Clinical and metabolic characteristics of patients with latent autoimmune diabetes in adults (LADA): absence of rapid beta-cell loss in patients with tight metabolic control.

AIM AND METHODS: The present study compared the clinical and metabolic characteristics of latent autoimmune diabetes in adults (LADA) with type 2 diabetes, as well as the residual beta-cell function and progression to insulin treatment, over a 2-year follow-up period, of antibody (Ab)-positive and Ab-negative patients who achieved tight glycaemic control (HbA(1c) 7.0+/-0.8% and 6.5+/-0.9%, respectively, at the time of entry into the study). RESULTS: Glutamic acid decarboxylase antibodies (GADA) and/or islet cell antibodies (ICA) were detected in 10% of patients presenting with non-insulin-dependent diabetes. Around half of Ab-positive patients required insulin treatment during the follow-up. Ab-positive patients displayed lower stimulated C-peptide levels both at entry and during the follow-up compared with Ab-negative patients, although no significant decline in C-peptide levels was observed in either subgroup over two years. Nevertheless, Ab-positive patients progressed more frequently to insulin treatment, and stimulated C-peptide tended to decrease in LADA patients who subsequently required insulin, whereas it remained stable in those who were non-insulin-dependent. In those who progressed, the trend towards C-peptide decline persisted even after starting insulin treatment. CONCLUSION: LADA patients demonstrate lower residual beta-cell function than do type 2 diabetes patients. However, those who achieve tight metabolic control do not present with a rapid decline in beta-cell function. Further studies are needed to determine the optimal treatment strategy in such patients.

Diabetes and impaired fasting glucose in rural and urban populations in Futa Jallon (Guinea): prevalence and associated risk factors.

AIM: The authors present the results of the first survey conducted among the population of the Futa Jallon province in Guinea on the prevalence of diabetes mellitus (DM) and impaired fasting glucose (IFG) and associated risk factors for diabetes. METHOD: A random sample of the study population selected by cluster house sampling method included 1537 Guineans (807 women and 730 men) aged 35 years and above in urban (Labé) and rural (Fellö Koundoua-Tougué) areas. Participants were examined and administered a capillary whole blood glycemia test. RESULTS: The mean age of subjects was 49.4 years. Participation rate was 77%. Overall crude diabetes and IFG prevalence were 6.1% and 13.4%, respectively. The age-adjusted prevalence of diabetes using the standardized age distribution of Segi was 6.7% (95% CI: 5.5-7.9%). Subjects in the urban area had twice as much DM as in the rural area (OR 2.0, 95% CI: 1.3-3.2). Out of the 94 subjects with DM, 66 had no prior history of disease. Urban location, age, waist to hip ratio, excess waist circumference, hypertension, raised systolic and diastolic blood pressures were significantly positively associated with DM. In multivariate analysis, only age (P=0.002) and waist circumference (P<0.05) remained independently associated with DM. CONCLUSION: The prevalence of DM was higher than expected in urban and rural areas. The data support the conclusion that prevalence of DM is expected to increase with the aging of the population. The factors associated with diabetes are potentially modifiable. Therefore, primary prevention through lifestyle modifications may play a critical role in the control of DM.

[Erectile dysfunction and diabetes in Conakry (Guinea): frequency and clinical characteristics from 187 diabetic patients]. / Dysfonction érectile et diabète à Conakry (Guinée): fréquence et profil clinique à partir de 187 observations.

Sexual dysfunction is frequent in the diabetic population. In Africa, medical care for erectile dysfunction is underprovided, profoundly altering the quality of life of the patients. We report the prevalence of erectile dysfunction in 187 diabetic patients followed in the department of Endocrinology of the Conakry teaching hospital. Prevalence was estimated from the French version of the International Index of Erectile Function (IIEF). Erectile dysfunction concerned 90 patients (48%) of whom a severe form was observed in 54%, a moderate form in 35% and a mild form in 12%. The patients who presented erectile dysfunction were significantly older, displayed longer duration of diabetes with more complications (sensorial neuropathy and macroangiopathy) and often took drugs for associated cardiovascular diseases. In 28% of the cases, erectile dysfunction was associated with a decline in libido and in 26% with ejaculation disorders. In conclusion, erectile dysfunction is frequent and severe among diabetic patients in Guinea. The medical staff plays an essential role to initiate early diagnosis, promote psychological support and provide medication, if possible.

