Low-protein diets (LPD) are recommended in chronic kidney disease (CKD) to reduce disease progression. However, their clinical efficacy and safety are debated due to the risk of protein-energy wasting. A deeper mechanistic understanding is therefore required. Herein, the metabolic effects of LPD in both murine models and a randomized controlled trial in nondiabetic CKD patients were investigated, focusing on glucose homeostasis, plasmatic uremic toxin (UTs) levels, gut microbiota remodeling, and endocrine adaptations. In both experimental and clinical settings, LPD improved glucose tolerance and significantly decreased circulating levels of gut-derived UTs while reducing body weight (-33% weight gain in mice and a decrease in body mass index of ~-0.5 kg/m2 in humans). These metabolic improvements were associated with alterations in gut microbiota composition and function, including the downregulation of microbial pathways involved in aromatic amino acid biosynthesis. In both mice and patients, LPD triggered a significant hepatic induction of fibroblast growth factor 21 (FGF21), an endocrine regulator of amino acid deficiency (+2.9-fold in human and 28-fold in mice) FGF21 levels correlated negatively with lean mass and positively with fat mass and glycemic control, supporting a dual role in metabolic adaptation and catabolic signaling. To mitigate the adverse nutritional effects of LPD, we administered Lactiplantibacillus plantarum WJL (LpWJL), a probiotic previously found to enhance growth of under nutritional stress in CKD mice. LpWJL restored circulating amino acid levels, suppressed FGF21 induction (-26%) and stress-related biosynthetic responses, and preserved body weight (+247% weight gain) and composition, without impairing the benefits of LPD on kidney and metabolic parameters. The present findings identify UTs and FGF21 as crucial factors of the metabolic response to LPD, and support microbiota-targeted strategies, such as LpWJL supplementation, to enhance LPD efficacy. Clinical trials are, however, required to confirm their relevance in CKD management.

Background: Chronological age is an imperfect proxy for risk assessment in geriatric oncology. There is an urgent need for an objective, easily measurable biological aging signature to refine patient stratification and personalize therapeutic decisions. Methods: We analyzed a panel of seven aging-related biomarkers (including markers of inflammation, anabolic reserve, and telomere status) in 244 nonmetastatic breast cancer patients from two age groups (“Old”, ≥70 years, N = 162; “Young”, ≤60 years, N = 82). We used Latent Class Analysis (LCA) to integrate these markers and identify distinct biological risk profiles. These profiles were then evaluated for their association with Overall Survival (OS) and Cancer-Specific Death (CSD) via Competing Risk Analysis. Results: LCA identified two patient profiles. The Unfavorable Biologic Profile (56.1% of the cohort) was defined by a triad of high MCP-1, high Chitinase activity, and low IGF-1. This profile was strongly associated with poorer OS (Age-adjusted HR=1.82, p = 0.018). Crucially, 15% of chronologically “Young” patients were assigned to this high-risk profile, while 23% of “Old” patients were assigned to the Favorable Profile. Furthermore, the Unfavorable Profile was more strongly and specifically associated with CSD (Subdistribution HR: 2.05, p = 0.012) than with Non-Cancer Death. Conclusion: Our results delineate an unfavorable, trans-chronological biological profile that identifies patients with low host reserve, largely driven by inflammaging and catabolism. This integrated signature provides a robust, objective screening tool to identify biologically frail patients, validating the need for Comprehensive Geriatric Assessment (CGA) and biomarker-guided therapeutic de-escalation (e.g., avoiding adjuvant chemotherapy) to improve individualized outcomes in oncology.Trial registration: BS32220096117.

