Dosage de thyroglobuline de nouvelle génération (performances et implications pour le suivi des patients atteints de cancer thyroïdien différencié)

Les cancers thyroïdiens différenciés nécessitent un suivi à long terme, du fait du risque de récidives, assuré notamment par le dosage sérique de thyroglobuline. Les recommandations actuelles font état d'un dosage basal sous traitement hormonal à 3 mois, puis d'un dosage après stimulation par TSH humaine recombinante à 6-12 mois du traitement initial; cette stimulation permettant d'améliorer la sensibilité du dosage. Une trousse de dosage de nouvelle génération permettrait, du fait d'une limite de quantification plus basse, d'améliorer la sensibilité du dosage basal avec une détection plus précoce des récidives, et ainsi de ne plus recourir à la stimulation. ! Nous avons donc réalisé au laboratoire de biologie médicale du Centre Hospitalier Lyon Sud une validation de méthode du dosage sérique de la thyroglobuline de deuxième génération, avec étude de la corrélation avec la réponse à la rhTSH. Pour cela nous avons constitué des pools de sérum dans les concentrations basses, et inclus des patients suivis pour cancer thyroïdien différencié et pour lesquels étaient en sérothèque un sérum au temps basal et un au temps stimulé. L'étude a montré une technique robuste et fiable, bien corrélée à la technique actuellement utilisée aux Hospices Civils de Lyon. Sur 54 patients, aucun n'a été considéré comme faux-négatif, ce qui était notre objectif de choix de seuil, et cinq comme faux-positifs, pour des seuils de thyroglobuline de 0,1 11g1L en basal et 1,0 11g1L en stimulé. Les valeurs prédictives positives et négatives ont donc été de 100 % et 87,8 % respectivement. Ces résultats nous ont permis de proposer une modification de l'algorithme de suivi des patients atteints de cancer thyroïdien différencié, incluant le dosage de thyroglobuline de nouvelle génération en remplacement du test à la rhTSH lors de l'évaluation post-thérapeutique à 6-12 mois du traitement initial.LYON1-BU Santé (693882101) / SudocSudocFranceF

Variability among TSH measurements can be reduced by combining a glycoengineered calibrator to epitope-defined immunoassays

Objectives: Measuring protein markers with variable glycosylation, such as thyroid-stimulating hormone (TSH), with high accuracy is not an easy task. Despite highly sensitive third-generation tests, discrepancies among TSH assays still remain unsolved and are the focus of important standardization efforts. Earlier work from our group showed that a lack of similarity in epitope expression between standards and samples may account for discordant hormone measurements. In this study, we aimed at producing a glycoengineered TSH with serum-type glycosylation and compared its immunological behavior to that of the international standards. Study Design: Recombinant glycoengineered TSH (rgTSH) was produced in glycoengineered Chinese hamster ovary cells to express a highly sialylated TSH and tested in newly designed assays. Two groups of assays targeting defined epitopes were constructed and TSH levels were estimated in a panel of 84 clinical samples (2.1-22.4 mIU/l) based on the use of the current 3rd IS 81/565, the 1st IRP 94/674 and rgTSH calibrations. Results: Calibration based on rgTSH was found to significantly reduce the percentage difference means of assays compared to the pituitary standard. We also found that a switch from a mIU/l (3rd IS 81/565) to ng/l (rgTSH) basis can be established within the normal as well as in the mid to upper normal range of TSH levels. Of interest, TSH assays targeting the main immunogenic region displayed variable TSH values, indicating that, in this region, epitopes should be defined for assays to deliver similar values. Conclusions: A glycoengineered TSH with serum-type glycosylation proved to be a new calibrator efficient in harmonizing TSH values

Plasma acyl-ghrelin increases after meal initiation: a new insight

BACKGROUND/OBJECTIVES: Plasma ghrelin secretion over time in humans is characterized by pre-prandial increases and by post-prandial decreases all day long. However, some authors who measured ghrelin concentrations around meals showed a rise in plasma ghrelin concentration after meal initiation followed by the typical post-prandial decrease. In order to confirm this observation that has never been discussed, we described ghrelin profiles around four eating episodes in the morning in adult men.SUBJECTS/METHODS: Twenty normal-weight and 17 obese men were instructed to eat four fixed meals (706 kJ) 10 min long at 0800 h, 0900 h, 1000 h and 1100 h. Using frequent blood sampling, we determined plasma acyl-ghrelin concentrations around those eating episodes. Glucose, insulin and GLP-1 concentrations were also measured.RESULTS: The meals consumption induced a significant increase in plasma acyl-ghrelin concentrations 10 min after meal initiation (P<0.0001): +20.9 +/- 5.8 and +10.7 +/- 3.3 pg/ml in normal-weight and obese subjects for the first meal; +10.4 +/- 3.0 and +5.5 +/- 3.9 pg/ml in normal-weight and obese subjects for the second meal; +12.4 +/- 3.6 and +4.2 +/- 2.1 pg/ml in normal-weight and obese subjects for the third meal; and +4.4 +/- 4.1 and +3.3 +/- 2.61 pg/ml in normal-weight and obese subjects for the fourth meal.CONCLUSIONS: This study is the first to describe and discuss the post-meal initiation ghrelin increase. This finding is consistent in normal-weight and obese individuals

