Aberrant levels of hematopoietic/neuronal growth and differentiation factors in euthyroid women at risk for autoimmune thyroid disease

Background Subjects at risk for major mood disorders have a higher risk to develop autoimmune thyroid disease (AITD) and vice-versa, implying a shared pathogenesis. In mood disorder patients, an abnormal profile of hematopoietic/neuronal growth factors is observed, suggesting that growth/differentiation abnormalities of these cell lineages may predispose to mood disorders. The first objective of our study was to investigate whether an aberrant profile of these hematopoietic/neuronal growth factors is also detectable in subjects at risk for AITD. A second objective was to study the inter relationship of these factors with previously determined and published growth factors/cytokines in the same subjects. Methods We studied 64 TPO-Ab-negative females with at least 1 first-or second-degree relative with AITD, 32 of whom did and 32 who did not seroconvert to TPO-Ab positivity in 5-year follow-up. Subjects were compared with 32 healthy controls (HCs). We measured serum levels of brain-derived neurotrophic factor (BDNF), Stem Cell Factor (SCF), Insulin-like Growth Factor-Binding Protein 2 (IGFBP-2), Epidermal Growth Factor (EGF) and IL-7 at baseline. Results BDNF was significantly lower (8.2 vs 18.9 ng/ml, P<0.001), while EGF (506.9 vs 307.6 pg/ml, P = 0.003) and IGFBP-2 (388.3 vs 188.5 ng/ml, P = 0.028) were significantly higher in relatives than in HCs. Relatives who seroconverted in the next 5 years had significantly higher levels of SCF than non-seroconverters (26.5 vs 16.7 pg/ml, P = 0.017). In a cluster analysis with the previously published growth factors/cytokines SCF clustered together with IL-1β, IL-6 and CCL-3, of which high levels also prec

Early stages of thyroid autoimmunity: follow-up studies in the Amsterdam AITD cohort

Bij patiënten met een auto-immuun-schildklierziekte (AIZ) valt het eigen afweersysteem de schildklier aan. Grigoris Effraimidis bekeek gedurende vijf jaar een groep van 803 vrouwen die een familielid hebben met AIZ. Elk jaar onderzocht hij de concentratie schildklierhormoon, de antilichamen tegen de schildklier en vitamine D. Ook verzamelde Effraimidis gegevens over roken, alcohol, stress, jodiumconcentratie en besmetting met de bacterie Yersinia Enterocolitica. Hij onderzocht specifiek de rol van deze factoren bij het ontstaan van de ziekte

Discontinuation of Smoking Increases the Risk for Developing Thyroid Peroxidase Antibodies and/or Thyroglobulin Antibodies: A Prospective Study

Context: Autoimmune thyroid disease develops in genetic susceptible subjects, provoked by environmental factors. Little is known of the environment in the early stages of autoimmunity. Objective: We evaluated environmental factors contributing to de novo occurrence of thyroid antibodies. Design: We conducted a prospective cohort study of 521 euthyroid women without thyroid antibodies in serum who were relatives of autoimmune thyroid disease patients. Follow-up was 5 yr. Baseline characteristics were related to the occurrence of thyroid peroxidase (TPO) and/or thyroglobulin (Tg) antibodies. Exposure to environmental factors in the year prior to the occurrence of antibodies was investigated in a nested case-control study. Results: The 5-yr probability for conversion to TPO antibodies (TPO-Ab) and/or Tg antibodies (Tg-Ab) was 20.1%, and for TPO-Ab alone the probability was 14.5%. None of the baseline characteristics except TSH contributed to the risk of seroconversion. Each case (occurrence of antibodies) was matched for age and duration of follow-up with two controls (no seroconversion). Exposure to environmental stimuli was similar between cases and controls except for smoking. At study entrance, current smokers among cases and controls were 31.3 and 35.5%, respectively (nonsignificant). Current smoking decreased in cases during follow-up. Consequently, the odds ratios (OR) of smoking for developing TPO-Ab and/or Tg-Ab were 0.62 [ 95% confidence interval (CI), 0.37-1.04] 1 yr before seroconversion and 0.59 (95% CI, 0.35-0.99) at seroconversion; for conversion to TPO-Ab, these figures are 0.58 (95% CI, 0.31-1.09) and 0.54 (95% CI, 0.29-1.02), respectively. Conclusion: Discontinuation of smoking is associated with an increased risk for occurrence of TPO-Ab and/or Tg-Ab in serum. The observation is in line with the decreased risk of hypothyroidism in smokers. (J Clin Endocrinol Metab 94: 1324-1328, 2009