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Biomedical subjects

L Baldet

Publications and source records attributed to L Baldet.

At least 37 records · Page 2Linked to original sources

Antigenic domains on the human thyroglobulin molecule recognized by autoantibodies in patients' sera and by natural autoantibodies isolated from the sera of healthy subjects.

We determined the regions on the human thyroglobulin (hTg) molecule recognized by anti-hTg autoantibodies (aAbs) in the sera of patients with Hashimoto's thyroiditis, Graves' disease, and thyroid carcinoma and by anti-hTg natural aAbs isolated from the sera of healthy subjects. Fifteen anti-hTg monoclonal antibodies (MAbs) directed against six distinct antigenic regions were used for this study. The anti-hTg aAbs in the patients' sera recognized mainly region II and occasionally region IV. The natural aAbs were present in the serum at low concentrations; consequently, we isolated and concentrated them for this investigation. The isolated natural aAbs inhibited the interaction of the anti-hTg MAbs with the majority of the antigenic regions identified. Region II was not well recognized, however, by these natural aAbs. This difference in specificity between the anti-hTg aAbs and the anti-hTg natural aAbs may have diagnostic significance.

Autoantibodies↗

Are pituitary and thyroid function tests useful for the monitoring of antithyroid drug treatment and the post therapeutic control of Graves' disease?

The control of Graves' disease patients treated with antithyroid drugs (ATD) involves monitoring the dose of ATD, the duration of therapy and the prediction of the long-term outcome of the disease. The sequential follow-up of free thyroid hormones and ultrasensitive TSH (USTSH) helps in monitoring of ATD therapy, except in patients complemented with thyroid hormones. The normalization of early thyroid uptake of radioiodine or pertechnetate, which seems to be closely related to circulating thyroid-stimulating immunoglobulins, confirms the remission that leads to stopping ATD therapy. The raise of plasma USTSH in a normal range within the six months following ATD withdrawal is another indicator of remission. However, the post therapeutic course of Graves' patients remains unpredictable: late relapses and hypothyroidism may occur despite the normalization of the pituitary-thyroid axis, leading to a yearly clinical control with USTSH evaluation.

Antithyroid Agents↗

Thyroid stimulating antibody: an index of thyroid stimulation in Graves' disease?

Early (20 min) thyroid radio-iodine uptake (ERU) and thyroid-stimulating antibodies (TSab) were determined in 27 untreated unselected patients with Graves' disease at the time of diagnosis. In 21 subjects the same tests were further performed in parallel during combined carbimazole-L-T3 therapy (mean duration of follow-up: 10.8 +/- 5.8 months; mean +/- SD). TSab was determined by a cAMP-human thyrocyte culture stimulation assay and expressed in microliter-equivalent of a TSab standard/ml (microliter-eq/ml). Before treatment, ERU, ranging from 15 to 54% of the injected dose (normal less than or equal to 8% dose) correlated with serum T3 (r: 0.54; P less than 0.01); TSab, ranging from 6 to 85 microliter-eq/ml was detected in 21/27 patients. There was a significant correlation between ERU and TSab (Spearman rank test: r: 0.57; P less than 0.01). During the first months of treatment, 5 of the 21 patients sequentially studied had undetectable TSab levels throughout the study and in these patients ERU decreased by 57% of its initial value; the remaining 16 subjects were divided into two groups according to ERU changes: in group A (9 patients), initial ERU decreased by 50% or more or the absolute value became less than 20% of the dose and TSab decreased from 10.9 +/- 4.8 microliter-eq/ml to 5.3 +/- 1.6 microliter-eq/ml (P less than 0.01); in group B (7 patients), the fall of ERU was less than 50% or the absolute value remained greater than 20% of the dose and TSab values remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Value of the assay of thyroglobulin for postoperative surveillance of differentiated thyroid cancers].

Thyroglobulin has been evaluated among 30 control subjects and 81 thyroidectomized patients with differentiated thyroid carcinoma (50 papillary, 15 follicular, 16 mixed). 40 presented without residual thyroid tissue in the neck, 27 with residual tissue, 14 with metastases. Tg evaluation was performed on (78 dosages) and off thyroid hormone therapy (74 dosages), before and after withdrawal of thyroid medication in 25 patients. Tg was measured at different periods after surgical or radioiodine therapy of metastases (7 cases). The sera containing anti-Tg antibodies are rejected. The mean Tg levels was 11.9 +/- 8.5 ng/ml in the control group. In the group of patients with thyroid cancer, Tg levels were dependent on several factors: presence or not of residual thyroid tissue, presence or absence of a replacement therapy. All the patients on or off thyroid medication with metastases except one, presented with plasma Tg levels alone 5 ng/ml. In conclusion, plasma Tg appears as a good index for the research of metastases but only in patients without anti-Tg antibodies and residual thyroid tissue in the neck. Despite the existence of false negative results, a Tg undetectable in treated patients presenting a normal roentgen chest leads to avoid total body radioiodine scan and other usual radiologic investigations. On a opposite hand a plasma Tg greater than 50 ng/ml is highly suggestive of the presence of metastases.