Objectives: Although the mechanism of action of the antidiabetic drug metformin is still a matter of discussions, increasing evidence points to a pivotal role of the gut. Aiming to clarify whether metformin-induced changes in the intestinal tract directly contribute to metabolic improvement, we evaluated the effects of escalating doses (from 50 to 200 mg/kg/day) of metformin orally administered for 4 weeks in mice made glucose intolerant by ten weeks of high fat high sucrose diet. Methods: Several intestinal parameters were studied, including caecal microbiota composition and bile acids profile, ileal FXR signaling, abundance of GLP1-producing cells and goblet cells and blood metabolome. Results: Metformin restored glucose tolerance, fasting insulinemia and HOMA-IR index in a dose-dependent manner. Only a subset of gut-related effects, including mucus production and GLP-1 expression, exhibited a parallel dose–response relationship, suggesting a possible contribution to the observed metabolic improvements. In contrast, other changes, including ileal Fxr-Fgf15 inhibition and hepatic ceramide reduction did not scale with dose, suggesting they are not the main drivers of metformin dose-dependent effects on glycemic control. We also pointed out marked differential sensitivity of gut bacteria to metformin supporting complex interactions of the drug with the microbial ecosystem. Conclusion: Finally, metformin enhanced the proliferation of intestinal epithelium, resulting in increased length of ileal villi. Altogether, this study offers new insights into the metformin mechanism of action and revealed potential novel microbial biomarkers and targets for enhancing its therapeutic efficacy.

Metabolomics is an approach to systems biology which studies the metabolic profiles of biological fluids, cells, tissues or organisms as a function of pathophysiological conditions or in response to different stimuli or treatments. Despite its development in research, its use in laboratory medicine remains limited and the contours of clinical metabolomics are not clearly defined. In June 2024, the French Society of Clinical Biology (SFBC)'s 'Clinical Metabolomics in Laboratory Medicine' working group conducted an online survey to establish the current status of clinical metabolomics players in France and to better define the issues and expectations involved. Of the 37 specialists who responded, 75% were affiliated to laboratory medicine, while the others were only affiliated to a research unit. The results revealed a wide range of analytical approaches, with mass spectrometry being the most widespread, with targeted and untargeted approaches depending on the objectives of the laboratories. The most frequently mentioned clinical areas of application were hereditary metabolic diseases (45%), metabolic diseases (45%), nutrition (35%), oncology (32%) and neurology (26%). The definitions of clinical metabolomics varied widely depending on the context in which the participants practiced. In this publication, the SFBC Working Group aims to define the scope and objectives of clinical metabolomics in laboratory medicine, relying in particular on a glossary designed to harmonize dedicated terminology.

Abstract Background and Aims Despite the demonstrated efficacy of a low-protein diet (LPD) in slowing the progression of chronic kidney disease (CKD), the underlying mechanisms remain inadequately understood. Given the potential drawbacks, including poor compliance and a risk of malnutrition, gaining insights into the molecular mechanisms driving these benefits is crucial for safe clinical translation. In this study, our objectives were to 1) assess the impact of an LPD on the metabolic health of individuals and mice with CKD; 2) investigate the hypothesis that these effects are mediated by a reduction in uremic toxins; and 3) explore whether the combination of an LPD and supplementation with a strain of Lactiplantibacillus plantarum (strain LpWJL), selected for its ability to enhance growth in a Drosophila model of diet-induced stunting, could synergistically amplify the positive effects of the LPD while minimizing its potential adverse consequences. Method We recruited CKD patients with no diabetes or prediabetes, who were randomized to a LPD and cetoanalogues (0.4 g/kg/day) (n = 5) or a normal diet (ND) (0.8 g/kg/day, n = 6) for 3 months. A glucose tolerance test was measured at baseline and after 3 months. Four groups of mice were studied: a sham group with a ND (n = 4), 5/6th nephrectomized mice with a ND (n = 7), and 5/6th nephrectomized mice with LPD (5% w/w) and LPwjl (n = 7) or placebo (n = 7) for 6 weeks. Blood samples and liver tissues were analyzed with the MxP 500 Quant® (Biocrates) kit by LC-MS/MS (XEVO TQ-XS, Waters). Results Under LPD, beta cell function showed improvement (Matsuda index, P = 0.049, and AUC insulin, P = 0.02). Although the diet did not influence body composition, the LPD group exhibited a reduction in muscle strength (P = 0.02). LPD decreased blood concentration several uremic toxins such as indoxyl sulfate and TMAO. Insulin sensitivity and beta-cell function demonstrated negative correlations with urea, TMAO, and indoxyl sulfate. Mouse studies confirmed the positive impact of LPD on glucose homeostasis but also revealed detrimental effects on lean mass and fat mass. Supplementation with LpWJL during LPD mitigated the loss of fat mass, improved the insulin tolerance test, and enhanced the reduction of certain blood uremic toxins, including indoxyl sulfate. LpWJL supplementation exerted a substantial impact on the hepatic metabolome, resulting in increased triglyceride accumulation and decreased levels of diglycerides, acylcarnitines, and phosphocholines. Conclusion We have highlighted the substantial benefits of a 3-month LPD on markers of glucose homeostasis and uremic toxins in mice and humans without diabetes. LpWJL induced profound modifications in both blood and liver metabolome and was associated with a limitation of trophic alterations in LPD diet-induced CKD mice, while also enhancing glucose homeostasis. Further studies are essential to gain a better understanding of the underlying mechanisms involved.

