Lipidomic differentiation of Graves' ophthalmopathy in plasma and urine from Graves' disease patients.

Approximately 50% of patients with Graves' disease (GD) develop retracted eyelids with bulging eyes, known as Graves' ophthalmopathy (GO). However, no simple diagnostic blood marker for distinguishing GO from GD has been developed yet. The objective of this study was to conduct comprehensive profiling of lipids using plasma and urine samples from patients with GD and GO undergoing antithyroid therapy using nanoflow ultrahigh performance liquid chromatography electrospray ionization tandem mass spectrometry. Plasma (n = 86) and urine (n = 75) samples were collected from 23 patients with GD without GO, 31 patients with GO, and 32 healthy controls. Among 389 plasma and 273 urinary lipids that were structurally identified, 281 plasma and 191 urinary lipids were quantified in selected reaction monitoring mode. High-abundance lipids were significantly altered, indicating that the development of GD is evidently related to altered lipid metabolism in both plasma and urine. Several urinary lysophosphatidylcholine species were found to be increased (3- to 10-fold) in both GD and GO. While the overall lipid profiles between GD and GO were similar, significant changes (area under receiver operating curve > 0.8) in GO vs. GD were observed in a few lipid profiles: 58:7-TG and (16:1,18:0)-DG from plasma, 16:1-PC and 50:1-TG from urine, and d18:1-S1P from both plasma and urine samples. An altered metabolism of lipids associated with the additional development of ophthalmopathy was confirmed with the discovery of several candidate markers. These can be suggested as candidate markers for differentiating the state of GO and GD patients based on plasma or urinary lipidomic analysis. Graphical abstract.

Thyroid-Associated Orbitopathy and Biomarkers: Where We Are and What We Can Hope for the Future.

BACKGROUND: Thyroid-associated orbitopathy (TAO) is the most common autoimmune disease of the orbit. It occurs more often in patients presenting with hyperthyroidism, characteristic of Graves' disease, but may be associated with hypothyroidism or euthyroidism. The diagnosis of TAO is based on clinical orbital features, radiological criteria, and the potential association with thyroid disease. To date, there is no specific marker of the orbital disease, making the early diagnosis difficult, especially if the orbital involvement precedes the thyroid dysfunction. SUMMARY: The goal of this review is to present the disease and combine the available data in the literature concerning investigation of TAO biomarkers. CONCLUSIONS: Despite the progress done in the understanding of TAO disease, some important pieces are still missing. Typically, for the future, major efforts have to be done in the discovery of new biomarkers, validation of the suspected candidates on multicenter cohorts with standardized methodologies, and establishment of their clinical performances on the specific clinical application fields in order to improve not only the management of the TAO patients but also the therapeutic options and follow-up.

Efficacy and safety of radioiodine therapy for mild Graves ophthalmopathy depending on cigarette consumption: a 6­month follow­up.

INTRODUCTION    Graves ophthalmopathy (GO) is an autoimmune disease associated with Graves disease. Its treatment is largely dependent on the severity and activity of ocular lesions. Particular attention should be given to radioiodine (RAI) therapy. Although its use is a valuable therapeutic option for hyperthyroidism, it may be followed by worsening of GO.  OBJECTIVES    The aim of the present study was to analyze how the severity of nicotine addiction affects the response to RAI treatment in patients with GO. PATIENTS AND METHODS    A total of 106 patients (58 smokers and 48 nonsmokers) with mild GO treated with 800 MBq of RAI were included to the study. We assessed the serum levels of thyroid­stimulating hormone (TSH), thyroid hormones, autoantibodies against thyroperoxidase, thyroglobulin, and TSH receptor (TSHR­Abs), as well as urinary cotinine levels and severity of ophthalmopathy. Analyses were conducted at baseline (before RAI treatment) and 2 and 6 months after the therapy. RESULTS    Significant differences in serum levels of TSHR­Abs were found between nonsmokers and smokers at 2 and 6 months after RAI therapy, whereas there were no differences at baseline. In smokers, there were significant differences in the severity of ophthalmopathy and the concentration of serum TSHR­Abs assessed at baseline and at 6 months of follow­up. Six months after RAI therapy, 46.2% of smokers and 4.3% of nonsmokers (P <0.001) progressed from mild to moderate GO.  CONCLUSIONS    High urinary cotinine levels in smokers were associated with the deterioration of ocular lesions after RAI treatment. A high dose of RAI did not induce an exacerbation of GO in nonsmokers who were administered oral steroid prophylaxis.

Oxidative stress in patients with Graves' ophthalmopathy: relationship between oxidative DNA damage and clinical evolution.

PURPOSE: To evaluate the relationship between oxidative stress and clinical evolution in patients with Graves' ophthalmopathy (GO). METHODS: Thirty-one euthyroid GO patients and 25 healthy subjects participated in this study. Oxidative DNA damage was assessed by determination of the 8-hydroxy-2'-deoxyguanosine (8-OHdG) level in urine by ELISA. The relationship of oxidative DNA damage to the clinical evolutions of GO, especially the smoking status, clinical activity scores (CAS), and ophthalmopathy index was examined. RESULTS: The mean 8-OHdG was significantly higher in GO patients than that of normal controls (12.6+/-5.7 vs 6.7+/-2.5 ng/mg creatinine, P<0.001). Smokers had significant higher 8-OHdG than did never smokers in GO patients (P=0.029), but not in healthy controls (P=0.374). Among GO patients, only CAS remained significantly correlated with 8-OHdG (P=0.001) after adjusting for age, sex, disease duration, the status of antithyroid drug and smoking, and thyroid-stimulating hormone level. Patients with active GO (CAS>3) had higher 8-OHdG than did the patients with CAS

Oxidative stress change by systemic corticosteroid treatment among patients having active graves ophthalmopathy.