Adult↗

Maximum calorie (sub-threshold) dieting of the obese and its hormonal response.

Severe calorie restriction for treating the obese reduces serum triiodothyronine (T3) and energy expenditure, and may be counterproductive. In order to avoid severe calorie deficiency, we measured the individual minimum energy requirements (threshold, T) in 17 obese females and fed each on a sub-threshold diet, comprising the maximum number of calories commensurate with weight loss (T-200 cals). Mean T-200 was 1318 +/- 96 cals, but the mean weight loss after 16 weeks on a sub-threshold diet (STD) was identical (17 kg) to that obtained by 22 age-matched female controls on a classical diet of 659 +/- 59 cals, exactly half the intake. Weight loss on the classical diet was initially rapid but decelerated sharply after 8 weeks, while on the sub-threshold diet the rate of loss remained constant throughout. In a second study, thyroid hormone measurements were performed three times weekly in 27 obese females during the 4 week period required to establish T. The mean weight loss was 4.02 +/- 0.3 kg, but T3 levels varied minimally and very transiently. STD produces short-term results similar to those obtained by severe calorie deprivation, but is more acceptable to the patient. It appears not to provoke the fat-saving reflexes provoked by the classical, low-calorie diet.

Adult↗

The influence on thyroid function of two iodine-containing radiological contrast media.

The aim of this study was to establish the effects of two iodine-containing radiological contrast media (ioxaglate and diatrizoate) on plasma iodide, thyroid hormones and TSH in a group of 20 subjects (8 females, 12 males). The following were evaluated two, eight and 30 days after administration of the drugs: plasma iodide, T4, T3, rT3, FT41, TSH before and after TRH (250 micrograms IV). 131I uptake was measured before the media were given and 30 days afterwards. The results were compared at the different times during the investigation using Wilcoxon's signed ranking test for non-parametric variables. Plasma iodide was found to be above the normal range two to eight days after ioxaglate and two to eight and 30 days after diatrizoate. After ioxaglate, rT3 was increased at eight days and T3 at 30 days. 131I uptake remained low after the 30th day. After diatrizoate, T4 was decreased on the second day and FT41 was low, on the eighth and 30th day. All figures represent statistically significant but nevertheless minor variations of the initial value of each parameter. In conclusion, although ioxaglate and diatrizoate lead to variations in plasma thyroid hormone levels, they are of little importance.

Adult↗

T3 kinetics in euthyroid Graves' disease patients who exhibit hyper-responsiveness to TRH after radioiodine treatment.

A major reduction in T3 turnover has been demonstrated previously in clinically hypothyroid patients. We have used non-compartmental (NC) and monocompartmental (MC) analysis to study ten patients with Graves' disease who, following treatment with radioactive iodine (RAI), are now clinically euthyroid but who showed hyper-responsiveness to TRH although serum T3 and T4 concentrations are within the normal range. T3 production rate (PR), metabolic clearance rate (MRC) and fractional-turnover (K) were all significantly reduced in patients compared with seven controls (P less than 0.01). T3, MCR and PR were consistently higher, and T3 K lower, when calculated by MC, than values calculated by NC analysis. The difference in T3 production rates between patients (mean 16.6 nmol/day) and controls (mean 38.9 nmol/day) raises the question of replacement therapy in patients who are apparently euthyroid but TRH hyper-responsive.

Adult↗

The TRG Test. Which is the best index of TSH release?.

Prolonged (two hours) TRH tests were performed on 29 controls and 182 thyrotoxicosis patients of varying thyroid status after treatment with radioiodine. The object was to find which of the simple measurements of TSH from the TRH test most faithfully reflected the total amount of TSH (TTSH) released in response to the TRH. The simple indices compared were the absolute levels of TSH (ATSH) achieved at intervals during the test, and the increments in TSH (delta TSH) recorded at the same points in time. TTSH was measured by planimetry of the area beneath the response curve. Patients were classified as normo-responders, hyper-responders or hypo-responders according to normal limits for TTSH deduced from the controls. When each simple index of TSH response was substituted in turn for TTSH, the overall frequency of misclassification was considerably greater for ATSH than for delta TSH. This was largely due to the wide variability of passive or basal TSH secretion, which seriously confused the distinction between normally-responsive and hypo-responsive patients when ATSH was used. The delta TSH measured at 30 minutes gave the best overall results in terms of least classification error and closest correlation with TTSH.

