INTRODUCTIONAnti-thyroid antibodies are associated with extra-thyroid diseases such as Graves' ophthalmopathy and Hashimoto's encephalopathy. Some evidence suggests that anti-thyroid antibodies are also associated with depression. Interleukin (IL)-17 appears to play an important role in autoimmune thyroid disease. This study investigated whether specific thyroid autoantibodies and IL-17 distinguished persons with depression from non-depressed controls.

MATERIALS AND METHODSForty-seven adult females with non-psychotic, current major depressive disorder and 80 healthy female controls participated in this study. Thyroid peroxidase antibodies, thyroglobulin antibodies, thyroid-stimulating hormone (TSH) receptor antibodies, free T3 and T4, TSH and IL-17 were measured from the serum. Measurements were repeated to assess test-retest reliability. Receiver operating characteristic (ROC) curves were used to estimate discriminatory values of the measurements. Differences between groups and associations between the clinical and biochemical assessments were analysed.

RESULTSMedian TSH receptor antibody concentration was significantly higher in the depressed than control group (P <0.001). Area under the ROC curve was 0.80 (95% CI, 0.73 to 0.88). Higher TSH receptor antibody titres were associated with greater depression severity scores (r = 0.33, P <0.05). IL-17 levels were not associated with TSH receptor antibody levels or depression severity scores. Thyroid function and other thyroid autoantibodies were not associated with depression severity.

CONCLUSIONTSH receptor antibodies might be a biomarker of immune dysfunction in depression.

Adult ; Autoantibodies ; blood ; Biomarkers ; blood ; Depressive Disorder, Major ; diagnosis ; immunology ; Female ; Humans ; Immunoglobulins, Thyroid-Stimulating ; blood ; Interleukin-17 ; blood ; Middle Aged ; Psychiatric Status Rating Scales ; ROC Curve ; Statistics as Topic ; Thyroid Gland ; immunology

BACKGROUND: It has been widely accepted that the epitope(s) and/or functional characteristics of thyrotropin receptor antibodies (TSHRAb) from Graves' patients are heterogenous among patients. However, the clinical significance of such heterogeneity has not been systematically evaluated yet. We were to elucidate and find the clinical significance of heterogeneity for TSH receptor antibodies in Graves' disease. METHODS: We measured stimulating TSHRAb (TSAb) activities using CHO-hTSHR cells, FRTL-5 cells and chimeric receptor expressing cells (Mc1 + 2 and Mc2), specific blocking TSHRAb (TSBAb) activities using Mc2 cells and TBII activities using porcine thyroid membrane in 136 patients with untreated hyperthyroid Graves' disease. RESULTS: Based on various TSHRAb activities from each patient, the patients could be categorized into 7 subgroups by cluster analysis; 1) Group 1 (n = 41) was characterized by moderate TSAb activities both in CHO-hTSHR cells and in FRTL-5 cells, typical TSAb epitope, rare blocking antibodies and high TBII activities. 2) Group 2 (n = 16) was characterized by the presence of blocking TSHRAb in most patients, albeit the other characteristics were the same as those in Group 1. 3) Group 3 (n = 19) patients had low TSAb activities both in CHO-hTSHR cells and in FRTL-5 cells, seldom had blocking TSHRAb, but they had high TBII activities. 4) Group 4 (n = 30) could be categorized as 'mild disease' group, as they had low activities in all kinds of TSHRAb assay and had low antimicrosomal antibody activities. 5) Group 5 (n = 14) was characterized by moderate TSAb activities with atypical epitope(s), rare blocking TSHRAb and moderate TBII activities. 6) Group 6 (n = 10) patients had very high TSAb activities with typical epitopes, seldom blocking TSHRAb and low TBII activities. 7) Group 7 (n = 6) was characterized by very high TSAb activities with atypical epitopes and high TBII activities. Pretreatment serum thyroid hormone level was low only in group 4 patients compared to the other 6 groups (p < 0.05). The size of goiter was significantly larger in those in group 1 and group 3 (p < 0.05) compared to the other 5 groups. The prevalence of clinically significant ophthalmopathy was higher in group 2 patients than the other 6 groups (50% vs. 27.5%, p = 0.06). Among 6 kinds of TSHRAb activities, only the blocking TSHRAb activity was significantly associated with the presence of ophthalmopathy in multivariate analysis. CONCLUSION: These results suggest that the differences in epitopes for TSAb or the presence of blocking TSHRAb is not a major factor in determining the degree of thyrotoxicosis in Graves' disease. Although the pathogenic mechanism is not clear yet, we suggest that patients with ophthalmopathy have different TSHRAb repertoire from those without ophthalmopathy in Graves' disease.
Adolescent ; Adult ; Aged ; Cluster Analysis ; Comparative Study ; Female ; Graves' Disease/*classification/*immunology ; Human ; Immunoglobulins, Thyroid-Stimulating/*analysis/blood ; Logistic Models ; Male ; Middle Age ; Multivariate Analysis ; Receptors, Thyrotropin/analysis/*immunology ; Sensitivity and Specificity ; Severity of Illness Index