Background: Determining the cause of hypoglycemia partly relies on blood insulin and C-peptide assays. Although the pancreatic secretion of these peptides is equimolar, discrepancies in their concentrations may occur. Case presentation: We report the case of a 73-year-old woman with type 2 diabetes mellitus (T2DM) and a history of gastric bypass. The T2DM was initially treated with insulin analogs, which were interrupted due to transient hypoglycemia episodes three years before hospitalization in our endocrinology department. During this hospitalization, the most common etiologies of hypoglycemia were excluded. Fasting insulin level was high (190 mIU/L, reference values (RV): 5–25) on Architect i2000 (an assay recognizing insulin analogs) despite normal blood C-peptide (4.5 μg/L, RV: 0.8–5.2) and slight hypoglycemia (4.5 mmol/L, RV: 4.6–6.1). Insulin level using the Elecsys assay (an assay with low sensitivity to insulin analogs) was very high (>1000 mIU/L, RV: 2.6–24.9). This pattern was observed on several samples, including some taken during a fasting test. Insulin level was only slightly increased using the Mercodia iso-insulin ELISA kit (an assay recognizing insulin analogs). These results excluded an exogenous insulin intake and were suggestive of an interference on insulin assays. To explore the latter possibility, free anti-insulin antibodies were measured and found strongly positive. The presence of interfering insulin-antibody complexes was further investigated using gel filtration chromatography, polyethylene glycol precipitation, and dilution test. Based on these findings, an insulin autoimmune syndrome (IAS) was suspected to cause the hypoglycemic episodes observed. Conclusion: Although a discrepancy between blood insulin and C-peptide levels points to insulin analog intake, IAS should also be considered, particularly in a patient with transient hypoglycemia. IAS is characterized by the presence of insulin-antibody complexes, which can induce varying degrees of interference on insulin immunoassays and may lead to discordant insulin and C-peptide levels according to the insulin immunoassay used.

(1) Background: Dysregulated serum amino acids (AA) are known to be associated with obesity and risk of Type 2 Diabetes (T2D) in adults, and recent studies support the same notion in the pubertal age. It is, however, unknown whether childhood overweight may already display alterations of circulating AA. (2) Methods: We used liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS)—targeted metabolomics to determine plasma concentrations of AA and AA-related molecules in 36 children aged 7–12 years with normal weight or overweight. Clinical and anthropometric parameters were measured. (3) Results: Overweight in children is associated with an altered AA profile, with increased branched-chain amino acids (BCAA) and decreased glycine levels, with no clinically manifested metabolic conditions. Moreover, z-BMI was positively and negatively correlated with BCAA and glycine levels, respectively, even after adjustment for age and gender. We also found a correlation between the AA profile and clinical parameters such as lipids profile and glycemia. (4) Conclusions: A pattern of low glycine, and increased BCAA is correlated to z-BMI, total cholesterol, and triglycerides in overweight but otherwise healthy children. Our data suggest that, in childhood overweight, AA disturbances may precede other clinical parameters, thus providing an early indicator for the later development of metabolic disease.

Delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH) is a major cause of complications and death. Here, we set out to identify high-performance predictive biomarkers of DCI and its underlying metabolic disruptions using metabolomics and lipidomics approaches. This single-center prospective observational study enrolled 61 consecutive patients with severe aSAH; among them, 22 experienced a DCI. Nine patients without aSAH were included as validation controls. Blood and cerebrospinal fluid (CSF) were sampled within the first 24 h after admission. We identified a panel of 20 metabolites that, together, showed high predictive performance for DCI. This panel of metabolites included lactate, cotinine, salicylate, 6 phosphatidylcholines, and 4 sphingomyelins. The interplay of the metabolome and the lipidome found between CSF and plasma in our patients underscores that aSAH and its associated DCI complications can extend beyond cerebral implications, with a peripheral dimension as well. As an illustration, early biological disruptions that might explain the subsequent DCI found systemic hypoxia driven mainly by higher blood lactate, arginine, and proline metabolism likely associated with vascular NO and disrupted ceramide/sphingolipid metabolism. We conclude that targeting early peripheral hypoxia preceding DCI could provide an interesting strategy for the prevention of vascular dysfunction.