Technical risks with subcutaneous insulin infusion.

The popularity of continuous subcutaneous insulin infusion (CSII), as a way for achieving long term strict glycaemic control in diabetic patients, has increased over the last ten years. Most reports on technical faults, often leading to metabolic emergencies, mainly ketoacidosis, have been published in the 1980s. Obstruction of infusion set and infection of infusion site are the most frequent events. Insulin precipitation or aggregation is thought to be one of the precipitating factors. Few data are available about failures of the pump itself. We report our experience of pump malfunctions recorded between 2001 and 2004 in 376 pumps used by patients treated with CSII therapy in Brittany. Recent studies indicate a decrease of metabolic complication frequency during CSII. This suggests technical improvements and/or a greater experience of physicians in selecting and educating patients. We report instructions for monitoring insulin pump therapy that should be included in a formal educational program for pump users. Clinical studies using newly available devices should reassess technical risks associated with CSII.

Herbal medicine and treatment of diabetes in Africa: an example from Guinea.

AIM: Use of medicinal plants is widespread in Africa, particularly in Guinea where oral transmission of practices is part of the social ritual. The purpose of this study was to determine the proportion of diabetic patients who use herbal medicine and identify the types of plants in use. Reasons for using herbal medicine and the formulations employed were also noted. METHODS: A questionnaire on use of herbal medicine was proposed to all diabetic patients hospitalized or consulting the Endocrinology Unit of the Conakry University Hospital between April 1 and June 30, 2003. RESULTS: A total of 397 patients responded; 33% declared they used herbal medicine. They proposed many motivations, sometimes in association: belief in its efficacy (74%), easy access to medicinal plants (70%), lower cost (48%), and search for complete cure of diabetes (37%). Hearing about a positive experience had convinced 78% of the users to use herbal medicine. The majority of the users were satisfied (85%). One or more clinical manifestations occurring concomitantly with use of herbs was observed in 23 patients (18%), particularly gastrointestinal disorders (n = 10) and skin problems (n = 8). Two cases of hypoglycaemia were noted. CONCLUSION: Herbal medicine plays an important role in anti-diabetes treatment in Guinea. This type of treatment should be based on scientific evidence but very few studies have been conducted. Conditions of use should be better defined and patients should be informed of potential adverse effects.

Diagnosis of osteomyelitis in the diabetic foot with a 99mTc-HMPAO leucocyte scintigraphy combined with a 99mTc-MDP bone scintigraphy.

BACKGROUND: The aim of this prospective study was to assess the role of 99mTc-HMPAO leucocyte scintigraphy combined with a 99mTc-MDP bone scintigraphy in the diagnosis of the diabetic foot infection (HMPAO-Leu/MDP). METHODS: 75 diabetic patients with suspected osteomyelitis were included. The HMPAO-Leu/MDP scan was considered to be consistent with osteomyelitis when the HMPAO-Leu uptake was concordant in all the incidences with an MDP bone uptake. A HMPAO-Leu uptake without concordant bone MDP activity was considered as a soft-tissue infection. The results of the HMPAO-Leu/MDP scan were compared to the following diagnostic criteria: bone infection was confirmed by radiological follow-up or bone biopsy; the absence of bone infection was confirmed by clinical (healing of the ulcer without antibiotherapy) and radiological follow up. RESULTS: According to these criteria, among the 83 ulcers, bone infection was observed in 41 (49.4%): the HMPAO-Leu/MDP scan was positive in 38 cases, including 14 ulcers with normal or doubtful radiographs at inclusion. In the group of 42 ulcers without proven bone infection, the HMPAO-Leu/MDP scan was negative in 41 cases, including 17 lesions with a soft-tissue infection. CONCLUSION: With a sensitivity of 92.6%, a specificity of 97.6%, the HMPAO-Leu/MDP scan is a reliable tool for the diagnosis of osteomyelitis in the diabetic foot. Neuroarthropathy did not affect the performances of the HMPAO-Leu/MDP scan. Owing to a high spatial resolution this test is very helpful to differentiate bone infection from soft-tissue infection especially in case of neuroarthropathy.

