Marie-Liesse Piketty

Bio: Marie-Liesse Piketty is an academic researcher from Necker-Enfants Malades Hospital. The author has contributed to research in topics: Internal medicine & Medicine. The author has an hindex of 7, co-authored 14 publications receiving 350 citations.

High-dose biotin therapy leading to false biochemical endocrine profiles: validation of a simple method to overcome biotin interference.

Abstract: Background High-dose biotin therapy is beneficial in progressive multiple sclerosis (MS) and is expected to be adopted by a large number of patients. Biotin therapy leads to analytical interference in many immunoassays that utilize streptavidin-biotin capture techniques, yielding skewed results that can mimic various endocrine disorders. We aimed at exploring this interference, to be able to remove biotin and avoid misleading results. Methods We measured free triiodothyronine (fT3), free thyroxine (fT4), thyroid-stimulating hormone (TSH), parathyroid homrone (PTH), 25-hydroxyvitamin D (25OHD), follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, C-peptide, cortisol (Roche Diagnostics assays), biotin and its main metabolites (liquid chromatography tandem mass spectrometry) in 23 plasmas from MS patients and healthy volunteers receiving high-dose biotin, and in 39 biotin-unsupplemented patients, before and after a simple procedure (designated N5) designed to remove biotin by means of streptavidin-coated microparticles. We also assayed fT4, TSH and PTH in the 23 high-biotin plasmas using assays not employing streptavidin-biotin binding. Results The biotin concentration ranged from 31.7 to 1160 µg/L in the 23 high-biotin plasmas samples. After the N5 protocol, the biotin concentration was below the detection limit in all but two samples (8.3 and 27.6 μg/L). Most hormones results were abnormal, but normalized after N5. All results with the alternative methods were normal except two slight PTH elevations. In the 39 biotin-unsupplemented patients, the N5 protocol did not affect the results for any of the hormones, apart from an 8.4% decrease in PTH. Conclusions We confirm that most streptavidin-biotin hormone immunoassays are affected by high biotin concentrations, leading to a risk of misdiagnosis. Our simple neutralization method efficiently suppresses biotin interference.

Reference Values for IGF-I Serum Concentrations: Comparison of Six Immunoassays

Abstract: Context: Measurement of IGF-I is essential for diagnosis and management of patients with disorders affecting the somatotropic axis. However, even when IGF-I kit manufacturers follow recent consensus guidelines, different kits can give very different results for a given sample. Objectives: We sought to establish normative data for six IGF-I assay kits based on a large random sample of the French general adult population. Subjects and Methods: In a cross-sectional multicenter cohort study, we measured IGF-I in 911 healthy adults (18-90 years) with six immunoassays (iSYS, LIAISON XL, IMMULITE, IGFI RIACT, Mediagnost ELISA, and Mediagnost RIA). Pairwise concordance between assays was assessed with Bland-Altman plots for both IGF-1 raw data and standard deviation scores (SDS), as well as with the percentage of observed agreement and the weighted Kappa coefficient for categorized IGF-I SDS. Results: Normative data included the range of values (2.5-97.5 percentiles) given by the six IGF-I assays according to age group and sex. A formula for SDS calculation is provided. Although the lower limits of the reference intervals of the six assays were similar, the upper limits varied markedly. Pairwise concordances were moderate to good (0.38-0.70). Conclusion: Despite being obtained in the same healthy population, the reference intervals of the six commercial IGF-1 assay kits showed noteworthy differences. Agreement between methods was moderate to good.

False biochemical diagnosis of hyperthyroidism in streptavidin-biotin-based immunoassays: the problem of biotin intake and related interferences

Abstract: Immunoassays are now commonly used for hormone measurement, in high throughput analytical platforms. Immunoassays are generally robust to interference. However, endogenous analytical error may occur in some patients; this may be encountered in biotin supplementation or in the presence of anti-streptavidin antibody, in immunoassays involving streptavidin-biotin interaction. In these cases, the interference may induce both false positive and false negative results, and simulate a seemingly coherent hormonal profile. It is to be feared that this type of errors will be more frequently observed. This review underlines the importance of keeping close interactions between biologists and clinicians to be able to correlate the hormonal assay results with the clinical picture.