Progressive decline in pancreatic beta-cell function is central to the pathogenesis of type 2 diabetes (T2D). Here, we explore the relationship between the beta cell and its nutritional environment, asking how an excess of energy substrate leads to altered energy production and subsequent insulin secretion. Alterations in intracellular metabolic homeostasis are key markers of islets with T2D, but changes in cellular metabolite exchanges with their environment remain unknown. We answered this question using nuclear magnetic resonance-based quantitative metabolomics and evaluated the consumption or secretion of 31 extracellular metabolites from healthy and T2D human islets. Islets were also cultured under high levels of glucose and/or palmitate to induce gluco-, lipo-, and glucolipotoxicity. Biochemical analyses revealed drastic alterations in the pyruvate and citrate pathways, which appear to be associated with mitochondrial oxoglutarate dehydrogenase (OGDH) downregulation. We repeated these manipulations on the rat insulinoma-derived beta-pancreatic cell line (INS-1E). Our results highlight an OGDH downregulation with a clear effect on the pyruvate and citrate pathways. However, citrate is directed to lipogenesis in the INS-1E cells instead of being secreted as in human islets. Our results demonstrate the ability of metabolomic approaches performed on culture media to easily discriminate T2D from healthy and functional islets.

Les dosages d’insuline et de peptide C sanguins font partie du bilan étiologique des hypoglycémies, et bien que leur sécrétion pancréatique soit équimolaire, certaines situations conduisent à des discordances de leurs concentrations. Nous rapportons le cas d’une femme de 73 ans hospitalisée en service d’endocrinologie pour bilan d’hypoglycémies transitoires avec hyperinsulinisme connu depuis trois ans. Elle présentait un diabète de type 2 traité par antidiabétiques oraux et insulinothérapie depuis quinze ans, traitement relayé par acarbose trois ans auparavant face aux épisodes d’hypoglycémies et arrêté deux semaines avant l’hospitalisation. Elle n’avait aucun antécédent de maladie auto-immune. À jeun, l’insulinémie était très élevée sur Architect I2000 (dosage reconnaissant les analogues de l’insuline) et sur Cobas e411 (dosage ne reconnaissant pas les analogues de l’insuline) contrairement à un peptide C normal et une glycémie à 4,5 mmol/L (normes 4,6–6,1). Une épreuve de jeune sans hypoglycémie, un scanner abdominal sans lésion pancréatique, l’absence de troubles digestifs, des dosages sanguins normaux de cortisol à 8 h, IGF1, pro-insuline, les recherches négatives d’insuline exogène et sulfamides hypoglycémiants ont permis d’exclure certaines étiologies d’hypoglycémies. Finalement, les anticorps anti-insuline libres étaient fortement positifs permettant de suspecter le syndrome auto-immun anti-insuline (SAIAI). Une discordance entre l’insulinémie et le peptide C doit faire suspecter une prise d’analogue de l’insuline si la technique de dosage d’insuline y est sensible. Plus rarement, il peut s’agir du SAIAI caractérisé par la présence d’anticorps anti-insuline qui captent l’insuline endogène et la relarguent ensuite indépendamment de la glycémie causant alors des hypoglycémies.

