Serum selenium and selenoprotein-P levels in autoimmune thyroid diseases patients in a select center: a transversal study

ABSTRACT Objective: Selenium (Se) supplementation has been used to help prevent the progression of Graves' ophthalmopathy (GO) and autoimmune thyroid diseases (AITD) patients. We investigated Se serum and selenoprotein P (SePP) levels in Graves' disease (GD) with and without GO, Hashimoto's thyroiditis (HT) patients and in 27 control individuals (C). Subjects and methods: We studied 54 female and 19 male patients: 19 with GD without GO, 21 GD with GO, 14 with HT and 19 with HT+LT4. Se values were measured using graphite furnace atomic absorption spectrophotometry. Serum SePP levels were measured by ELISA. Results: Median Se levels were similar among all groups; GD patients: 54.2 (46.5-61.1 μg/L), GO: 53.6 (43.5-60.0 μg/L), HT: 51.9 (44.6-58.5 μg/L), HT+LT4 54.4 (44-63.4) and C group patients: 56.0 (52.4-61.5 μg/L); P = 0.48. However, serum SePP was lower in GO patients: 0.30 (0.15-1.05 μg/mL) and in HT patients: 0.35 (0.2-1.17 μg/mL) compared to C group patients: 1.00 (0.564.21 μg/mL) as well as to GD patients: 1.19 (0.62-2.5 μg/mL) and HT+LT4 patients: 0.7 (0,25-1.95); P = 0.002. Linear regression analysis showed a significant relationship between SePP and TPOAb values (r = 0.445, R2 = 0.293; P < 0.0001). Multiple regression analysis found no independent variables related to Se or SePP. Conclusion: A serum Se concentration was lower than in some other countries, but not significantly among AITD patients. The low serum SePP levels in GO and HT patients seems to express inflammatory reactions with a subsequent increase in Se-dependent protein consumption remains unclear.

Clinical Association of Thyroid Stimulating Hormone Receptor Antibody Levels with Disease Severity in the Chronic Inactive Stage of Graves' Orbitopathy

PURPOSE: To investigate associations between serum thyroid stimulating hormone (TSH) receptor antibody (TRAb) levels and Graves' orbitopathy (GO) activity/severity in chronic-stage GO and compare the performance of two newly-developed TRAb assays (third-generation TSH-binding inhibition immunoglobulin [TBII] assay versus Mc4 thyroid-stimulating immunoglobulin [TSI] bioassay). METHODS: This study is a retrospective review of medical charts and blood tests from Korean GO patients who first visited the departments of ophthalmology and endocrinology, Yonsei University College of Medicine from January 2008 to December 2011, were diagnosed with GO and Graves' hyperthyroidism, and were followed up for > or =18 months. Third-generation M22-TBII and Mc4-TSI assays were performed in the chronic-inactive GO patients in whom euthyroidism status was restored. Patients' GO activity/severity clinical activity scores (CAS), and modified NOSPECS scores were examined for a correlation with TRAb assays. RESULTS: Fifty patients (mean age, 41.3 years; 41 females) were analyzed. The mean duration of Graves' hyperthyroidism symptom was 63 months (range, 18 to 401 months) and that of GO was 46 months (range, 18 to 240 months). All patients had been treated previously with anti-thyroid drugs for a median period of 52.3 months, and two patients underwent either radioiodine therapy or total thyroidectomy. Mean CAS and NOSPECS scores were 0.5 +/- 0.9 (standard deviation) and 4.8 +/- 3.1, respectively. Mean M22-TBII and Mc4-TSI values were 7.5 +/- 10.2 IL/L and 325.9 +/- 210.1 specimen-to-reference control ratio. TSI was significantly correlated with NOSPECS score (R = 0.479, p 0.05), because GO inflammatory activity subsided in the chronic stages of GO. CONCLUSIONS: In chronic-inactive GO after euthyroid restoration, GO activity score did not associate with serum levels of TRAb or TBII. However, levels of the functional antibody Mc4-TSI did correlate with GO severity. Therefore, the TSI bioassay is a clinically relevant measure of disease severity even in chronic inactive GO.

Correlation between TSH Receptor Antibody Assays and Clinical Manifestations of Graves' Orbitopathy

