Prediabetes and deprivation: A couple at high risk of diabetes.

AIM: The higher prevalence of diabetes in deprived populations is well documented but little is known about the risk of diabetes associated with deprivation among pre-diabetic subjects. The aim of the study was to evaluate the risk of diabetes in a population of deprived pre-diabetic patients. METHODS: 2743 pre-diabetic subjects identified using the American Diabetes Association (ADA) criteria, 16 to 85 years old, 1656 non-deprived and 1087 deprived, had at least two health check-ups at an interval of 4.95 (2.04) vs 3.20 (1.71) years, P<0.0001, respectively. At the first visit, socioeconomic status was assessed using the EPICES score to differentiate deprived and non-deprived subjects. RESULTS: At the second visit, the prevalence of overt diabetes was 9.5% among deprived vs 5.1% in the non-deprived group (P<0.001). After adjustment on confounding factors, deprivation was found independently associated with occurrence of diabetes [1.70 (1.15-2.51), P=0.01]. Beyond social deprivation, Fasting Plasma Glucose and waist circumference were the main independent predictors of new-onset diabetes. CONCLUSION: After 4 years of follow-up, among subjects with prediabetes, prevalence of diabetes was twice as high among deprived compared with non-deprived subjects. Deprived populations with pre-diabetes may require specific public health approaches to avoid the occurrence of overt diabetes.

The natural protein kinase C alpha mutant is present in human thyroid neoplasms.

An altered protein expression of Ca(2+)-dependent protein kinase C (PKC) isoforms and a point mutation in the PKC alpha cDNA (position 908 of the nucleotide sequence, position 294 of the amino acid sequence, substitution of an aspartic acid by a glycine) have been previously described in a subpopulation of human pituitary tumors. In this work, we screened 16 thyroid tissue samples (four follicular adenomas, five colloid adenomas, three papillary carcinomas, one follicular carcinoma and three normal tissues adjacent to the tumors) for the presence of the PKC alpha point mutation and for PKC alpha, beta 1, beta 2, epsilon and delta protein expression. Screening for the presence of the PKC alpha mutant was performed by a subcloning technic. The polymerase chain reaction products were generated using reverse-transcribed cDNAs, subcloned and sequenced (10 clones were routinely sequenced). The PKC alpha point mutation at position 908 of the cDNA sequence was found in four out of the nine adenomas and in the follicular carcinoma. It was neither detected in the papillary carcinomas nor in the adjacent normal tissues (one was the adjacent normal tissue of the follicular carcinoma; in this sample, genomic DNA and cDNA were used to look for the presence of the mutant), demonstrating the somatic nature of this mutant. Western blot analysis of PKC isoforms showed that the expression of all isoforms was higher in the thyroid neoplasms as compared with their adjacent normal tissue (n = 3). It was also higher in the samples containing the PKC mutant (two follicular adenomas, two colloid adenomas and the follicular carcinoma) as compared with the tumors where it was not detected (three papillary carcinomas and five adenomas). Samples could be ordered according to their increasing PKC expression as follows: normal adjacent tissue < follicular adenomas without PKC alpha mutant < or = papillary carcinoma < follicular adenomas with PKC mutant < follicular carcinoma with PKC mutant. In conclusion, the discovery of the PKC alpha mutant in thyroid neoplasms demonstrates that this mutant is not particular to human pituitary tumors where it was originally detected. It is a somatic mutation and its presence is concomitant with high levels of all of the PKC isoforms analysed. The presence of the PKC mutant in thyroid neoplasms raises the question of its importance in thyroid tumorigenesis.

Complications of the pump pocket may represent a significant cause of incidents with implanted systems for intraperitoneal insulin delivery.