Non-hyperfunctioning nodules from multinodular goiters: a minor role in pathogenesis for somatic activating mutations in the TSH-receptor and Gsalpha subunit genes.

Constitutive activation of the cAMP pathway stimulates thyrocyte proliferation. Gain-of-function mutations in Gsalpha protein have already been identified in thyroid nodules which have lost the ability to trap iodine. In contrast, most of the studies failed to detect somatic activating mutations in the thyrotropin receptor (TSH-R) in non-hyperfunctioning thyroid tumors. The aim of this study was to screen for mutations TSH-R exon 10, encoding the whole intracytoplasmic area involved in signal transduction, and Gsalpha exons 8 and 9, containing the two hot-spot codons 201 and 227, in a subset of non-hyperfunctioning nodules from multinodular goiter. Identified by matching ultrasonography and scintiscan, 22 eufunctioning (normal 99Tc uptake) and 15 nonfunctioning (decreased 99Tc uptake) nodules from 27 non-toxic multinodular goiters were isolated. After DNA extraction, TSH-R exon 10 was analyzed by direct sequencing of the PCR products and Gsalpha exons 8 and 9 by Denaturing Gradient Gel Electrophoresis. No mutation of TSH-R or Gsalpha was detected in the 37 nodules analyzed. This absence of mutation, despite the use of two sensitive screening methods associated with the analysis of the TSH-R whole intracytoplasmic area and Gsalpha two hot-spot codons, suggests that TSH-R and Gsalpha play a minor role in the pathogenesis of non-toxic nodules from multinodular goiters.

[Nuclear medicine in the diagnosis of diabetic foot osteomyelitis]. / Place de la médecine nucléaire dans le diagnostic d'ostéite du pied diabétique.

The diagnosis of diabetic foot osteomyelitis is often difficult both clinically and radiologically with a delay in radiological sign occurrence and difficulties of imaging interpretation. Bone biopsy is known to be the diagnosis gold standard. However, if negative, the diagnosis of osteomyelitis cannot be excluded and this method is not harmless. An early diagnosis of osteomyelitis is necessary to start an antibiotic treatment in conjunction with conservative surgery. (99m)Tc-HMPAO labelled leucocyte scintigraphy performed in conjunction with bone scintigraphy significantly contributes to the diagnosis of osteomyelitis (sensitivity=100% and specificity > 95%). In case of osteomyelitis suspicion, after plain radiography, the (99m)Tc-MDP bone scintigraphy is the first step. If negative, osteomyelitis is unlikely. If positive, a (99m)Tc-HMPAO leucocyte scintigraphy should be performed in order to exclude or to confirm the diagnosis of bone infection.

Clinical value of a new TSH binding inihibitory activity assay using human TSH receptors in the follow-up of antithyroid drug treated Graves' disease. Comparison with thyroid stimulating antibody bioassay.