12037 Background: The aging process is heterogeneous and the result of different biological mechanisms. Blood biomarkers involved in the aging process, aside from comprehensive geriatric assessment, may help clinicians when facing equivocal therapeutic decisions, for example adjuvant treatment at high risk of toxicities. Methods: This study was conducted on a previously published cohort (PMID 25989735) including 162 patients aged ≥70 years (“Old”) and 82 patients aged ≤60 years (“Young”) with newly diagnosed non-metastatic breast cancer. Serum samples collected from all patients at breast cancer diagnosis, before any treatment were available from the extensive Leuven blood biobank. Overall survival was evaluated with October 7, 2022 as data cutoff. A panel of blood aging biomarkers attributed to inflammation: IL6, MCP1, RANTES, telomere shortening: telomeric DNA ratio T/S, telomeric dysfunction: CRAMP, chitinase activity, and anabolism : IGF1. Considering a high risk of collinearity, we performed a latent class analysis (LCA) on the whole cohort, to delineate the respective roles of inflammaging, replicative senescence and sarcopenia on patient clusters. Results: In univariate analysis were significantly associated with a poorer survival: high MCP1, hazard ratio (HR) = 1.57 (95%CI 1.32-1.87), high chitinase activity, HR = 1.33 (95%CI 1.12-1.57), and low IGF1, HR = 1.76 (95%CI 1.47-2.11). The biomarkers correlation matrix identified a significant correlation of Chitinase activity with MCP1, IGF1, CRAMP; of CRAMP with IL6; and IGF1 with T/S ratio. LCA identified 2 biologic profiles within the population, representing 137 (56.1%, class 1) and 107 (43,9%, class 2) patients. Class 1 was associated with a significantly poorer overall survival: HR = 3.52 (95%CI 2.28-5.45), and age-adjusted HR = 1.77 (95%CI 1.12-2.80). The best predictors for class 1 membership were low IGF1 (89%), high MCP1 (82%), high chitinase activity (79%), high IL6 (69%). Class 1 represented 77% of the “Old” and 15% of the “Young” populations. Conclusions: Our results delineate an unfavorable biologic profile that transcends chronological age and significantly predicts a poorer overall survival, underpinned by markers of both inflammaging, telomeric dysfunction and sarcopenia. The strong correlation between markers argues for a unique underlying biological pathway. Noteworthy, high IGF1, usually considered as a risk factor for breast cancer progression, was associated with a better prognosis. Low IGF1, high chitinase activity and high MCP1 appear as promising predictive biomarkers.

Introduction/Background Older patients with ovarian cancer have poor outcomes; the geriatric vulnerability score (GVS) was validated as a prognostic factor for survival. During aging the circulating Chitinase 3-like-1 (CHI3L1), and its related chitinase enzymatic activity increase, leading to propose them as 'aging biomarkers'. However, recent data supported the implication of chitinase-like proteins in the proliferation of several cancers. The EWOC-1 trial (NCT02001272) showed a lower efficacy of the carboplatin monotherapy (Cmono) arm compared to carboplatin-paclitaxel (CP) in vulnerable patients; a serum sampling was provided on inclusion, after 3 and 6 courses of chemotherapy for the measurement of chitinase activity in each arm (A: standard CP; B: Cmono; C: 3weeks/4 CP), to identify whether its association with patients' outcomes and inversely, the differential impact of the distinct treatment regimens on it. Methodology Chitinase activity was assessed as previously published. Were analyzed both its absolute value on inclusion ('chitinase baseline') and its kinetics after 3 chemotherapy courses ('chitinase response'). Results Serum samples could be retrieved for 46/120 patients on inclusion and 33 after 3 chemotherapy courses. Chitinase baseline median activity (in U/L, IQR) was 1727.9 (1459.3; 1878.3) at inclusion, similar in the 3 arms; no association was shown with any of the geriatric vulnerability parameters, nor the GVS, nor overall survival. Chitinase response was significantly different in the 3 arms, with a median (in U/L, IQR) of -160 (-297; 35.2) in the total cohort, -272 (-376; -122) in arm A, 105 (-109; 221) in arm B and -160 (-663; -109) in arm C, p=0.008. High chitinase response was associated with high CA-125 ELIMination rate constant K (KELIM), a marker of chemosensitivity (Fisher exact test, p=0.042). Conclusion Chitinase activity should not be considered, in the context of ovarian cancer as an aging biomarker, but chitinase response appears as a promising marker of chemosensitivity.

