progressive multiple sclerosis, was referred to our hospital for thyrotoxicosis. She was found to have markedly elevated thyroid hormones level (T3-T4) and decreased thyrotropin (TSH) level but she had no symptoms of hyperthyroidism. An ingestion of biotin, that is more and more frequent in patients with progressive multiple sclerosis, was found. Thyroid function tests normalized after discontinuation of biotin treatment. CONCLUSION: The discrepancy between a clinical exam which is not indicative of thyrotoxicosis and markedly abnormal thyroid function tests should lead to a search for biotin intake, which can interfere with thyroid function tests.

Type A competitiveness traits correlate with downregulation of c-Fos expression in patients with type 1 diabetes.

AIM: Type A personality has been associated with increased survival in people with type 1 diabetes (T1D). Systemic low-grade inflammation may play a critical role, as suggested in recent reports, although the links between the inflammatory circulating transcriptome and Type A remain unknown. This prompted our exploration of the potential associations between Type A personality and c-Fos gene expression, a candidate gene closely linked to inflammatory processes, in T1D. METHODS: Type A personality was assessed by Bortner questionnaire in patients with T1D, and two subscales - 'speed' and 'competitiveness' - were used to measure these specific dimensions of Type A. Expression of the c-Fos gene was assessed by a quantitative real-time polymerase chain reaction technique. RESULTS: This pilot study included 20 men with T1D. Multivariable analyses showed an independent inverse association between Type A competitiveness score and c-Fos expression, while a regression model adjusted for age, body mass index and HbA1c levels revealed a significant inverse relationship between c-Fos transcripts and Type A competitiveness (P = 0.003). CONCLUSION: This strong association between Type A competitiveness and reduced c-Fos expression is in line with recent data suggesting a psychobiological influence of the Type A profile in T1D via inflammatory pathways.

French Endocrine Society Guidance on endocrine side effects of immunotherapy.

The management of cancer patients has changed due to the considerably more frequent use of immune checkpoint inhibitors (ICPIs). However, the use of ICPI has a risk of side effects, particularly endocrine toxicity. Since the indications for ICPI are constantly expanding due to their efficacy, it is important that endocrinologists and oncologists know how to look for this type of toxicity and how to treat it when it arises. In view of this, the French Endocrine Society initiated the formulation of a consensus document on ICPI-related endocrine toxicity. In this paper, we will introduce data on the general pathophysiology of endocrine toxicity, and we will then outline expert opinion focusing primarily on methods for screening, management and monitoring for endocrine side effects in patients treated by ICPI. We will then look in turn at endocrinopathies that are induced by ICPI including dysthyroidism, hypophysitis, primary adrenal insufficiency and fulminant diabetes. In each chapter, expert opinion will be given on the diagnosis, management and monitoring for each complication. These expert opinions will also discuss the methodology for categorizing these side effects in oncology using 'common terminology criteria for adverse events' (CTCAE) and the difficulties in applying this to endocrine side effects in the case of these anti-cancer therapies. This is shown in particular by certain recommendations that are used for other side effects (high-dose corticosteroids, contraindicated in ICPI for example) and that cannot be considered as appropriate in the management of endocrine toxicity, as it usually does not require ICPI withdrawal or high-dose glucocorticoid intake.

European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD) and European Association for the Study of Obesity (EASO) clinical practice recommendations for the management of non-alcoholic fatty liver disease: evaluation of their application in people with Type 2 diabetes.

AIMS: To evaluate the application of the recently proposed recommendations by the European Association for the Study of the Liver, European Association for the Study of Diabetes and European Association for the Study of Obesity for the diagnosis, treatment and follow-up of non-alcoholic fatty liver disease in people with Type 2 diabetes. METHODS: A total of 179 people with Type 2 diabetes were included in this study. Liver fat content (assessed using proton magnetic resonance spectroscopy), fatty liver index score, non-alcoholic fatty liver disease fibrosis score, and SteatoTest and FibroTest scores were determined. RESULTS: According to proton magnetic resonance spectroscopy, 68.7% of participants had steatosis (liver fat content >5.5%). The application of the guidelines using several combinations (fatty liver index + non-alcoholic fatty liver disease fibrosis scores, Steatotest + FibroTest scores, proton magnetic resonance spectroscopy + non-alcoholic fatty liver disease fibrosis score, proton magnetic resonance spectroscopy + FibroTest) resulted in a referral to a liver clinic for 33.5-84.9% people with Type 2 diabetes. CONCLUSIONS: The application of these new algorithms for the diagnosis, and follow-up of non-alcoholic fatty liver disease would lead to an excessive number of people with Type 2 diabetes being referred to a liver clinic. We suggest that new clinical and/or biological biomarkers of steatosis and fibrosis be specifically validated in people with Type 2 diabetes.