OBJECTIVE: To increase awareness of adverse events associated with the use of programmable implantable pumps (PIPs). CASES: There were 7 cases of complications associated with the pump-pocket among 40 patients treated by PIP, and we searched for risk factors. RESULTS: Seven of 40 type I diabetic patients treated by PIP presented severe complications of the pump-pocket, resulting in five definitive explanations and nine other surgical interventions. The lesions included an exudative reaction in the pump-pocket and a skin retraction or atrophy, which were complicated by skin erosion in five patients. Coagulase-negative staphylococcus was identified in the pump-pocket in four patients, including three cases of skin erosion. No specific risk of local complications could be attributed to age, sex, duration of diabetes, body mass index, presence of retinopathy or peripheral neuropathy, HbA1c level since implantation, depth of implantation in the abdominal wall, or duration of experience with PIP. Usual physical activity corresponding to > 2,000 kcal energy expenditure per week, estimated by a questionnaire, appeared to be the only identified significant risk factor. CONCLUSIONS: From these results, we suggest that physical activity should be limited to moderate exercise and exclude vigorous efforts in diabetic patients treated by PIP to avoid an increased risk of complications at the implantation site.

Insulin underdelivery from implanted pumps using peritoneal route. Determinant role of insulin pump compatibility.

OBJECTIVE: To evaluate the incidence and investigate determinants of insulin underdelivery events occurring with implanted pumps using peritoneal route from a 103 patient-year experiment. RESEARCH DESIGN AND METHODS: Of the MiniMed (MIP 2001) pumps implanted in 47 type I diabetic patients, 70 were refilled quarterly with four successive batches (A, B, C, D) of U400 Hoechst 21 PH neutral insulin during a 3-year study period. Any reduction of insulin flow rate > 15% was considered as abnormal insulin delivery. Diagnosis of the cause of underdelivery was established according to the response to the following steps: 1) 0.01 mol/l NaOH rinse of pump circuits to solubilize insulin aggregates, 2) surgical examination and replacement of blocked catheters, and 3) postsurgical 0.01 mol/l NaOH rinse of pump. Step 2 was selected first if the increase of insulin requirements or reduction of flow rate were > 50%. Relative contributions of insulin and the implanted system to underdelivery events were analyzed. RESULTS: There were 76 episodes of insulin underdelivery that occurred during the study, resulting in an incidence of 74 events per 100 patient-years. Of 52 NaOH pump rinses, 30 restored normal flow rate. Surgery, performed after rinse failure (n = 22) or as the first step (n = 24), disclosed catheter blockages due to tip obstructions in 28 cases and omental encapsulations in 18 other cases. Five combined severe reductions of pump flow rate requiring pump replacements were diagnosed during surgery, and additional NaOH rinses had to be performed after catheter change in 12 other cases. Analysis of the incidence of underdelivery events indicated that both pump- and catheter-related problems were significantly increased while implanted systems infused batches B, C, and D versus batch A (P < 0.01), whereas the duration of pump implantation had no significant influence. CONCLUSIONS: Underdelivery events constitute serious limiting obstacles to prolonged peritoneal insulin infusion from implanted pumps. Progress in insulin pump compatibility is expected to reduce their occurrence and, thus, to improve the feasibility of this treatment.

Catheter complications associated with implantable systems for peritoneal insulin delivery. An analysis of frequency, predisposing factors, and obstructing materials.

