Introduction L’hyperthyroïdie infra-clinique (HIC) repose sur une définition biologique, mais aucune étude n’a évalué l’impact des méthodes de dosage sur la définition et sa gradation (G1 : 0,1 < TSH ...< 0,4mU/L, G2 : TSH < 0,1mU/L). Pirathes est un essai multicentrique randomisé évaluant l’intérêt du traitement par I131 sur le risque de fibrillation auriculaire chez des patients avec HIC. À l’inclusion, les patients avaient une TSH < 0,4 mU/L (à 2 reprises) et une T4L et T3L dans l’intervalle de référence des trousses utilisées localement. Méthodes Quatre-vingt-quatre femmes et vingt-cinq hommes âgés de 64 (50–86) ans ont été inclus. TSH, T4L, T3L ont été dosées dans la même série en utilisant les trousses Beckman, Abbott et Roche. Résultats À l’inclusion, la TSH était à 0,09 ± 0,09 mU/L. Parmi les patients, 27,5 % avaient une HIC G1 et 72,5 % une G2 avec les dosages locaux contre respectivement de 29,4 à 33 % et de 55 à 65,1 % avec les dosages centralisés. Suivant les trousses, le nombre de patients ayant une TSH > 0,4 mU/L variait de 3,7 à 11 %. Des valeurs au-dessus de l’intervalle de référence étaient constatées pour 4,6–6,4 % des patients pour la T4L et pour 4,6 à 25,2 % pour la T3L. Discussion Chez plus d’un tiers des patients, le diagnostic d’HIC n’aurait pas été porté avec les trousses de dosages centralisés (euthyroïdie 11 %, hyperthyroïdie 25 %). La notion de marge d’erreur dans les différents dosages de TSH, T4L et T3L devrait impérativement être prise en compte pour la définition et la gradation de l’HIC.
Obesity is a risk factor for cardiovascular diseases and venous thromboembolism. Circulating procoagulant microparticles (MP) have been described in various clinical situations associated with ...thrombosis and in diabetic patients. The aim of this preliminary study was to evaluate the presence of MP in obese patients without any other vascular risk factor in particular diabetes.
Fifty-eight obese women < 50 year-old without other cardiovascular risk factors were recruited from a single out-patient nutrition clinic. They were compared to 45 age-matched healthy normal weight controls. Main outcome was MP levels in patients and controls. Relationships between MP concentrations and parameters reflecting insulin resistance in patients were also studied.
Obese patients were 33.3 ± 1.2 years old and had a mean BMI of 42.4 ± 0.9 kg/m
2. There vas a greater proportion of smokers in the obese group (34.5 vs 15.6%). Mean MP levels were markedly higher in obese patients compared to controls (10.6 ± 0.5 vs 3.2 ± 0.3 nMPSeq, P < 0.001). There was no difference in MP concentrations between smokers and non smokers. In the obese group, there was a negative correlation between MP and BMI (r = -0.265, P < 0.05) but no relationship could be established between MP concentrations and markers of insulin resistance.
This increase in circulating MP levels reflects cell activation and could account for the increased risk of thrombotic complications in obesity. Further studies are ongoing to explore the relationships between MP levels and coagulation markers and to assess the effect of weight reduction.
Microparticules procoagulantes circulantes dans l'obésité
L'obésité est un facteur de risque de maladies cardiovasculaires et de thromboses veineuses. Les microparticules procoagulantes (MP) ont été décrites dans différentes situations cliniques associées à des thromboses et chez des diabétiques. Le but de cette étude préliminaire était d'évaluer la présence de MP chez des patientes obèses n'ayant pas d'autre facteur de risque vasculaire en particulier pas de diabète.
Cinquante-huit femmes obèses âgées de moins de 50 ans, sans autre facteur de risque cardiovasculaire recrutées à partir de la structure ambulatoire d'un service de Nutrition ont été comparées à 45 femmes de poids normal appariées sur l'âge. Le critère principal était la concentration de M P. Les relations entre MP et les marqueurs d'insulinorésistance ont également été étudiées chez les patientes.