Department of Endocrinology and Metabolic Diseases, Cardiovascular and Metabolic Unit, CHU Larrey, Toulouse, France Laboratoire de Biochimie et d'Hormonologie, Institut Fédératif de Biologie, Hôital Purpan, CHU Toulouse, Toulouse, France Laboratoire de Biochimie et Biologie Moléculaire—Centre Hospitalier Lyon Sud. ISPB, Faculté de Pharmacie de Lyon—UCBL1. Laboratoire CARMEN INSERM U1060, INRA U1397, Université Lyon 1, INSA Lyon, Lyon, France Division of Endocrinology, Hospital Saint Pierre, University of Brussels, Brussels, Belgium

Analysis of human insulin and its synthetic analogues is increasingly requested for clinical monitoring, for anti-doping purposes, but also for forensic cases. Indeed, insulin analogues may be abused for suicide or homicide whence their forensic interest. Collection and storage conditions, as well as the phenomenon of degradation make post-mortem serum samples analytically challenging and consequently, the rate of exogenous insulin administration as cause of death is undoubtedly underestimated. However, with recent technological advances and the development of new extraction techniques particularly for anti-doping analyses, detection of insulins in post-mortem samples seems to be achievable. This study describes the first validated quantitative method for analysis human insulin and its six analogues (lispro, aspart, glulisine, glargine, detemir and degludec) in plasma and post-mortem sera. Various extraction processes, namely precipitation + solid phase extraction (SPE), filtration + SPE, precipitation + SPE + immunopurification, and filtration + immunopurification, were assessed to evaluate the lowest limit of detection for all target analogues. The selected sample preparation consists of filtration step followed by immunopurification extraction with an anti-body precoated ELISA plate for plasma. For post-mortem sera, the first step of precipitation was added to remove matrix interferences. The extracts were analyzed by ultra-high-performance liquid chromatography-high resolution mass spectrometry (LC-HRMS), interfaced by electrospray (ESI). The method was validated with respect linearity, precision, accuracy, recovery, matrix effect, dilution and carryover. The limit of quantification (LOQ) in plasma was 0.5 ng/mL for human insulin and rapid-acting insulins, 1.0 ng/mL for glargine, 2.5 ng/mL for degludec and 10 ng/mL for detemir. Two types of post-mortem sera were studied based on the post-mortem interval (PMI): inferior or superior to 48 h. The obtained LOQ were the same for each analogue, independent from the PMI: 1.0 ng/mL for human insulin and rapid-acting insulins, 1.0 ng/mL for glargine, 2.5 ng/mL for degludec and 10 ng/mL for detemir. At the LOQ level, for all insulins and all samples, accuracy was between 70 and 130% and precision inferior to 30%. The validated method was applied to five subjects participating in therapeutic monitoring of insulin and to seven post-mortem cases.

Thyrotoxicosis is an adverse event associated with immune checkpoint inhibitors (ICPis) that occurs in 0.6 to 3.2% of treated patients, depending on ICPi class. Presentation usually consists of a biphasic thyroiditis with transient thyrotoxicosis and secondary hypothyroidism. ICPi-induced Graves' disease (GD), due to the stimulating activity of TSH-receptor autoantibodies (TRAb), is extremely rare. The aim of this retrospective study was to describe the characteristics and evolution of GD during ICPi therapy. Five among 243 patients followed for ICPi-induced thyrotoxicosis showed TRAb positivity (2% of the cohort). GD occurred quickly after initiation of ICPis; its course was typical for two patients, with prolonged requirement for antithyroid drug treatment (ATD). The three other patients experienced biphasic thyroiditis with secondary hypothyroidism requiring long-term substitution. Three other patients had a diagnosis of GD before starting ICPis; they evolved toward hypothyroidism with early cessation of ATD and long-term substitution treatment during ICPi treatment. None developed significant Graves' orbitopathy. ICPi treatment was not interrupted for thyroid dysfunction. In conclusion, GD is a rare, immune-related adverse event of ICPis with an unusual course and frequent evolution to biphasic thyroiditis. In the case of ICPi-induced thyrotoxicosis in the presence of TRAb, observing the spontaneous evolution and performing a scintigraphy are useful before starting ATD treatment. Pre-existing GD is not exacerbated by ICPis and tends to evolve towards hypothyroidism. ICPi treatment can be maintained with adequate biochemical surveillance.

