The role of environmental factors in autoimmune thyroiditis.

Environmental factors can play an important role in the development of autoimmune thyroiditis (AT) and other autoimmune diseases. This article reviews the role of heavy metals and infectious agents in AT. Currently, the genes responsible for a metal-induced pathology are known in experimental animals but similar knowledge is lacking in man. Metals such as nickel or mercury induce delayed type T cell hypersensitivity (allergy) which is relatively common, especially in women. T-cell allergy can be studied with the lymphocyte transformation test, LTT-MELISA. It has been found that patients with AT and other autoimmune diseases, such as multiple sclerosis, psoriasis, systemic lupus erythematosus and atopic eczema, show increased lymphocyte reactivity in vitro to inorganic mercury, nickel and other metals compared to healthy controls. The important source of mercury is dental amalgam. Replacement of amalgam in mercury-allergic subjects resulted in improvement of health in about 70% of patients. Several laboratory parameters such as mercury-specific lymphocyte responses in vitro and anti-thyroid autoantibodies were normalized as well. In contrast, no changes in health and laboratory results were observed in mercury-allergic patients who did not have their amalgams replaced. The same was true for non-allergic patients who underwent amalgam replacement. Infectious agents such as Helicobacter pylori (Hp) may cause chronic inflammation and autoimmune reactivity in susceptible subjects. The results of in vitro experiments performed with lymphocytes from Hp infected patients indicate that Hp can cause immunosuppression which might be eliminated by successful eradication therapy. In conclusion, heavy metals and Hp infection may play an important role in AT. Laboratory tests, such as LTT-MELISA, can help to determine the specific etiological agents causing inflammation in individual patients. The treatment of AT and other autoimmune diseases might be improved if such agents are eliminated and any future exposure restricted.

Adrenocortical function in young adults with diabetes mellitus type 1.

In 75 young adults with diabetes mellitus type 1 (DM 1) we have performed a cross-sectional study to gain more information about their adrenocortical function. We have found in a surprisingly large portion of patients (25%) a subnormal response (<500 nmol/L, low responders) of the serum cortisol during low-dose Synacthen test, accompanied by significantly decreased stimulated values of aldosterone and salivary cortisol. Basal serum cortisol, aldosterone, and dehydroepiandrosterone sulphate (in women only) were significantly reduced in low responders as well, while ACTH, cortisol binding globulin, plasma renin activity, urinary free cortisol/24h, and salivary cortisol did not differ. The results indicate that the disorder of adrenocortical function in low responders occurs in all adrenocortical zones. The patients with the highest risk in respect to revealed hypocorticalism were DM 1 with autoimmune thyroiditis, 13 out of 36 in contrast to 5 out of 39 suffered from isolated form of DM 1, with onset around 30 years, independently on sex. The biorhythm of salivary cortisol in low responders under real-life conditions did not significantly differ from normal responders, except of the decreased values in the morning. Antibodies against 21-hydroxylase and adrenal cortex were negative in the entire group of diabetics studied. In conclusion, this is the first study to demonstrate in as much as 25% of young adults with DM 1 patients without any signs of adrenal autoimmunity decreased both basal and stimulated serum cortisol and aldosterone levels, implying existence of subclinical primary hypocorticalism.

Removal of dental amalgam decreases anti-TPO and anti-Tg autoantibodies in patients with autoimmune thyroiditis.

OBJECTIVES: The impact of dental amalgam removal on the levels of anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-Tg) antibodies was studied in patients with autoimmune thyroiditis (AT) with and without mercury allergy. METHODS: Thirty-nine patients with AT were tested by an optimized lymphocyte proliferation test MELISA for allergy (hypersensitivity) to inorganic mercury. Patients were divided into two groups: Group I (n = 12) with no hypersensitivity to mercury and Group II (n = 27) with hypersensitivity to mercury. Amalgam fillings were removed from the oral cavities of 15 patients with hypersensitivity to mercury (Group IIA) and left in place in the remaining 12 patients (Group IIB). The laboratory markers of AT, anti-TPO and anti-Tg autoantibodies, were determined in all groups at the beginning of the study and six months later. RESULTS: Compared to levels at the beginning of the study, only patients with mercury hypersensitivity who underwent amalgam replacement (Group IIA) showed a significant decrease in the levels of both anti-Tg (p=0.001) and anti-TPO (p=0.0007) autoantibodies. The levels of autoantibodies in patients with or without mercury hypersensitivity (Group I and Group IIB) who did not replace amalgam did not change. CONCLUSION: Removal of mercury-containing dental amalgam in patients with mercury hypersensitivity may contribute to successful treatment of autoimmune thyroiditis.

Autoimmune thyroiditis and Helicobacter pylori--is there a connection?