Les patientes obèses étaient âgées de 33,3 ± 1,2 ans et avaient un IMC de 42,4 ± 0,9 kg/m
2. Il y avait une plus grande proportion de fumeuses chez les obèses par rapport aux témoins (34,5 vs 15,6 %). Les concentrations de MP étaient plus élevées chez les patientes obèses que chez les témoins (10,6 ± 0,5 vs 3,2 ± 0,3 nMPSeq, P < 0,001). Il n'y avait pas de différence de concentrations des MP entre les fumeuses et les non fumeuses. Chez les obèses, il y avait une corrélation négative entre les MP et l'IMC mais aucune relation n'a pu être établie entre les taux de MP et les marqueurs d'insulinorésistance.
L'élévation des MP témoigne d'une activation cellulaire et pourrait expliquer en partie l'augmentation du risque de thrombose dans l'obésité. Des études sont en cours pour explorer les relations entre les MP et des marqueurs de la coagulation et mesurer l'effet d'une réduction pondérale.
Summary
With the introduction of automated assays for measuring serum cobalamin levels over the last decades, the hematological manifestations related to cobalamin deficiency have been changed from ...the description reported in ‘old’ studies or textbooks. We studied the hematological manifestations or abnormalities in 201 patients (median age: 67 ± 6 years) with well‐documented cobalamin deficiency (mean serum vitamin B12 levels 125 ± 47 pg/ml) extracted from an observational cohort study (1995–2003). Assessment included clinical features, blood count and morphological review. Hematological abnormalities were reported in at least two‐third of the patients: anemia (37%), leukopenia (13.9%), thrombopenia (9.9%), macrocytosis (54%) and hypegmented neutrophils (32%). The mean hemoglobin level was 10.3 ± 0.4 g/dl and the mean erythrocyte cell volume 98.9 ± 25.6 fl. Approximately 10% of the patients have life‐threatening hematological manifestations with documented symptomatic pancytopenia (5%), ‘pseudo’ thrombotic microangiopathy (Moschkowitz; 2.5%), severe anemia (defined as Hb levels <6 g/dl; 2.5%) and hemolytic anemia (1.5%). Correction of the hematological abnormalities was achieved in at least two‐thirds of the patients, equally well in patients treated with either intramuscular or oral crystalline cyanocobalamin. This study, based on real data from a single institution with a large number of consecutive patients with well‐documented cobalamin deficiency, confirms several ‘older’ findings that were previously reported before the 1990s in several studies and in textbooks.
Increased reverse tritiodothyronine (T(3)) used to be described as a part of euthyroid sick syndrome (ESS). It was demonstrated to be associated with increased mortality in acutely ill patients. It ...can also be found with low or normal T(3) in non-severely ill subjects but its significance remains unclear.
The Alsanut study included a representative sample of 440 independently-living subjects aged 65 or over constituted between January 1988 and September 1989. Past and current medical history and nutritional data were collected at inclusion. Baseline thyroid hormone (TSH, FT(4), FT(3) and rT(3)) serum levels were measured. Life status was determined on 1 December 2005.
Of the 374 elderly subjects included in the final analysis, 52 had abnormal TSH (43 with hyperthyroidism, nine with hypothyroidism) and 80.7% had died by 1 December 2005. There was no statistical difference in survival between subjects according to thyroid function (P=0.54). Of the 322 elderly subjects with normal TSH, mortality rate was 81.1%. ESS was found in 3.4%, whereas 8.1% of the participants displayed elevated rT(3) with normal FT(3). Time to death was strongly related to rT(3) (P<0.0001) and FT(3) (P<0.0001) in a univariate analysis. After adjusting for other confounding variables, rT(3) was the only thyroid hormone associated with shorter survival (P=0.014).
RT(3) was the only thyroid hormone associated with shorter survival in a representative population of independently-living elderly. In these subjects, isolated elevated rT(3) might be an equivalent of ESS, reflecting declining health.
Obesity and cancer Schlienger, J-L; Luca, F; Vinzio, S ...
La revue de medecine interne
30, Issue:
9
Journal Article
Peer reviewed
Obesity which is now well recognized as a public health problem increases the risk of developing cancers. Some systematic review and meta-analyses assessed the strength of associations between body ...mass index and common cancers such as breast, endometrial, colon and adenocarcinoma of oesophagus. The causal mechanisms remain unexplained. However, epidemiological data and animal models have provided some evidence that hormonal alteration linked to obesity, such as hyperinsulinism, high insulin-like growth factor (IGF-1) levels or biodisponibility, low adiponectin serum level and high oestradiol serum level resulting from an enhanced aromatase activity may have mitogenic and antiapoptotic effects. The inflammation associated with visceral adiposity is another factor which promotes cancer. To date, there are no convincing data that weight loss could improve the prognosis of treated neoplasia. However, a regular physical activity and a limited caloric intake are probably safe in healthy subject to prevent cancer and also in cancer survivors.