First, to evaluate the performance level of a new TSH binding inhibitory antibody assay using human recombinant TSH receptors (h-TBII) in comparison with a thyroid stimulating antibody (TSAb) bioassay performed before, at the end of treatment (18 months) and after antithyroid drug withdrawal in Graves' disease patients; second, to assess the accuracy with which h-TBII levels could predict relapse and remission. Retrospective study on serum samples of Graves' disease patients treated by antithyroid drugs for 18 months. Serum samples from 140 patients (27 men and 113 women; median age 42 years) with recent onset hyperthyroidism due to Graves' disease were retrospectively tested for h-TBII at diagnosis, at 18 months and for 76 of them 6, 12, 24 and 36 months after drug withdrawal or at relapse. TSAb were also evaluated at each time. Thyroid blocking antibodies (TBAb) were measured in sera positive for h-TBII and negative for TSAb. h-TBII levels were measured with a radioreceptor assay using the human recombinant TSH receptor (DYNOtest TRAK human from B.R.A.H.M.S. Diagnostica, Berlin, Germany). TSAb and TBAb levels were assayed in thyrocyte cultures. At diagnosis, high levels of h-TBII were found in 138 of 140 patients with Graves' disease (98.6%). High TSAb values were also detected in the same 138 patients. The h-TBII and TSAb values were significantly correlated (r = 0.582, p < 0.0001). At 18 months, h-TBII were found in 48 of the 140 patients (34%) and TSAb in 43 patients (31%). The h-TBII and TSAb values were significantly correlated (r = 0.618, p < 0.0001) and fell significantly between diagnosis and 18 months (Z = - 9.84, p < 0.0001 and Z = - 9.19, p < 0.0001). TBAb were found in two of the 11 sera positive for h-TBII and negative for TSAb. At diagnosis, the median levels of h-TBII and TSAb were not significantly different between the patients who relapsed within the 3 years after the withdrawal of treatment (n = 60) and those who did not (n = 80) (Z = - 1.1, ns; Z = - 0.216, ns). At 18 months, the prevalences of h-TBII and TSAb were significantly increased in patients who relapsed compared to those who remained in remission at 3 years (60% vs. 15%, chi2 = 30.8, p < 0.0001 and 55% vs. 13%, chi2 = 29.1, p < 0.0001, respectively). h-TBII and TSAb median levels were also significantly increased in patients who relapsed compared to the others (Z = - 4,8, p < 0.0001; Z = - 3,01, P < 0.005). Among the 60 patients who relapsed, 36 (60%) displayed h-TBII and 33 (55%) TSAb at 18 months. The majority of patients who relapsed during the 2 years following the end of treatment, in contrast to those who relapsed later, were positive for h-TBII (67% vs. 27%, chi2 = 6.01, p = 0.035). Seventeen of the 18 tested patients who relapsed were negative for h-TBII at 18 months, were then positive for h-TBII at the time of relapse, whereas 15 of them were still negative, 6-12 months before the relapse. Among the 80 patients who remained in remission at 3 years, only 10 (13%) displayed TSAb and 12 (15%) h-TBII at 18 months. In 10 of these 12 patients who were further evaluated for h-TBII positivity, h-TBII fell to control levels during the 3 years following the end of treatment. The new h-TBII assay is a simple and rapid method with a performance level similar to that of TSAb determination. Its sensitivity is close to 100% at diagnosis. In the whole group, TBII level analysis is relevant as a predictor for short time relapse. However, some of the patients are "misclassified", due to the inter-individual variability in the time course of h-TBII activity. Our results confirm that, in addition to h-TBII, even when measured with a highly sensitive test, the concomitant analysis of other clinical and/or biological parameters is necessary to improve the prediction of treatment outcome.

Clinical validity of a new commercial method for detection of TSH-receptor binding antibodies in sera from patients with Graves' disease treated with antithyroid drugs.

In this work, we compared the activities of TSH binding inhibitory immunoglobulin (TBII) results obtained with a new human TBII assay (h-TBII) using the human recombinant TSH receptor with thyroid stimulating antibodies (TSAbs). Sera were obtained from 90 patients with Graves' disease before and after therapy with carbimazole (1-methyl-2-thio-3-carbethoxyimidazole). Before treatment, h-TBII were detected in 89/90 patients (98.9%) whereas TSAb activity was positive in 88/90 patients (97.7%). The two parameters fell during therapy. At the end of treatment, only h-TBII levels were significantly different between patients in remission and those in relapse (Z=-2.212; P=0.0270). The relapse rate in the patients with positive antibodies at drug withdrawal was significantly increased (chi(2)=6.057; P=0.0139 for h-TBII and chi(2)=8.988; P=0.0021 for TSAb). Most of patients (76%) relapsed during the 2 years following drug withdrawal. h-TBII or TSAb values were positive in 84.6% or in 80.8% of patients at the time of relapse. There was a significant correlation between the two antibody measurement methods before treatment, at drug withdrawal and at the time of relapse. These results indicate that the new TBII assay using human TSH receptor is as sensitive as the TSAb assay. Because of its much easier performance, it may advantageously replace TSAb measurement especially for the Graves' disease diagnosis and in the prediction of short-term relapse at the end of treatment.