Adrenal lymphoma: presentation, management and prognosis.

AIM: This study aimed to identify the clinical, radiological and prognostic features of primary adrenal lymphoma (PAL) in order to diagnose the disease more accurately. MATERIALS AND METHODS: A retrospective multi-centre study was conducted on the clinical, biological and radiological features as well as the treatment and overall survival outcomes in PAL. RESULTS: Between 1994 and 2014, 28 patients from five regions of eastern France were diagnosed with primary adrenal lymphoma. The revealing symptoms were a worsening general state (77%), weight loss (77%) and abdominal pain (42%). Biological features of PAL were almost omnipresent: increased LDH, ß2 microglobulin, CRP or ferritinaemia levels. The PAL was bilateral in 20 cases (71%), adrenal insufficiency was searched for in 11 patients and found in eight (73%). CT scans showed masses of various sizes measuring up to 180 mm. On MRI, the lesions were hypointense in T1 and hyperintense in T2. When done, positron emission tomography with fluorodeoxyglucose (FDG-PET) showed locations not seen on the CT and revealed extra-adrenal locations in 70% of examinations. Adrenalectomy brought no benefit. The overall survival rate was poor (61.9% at 2 years) despite polychemotherapy. CONCLUSION: The clinical presentation of PAL comprised major general symptoms. Adrenal insufficiency was very common in patients with bilateral involvement but was not systematically tested. PET was an efficient examination to visualize extra-adrenal locations. The preliminary results of MRI to distinguish between PAL and adrenocortical carcinoma should be confirmed. Further studies are needed to establish an optimal strategy for the management of these primary adrenal lymphomas.

Plasma apolipoprotein C1 concentration is associated with plasma triglyceride concentration, but not visceral fat, in patients with type 2 diabetes.

INTRODUCTION: Apolipoprotein C1 (apoC1) is likely to play an important role in triglyceride (TG) metabolism. Mice overexpressing human apoC1 present decreased adipose tissue stores. This study aimed to determine whether apoC1 concentration influences fat mass and distribution and liver fat content (LFC) in patients with type 2 diabetes (T2D). METHODS: ApoC1 concentrations were measured by ELISA in 113 T2D patients and 56 normolipidaemic-normoglycaemic subjects. Visceral and subcutaneous fat areas were determined by single-slice axial T1-weighted magnetic resonance imaging (MRI), while LFC was measured by hydrogen-1 ((1)H) MR spectroscopy. RESULTS: ApoC1 concentrations were higher in T2D patients than in normolipidaemic-normoglycaemic subjects (P<0.0001), and did not correlate with visceral or subcutaneous fat areas, but significantly correlated with TG (P<0.0001) and LFC (P=0.02) in T2D patients. However, the correlation between apoC1 and LFC was lost after adjusting for TG. ApoC1 concentration was also significantly higher in T2D patients with TG<1.5mmol/L than in control subjects (P<0.0001), although both groups had similar TG levels. On multivariate analysis performed in T2D patients with TG<1.5mmol/L and control subjects, apoC1 concentration was independently and positively associated with type 2 diabetes (P<0.0001) and TG levels (P=0.03). CONCLUSION: This study reports, for the first time, that apoC1 is increased in T2D patients and is significantly correlated with TG, whereas no association was found between apoC1 and adipose tissue. This indicates that, in T2D, apoC1 may play a role in TG metabolism, but is unlikely to modulate fat mass and distribution. This increased apoC1 concentration in T2D patients is not only explained by the increased TG level in T2D patients.

Potential influence of Type A personality on plasma C-reactive protein levels in people with diabetes.

AIM: Type A personality, although classically known as a factor linked to increased vascular risk, has recently been associated with increased survival in patients with diabetes. As low-grade inflammation predicts a poor outcome, the present study explored the potential associations between Type A and plasma levels of C-reactive protein (CRP) in diabetes. METHODS: Type A personality was assessed by the Bortner questionnaire in people with diabetes. The association between Type A and plasma CRP levels was examined by multivariable linear regression, and structural equation modelling (SEM) was performed to determine the impact of the major clinical, biological and psychological confounders. RESULTS: The study included 626 participants with type 1 and type 2 diabetes from the Diabetes and Psychological Profile study. Multivariable analyses showed an independent inverse association between Type A score and CRP levels. The structural model adjusted for age, gender, diabetes type and duration, body mass index (BMI), smoking status, alcohol abuse, oral antidiabetic and statin treatments, HbA1c levels, lipids, perceived stress, anxiety and depression revealed significant associations between CRP and Type A (ß=-0.135, 95% CI: -0.242, -0.028; P=0.014), BMI (ß=0.194, 95% CI: 0.038, 0.350; P=0.015) and HDL cholesterol (ß=-0.132, 95% CI: -0.245, -0.020; P=0.014). CONCLUSION: Our present study data indicate that Type A personality is independently associated with lower CRP levels. This lower level of inflammation might explain the better clinical outcomes associated with Type A personality in patients with diabetes.