Peripheral neuropathies sometimes complicate bariatric surgery.
We report the detailed clinical, electrophysiological, biological and histological characteristics of five patients who developed ...peripheral neuropathy after bariatric surgery.
Three patients presented with small fiber neuropathy, one presented with axonal polyneuropathy, and one with demyelinating polyradiculoneuropathy. All patients had in common prominent neuropathic pain, massive weight loss, and multiple nutritional deficiencies. The pathophysiology of postbariatric surgery polyneuropathies is complex and involves nutritional, infectious and dysimmune mechanisms.
The spectrum of peripheral neuropathies complicating bariatric surgery is wide, and includes pure small fiber neuropathy, axonal polyneuropathy, and demyelinating polyradiculoneuropathy. Treatment is mainly preventive, but sometimes surgical revision is needed.
In their comprehensive Seminar on varicella (Oct 14, p 1365),1 Ulrich Heininger and Jane Seward do not mention an unusual presentation of varicella-zoster virus reactivation that affects ...immunocoinpromised patients (eg, AIDS patients or recipients of stem-cell transplants).
Summary
Background
A new autoinflammatory syndrome related to somatic mutations of UBA1 was recently described and called VEXAS syndrome (‘Vacuoles, E1 Enzyme, X‐linked, Autoinflammatory, Somatic ...syndrome’).
Objectives
To describe clinical characteristics, laboratory findings and outcomes of VEXAS syndrome.
Methods
One hundred and sixteen patients with VEXAS syndrome were referred to a French multicentre registry between November 2020 and May 2021. The frequency and median of parameters and vital status, from diagnosis to the end of the follow‐up, were recorded.
Results
The main clinical features of VEXAS syndrome were found to be skin lesions (83%), noninfectious fever (64%), weight loss (62%), lung involvement (50%), ocular symptoms (39%), relapsing chondritis (36%), venous thrombosis (35%), lymph nodes (34%) and arthralgia (27%). Haematological disease was present in 58 cases (50%): myelodysplastic syndrome (MDS; n = 58) and monoclonal gammopathy of unknown significance (n = 12; all patients with MGUS also have a MDS). UBA1 mutations included p.M41T (45%), p.M41V (30%), p.M41L (18%) and splice mutations (7%). After a median follow‐up of 3 years, 18 patients died (15·5%; nine of infection and three due to MDS progression). Unsupervised analysis identified three clusters: cluster 1 (47%; mild‐to‐moderate disease); cluster 2 (16%; underlying MDS and higher mortality rates); and cluster 3 (37%; constitutional manifestations, higher C‐reactive protein levels and less frequent chondritis). The 5‐year probability of survival was 84·2% in cluster 1, 50·5% in cluster 2 and 89·6% in cluster 3. The UBA1 p.Met41Leu mutation was associated with a better prognosis.
Conclusions
VEXAS syndrome has a large spectrum of organ manifestations and shows different clinical and prognostic profiles. It also raises a potential impact of the identified UBA1 mutation.
What is already known about this topic?
VEXAS syndrome is a recently described autoinflammatory disease related to UBA1 mutation. The clinical phenotype includes patients with thrombosis, fever, chondritis, neutrophilic dermatosis and MDS.
What does this study add?
The main clinical features of VEXAS patients remain recurrent fever (64.7% vs. 72%, in original description by Beck et al.), skin lesions (83.6% vs. 88%), lung infiltrates (49.1% vs. 72%), unprovoked thrombosis (35.5% vs. 44%), with new features such as arthralgia (28.4%), ocular involvement (40.5%) or lymph node enlargement (34.5%), expanding the previous clinical phenotype of VEXAS syndrome.
We identified 3 clusters of VEXAS syndrome, including an MDS‐related phenotype; mild‐to‐moderate disease with less fever, chondritis and thromboembolism, and one with more ‘inflammatory' profile characterized by cutaneous vasculitis lesions and relapsing profile.
A phenotype–genotype association was observed for UBA1 p.Met41Leu which was associated with less ‘inflammatory' and mild‐to‐moderate phenotype and better overall prognosis.
Linked Comment: L.T. Nicholson and L.M. Madigan. Br J Dermatol 2022; 186:392–393.
Plain language summary available online
PDF