PURPOSE: To investigate an association between the levels of serum thyroid-stimulating hormone (TSH)-receptor autoantibodies (TRAbs) and Graves' orbitopathy (GO) activity/severity scores, and compare the performance of three different TRAb assays in assessing the clinical manifestations of GO. MATERIALS AND METHODS: Cross-sectional study. Medical records of 155 patients diagnosed with GO between January 2008 and December 2010 were reviewed. GO activity was assessed by clinical activity score (CAS) and severity graded with the modified NOSPECS score by a single observer. Serum TRAb was measured by three different methods: 1st generation thyrotropin-binding inhibitor immunoglobulin (TBII) assay (TRAb1st); 3rd generation TBII assay (TRAb3rd); and biological quantitative assay of thyroid-stimulating immunoglobulin (TSI) using Mc4-CHO cells (Mc4-CHO TSI assay). Results were correlated with scores of activity/severity of thyroid eye disease. RESULTS: All three assays (TRAb1st, TRAb3rd, and Mc4-CHO TSI) yielded results that were significantly positively correlated with CAS (beta=0.21, 0.21, and 0.46, respectively; p<0.05) and proptosis (beta=0.38, 0.34, and 0.33, respectively; p<0.05). Mc4-CHO TSI bioassay results were significantly positively correlated with all GO severity indices (soft tissue involvement, proptosis, extraocular muscle involvement, and total eye score; beta=0.31, 0.33, 0.25, and 0.39, respectively; p<0.05). CONCLUSION: Mc4-CHO TSI bioassay was superior over the two TBIIs in assessing active inflammation and muscle restriction due to GO, whereas TBII assay would be sufficient for evaluation of patients with proptosis.

Graves opthalmopathy and psychoendocrinopathies

To assess the psychiatric and endocrinological changes in patients with Graves ophthalmopathy [GO]. A prospective, controlled, University Hospital based study. The current study comprised 60 patients diagnosed with GO at Mansoura Ophthalmic Center. Thirty five patients of them with moderate to severe GO formed the study group and twenty five patients with negligible to very mild GO formed the control group in the euthyroid state. The study group was further subdivided based on their predominant clinical signs into a proptosis subgroup and a muscle restriction subgroup. Psychiatric changes were assessed with the Middlesex Hospital Questionnaire [MHQ]. Biochemical analyses included serum-free thyroxine and thyroid-stimulating hormone [TSH] concentrations, TSH receptor antibody [TRAb] activity and antrthyroglobulin particle agglutination [TGPA] and antithyroid microsomal particle agglutination [MCPA]. The proptosis group reported significantly higher scores on anxiety, depression, and phobia than the muscle restriction group [P<0.0001]. The proptosis and muscle restriction subgroups reported significantly higher scores on all subscales compared to the control group [P<0.05]. The scale scores of depression and phobia showed a positive correlation with scores of anxiety [P<0.0001]. The serum TRAb activity showed a significant correlation with anxiety, phobia and hysteria [P<0.0001]. The psychiatric aspect of GO should be evaluated during routine follow-up and should be considered when making management decisions. Thyroid specific antibodies may be useful in confirming the diagnosis of GO

Avaliação do tratamento clínico da doença de Graves / Evaluation of the medical treatment of Graves' disease (GD)

O tratamento da doença de Graves (DG) com drogas antitireoidianas (DAT) associa-se à remissão da doença em metade dos indivíduos tratados por no mínimo 6 meses, e o índice de recidiva é alto, variando de 60 a 80 por cento. A presença de fatores prognósticos de sucesso do tratamento medicamentoso da DG é tema de discussão na literatura. Neste estudo avaliamos a incidência de remissão e recidiva em resposta ao tratamento clínico da DG com diferentes esquemas de tratamento com as duas DAT disponíveis no Brasil (propiltiouracil - PTU e metimazol - MMI), bem como determinar a presença de possíveis fatores preditivos de remissão e recidiva da doença e o perfil de efeitos colaterais. Revimos, no Hospital Universitário Clementino Fraga Filho (HUCFF), prontuários de todos os pacientes submetidos ao tratamento clínico da DG (sem história de tratamento prévio) por pelo menos 6 meses e seguidos após a suspensão da DAT por no mínimo 12 meses. Foram identificados 127 pacientes (idades de 18 a 88 anos; média 39,3±12,8), nos quais remissão da doença foi observada em 58 (45,7 por cento) e recidiva em 31 deles (53,4 por cento), num período médio de 14,5±16,1 meses. Sexo, idade e tempo de duração dos sintomas antes do tratamento clínico não interferiram significativamente sobre as taxas de remissão e recidiva, enquanto a presença de bócio >40 gramas, oftalmopatia de Graves (OG) e uso de doses diárias de DAT >600mg de PTU / 60mg de MMI influenciaram negativamente a taxa de remissão. Além disso, pacientes que apresentaram níveis de TSH <0,4æIU/mL entre 4 e 5 semanas após a suspensão da DAT apresentaram maior probabilidade cumulativa de recidiva da doença. Nossos resultados confirmam que a taxa de remissão em longo prazo da DG tratada com DAT é relativamente baixa. Concluímos que a combinação de oftalmopatia, bócio >40g e uso de dose diária de PTU >600mg ou MMI >60mg relacionou-se fortemente ã341; ausência de remissão da DG. Ademais, observamos que a dosagem de TSH entre 4 e 5 semanas após a suspensão da DAT parece ser uma ferramenta útil na determinação da chance de remissão ou recidiva da doença.