Effects of a breakfast spread out over time on the food intake at lunch and the hormonal responses in obese men

The effects of frequent eating on health and particularly on appetite and metabolism are unclear. We have previously shown that frequent eating decreased appetite and energy intake at the subsequent meal in lean men. In the present study, we tested the same pattern in obese subjects. Seventeen obese men participated in: (i) two sessions consisting of a breakfast consumed in one eating episode at T0 (F1), or in four isocaloric eating episodes at T0, T60, T120, and T180 min (F4), followed by an ad libitum buffet (T240) in an experimental restaurant. Subjects rated their appetite throughout the sessions. (ii) two sessions consisting of the same breakfasts F1 and F4 in a Clinical Centre, followed by a standardized meal. Blood sampling was performed to study ghrelin, glucagon-like peptide-1 (GLP-1), and metabolic kinetics. Indirect calorimetry measurements were performed. After F4, at T240 min, ghrelin concentration (P = 0.03) and hunger ratings (P < 0.001) were lower while GLP-1 concentration (P = 0.006) and satiety ratings (P = 0.02) were higher. In F4, subjects consumed at the buffet, less food in grams (P = 0.04) and less energy from low energy dense foods (P = 0.01), but total energy intakes were not different between conditions. In F4, the area under the curve was lower for insulin (P = 0.02) and non-esterified fatty acids (NEFA) (P = 0.03). Diet induced thermogenesis was reduced in F4 (P = 0.03) between T0 and T240. Even if subjective and physiological data suggest a beneficial effect of frequent eating on appetite in obese men, no effect was demonstrated on energy intake. Moreover, the decrease in diet induced thermogenesis and lipolysis, reflected by NEFA profiles, could be deleterious on energy balance in the long run

Fetal hypothyroidism induced by maternal anti-TSH receptor blocking antibodies and complicated by polyhydramnios despite the absence of goiter. Treatment by intra-amniotic injections of levothyroxine

Fetal hypothyroidism induced by maternal anti-TSH receptor blocking antibodies and complicated by polyhydramnios despite the absence of goiter. Treatment by intra-amniotic injections of levothyroxin

An isocaloric inscrease of eating episodes in the morning contribute to decrease energy intake at lunch in lean men

The effects of increasing eating frequency on human health are unclear. This study used an integrated approach to assess the short-term consequences on appetite and metabolism. Twenty normal-weight men participated in: (i) two sessions consisting of a breakfast consumed in one eating episode at T0 (F1), or in four isocaloric eating episodes at T0, T60, T120, and T180 min (F4), and followed by an ecological ad libitum buffet meal (T240) designed in an experimental restaurant. Intakes were assessed for the whole buffet meal and for each temporal quarter of the meal. (ii) two sessions consisting of the same two breakfasts F1 and F4 in a Clinical Investigation Centre. Blood sampling was performed to study the kinetics of ghrelin, glucagon-like peptide-1 (GLP-1), glucose, insulin, triglycerides and non-esterified fatty acids (NEFA). Substrate oxidation was measured by indirect calorimetry. During each of the 4 sessions, participants rated their appetite throughout the experiment. After F4, at T240 min, GLP-1 concentration was higher (P = 0.006) while ghrelin concentration and hunger ratings were lower (P < 0.001). We showed a trend for subjects to consume less energy (− 88 ± 61 kcal, P = 0.08) at the buffet after F4, explained by a decrease in lipid intake (P = 0.04). Marked differences in consumption were observed during the last temporal quarter of the meal for total energy and lipid intake (P = 0.03). Mixed models highlighted differences between F1 and F4 for the kinetics of glucose, insulin and NEFA (P < 0.001). The area under the curve was lower for insulin (P < 0.001) and NEFA in F4 (P = 0.03). Diet induced thermogenesis was reduced in F4 (P < 0.05). This study demonstrated the beneficial short-term effect of increasing eating frequency on appetite in lean men considering subjective, physiological and behavioral data. However, the loss of the inter-prandial fast was associated with an inhibition of lipolysis, reflected by NEFA profiles, and a decrease in energy expenditure