OBJECTIVES: In this study we examined the anti-Helicobacter pylori (anti-H. pylori) antibodies in patients with autoimmune thyroiditis, with and without different polyglandular involvement, and in healthy controls. MATERIAL & METHODS: Patients with autoimmune thyroiditis (AT) were divided into three groups: Group A: 23 patients with isolated AT, Group B: 30 patients with AT as a part of polyglandular activation of autoimmunity, and Group C: 7 patients with AT as a part of autoimmune polyglandular syndrome type II. Thirty healthy individuals served as controls (Group D). Anti-H. pylori antibodies were determined first by ELISA for classes IgG, IgA, and IgM, and subsequently by immunoblot for classes IgG and IgA. RESULTS: ELISA: The number of patients with IgA antibodies in Group A (39%) and Group B (30%) differed significantly from controls (7%, p<0.05). Immunoblot: Anti-CagA antibodies were found in 13% of patients in Group A, 7% of Group B, 0% of Group C, and 20% of Group D. A higher seroprevalence, as compared to controls, was found for IgG to the VacA (p=0.01), 30 kDa (p=0.001), and 17 kDa (p=0.008) antigens in Group A and for IgG to the 30 kDa antigen in Group C (p=0.037). A significantly higher seroprevalence, as compared to controls, was likewise found for IgA to the 17 kDa antigen in Group A (p=0.015). CONCLUSIONS: A different distribution of antibodies to H. pylori antigens was found in patients with isolated AT compared to patients with AT coupled with a polyglandular syndrome.

Immunomodulatory cytokines in human seminal plasma correlate with immunomodulatory steroids.

7alpha-Hydroxy-dehydroepiandrosterone and its 7beta-hydroxyepimer, which act as local immunomodulatory agents, dehydroepiandrosterone, cortisol, and major androgens, together with four cytokines-interleukins 2, 4, 10, and IFN-gamma, reflecting the activity of TH1 or TH2 cells present in semen, were measured in seminal plasma from 35 male donors. Cortisol, dehydroepiandrosterone, its sulfate, 7-hydroxy-dehydroepiandrosterone epimers, testosterone, and estradiol were also measured in their blood serum. Steroids and interleukins in semen as well as serum steroids and seminal interleukins were mutually correlated to find out whether a relationship between immunomodulatory steroids and cytokines influencing the immune environment does exist. A highly significant (P<0.001) positive correlation was found between seminal 7beta-hydroxy-dehydroepiandrosterone and IFN-gamma, while a negative correlation was found between cortisol and IL-10. Highly significant positive correlations were also found between serum 7alpha-hydroxy-dehydroepiandrosterone and seminal IFN-gamma and between serum 7beta-hydroxy-dehydroepiandrosterone and seminal IL-2, while a negative correlation was found between serum dehydroepiandrosterone and seminal IL-10. Different and in some instances, even contradictory findings concerning the influence of dehydroepiandrosterone and cortisol on TH1 and TH2 cytokines were observed in seminal plasma as compared to those found by others in serum. The differences can be ascribed to the different environments of mucosal and systemic immunity. Correlations between the levels of steroids and cytokines in seminal plasma did not always correspond to the correlations between given cytokines and hormones in sera. The results, however, are in agreement with our recent finding of an autonomous production of these steroids in the male reproductive tract.

Mercury and nickel allergy: risk factors in fatigue and autoimmunity.

This study examined the presence of hypersensitivity to dental and environmental metals in patients with clinical disorders complicated with chronic fatigue syndrome. Three groups of patients were examined through medical history, dental examination, and by using a modified test of blast transformation for metals-MELISA(R). The three groups consisted of the following: 22 patients with autoimmune thyroiditis with or without polyglandular autoimmune activation; 28 fatigued patients free from endocrinopathy; and 22 fatigued professionals without evidence of autoimmunity. As controls, a population sample or 13 healthy subjects without any evidence of metal sensitivity was included. Healthy controls did not complain of marked fatigue and their laboratory tests did not show signs of autoimmunity and endocrinopathy. We have found that fatigue, regardless of the underlying disease, is primarily associated with hypersensitivity to inorganic mercury and nickel. The lymphocyte stimulation by other metals was similar in fatigued and control groups. To evaluate clinical relevance of positive in vitro findings, the replacement of amalgam with metal-free restorations was performed in some of the patients. At a six-month follow-up, patients reported considerably alleviated fatigue and disappearance of many symptoms previously encountered; in parallel, lymphocyte responses to metals decreased as well. We suggest that metal-driven inflammation may affect the hypothalamic-pituitary-adrenal axis (HPA axis) and indirectly trigger psychosomatic multisymptoms characterizing chronic fatigue syndrome, fibromyalgia, and other diseases of unknown etiology.