Advanced glycation end products are known to play an important role in diabetes complications, such as diabetic nephropathy. Most known pathways of diabetic complications involve oxidative stress, that have pivotal role in cell dysfunction onset and progression of angiopathies. This review will explore how AGEs cause endothelial dysfunction in diabetes and what current biochemical mechanisms have been proposed as an explanation for the development of diabetic nephropathy.

Introduction: GD is an autoimmune disease mediated by immunoglobulins (Igs) that activate TSH receptor (rTSH). Relapse after withdrawal of antithyroid drugs (ATD) can reach 60%. Measurement of TSH receptor antibodies (TRAb) and thyroid stimulating immunoglobulin (TSI) could be an indirect indicator of GD activity. TRAb assays measures thyroid-stimulating, thyroid-blocking and neutral Igs; TSI assays measures only stimulating Igs. Objetive: Evaluate, prospectively, autoimmunity before and after ATD therapy for thyrotoxicosis through TSI measurement. Methods: Patients were evaluated at the first visit and at the time of ATD withdrawal. TSH, thyroid hormones, TPO antibody, thyroglobulin antibody, and TRAb were measured using eletrochemiluminescent assays Roche Diagnostics; TSI was determined by chemiluminescent assay Siemens Diagnostics. According to manufacturers, TRAb < 1.75 IU/L and TSI < 0.55 IU/L were negative. Results: Sixty-seven patients mean age 45,7±2,45 years, 65 women, were evaluated: 50 at the first visit, 40 (80%) with GD, and 10 (20%) with toxic multinodular goiter (TMNG). TSI diagnostic sensitivity (Sen%) and specificity (Spe%) to diagnose GD were 90% and 100% respectively, similar to that of TRAb, of 89% and 100%. Thirty-six patients were evaluated for recurrence after suspension of ATD (19 of them also had the initial assessment): 21 (58.3%) did not present recurrence in an mean period of 9.5±2.1 months (3-18); and 15 (41.7%) relapsed in 4.4±2.6 months (2-12). In 10/21 patients who did not relapse, and whose TRAb was negative, TSI was positive at low levels, which was responsible for the low Spe% of this test. Assessing possible other cutoff points for the TSI in the recurrence assessment, an adjustment to 1.4 (TSI <1.4 IU/L = negative) raised the Spe% to 86%. Conclusions: In this group, TSI and TRAb were equivalent for GD diagnosis. Many clinical factors have been suggested and TRAb measurement is known to be useful for predicting GD relapse because of the active pathogenic role of TRAb. For predicting recurrence, with the proposed cutoff point proposed by the kit manufacturer for TSI, a better sensitivity was obtained when compared with TRAb (93% versus 67%), despite very low specificity (38%); by raising the cutting point to 1.4 specificity could be increased to 86% without reduced sensitivity. A larger sample in needed to support a higher TSI cutoff point in the clinical routine for the assessment of GD recurrence after ATD.

Background: TSH receptor (TSHr)-stimulating immunoglobulins (Igs) can be used as diagnostic markers of Graves’ disease (GD). Thyroid-stimulating immunoglobulin (TSI) assays exclusively detect these specific Igs. Materials and Methods: This was a prospective longitudinal study in which hyperthyroid patients with GD and toxic nodular goitres were evaluated at diagnosis. GD patients were also evaluated at antithyroid drug (ATD) withdrawal. An automated chemiluminescent assay measured TSI. According to the manufacturer TSI less than 0.55 IU/L was a non-reactive result. The authors evaluated the Se and Sp of the cutoff point provided by the TSI assay manufacturer, and tested other cutting points through a ROC curve, to assess relapse risk of Graves’ disease. Results: At diagnosis, were evaluated 92 (85.2%) GD patients aged 41.2 ± 2.0 years, and 16 patients (14.8%) with toxic multinodular goiter (TMNG) or toxic adenoma (TA), aged 60.8 ± 4.8 years. They were re-evaluated after 18 ± 4 months with methimazole (MMI) treatment. The follow-up after treatment suspension was of 20 ± 6 months. At diagnosis, the TSI (Se) and (Sp) were 98.9% and 100%, respectively. At ATD withdrawal, despite a high Se (95.5%), Sp was low (59.6%). By adjusting the cut-off to 1.11 (TSI <1.11 IU/L non-reactive), TSI presented the best Sp (89.4%) with a small decrease in Se (93.3%) in predicting GD relapse. Conclusions: TSI had high Se and Sp in GD differential diagnosis with nodular goiters. In the assessment for GD relapse, by raising the cutting point to 1.11 IU/L, a better Sp was obtained at the expense of a small drop in Se. A larger sample is needed to support a higher TSI cut-off point in the clinical routine to assess GD relapse after ATD.

Introduction: GD, mediated by TSH receptor-stimulating immunoglobulins (Igs) (rTSH), can lead to fetal thyroid dysfunction through the passage of Igs through the placenta during pregnancy. TRAb levels, used for prognostic evaluation, measure rTSH-stimulating and blocking Igs while TSI evaluates only as stimulating Igs. Objective: To prospectively evaluate pregnant women with DG and newborns (NB) by measuring TRAb and TSI and their correlation with thyroid function and postpartum complications. Methods: The patients were evaluated during pregnancy and the puerperium and the respective newborns. TSH, thyroid hormones and TRAb were evaluated by electrochemiluminescent method (Roche) and TSI by chemiluminescent assay (Siemens). TRAb&lt;1.75IU/L and TSI&lt;0.55IU/L were considered negative. Results: Nine patients were evaluated, with a mean age of 27.4±5.7 years: 6 had TRAb and TSI positive in the 1st trimester (1st-tri), when they maintained or started DAT; one with both negative (without DAT) and one with weakly positive TSI, when DAT was suspended. These last two remained euthyroid during pregnancy and puerperium. Of the first 6, 4 were evaluated in the 3rd-tri: three negative for TRAb and maintained positive TSI, 2 in low leves and one for high titles, when DAT was suspended or reduced; one kept both at very high levels. A patient with post-DT hypothyroidism, performed 3 years ago, using levothyroxine, evaluated in the 3rd-tri, had a negative TRAb and a highly positive TSI and remained so after pregnancy. The two patients who presented weakly positive TSI in the 3rd-tri evolved with their negative results and without DAT in the puerperium. The patient with TSI in high titers evolved with elevated levels as well as positive TRAb titers and postpartum decompensation. The patient with positive antibodies remained compensated for stable doses of DAT. Four NB were evaluated: all healthy, with normal thyroid function and negative TRAb. TSI was positive in 2 in the postpartum period; TSI was negative afterwards, while in the other 2 both antibodies were negative. Conclusions: TSI was not associated with thyroid dysfunction in NB, although it was associated with worsening hyperthyroidism in pregnant women, when at high titers. Positive TSI at low levels were not associated with worsening of the condition, which requires further studies to determine the cutoff point for assessing treatment suspension.