OBJECTIVE: To evaluate catheter survival and identify mechanisms involved in catheter obstructions during a 109.8 patient-year experience with implanted pumps for peritoneal insulin delivery. RESEARCH DESIGN AND METHODS: Fifty-one type I diabetic patients were recruited in feasibility studies of two models of implanted systems for peritoneal insulin delivery. Both systems had a silicone-coated polyethylene catheter and infused Hoechst 21 PH neutral insulin (U400 or U100). Catheter obstruction was suspected each time the increase of insulin flow rate over 50% of usual need was insufficient to correct an impairment of glycemic control in the absence of of intercurrent factors. A laparoscopic examination was then systematically performed under general anesthesia. The disclosed material occluding the catheter was submitted to a pathological analysis. By actuarial analysis, we examined the estimated effects of the potential determinants of the catheters' duration of proper operation on catheter survival. RESULTS: Over an implantation duration of 25.8 +/- 14.0 months (mean +/- SD), 34 catheter obstructions were diagnosed in 24 patients, resulting in an incidence of 31 events per 100 patient-years. Fifty percent survival rate of the first implanted catheter was 27 months (95% confidence interval [CI]: 19-32) on actuarial analysis. Six catheters were cleared under laparoscopy and 24 were replaced, while 2 systems were definitively explanted and 2 combined replacements of pump and catheter were performed because of an associated pump slowdown. In five cases, an alkaline rinse procedure of the pump was necessary after catheter replacement to restore usual insulin needs, suggesting an associated insulin aggregation in the pump. Twenty obstructions were due to a fibrin clot at the catheter tip, and 14 obstructions were created by a tissue encapsulation around the catheter. A previous experience of peritoneal insulin infusion from portable pumps or a longer duration of diabetes ( > 21 years) both appeared as conditions significantly reducing the time of a catheter's proper operation (P < 0.01 and P < 0.05, respectively) either by tip obstructions or by encapsulations. Pathological analysis of catheter encapsulations showed a collagen fibrosis in all studied patients (n = 11), which was associated with a lymphocytic infiltrate in five patients and also with anti-insulin immunoreactive amyloid deposits in four patients. Catheter tip clots were composed of fibrinlike material, nonreactive to anti-insulin antibodies. CONCLUSIONS: Catheter obstruction is a frequent adverse technical event occurring with implanted insulin pumps. Progress is expected in the biocompatibility of catheter material and more specifically in the stability of insulin preparations to prevent immuno-inflammatory reactions and insulin amyloid deposits that appear to be involved in catheter failures.

Degree of thyrotropin suppression as a prognostic determinant in differentiated thyroid cancer.

We investigate whether the prognosis of patients with differentiated thyroid cancer is improved by maintaining a greater level of TSH suppression. One hundred and forty-one patients who underwent hormone therapy after thyroidectomy were followed up from 1970 to 1993 (mean, 95 months). Patients received levothyroxine (L-T4; mean dose, 2.6 micrograms/kg-day). TSH suppression was evaluated by TRH stimulation test until 1986 and thereafter by a second generation immunoradiometric assay. As TSH underwent fluctuation over time in most patients, we focused on subgroups of patients with relatively constant TSH levels during the follow-up. The relapse-free survival (RFS) was longer in the group with constantly suppressed TSH (all TSH values, < or = 0.05 mU/L; n = 18) than in the group with nonsuppressed TSH (all TSH values, > or = 1 mU/L; n = 15; P < 0.01). Age, sex, tumor node metastasis stage, and initial therapy were not different between the suppressed and nonsuppressed TSH groups. In the overall population, we analyzed the level of TSH suppression by studying the percentage of undetectable TSH values (< or = 0.05 mU/L) during the follow-up. The patients with a greater degree of TSH suppression (> 90% of undetectable TSH values; n = 19) had a trend toward a longer RFS than the remaining population (n = 102; P = 0.14). The patients with a lesser degree of TSH suppression (< 10% of undetectable TSH values; n = 27) had a shorter RFS than the remaining patients (n = 94; P < 0.01). In multivariate analysis that included TSH suppression, age, sex, histology, and tumor node metastasis stage, the degree of TSH suppression predicted RFS independently of other factors (P = 0.02). This study shows that a lesser degree of TSH suppression is associated with an increased incidence of relapse, supporting the hypothesis that a high level of TSH suppression is required for the endocrine management of thyroid cancer.

Influence of the frequency of gonadotropin-releasing hormone (GnRH) administration on ovulatory responses in women with anovulation.