[Pseudohypoparathyroidism or hypoparathyroidism? A misleading clinical presentation]. / Pseudohypoparathyroïdie ou hypoparathyroïdie?

We report the case of a 27-year old woman who presented hypocalcemia and hyperphosphoremia during her first pregnancy. Her phenotype was in favor of Albright's hereditary osteodystrophy: short stature, obesity, round face, brachymetacarpy and mental retardation. However, the diagnosis of pseudohypopara thyroidism type Ia was ruled out due to low PTH level (10 pg/ml). The patient's 22q11 microdeletion was suspected and identified because of the association of severe neonatal hypocalcemia, abnormal face and renal malformation in her children. Deletion 22q11 leads to various syndromes, including Di George syndrome, also referred to as CATCH 22 syndrome (Cardiac defect (C), Abnormal face (A), Thymic hypoplasia (T), Cleft palate (C) and Hypocalcemia (H)). Retrospectively, the patient presented with symptoms suggestive of CATCH 22: abnormal face, hypernasal voice suggestive of velopharyngeal insufficiency, mental retardation, recurrent otitis in childhood. It is also noteworthy that there was an idiopathic thrombocytopenic purpura. In conclusion, while the phenotype was suggestive of Albright's hereditary osteodystrophy, the constatation of a low PTH level would cast doubt on this diagnosis. Furthermore, the 22q11 microdeletion should be searched by FISH (Fluorescence In Situ Hybridization) in all patients with hypopara thyroidism of unknown origin, even in the absence of cardiac malformations. Finally, it seems that patients with CATCH 22 would be predisposed to auto-immune disease as a result of thymic dysfunction.

[Gestational diabetes: the Rennes Study of joint obstetrical and endocrinological management]. / Le diabète gestationnel : étude rennaise prise en charge conjointe obstétricale et endocrinienne.

OBJECTIVE: To assess the efficacy of a co-program of care in gestational diabetes conducted by the obstetrical and endocrinological units of the Rennes South Hospital (Hopital Sud) and the possibility of adapting obstetrical care to existing risk factors. PATIENTS AND METHODS: A retrospective analysis was made of 200 cases of gestational diabetes diagnosed between January 1993 and December 1996 in the obstetrical units. RESULTS: Instrumental extraction and cesarean section were required for 13.5% and 20.5% of the deliveries respectively. Shoulder dystocia occurred in 2%. 19.9% of the infants had macrosomia and 5. 3% were small for gestational age. Neonatal morbidity required transfer to the pediatric intensive care unit for only 2.9% of the infants. Frequency of cesarean section and macrosomia correlated with poor blood glucose control and excess maternal weight for gravidic hypertension. At 3 months post-partum, glucose intolerance and non-insulin-dependent diabetes were diagnosed in 13% and 2% respectively. CONCLUSION: Systemic screening and obstetrical and endocrinological care allowed patients to prevent maternal and fetal complications in gestational diabetes and to initiate hygiene and dietary habits for the prevention of post-partum non-insulin-dependent diabetes. Obstetrical care can be adapted to risk factors such as overweight, late screening or poor blood glucose control.

Use of Chinese hamster ovary cell lines transfected with cloned human thyrotropin receptor for the measurement of thyroid-stimulating antibodies: advantages and difficulties.