Type 1 diabetes is not associated with an increased prevalence of hepatic steatosis.

AIM: Non-alcoholic fatty liver disease (NAFLD) is commonly associated with Type 2 diabetes. Recently, it has been suggested that NAFLD is also frequently associated with Type 1 diabetes and diabetic complications. In this study, we set out to determine whether Type 1 diabetes was associated with liver fat content measured using magnetic resonance imaging. METHODS: One hundred and twenty-eight patients with Type 1 diabetes, 264 patients with Type 2 diabetes and 67 participants without diabetes were included in this study. Hepatic steatosis was defined as a liver fat content > 5.5%. RESULTS: People with Type 1 diabetes and controls were similar for age and BMI. Liver fat content was significantly higher in patients with Type 2 diabetes than in patients with Type 1 diabetes and controls. In the control group, nine people (13.4%) had steatosis compared with six (4.7%) patients with Type 1 diabetes (P = 0.04). Among patients with Type 2 diabetes group, 166 (62.8%) had steatosis. In multivariate analysis that included patients with Type 1 diabetes and participants without diabetes, steatosis was associated only with BMI, whereas age, sex, statin therapy and Type 1 diabetes were not. In patients with Type 1 diabetes, there was no correlation between liver fat content and estimated glomerular filtration rate or carotid intima media thickness. CONCLUSIONS: Our data showed that Type 1 diabetes was not associated with an increased prevalence of steatosis. Moreover, our study provided no specific arguments concerning a link between liver fat content and diabetic complications in patients with Type 1 diabetes.

Optimization of bone-block positioning in the Bristow-Latarjet procedure: a biomechanical study.

BACKGROUND: In the Bristow-Latarjet procedure, optimal positioning of the coracoid bone-block on the anterior aspect of the glenoid (standing or lying on the glenoid rim) remains debated. A biomechanical study assessed the effect of the position of the bone-block with its attached conjoint tendon on anterior and inferior stabilization of the humeral head. MATERIALS AND METHODS: The Bristow-Latarjet procedure was performed on 8 fresh cadaveric shoulders. The bone-block size was systematically at 2.5×1×1 cm. Anterior translation of the humeral head was stress induced under 30-N traction, in maximum external rotation at 0° and at 90° abduction: respectively, adduction and external rotation (ADER), and abduction and external rotation (ABER). Under radiological control, displacement of the center of the humeral head was compared with the glenoid surface at the 3, 4 and 5 o'clock (medial, antero-inferior and inferior) positions for the 2 bone-block positionings. RESULTS: The lying position at 4 o'clock substantially decreased anterior and inferior displacement of the humeral head respectively in ADER and ABER; and in ABER it also tended to decrease anterior translation, but not significantly. The standing bone-block position did not affect translation. CONCLUSIONS: Positioning the bone-block so that it lies on the anterior aspect of the glenoid in the middle of the antero-inferior quarter of the rim at 4 o'clock can decrease anterior displacement of the humeral head and inferior glenohumeral translation, especially in ADER for anterior displacement and in ABER for inferior displacement. STUDY DESIGN: Laboratory study.

Complex primary total hip arthroplasty.

Although total hip arthroplasty is now a classic procedure that is well controlled by orthopedic surgeons, some cases remain complex. Difficulties may be due to co-morbidities: obesity, skin problems, muscular problems, a history of neurological disease or associated morphological bone deformities. Obese patients must be informed of their specific risks and a surgical approach must be used that obtains maximum exposure. Healing of incisions is not a particular problem, but adhesions must be assessed. Neurological diseases may require tenotomy and the use of implants that limit instability. Specific techniques or implants are necessary to respect hip biomechanics (offset, neck-shaft angle) in case of a large lever arm or coxa vara. In case of arthrodesis, before THA can be performed, the risk of infection must be specifically evaluated if the etiology is infection, and the strength of the gluteal muscles must be determined. Congenital hip dysplasia presents three problems: the position and coverage of the cup, placement of a specific or custom made femoral stem, with an osteotomy if necessary, and finally lowering the femoral head into the cup by freeing the soft tissues or a shortening osteotomy. Acetabular dysplasia should not be underestimated in the presence of significant bone defect (BD), and reconstruction with a bone graft can be proposed. Sequelae from acetabular fractures presents a problem of associated BD. Internal fixation hardware is rarely an obstacle but the surgical approach should take this into account. Treatment of acetabular protrusio should restore a normal center of rotation, and prevent recurrent progressive protrusion. The use of bone grafts and reinforcement rings are indispensible. Femoral deformities may be congenital or secondary to trauma or osteotomy. They must be evaluated to restore hip biomechanics that are as close to normal as possible. Fixation of implants should restore anteversion, length and the lever arm. Most problems that can make THA a difficult procedure may be anticipated with proper understanding of the case and thorough preoperative planning.