How the reference values for serum parathyroid hormone concentration are (or should be) established

Abstract: Well-validated reference values are necessary for a correct interpretation of a serum PTH concentration. Establishing PTH reference values needs recruiting a large reference population. Exclusion criteria for this population can be defined as any situation possibly inducing an increase or a decrease in PTH concentration. As recommended in the recent guidelines on the diagnosis and management of asymptomatic primary hyperparathyroidism, PTH reference values should be established in vitamin D-replete subjects with a normal renal function with possible stratification according to various factors such as age, gender, menopausal status, body mass index, and race. A consensus about analytical/pre-analytical aspects of PTH measurement is also needed with special emphasis on the nature of the sample (plasma or serum), the time and the fasting/non-fasting status of the blood sample. Our opinion is that blood sample for PTH measurement should be obtained in the morning after an overnight fast. Furthermore, despite longer stability of the PTH molecule in EDTA plasma, we prefer serum as it allows to measure calcium, a prerequisite for a correct interpretation of a PTH concentration, on the same sample. Once a consensus is reached, we believe an important international multicentre work should be performed to recruit a very extensive reference population of apparently healthy vitamin D-replete subjects with a normal renal function in order to establish the PTH normative data. Due to the huge inter-method variability in PTH measurement, a sufficient quantity of blood sample should be obtained to allow measurement with as many PTH kits as possible.

Evaluation of a New Fully Automated Assay for Plasma Intact FGF23

Abstract: Several FGF23 immunoassays are available. However, they are reserved for research purposes as none have been approved for clinical use. We evaluated the performances of a new automated assay for intact FGF23 on the DiaSorin Liaison platform which is approved for clinical use. We established reference values in 908 healthy French subjects aged 18–89 years, and measured iFGF23 in patients with disorders of phosphate metabolism and in patients with chronic kidney disease (CKD). Intra-assay CV was 1.04–2.86% and inter-assay CV was 4.01–6.3%. The limit of quantification was <10 ng/L. Serum iFGF23 concentrations were considerably lower than EDTA values highlighting the importance of using exclusively EDTA plasma. Liaison iFGF23 values were approximately 25% higher than Immutopics values. In the 908 healthy subjects, distribution of the Liaison iFGF23 values was Gaussian with a mean ± 2SD interval of 22.7–93.1 ng/L. Men had a slightly higher level than women (60.3 ± 17.6 and 55.2 ± 17.2 ng/L, respectively). Plasma iFGF23 concentration in 11 patients with tumour-induced osteomalacia, 8 patients with X-linked hypophosphatemic rickets, 43 stage 3a, 43 stage 3b, 43 stage 4, 44 stage 5 CKD patients, and 44 dialysis patients were 217.2 ± 144.0, 150.9 ± 28.6, 98.5 ± 42.0, 130.8 ± 88.6, 130.8 ± 88.6, 331.7 ± 468.2, 788.8 ± 1306.6 and 6103.9 ± 11,178.8 ng/L, respectively. This new iFGF23 assay available on a platform that already allows the measurement of other important parameters of the mineral metabolism is a real improvement for the laboratories and clinicians/researchers involved in this field.

Guidelines for Growth Hormone and Insulin-Like Growth Factor-I Treatment in Children and Adolescents: Growth Hormone Deficiency, Idiopathic Short Stature, and Primary Insulin-Like Growth Factor-I Deficiency.

Abstract: Background/Aims: On behalf of the Drug and Therapeutics, and Ethics Committees of the Pediatric Endocrine Society, we sought to update the guidelines published in

A Consensus Statement on acromegaly therapeutic outcomes

Abstract: The 11th Acromegaly Consensus Conference in April 2017 was convened to update recommendations on therapeutic outcomes for patients with acromegaly. Consensus guidelines on the medical management of acromegaly were last published in 2014; since then, new pharmacological agents have been developed and new approaches to treatment sequencing have been considered. Thirty-seven experts in the management of patients with acromegaly reviewed the current literature and assessed changes in drug approvals, clinical practice standards and clinical opinion. They considered current treatment outcome goals with a focus on the impact of current and emerging somatostatin receptor ligands, growth hormone receptor antagonists and dopamine agonists on biochemical, clinical, tumour mass and surgical outcomes. The participants discussed factors that would determine pharmacological choices as well as the proposed place of each agent in the guidelines. We present consensus recommendations highlighting how acromegaly management could be optimized in clinical practice.