We compared the activities of thyroid-stimulating antibodies (TSAb) as measured with two cell lines (JP26 and JP26/26) transfected with cloned human thyrotropin (TSH) receptor and the values for TSAb measured on human thyrocytes cultures. Sera were obtained from patients with Graves' disease, before, during and after therapy with carbimazole (1-methyl-2-thio-3-carbethoxyimidazole). The activities of TSAb performed with the three assays correlated significantly. The TSAb technique using JP26/26 cells was as sensitive as the method performed on human thyrocyte cultures since positive TSAb values were found in 45 out of 47 (95.7%) newly diagnosed patients, in 100% of patients who relapsed after drug withdrawal and in none in remission. When the JP26 cell line was used, sensitivity decreased as the detection rate was only 53.2 and 55.5% before treatment and in case of relapse, respectively. The TSH receptors analysis showed a receptor density two times higher for JP26/26 than for JP26. JP26/26 cells provide similar diagnostic information on human thyrocytes in patients with Graves' disease. Moreover with these cells, the procedure for cell culture is less cumbersome and precision is better. However, rigorous culture conditions are required to maintain TSH receptor expression in transfected cells.

[Anti-TPO antibodies and screening of thyroid dysfunction in type 1 diabetic patients]. / Intérêt du dosage des anticorps anti-TPO pour le dépistage d'une dysthyroïdie chez des patients diabétiques de type 1.

The diagnosis of thyroid dysfunction is often late in type 1 diabetic population. So, the aims of this study were 1) to evaluate the prevalences of thyroperoxydase (TPO) and thyroglobulin (Tg) autoantibodies detected by highly sensitive radioimmunological method in a cohort of 258 adult type 1 diabetic patients without evidence of clinical thyroid disease; 2) to determine whether or not measurement of TPO and/or Tg antibodies can identify subjects at risk of clinical or infraclinical thyroid dysfunction by measuring TSH in the entire group. TPO antibodies were found in 45 of the 258 diabetic patients (17%). The prevalence of TPO antibodies was not influenced by the following factors: gender, duration of disease, age at screening and at diabetes diagnosis, positivity of familial history. Tg antibodies were found in 19 patients (7%), including 13 cases with TPO antibodies. All patients without TPO antibody (n=213), including Tg-positive patients displayed TSH values in normal range. Among the 45 TPO-positive patients, 11 patients displayed infraclinical thyroid dysfunction. At the end of the 5-year follow-up, only 2/45 patients became anti-TPO negative. Thirteen of the 45 patients developed subclinical or clinical thyroid diseases (4 Graves'disease and 9 thyroiditis with hypothyroidism). By contrast, none of 45 TPO negative patients, sex and age matched with the TPO-positive patients, developed during follow-up anti-TPO positivity and/or infraclinical thyroid dysfunction. In conclusion, the determination of TPO antibodies by a highly sensitive method allows identifying diabetic patients with thyroid autoimmunity and at risk of subsequent impaired thyroid function, whatever age at diagnosis and diabetes duration. By contrast, anti-Tg determination did not give further information about subsequent thyroid dysfunction. In TPO antibody positive patients repeated thyroid clinical examination and TSH determination could be recommended to detect infraclinical thyroid dysfunction.

Longitudinal study of soluble intercellular adhesion molecule-1 (ICAM-1) in sera of patients with Graves' disease.