A 25-year-old woman presented with jaundice, palpitation, and weight loss of 5 kg during a period of 2 weeks. Laboratory tests showed elevated levels of liver enzymes (AST 1,282 IU/L, ALT 1,119 IU/L) and total bilirubin (6.4 mg/dL); negative for hepatitis virus infection; elevated serum levels of triiodothyronine (T3, 3.60 ng/dL), free thyroxine (fT4, 3.82 ng/dL), and lowered serum level of thyroid stimulating hormone (TSH, <0.025 microIU/mL); and positive for thyroid stimulating antibody and anti-mitochondrial antibody (AMA). The liver biopsy findings were consistent with autoimmune hepatitis (AIH). Accordingly, oral steroid therapy was started with 60 mg of prednisolone under the impression of AIH associated with Graves' disease. After a week of steroid therapy, the clinical manifestation showed significant improvement, with normalization of both liver and thyroid functions. Diagnosis of the liver condition of patients who present with hyperthyroidism and liver dysfunction is important, so that appropriate therapy can be promptly initiated.
Adult ; Alanine Transaminase/analysis ; Antibodies, Antinuclear/blood ; Aspartate Aminotransferases/analysis ; Bilirubin/blood ; Female ; Graves Disease/complications/*diagnosis/drug therapy ; Hepatitis, Autoimmune/complications/*diagnosis/drug therapy ; Humans ; Immunoglobulins, Thyroid-Stimulating/blood ; Liver/enzymology/metabolism/pathology ; Prednisolone/therapeutic use ; Steroids/therapeutic use ; Thyrotropin/blood

BACKGROUND/AIMS: Graves' disease (GD) is caused by thyroid-stimulating hormone receptor (TSHR) and thyroid-stimulating immunoglobulin (TSI). We used a recently introduced, technically enhanced TSI bioassay to assess its diagnostic value and determine the cut-off in patients in high iodine intake area. METHODS: In a cross-sectional setting, we collected serum from 67 patients with untreated GD, 130 with GD under treatment, 22 with GD in remission, 42 with Hashimoto's thyroiditis, 12 with subacute thyroiditis, 20 with postpartum thyroiditis, and 93 euthyroid controls. TSI was measured using the Thyretaintrade mark bioassay, which is based on Chinese hamster ovary cells transfected with chimeric TSHR (Mc4). TSI levels are reported as a specimen-to-reference ratio percentage (SRR%). RESULTS: The TSI levels in patients with GD (either treated or not) were significantly higher than those of the remaining patients (p < 0.05). The new bioassay showed a sensitivity of 97.0% and a specificity of 95.9% with a cut-off value of 123.0 SRR% for GD. A weak correlation was found between TSI and thyrotropin-binding inhibiting immunoglobulin (TBII) (rs = 0.259, p = 0.03), but no correlation was found between TSI and tri-iodothyronine or free thyroxine. CONCLUSIONS: The Mc4-CHO bioassay showed comparable diagnostic value for GD with the conventional TBII assay. We propose a cut-off of 123.0 SRR% in areas where iodine intake is high.
Adult ; Animals ; *Biological Assay ; Biological Markers/blood ; CHO Cells ; Case-Control Studies ; Cricetinae ; Cricetulus ; Cross-Sectional Studies ; Female ; Genes, Reporter ; Graves Disease/*diagnosis/immunology/therapy ; Hashimoto Disease/diagnosis ; Humans ; Immunoglobulins, Thyroid-Stimulating/*blood ; Luciferases/genetics/metabolism ; Male ; Middle Aged ; Postpartum Thyroiditis/diagnosis ; Predictive Value of Tests ; Protein Binding ; Radioimmunoassay ; Receptors, Thyrotropin/genetics/*metabolism ; Recombinant Fusion Proteins/metabolism ; Republic of Korea ; Sensitivity and Specificity ; Thyroiditis, Subacute/diagnosis ; Transfection