In attempt to optimize gonadotropin-releasing hormone (GnRH) treatment of anovulation, we compared the effect of intravenous GnRH administration at three pulse intervals (PI) during 63 cycles in 30 anovulatory patients who had: (1) amenorrhea secondary to anorexia nervosa (group I: 10 patients, 21 cycles); (2) unexplained anovulation with normal to high luteinizing hormone plasma levels (group II: 12 patients, 24 cycles); and (3) polycystic ovarian disease (PCOD) (group III: 8 patients, 18 cycles). Ovulation was achieved more frequently in group I (85%) than in group II (41%) or in group III (50%). In both groups I and II, the frequency of ovulatory responses was not different with the PI used, and 6 of the 17 women treated for infertility conceived; 3 with 90-minute PIs, 2 with 64-minute PIs, and 1 with 128-minute PIs. In women with PCOD, seven of the nine ovulatory responses and three pregnancies were obtained with 128-minute PIs. The overweight women with PCOD did not respond reliably to GnRH at the doses used, i.e., 4 to 15 micrograms per pulse. In all groups, the urinary estrone and estradiol preovulatory peak, duration of luteal phase, progesterone levels, and preovulatory follicle diameter were unrelated to the frequency of GnRH administration.

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.

[Multidimensional discriminative analysis for predicting the outcome of Graves' disease (author's transl)]. / Le choix thérapeutique dans la maladie de Basedow. Peut-on établir prércocément un prognostic évolutif?

Attempts to identify at an early stage of Graves' disease patients who will respond favorably to the various treatments available have been largely unsuccessful. However, all such studies have been based on the measurement of a single discriminant at a time, and in an attempt to improve predictive accuracy we have made use of multidimensional techniques which analyse several factors simultaneously. The overall accuracy in predicting the outcome in drug-treated patients, before treatment was started, was 79% ; in RAI treated patients 88 %. There remains a residuum of patients whose fluctuations in disease activity are such as to defy all prediction of outcome.

[Proceedings: Kinetics and disposal rate of triiodothyronine in patients with atuonomous hot nodular goiter, with or without thyrotoxicosis (author's transl)]. / Etude du métabolisme de la triiodithyronine au cours du nodule chaud autonome, avec ou sans hyperthyroïdie

Eight female patients are studied, four of them without hyperthyroidism. The following were measured before and after surgery = hormonal iodine by column, serum concentrations of T T3, AF T3, TSH, total T3 distribution space, T3 pool size T3 fractional turnover rate. T T3 is measured in the serum of peripheral venous blood, nodular venous blood and of jugular venous blood of the opposite side of the adenoma. Before surgery, the mean of T T3 in patients with hyperthyroidism is increased in serum obtained from brachial and not nodule venous blood. Are also increased AF T3 and T3 production rate. In patients without hyperthyroidism, T T3, AF T3 are increased in two subjects only, but T3 production rate is rised among three of them. After surgery the previous values are not different with normal values. These data are in good agreement with the hypothesis that, in patients without thyrotoxicosis, there is an increase in T3 production from not nodular goiter. There phenomena may explain unresponsiveness to TRH test and inactivity of normal thyroid. Absence of hyperthyroidism may be due to a lack of sensitivity of peripheral tissues to the increase of T3.

[Pathology of thyroid hormone receptors]. / Pathologie des récepteurs des hormones thyroïdiennes.

The syndrome of resistance to thyroid hormones may affect overall or only some tissues. The generalized resistance associates a familial eu or hypometabolic goiter, increased free thyroid hormones with normal or elevated plasma TSH levels. The inheritance of the disease is autosomal dominant in most of the patients. In vivo or in vitro tests may be used to assess the diagnosis. Therapy refers to high doses of T3 or T4. Pituitary resistance to thyroid hormones leads to hyperthyroidism with normal or high TSH levels. The treatment uses different TSH suppressive drugs. Peripheral resistance associates hypometabolism with normal T4-T3 secretion and needs high T3 doses for therapy. An inherited abnormality of T3 nuclear receptor seems to be the consequence of a mutant gene. Hypersensitivity to thyroid hormones associates hypermetabolism with low or normal free thyroid hormone levels and increased T3 nuclear receptors.

[Iodine consumption in France. National results of the Thyromobile project in a population of schoolchildren aged 6-14 years]. / Apport iodé en France. Résultats nationaux du projet Thyromobile dans une population d'enfants scolarisés de 6 à 14 ans.