OBJECTIVES: To measure the 8-hydroxy-2'-deoxyguanosine (8-OHdG) level in patients having active Graves ophthalmopathy (GO) and to compare this oxidative stress biomarker and the clinical evolution of patients after systemic corticosteroid treatment. METHODS: In 8 euthyroid patients having active GO, we determined the 8-OHdG levels in urine before, during, and after intensive corticosteroid therapy. Clinical activity and ophthalmopathy index scores were assessed. Nine age- and sex-matched healthy volunteers served as control subjects. RESULTS: The mean 8-OHdG level was statistically significantly increased in patients having active GO compared with that of controls (17.47 vs 5.97 ng/mg of creatinine, P < .001). During and after maximal systemic corticosteroid treatment, patients had statistically significantly lower mean 8-OHdG levels (7.19 and 10.18 ng/mg of creatinine, respectively) compared with the mean level before treatment. These changes were accompanied by decreases in clinical activity and ophthalmopathy index scores. The urinary 8-OHdG levels were subsequently elevated in 2 patients having recurrent active GO when corticosteroid therapy was tapered or withdrawn. CONCLUSIONS: Oxidative stress may have a role in the pathogenesis of GO. Urinary 8-OHdG level can be used not only as a noninvasive biomarker of oxidative stress in patients having GO but also as an objective and quantitative parameter in the follow-up of patients during immunosuppressive treatment.

Tratamento cirúrgico da proptose na doença de graves / Surgical treatment in graves disease proptosis

Introdução: a proptose é uma protusão anormal, para diante, de um ou ambos os olhos. É a manifestação extratireoidiana mais comum da doença de Graves. Os problemas estéticos e funcionais apresentam muitostranstornos aos pacientes. Objetivo: demonstrar a melhora estética e funcional dos pacientes operados. Métodos: foram operados 3 pacientes eutireoideos com proptose bilateral há mais de 6 meses, removendo 3 paredesda órbita. Resultados: todos os pacientes apresentaram melhora estética e funcional. Conclusões: aremoção óssea na proptose é método eficaz e de baixo risco cirúrgico.

Background: Proptosis is anabnormal protrusion, anteriorly, either unilateral orbilateral.It is the commonestextra-thyroidien manifestation of Graves’ disease. Patientsexperiment aesthetic and functional problems. Objective: Show the aesthetic and functional improvement ofoperated patients.Methods: Three euthyroidien patients were operated to correct a 6 months older bilateralproptosis where it was removed three wall of the orbit. Results: All the patients presented aesthetic and functiona limprovement.Conclusions: Orbit bonesresection in proptosis is an efficient and low risk surgical method.

[The level of cotinine - marker of tobacco smoking, in patients with hyperthyroidism]. / Stezenie kotyniny - markera nikotynizmu - u pacjentów z nadczynnoscia tarczycy.

INTRODUCTION: Orbitopathy associated with Graves' disease TAO (thyroid associated orbitopathy) is likewise connected with environmental factors including tobacco smoking. Tobacco smoking increases the risk of ophthalmologic pathology and leads to the orbital tissue damage due to the hypoxia. The aim of the study was to correlate the concentration of urinecotinine (marker of tobacco smoking) in Graves' disease patients with TAO with points received on the Fagerström questionnaire. MATERIALS AND METHODS: Thirty women with different degree of exacerbation of TAO in Graves' disease (34.28 +/- 12.04 yr.) were examined. As control we used 29 women with Graves' disease without TAO (29.35 +/- 12.33 yr.). The diagnosis was established according to level of TSH and level of thyrotropin receptor antibodies (TRAb). Measure of tobacco smoking or exposure to second hand tobacco smoke ETS (environmental tobacco smoke) carried out according to the Fagerström questionnaire, and measured cotinine level (the major metabolite of nicotine in urine). The level of clinical ophtalmopathy was measured according to the CAS (Clinical Activity Score) scale and degree of progression of TAO according to American Thyroid Association (NOSPECS scale). Additionally increase of exophthalmus was measured using the Hertl's exophthalmometer. RESULTS: In the group with TAO: 19 (63.3%) persons had mild exophthalmos (according to CAS), medium in 13 (43.3%) patients, and pronounced exophthalmous in 10 (33%) patients. There was statistically significant difference in the level of TRAb (18.4 +/- 8.2 vs. 5.1 +/- 3.4 IU/l; p < 0.0001) between TAO and controls. There was no correlation between TSH (0.6 +/- 0.02 vs. 0.4 +/- 0.04; p = 0.18) and fT4 (38.8 +/- 29.3 vs. 26.1 +/- 17.3; p = 0.026) in both analyzed groups. Smokers and non-smokers with TAO had no statistically significant in level of TRAb (Mann-Whitney test p = 0.16). No correlation was found between smoking tobacco (cotinine level) and the level of TRAb in patients with TAO (Pearson r = 0.28 p = 0.58). There was a statistically significant difference between the level of urine cotinine in smoking patients with TAO in the highest level of ophthalmopathy exacerbation (> 24 mm; > or = 4 points according to CAS) and those without TAO (Mann-Whitney's test p = 0.04). CONCLUSIONS: 1. In patients with Graves' disease with TAO the highest score of tobacco smoking has been found in persons with the highest ophthalmopathy exacerbation. 2. Estimation of cotinine concentration in urine is the most objective and useful method of tobacco smoking.