Clinical practice recommendations for the diagnosis and management of X-linked hypophosphataemia

Abstract: X-linked hypophosphataemia (XLH) is the most common cause of inherited phosphate wasting and is associated with severe complications such as rickets, lower limb deformities, pain, poor mineralization of the teeth and disproportionate short stature in children as well as hyperparathyroidism, osteomalacia, enthesopathies, osteoarthritis and pseudofractures in adults. The characteristics and severity of XLH vary between patients. Because of its rarity, the diagnosis and specific treatment of XLH are frequently delayed, which has a detrimental effect on patient outcomes. In this Evidence-Based Guideline, we recommend that the diagnosis of XLH is based on signs of rickets and/or osteomalacia in association with hypophosphataemia and renal phosphate wasting in the absence of vitamin D or calcium deficiency. Whenever possible, the diagnosis should be confirmed by molecular genetic analysis or measurement of levels of fibroblast growth factor 23 (FGF23) before treatment. Owing to the multisystemic nature of the disease, patients should be seen regularly by multidisciplinary teams organized by a metabolic bone disease expert. In this article, we summarize the current evidence and provide recommendations on features of the disease, including new treatment modalities, to improve knowledge and provide guidance for diagnosis and multidisciplinary care. In this Evidence-Based Guideline on X-linked hypophosphataemia, the authors identify the criteria for diagnosis of this disease, provide guidance for medical and surgical treatment and explain the challenges of follow-up.

Interferences With Thyroid Function Immunoassays: Clinical Implications and Detection Algorithm.

Abstract: Automated immunoassays used to evaluate thyroid function are vulnerable to different types of interference that can affect clinical decisions. This review provides a detailed overview of the six main types of interference known to affect measurements of thyroid stimulating hormone (TSH), free thyroxine (T4) and free triiodothyronine (T3): macro-TSH, biotin, antistreptavidin antibodies, anti-ruthenium antibodies, thyroid hormone autoantibodies, and heterophilic antibodies. Because the prevalence of some of these conditions has been reported to approach 1% and the frequency of testing for thyroid dysfunction is important, the scale of the problem might be tremendous. Potential interferences in thyroid function testing should always be suspected whenever clinical or biochemical discrepancies arise. Their identification usually relies on additional laboratory tests, including assay method comparison, dilution procedures, blocking reagents studies, and polyethylene glycol precipitation. Based on the pattern of thyroid function test alterations, to screen for the six aforementioned types of interference, we propose a detection algorithm, which should facilitate their identification in clinical practice. The review also evaluates the clinical impact of thyroid interference on immunoassays. On review of reported data from more than 150 patients, we found that ≥50% of documented thyroid interferences led to misdiagnosis and/or inappropriate management, including prescription of an unnecessary treatment (with adverse effects in some situations), inappropriate suppression or modification of an ongoing treatment, or use of unnecessary complementary tests such as an I123 thyroid scan. Strong interaction between the clinician and the laboratory is necessary to avoid such pitfalls.

The human plasma-metabolome: Reference values in 800 French healthy volunteers; impact of cholesterol, gender and age.

Abstract: Metabolomic approaches are increasingly used to identify new disease biomarkers, yet normal values of many plasma metabolites remain poorly defined. The aim of this study was to define the "normal" metabolome in healthy volunteers. We included 800 French volunteers aged between 18 and 86, equally distributed according to sex, free of any medication and considered healthy on the basis of their medical history, clinical examination and standard laboratory tests. We quantified 185 plasma metabolites, including amino acids, biogenic amines, acylcarnitines, phosphatidylcholines, sphingomyelins and hexose, using tandem mass spectrometry with the Biocrates AbsoluteIDQ p180 kit. Principal components analysis was applied to identify the main factors responsible for metabolome variability and orthogonal projection to latent structures analysis was employed to confirm the observed patterns and identify pattern-related metabolites. We established a plasma metabolite reference dataset for 144/185 metabolites. Total blood cholesterol, gender and age were identified as the principal factors explaining metabolome variability. High total blood cholesterol levels were associated with higher plasma sphingomyelins and phosphatidylcholines concentrations. Compared to women, men had higher concentrations of creatinine, branched-chain amino acids and lysophosphatidylcholines, and lower concentrations of sphingomyelins and phosphatidylcholines. Elderly healthy subjects had higher sphingomyelins and phosphatidylcholines plasma levels than young subjects. We established reference human metabolome values in a large and well-defined population of French healthy volunteers. This study provides an essential baseline for defining the "normal" metabolome and its main sources of variation.