[Type 2 diabetes in the elderly, which specific features?]. / Diabète de type 2 chez le sujet âgé: quelles spécificités?

Type 2 diabetes, whose prevalence has increased among elderly aged over 75 years, has a number of specific features which differ from that in young people: heterogeneous population, association with other cardiovascular risk factors and several comorbidities, different therapeutic constraints and risks, and lower life expectancy. By using a standardized geriatric assessment it is possible to determine therapeutic and glycemic goals for each patient. In the elderly, main complications of diabetes are hypoglycemia and foot lesions. In order to avoid malnutrition, lifestyle and dietary rules should not be too strict. Recommendations for the prescription of oral antidiabetic agents are the same for both elderly and young subjects, but with increased monitoring in the elderly because of the high risk of complications including iatrogenic hypoglycemia. Insulin therapy should be preferred.

Increased erythrocytes n-3 and n-6 polyunsaturated fatty acids is significantly associated with a lower prevalence of steatosis in patients with type 2 diabetes.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is commonly associated with obesity, metabolic syndrome and type 2 diabetes. Although dietary fat contributes substantially to the accumulation of liver fat, the role of individual fatty acids in this accumulation is unclear. OBJECTIVE: In this study, we set out to determine whether liver fat content (LFC), was associated with red blood cell fatty acid (RBC-FA) composition in people with type 2 diabetes. DESIGN, SETTINGS, AND PARTICIPANTS: One hundred and sixty-two type 2 diabetic patients were included in this study. LFC was measured using (1)H-MR Spectroscopy. RBC-FA composition was measured by gas chromatography. RESULTS: One hundred and nine (67.2%) patients had steatosis. Patients with steatosis had a higher BMI (p = 0.0005), and higher plasma triglyceride levels (p = 0.009) than did patients without steatosis. We report a significant association between palmitic acid (16:0), palmitoleic acid (16:1n-7) concentrations and ratio of monounsaturated to saturated fatty acid (palmitoleic acid to palmitic acid) and higher liver fat content. Total polyunsaturated fatty acid (PUFA), homo-gamma-linolenic acid (20:3n-6), docosahexaenoic acid (22:6n-3), and arachidonic acid (20:4 n-6) were associated with lower LFC. CONCLUSIONS: Our data showed that an increased erythrocytes long-chain n-3 and n-6 fatty acids was associated with a lower prevalence of steatosis in patients with type 2 diabetes. These results suggest that n-3 and n-6 fatty acids supplementation could be a promising treatment for NAFLD in patients with type 2 diabetes.

Non-ultrasound-guided ethanol sclerotherapy for the treatment of thyroid cysts.

OBJECTIVE: Ethanol injection under ultrasound (US) guidance has been proposed as an alternative to surgery in the treatment of recurrent benign thyroid cysts following aspiration. We aimed to set up a new procedure of ethanol sclerotherapy without US guidance for the treatment of pure thyroid cysts in order to make this useful treatment, available to more patients, more particularly when access to centers specialized in thyroid ultrasonography is limited. PATIENTS AND METHODS: Nine patients with recurrent large thyroid cysts following aspiration, and showing symptoms of compression and/or cosmetic complaints were treated by ethanol injection without US guidance and followed for up to 11 years. RESULTS: After ethanol injection, mean cyst volume was significantly reduced (9.9 ± 13.6 vs. 31.3 ± 34.1 ml, P=0.007) and the mean percentage volume reduction was 72.7%. A size reduction of the thyroid lesion more than 50% was achieved in eight of the nine patients (89%). Compressive symptoms and cosmetic complaints totally disappeared after sclerotherapy in all patients. During a mean follow-up of 48 months (ranging from 12 to 135 months), no recurrences were observed. The treatment was well tolerated with no major side effects. CONCLUSION: Non-US-guided ethanol sclerotherapy is a safe and "easy-to-use" procedure to treat benign thyroid cysts effectively. Because this new treatment does not need US-guidance, it can be performed by endocrinologists during outpatient visits. This new procedure may be useful in some areas, such as developing countries, where access to US examination is limited.