Adhesion molecules, such as Intercellular Adhesion Molecule-1 (ICAM-1), play an important role during the autoimmune process of Graves' disease (GD). So the objective of the study was to evaluate the time-course of the soluble ICAM-1 (sICAM-1) in GD. Concentrations of sICAM-1, thyroid hormones and TSAb (thyroid-stimulating antibodies) were determined in sera from 30 healthy controls, 41 untreated GD patients and after 3, 6, 12, 18 months of carbimazole therapy (no.=30), at relapse (no.=11) or 2 years after the end of therapy when remission (no.=13). Mean sICAM-1 concentration was significantly higher in untreated GD patients than in controls (mean+/-SD: 371+/-108 ng/ml vs 243+/-47 ng/ml, p<0.0001) until 6 months of therapy (289+/-102 ng/ml; NS). The number of positive patients (sICAM-1 levels>mean of the controls+2 SD) declined from 56% (23/41) at the time of the diagnosis to 10% (3/29) at 18 months. At relapse, mean sICAM-1 level significantly increased compared to that at 18 months of therapy (288+/-65 vs 236+/-59 ng/ml, p=0.005). At remission mean sICAM-1 level was significantly lower than in relapse patients (240+/-48 ng/ml, p=0.04); no patient displayed sICAM-1 positive values. In conclusion, sICAM-1 concentrations were increased in sera of newly diagnosed GD patients, declined significantly during carbimazole therapy and could again be increased at relapse. sICAM-1 could reflect an ongoing immune process and help to affirm the presence of an autoimmunity notably in some cases of TSAb negative patients. However its precise interest in clinical practice remains to be determined in further studies.

Combined analysis of long-term anti-beta-cell humoral reactivity in type 1 diabetes with and without thyroid disease.

The prevalence and levels of islet-cell antibodies (ICA) decrease in the years following diabetes onset but may persist, particularly in patients with concomitant autoimmune disease. The aim of this cross-sectional study was to investigate the frequencies, associations and levels of the major anti-beta-cell antibodies in long-standing diabetic patients (median duration: 14 years; range 5-47 years) with and without autoimmune thyroid disease (ATD) in order to consider the specific antipancreatic immunologic features associated with endocrine autoimmunity. Both ICA and glutamic acid decarboxylase (GAD) antibody (GAD-A) frequencies were increased in diabetic patients with ATD (38 vs 23%, p = 0.03 and 70 vs 21%, p < 10(-4) respectively). Although IA2-A frequency tended to be higher in diabetic patients with ATD, no significant difference was seen (37 vs 26%, p = 0.14). GAD median level was significantly higher in the diabetic group with ATD (15 vs 5 units, p < 10(-4)). IA2-A and ICA median levels were similar in both groups. Regardless of the combined analysis performed (ICA/GAD-A, ICA/IA2-A or GAD-A/IA2-A), the prevalence of combined antibody positivity was higher in diabetic patients with than without ATD. In both diabetic populations, ICA and GA-DA were significantly associated (p < 10(-4), and their levels were correlated (r = 0.42, p < 10(-4) and r = 0.584, p < 10(-4) respectively). No significant correlation was seen between IA2-A levels and either ICA or GAD-A titres. It is concluded that Type 1 diabetes mellitus with ATD is characterised by increased persistent humoral islet-related reactivity, particularly directed towards GAD.

Antithyroid drugs and Graves' disease--prospective randomized assessment of long-term treatment.

OBJECTIVE: Although antithyroid drugs (ATD) are widely used in the treatment of Graves' disease, management protocols, especially treatment duration, remain a subject of debate. The rate of relapse after short-term regimens of less than 6 months with ATD at decreasing doses is higher than after longer treatments from 12 to 24 months. As no prospective study has provided data on even longer protocols exceeding 2 years, we conducted a prospective trial to determine potential benefits of a 42-month treatment compared with an 18-month treatment. DESIGN, PATIENTS AND MEASUREMENTS: The aim of this prospective randomized trial was to compare relapse rates achieved two years after treatment withdrawal in patients who received carbimazole at decreasing doses for 18 months (n = 62) vs 42 months (n = 72). In addition to clinical relapse rate, the percentage of patients who normalized antithyroperoxidase (TPO) antibody and anti-TSH receptor stimulating antibody (TSAb) levels and early iodine uptake at the end of treatment were assessed as outcome criteria. RESULTS: The relapse rate two years after discontinuation of treatment did not differ significantly in patients treated for 18 months from those treated for 42 months (36% vs 29%, NS). At the end of treatment, there was no significant difference between the two groups in the percentage of anti-TPO positive patients (53% vs 46%, NS) or early iodine uptake (27% vs 21%, NS). Although the percentage of patients with TSAb was significantly lower in the 42-month treatment group (18% vs 42%, P = 0.004) at treatment withdrawal, the percentage of TSAb-positive patients did not significantly decrease between 18 and 42 months in this group (27% vs 18%, NS). CONCLUSION: Treatment duration greater than 18 months did not improve remission rate determined 2 years after treatment withdrawal or immunological variables or early iodine uptake measured at the time of discontinuation of treatment. These findings would indicate that, when a defined duration treatment is planned, prolonging treatment beyond 18 months does not provide any additional benefit.