Background Thyroglobulin (Tg) assay in washout fluids of fine needles, after cervical lymph nodes aspiration, is used for detecting metastases from differentiated thyroid carcinomas. Assay methods are the same as for Tg in serum. However, with non-serum samples, methods require extensive validation to notably check for the absence of matrix effect. This study fits this context. Our objectives were to assess analytic performances, in washout fluid, of eight different Tg assay methods and to compare them to validated data in serum. Methods Eleven medical laboratories participated in this study. The matrix tested was phosphate-buffer saline containing 1% bovine serum albumin (PBS-1% BSA). Samples used were dilutions, in this buffer, of Certified Reference Material (CRM 457). We verified, for all methods, the limit of detection, precision, linearity, trueness and accuracy. Results In PBS-1% BSA, the functional sensitivities (FS) were comparable to those expected for serum. All the methods were linear. The relative biases of trueness were between –24.5 and 10.2% around 1 µg/L. Total analytical error was ≤40% near the functional sensitivity values. Conclusion No quantitatively important matrix effect was observed. All the methods showed their ability to measure Tg in PBS-1% BSA, over the concentration range of interest, with acceptable total analytical error. We validated the functional sensitivity value as a decision threshold in thyroidectomized patients after treatment and with low concentrations of serum Tg.

Introduction: Maternal TSH receptor antibodies (TRAbs) can cross the placenta and affect fetal and neonatal thyroid function. Maternal TSH receptor-blocking antibodies (TBAbs) are a rare cause of congenital hypothyroidism. Case Report: Following the discovery of a highly elevated TSH on her neonatal screening test, a 10-day-old girl with no familial history of thyroid disorder was referred to the pediatric endocrinology unit. Hypothyroidism was confirmed with a highly elevated TSH (817 mIU/L, reference range 0.4-3.1) and very low levels of FT4 (1.8 pmol/L, reference range 12-22). Anti-TPO antibodies were at 81 IU/mL (reference range <34), TRAbs at 1.7 IU/L (reference range <1.75), and thyroglobulin at 9.4 mu g/L (reference range 3.5-77). The thyroid appeared normal on ultrasonography, and no radioiodine uptake was seen on the scintigraphy after the perchlorate discharge test. Concomitantly, a severe maternal hypothyroidism was discovered (TSH 224 mIU/L). The maternal ultrasound appeared normal, anti-TPO antibodies were moderately elevated, and TRAbs were at 3.2 IU/L. TBAbs activity was measured in the mother and her daughter, and a very high and similar blocking activity was observed in both patients (TBAbs 89%, reference range <10%). L-thyroxine treatment was introduced in the newborn and was successfully discontinued at 6.5 months of age, as the TBAbs activity decreased. Conclusion: We report herein a case of transient congenital hypothyroidism with a normal neonatal TRAbs level. In case of maternal TBAbs, similar activity of maternal TBAbs must be expected in the neonate, independently of the neonatal level of TRAbs.

L’acropachie est une manifestation cutanée rare qui complique 0,3 % des maladies de Basedow (MB). Elle est plus fréquente s’il existe un myxœdeme pré-tibial (MPT) et d’autant plus si celui-ci est sévère (20 % des MPT, 50 % des formes éléphantiasiques). Sa physiopathologie mal connue est probablement similaire à celle du MPT (facteurs immunologiques, cellulaires, mécaniques, environnementaux). Le tabac et un taux élevé d’anticorps antirécepteurs de la TSH (anti-RTSH) semblent être les facteurs majeurs de prédisposition. (1) Patient de 52 ans tabagique, qui présente depuis 6 mois une MB avec orbitopathie. Les anticorps anti-RTSH étaient initialement à 318 UI/L. Apparition d’un MPT important, et d’œdèmes douloureux progressifs et ascendants des pieds et des mains. Les radiographies montrent des appositions périostées diaphysaires typiques d’une acropachie. (2) Patient de 65 ans tabagique avec maladie de Basedow, orbitopathie peu inflammatoire pour laquelle il n’a pas eu de corticothérapie, et un MPT. Les anticorps anti-RTSH étaient à 295 UI/L malgré thyroïdectomie. Évolution défavorable du MPT vers une forme éléphantiasique progressive et apparition d’œdèmes des mains typiques d’une acropachie. L’acropachie est une complication rare mais invalidante de la MB et nécessite d’être recherchée. Les radiographies des extrémités et la scintigraphie osseuse peuvent être des aides diagnostiques. Il n’y a pas de traitement spécifique validé ; la corticothérapie de l’orbitopathie pourrait l’améliorer. Son apparition semble être le reflet d’une atteinte auto-immune sévère, et les perspectives des nouvelles immunothérapies en développement dans l’orbitopathie Basedowienne pourraient être des pistes thérapeutiques.