The "Thyromobile" project was initiated to update information on iodine supply in school-children aged 6-14 years in Europe. It involved 4 places in France: Lorraine, Rhône-Alpes, Languedoc-Roussillon, Midi-Pyrénées. Schools of the three former places had been investigated in 1986 during the Mornex's study whereas in the latter they had never been investigated in the past. With a mobile unit, all children (n = 1522) had a thyroid echography performed by the same trained investigator, and urinary iodine concentration was determined in 1458 of them. The mean +/- SD of urinary iodine concentration was 13.0 +/- 7.4 micrograms/dl, but 38% of urinary iodine concentrations were below 10 micrograms/dl and 10% were under 5 micrograms/dl. The prevalence of goitre was 4.1% in boys and 3.1% in girls. There was a negative correlation between urinary iodine concentration and thyroid volume (p < 0.001). Therefore, the results of the "Thyromobile" project show that the places, investigated in France, are not in an area of endemic goitre due to iodine deficiency. However, other epidemiological studies must be done to provide further information about iodine supply in all parts of France.

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.

[New techniques of thyroid medical imaging. Value and limitations in the exploration of isolated thyroid nodules]. / Nouvelles techniques d'imagerie médicale thyroïdienne. Intérêt et limites dans l'exploration des nodules thyroïdiens isolés.

The exploration of thyroid nodules deals mainly with the problem of detection of malignancy. Except in the cases of characteristic clinical situations which suggest at once malignancy, classical investigations offer mostly an insufficient approach including erroneous conclusions. Scintigraphy, whose morphological definition remains limited, can miss non- or hypofixing lesions. Pharmacological tests of nodule reduction by suppression of thyreostimulin do not provide specific informations. Fine needle- biopsy cannot absolutely exclude malignancy, depending too much of the sites of punction and of the difficulties of cytological analysis. Echography brings an important progress in the precision of thyroid volume, nodules counting and gross connections. The liquid or solid characterization is an important echographic information as well. Tomodensitometry provides useful data in the retrosternal and retrotracheal areas. The connections with aerodigestive tract are more clearly pointed out and the presence of metastatic nodes as well. Magnetic resonance imaging gives further information because of the ability of multiple longitudinal slices, and of the trial of a tissular characterization from signal analysis and ultrastructural macroanatomic study. Additive precisions will be likely in the future by a more accurate determination of criteria of malignancy. The complementarity of magnetic resonance imagery and fine needle-biopsy should lead to a more frequent use of these investigations before the decision of surgical removal.

[Chronologic study of free T3 and T4, of responses to TRH and of the suppression test during treatment of Basedow's disease]. / Etude chronologique de la T3 et de la T4 libres, des réponses à la TRH et du test de freinage, au cours de la maladie de Basedow traitée.

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.

[The 20 min. iodine uptake in Graves' disease. 1. Technique and reliability (author's transl)]. / Intérêt de la mesure de la captation précoce de l'iode radioactif (20e minute) dans la maladie de Basedow. 1: Technique et fiabilité.

The 20 minute intravenous radioiodine uptake technique is described in detail and results compared with those from the classical 2 1/2 hour oral uptake in 93 Graves' disease patients. Two methods used in correcting for extrathyroidal radioactivity in the early uptake are similarly compared. The 20 minute uptake was normal (locally less than 8% dose) in only 6,5% of the patients while the 2 1/2 hour uptake was normal (locally less than 35% dose) in 18,5%; in six patients the uptake at 20 min. was higher than at 2 1/2 h, observations indicating the superior sensitivity and diagnostic value of the early uptake. The suppression test performed at 20 minutes was, furthermore, pathological in 97,8% of patients. The comparison of methods to correct for extrathyroidal radioactivity in the 20-minute test showed excellent agreement between thigh count subtraction and application of a formula based on the thyroid uptake at 2 minutes. The former technique, however, was considered to be simpler. We conclude that the 20 minute intravenous iodine uptake technique is not only simpler to perform than the classical oral method, but is also diagnostically more accurate. A high quality scan was obtained 30-60 minutes after the injection of radioiodine in most of these patients.

