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

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

Vitamin D deficiency is not associated with early stages of thyroid autoimmunity

Context: Vitamin D deficiency has been identified as a risk factor for a number of autoimmune diseases including type 1 diabetes and multiple sclerosis. Objective: We hypothesized that low levels of vitamin D are related to the early stages of autoimmune thyroid disease (AITD). Design: Two case-control studies were performed. In the cross-sectional study A, euthyroid subjects with genetic susceptibility for AITD but without thyroid antibodies were compared with controls. Cases were subjects from the Amsterdam AITD cohort (euthyroid women who had first- or second-degree relatives with overt AITD) who at baseline had normal TSH and no thyroid antibodies; controls were healthy women examined at the same period. In the longitudinal study B, subjects who developed de novo thyroid peroxidase antibody (TPO-Ab) were compared with those who did not. Cases and controls were subjects from the Amsterdam AITD cohort who at baseline had normal TSH and no thyroid antibodies and during follow-up developed TPO-Ab (cases) or remained without thyroid antibodies (controls). Controls in both studies were matched for age, BMI, smoking status, estrogen use, month of blood sampling, and in study B for the duration of follow-up. Results: Serum 25(OH) D levels were as follows: study A: 21.0 +/- 7.9 vs 18.0 +/- 6.4 ng/ml (78 cases vs 78 controls, P=0.01); study B: baseline, 22.6 +/- 10.3 vs 23.4 +/- 9.1; follow-up 21.6 +/- 9.2 vs 21.2 +/- 9.3 ng/ml (67 cases vs 67 controls, NS). Conclusions: Early stages of thyroid autoimmunity (in study A genetic susceptibility and in study B development of TPO-Ab) are not associated with low vitamin D level

Involvement of stress in the pathogenesis of autoimmune thyroid disease: A prospective study

Background: An association between stress and autoimmune thyroid disease (AITD) (especially Graves' hyperthyroidism) has been reported, but all studies so far on this topic have been retrospective. Objective: To evaluate prospectively the relationship between stress and (i) de novo occurrence of thyroid antibodies and (ii) development of overt autoimmune hyper-/hypothyroidism. Study design: Two nested case-control studies in a prospective cohort of 790 euthyroid women who were 1st or 2nd degree relatives of AITD patients. Follow-up was five year, with annual assessments including questionnaires on stressful life events, daily hassles, and mood. In study A, cases were subjects who developed TPO-Ab but remained euthyroid during follow-up (called event). In study B, cases were subjects who developed overt hypothyroidism (TSH > 5.7 mU/l and FT4 20.1 pmol/l) during follow-up (called event). For each case, two controls were selected, matched for age and duration of follow-up; controls in study A remained TPO-Ab negative, and in study 8 remained without overt hyper-/hypothyroidism. Outcomes: Contrast in questionnaire responses between cases and controls at baseline, at one year prior to the event and at time of event. Results: Exposure to stress was not different between subjects who developed or did not develop TPO-Ab (study A). No differences were observed in stress questionnaires between hyper-/hypothyroid cases and controls at any time point, but hypothyroid cases had less negative feelings than controls at the time of diagnosis (study B). Conclusion: The data suggest that stress is not involved in the pathogenesis of AITD. (C) 2012 Elsevier Ltd. All rights reserve

Natural history of the transition from euthyroidism to overt autoimmune hypo- or hyperthyroidism: a prospective study

Objective: To evaluate the progression in time from euthyroidism to overt autoimmune hypothyroidism or to overt autoimmune hyperthyroidism. Subjects and methods: The design is that of a nested case-control study within the prospective Amsterdam autoimmune thyroid disease (AITD) cohort study in which 790 healthy euthyroid women with at least one first or second degree relative with documented AITD were followed for 5 years. Thyroid function tests were assessed annually. Contrast between cases (overt hypothyroidism - TSH > 5.7 mU/l and free thyroxine (FT4) 20.1 pmol/l, also referred to as events) and controls (matched for age and duration of follow-up). Results: At baseline, the 38 hypothyroid cases had already higher TSH and lower FT4 concentrations than their 76 controls, and the difference between both the groups persisted 1 year before occurrence of the event. In contrast, neither TSH nor FT4 values differed between the 13 hyperthyroid cases and their 26 controls at baseline or 1 year before the event. The prevalence of thyroid peroxidase-Ab was higher in both hypothyroid and hyperthyroid cases than in controls. At the time of event, hypothyroid cases were less common among current smokers (P = 0.083) and more common in the postpartum period (P = 0.006) than their controls, whereas hyperthyroid cases were pregnant more frequently (P = 0.063). Conclusions: The data suggest that progression toward overt autoimmune hypothyroidism is a gradual process taking several years, but in contrast overt autoimmune hyperthyroidism develops faster in terms of month