Peripheral blood and intrathyroidal T cell clones from patients with thyroid autoimmune diseases.

For a better understanding of the pathogenesis of thyroid autoimmune diseases, we have studied morphological and functional properties of T clones from peripheral blood lymphocytes (PBL) and from intrathyroidal lymphocytes (ITL) obtained from 3 patients with Graves' disease or 1 Hashimoto's thyroiditis. Investigations were carried out on clones cultured alone or cocultured with autologous thyrocytes. Clonage efficiency ranged from 30% to 33% for PBL and 10% to 36% for ITL. A predominance of CD4-positive clones was observed whatever the origin of the lymphocytes or the autoimmune pathology. Gamma interferon (IFN-gamma) was detected in the majority (17/19) of the clones tested. Intracytoplasmic interleukin (IL-4) was secreted in 7/19 clones and both cytokines were produced in 5/19 clones. In coculture a proliferative response and tumour necrosis factor (TNF-alpha) production were observed with 6 clones (4 from Graves thyrocytes and 2 from thyroiditis). No cytotoxic clone was derived from Graves or thyroiditis tissues. These data demonstrate that the large majority of T clones are principally CD4-T cells; all the clones secreted TNF-alpha and a large majority produced IFN-gamma. Only a few clones produced IL-4 alone or associated with IFN-gamma. Six T clones induced proliferative response and of TNF-alpha secretion in coculture. Further investigations must be performed on these antigen-reactive T clones to analyse their role in the pathogenesis of the human thyroid autoimmune diseases.

Clinical and statistical evaluation of self-monitoring blood glucose meters.

OBJECTIVE: Our objective was to compare statistical and clinical methods for the evaluation of five self-monitoring blood glucose (SMBG) meters. RESEARCH DESIGN AND METHODS: Two successive capillary blood glucose measurements were performed, and a simultaneous laboratory venous glucose measurement was used as the reference value. Accuracy was studied by comparing each of the two successive meter values with the reference value by 1) a Spearman's correlation test, 2) a Wilcoxon's paired test, 3) the percentage of values within the 10% interval of the reference value according to the American Diabetes Association consensus statement, and 4) the error grid analysis. RESULTS: The first two methods did not discriminate between the SMBG systems: r was >0.92 for the five meters, and a significant difference between the meter and reference values was found for all but one meter. The two other methods allowed classification of the devices into three groups according to their accuracy: good (two meters), acceptable (two meters), and unacceptable (one meter). These two methods gave consistent results and both had a good reproducibility, because the classification was similar for the two successive measurements. CONCLUSIONS: Both the Spearman's and Wilcoxon's paired tests, although commonly used, are inappropriate to evaluate SMBG systems. The percentage of SMBG values within the +/-10% interval and the error grid analysis are more accurate, because they consistently classified the five glucose meters tested in our study with a high degree of reproducibility.

[Primary adrenal lymphoma with latent adrenal insufficiency: a case report and literature review]. / Lymphome primitif des surrénales avec insuffisance surrénalienne latente: à propos d'un nouveau cas et revue de la littérature.

We report a new case of primary adrenal lymphoma with latent adrenal insufficiency and long-term remission after hydrocortisone replacement therapy. We have analyzed 29 other cases described in the literature. This disease with poor prognosis can be revealed by an incidentally discovered, frequently bilateral, adrenal mass. Adrenal insufficiency may be latent and the diagnostic procedure should include both cortisol and ACTH determination with an additional ACTH stimulation test if appropriate. Early adrenal substitution can improve patient survival.