[The 20-minute iodine uptake in Graves' disease. 2. Natural course during medical treatment (author's transl)]. / Intérêt de la mesure porécoce de la captation de l'iode radioactif (20e minute) dans la maladie de Basedow. 2 : Evolution lors du traitement médical.

The early (20 min) radioiodine uptake has been used to monitor the fluctuations in disease activity among 35 Graves' disease patients treated for 18 months with carbimazole and T3. A wide variety of behaviour was observed. Although as a group the uptake tended to fall progressively with time, in some it fell only to rise again and in others it fluctuated erratically. The initial fall in uptake in a substantial minority of patients was sufficient to suggest that carbimazole may exert a fundamental and beneficial influence of the immunological disturbance in Graves' disease.

[The 20-minute iodine uptake in Graves' disease. 3. Prognostic value (author's transl)]. / Intérêt de la mesure précoce de la captation de l'iode radioactif (20e minute) dans la maladie de Basedow. 3 : Valeur pronostique.

The early (20-min.) radioiodine uptake was used to monitor disease activity in 35 Graves' patients undergoing an 18-month course of treatment with carbimazole and T3. T3 alone produced no change in uptake, but four weeks after the introduction of carbimazole, the mean uptake had fallen by more than 50%. Six months after completion of treatment, 20 patients (group R) had relapsed, and 15 (group E) were in remission. The only quantitative difference in mean uptake behaviour between R and E patients was one of degree, their slopes being parallel. Thus, while the mean uptake of both groups fell progressively towards normal, that of group E patients arrived much the earlier, and carbimazole seemed to hasten both. Major fluctuations in thyroid uptake were observed in most individuals, but certain defined patterns emerged. While the uptake suppressed at some time during treatment in 32 (91,4%) patients, remission was associated only with early (ie before month 5) and stable suppression. The predictive value of the uptake test early during treatment was limited to identifying a group certain to relapse, but these non-suppressors accounted for only 40% of all patients, and it was not possible to identify with any certainty those who would ultimately remit.

[Study of the HL-A system in Basedow's disease (author's transl)]. / Etude du système hla au cours de la maladie de basedow

HL-A typing has been carried out in 100 caucasians with Graves' disease and compared with 270 healthy controls. 25 HL-A antigens were characterized using a lymphocytotoxicity microtechnique. Analysis of the results reveals an increased incidence of HL-A8 antigen (35% in patients as compared to 16,3% in controls), with a high degree of statistical significance: p=0.0002 and corrected p X 25) = 0.005. We did not observe a clearcut correlation between the presence of HL-A8 and different characteristics of the disease: sex, age of onset, familial history, exophtalmia, goiter, severity. The knowledge of the relationships between the HL-A8 gene and several auto-immune diseases is a strong argument in favor of the auto-immune nature of Graves' disease. The association between HL-A8 and Graves' disease could be explained by a close linkage between the second HL-A locus and one or several Ir-IgG loci occupied in predisposed individuals by predisposing alleles. In these subjects, an antigenic contact with an exogenous etiological agent would induce a pathological immune response, with production of thyroid stimulating IgG.

[HLA B8 and Graves' disease (author's transl)]. / Système HLA et maladie de Basedow

HLA typing has been carried out in 100 caucasions with Graves' disease and compared with 270 healthy controls. 25 HL-A antigens were characterized using a lymphocytotoxicity micro-technique. Analysis of the results reveals an increased incidence of HLA-B8 antigen (35% in patients as compared to 16.3% in controls) with a high degree of statistical significance: p = 0.0002 and corrected p (X 25) = 0.005. We did not observe a clear-cut correlation between the presence of HLA-B8 and different characteristics of the disease: sex, age of onset, familial history, exophtalmia, goiter, severity. The knowledge of the relationships between the HLA B8 gene and several auto-immune diseases is a strong argument in favor of the auto-immune nature of Graves' disease. The association between HLA B8 and Graves' disease could be explained by a close linkage between the second HLA locus and one or several Ir-IrG loci, occupied in predisposed individuals by "predisposing" alleles. In these subjects, an antigenic contact with an exogenous etiological agent would induce a pathological immune response, with production of thyroid stimulating IgG.