Adult↗

[Hyperthyroidism].

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Graves Disease↗

[Chronologic study of free T3 and T4, of responses to TRH and of the suppression test during treatment of Basedow's disease].

32 patients with Graves' Disease were investigated before treatment, during ATD therapy and after recovery with a normal T3 suppression test. Before treatment, TRH response was negative with elevated values of plasma TT4, AFT4, TT3 and AFT3. The 3d, 6 - 9 and 12-18 months and after recovery, several patients remained unresponders to TRH despite normal AFT4 and AFT3 in serum. In an opposite way some patients were responders, 1 month after ATD withdrawal, at the 6-9 month, with elevated values of AFT4 or AFT3. The discrepancy between TRH response and T3 suppression test is pointed out after recovery. The unresponsiveness of TSH to TRH unexplained by serum AFT4 or AFT3 may be due to : 1) a decrease in pituitary TSH stores. 2) an unknown factor inhibiting TSH release during Graves' disease 3) an hypersensitivity of thyreotrop cells to T3.

Graves Disease↗

[Interference of T4 in different serum T3 radioimmunologic determination kits].

The cross reactivity of T3 antibodies for T4 was studied with five T3 RIA kits. T4 used was provided from T4 RIA Kits (Abbot Beckman, Corning). The results are shown on the table indicating the concentration of T3 or T4 required to displace 50% of the T3 125 from anti T3. The cross reactivity for T4 of T3 antibodies from Lepetit and Phadebas was the same and was smaller than cross reactivity with the other laboratories. In clinical practice serum T4 levels of hypo and euthyroid subjects are not so high to false T3 determination. In hyperthyroid subjects the diagnosis cannot be influenced by this cross reactivity. However, the study of the kinetic and monodeiodination of T4 into T3 may be wrong when T4/T3 ratio increases.

Cross Reactions↗

Short and long term effects of radioiodine and antithyroid drugs on T4 binding proteins, free T4 and T3, during Graves' disease therapy.

Ninety five patients with Graves' disease were studied before and at three months intervals after antithyroid drugs (ATD) (31 cases) or radioiodine (64 cases) therapy until recovery. Before treatment, the T4 maxima binding capacity of TBPA was significantly decreased 253.5 +/- 11.4 mug/100 ml)(mean + se) (control values: 287 +/- 10.4 mug/100 ml) (alpha = 0.04), especially in 53.7% of patients (m = 177 +/- 8 mug/100 ml). The mean of TBG (m = 20.7 +/- 0.9 mug/100 ml) was not different from euthyroid subjects (m = 19.7 +/- 1.7 mug/100 ml) except in 51.2% of patients who had a low TBG (m = 14.3 +/- 1.1 mug/100 ml). An inverse linear correlation was found between TBG-DFT4 (alpha = 0.05) and DF T 3 (alpha = 0.002), TBPA-log DF T4 (alpha = 0.05) but not between TBG and TBPA. The physiological relationship between DFT3, DFT4, TT3, TBG and TBPA was studied in vitro; after adding increased quantities of T4 to a pool of sera collected from eu, hypo or hyperthyroid patients, DFT4, DFT3, FT3 index increased in linear positive relationship with TT4 concentrations, the kinetic of this phenomena was inversely correlated with T4 maximal binding capacity of TBG or TBPA for T4. Addition of T3 to the same sera did not show any effect on the previous parameters. DFT3 depended on the level of T4 in serum more than T3 concentration and was in inverse relationship with the maximal binding capacity of TBG. This data might explain the paradoxal normal or slightly increased values of DFT3 found in T3 thyrotoxicosis. In patients treated with ATD or radioiodine, TBPA but not TBG increased significantly on year after. However, in subjects with an initial very low TGB or TBPA, this phenomenon occurred on the third month after radioiodine or ATD. During the same period, DF T4 and DF T3 were inversely correlated to TBG and TBPA. In conclusion, important changes in T4 binding proteins and free fractions of thyroid hormones were observed in Graves' disease but were corrected by antithyroid therapy. All these data were in good agreement with the normalisation of thyroid function.

Adolescent↗