Autoimmunity
  Guimaraes et al., Chicago, IL, USA, report a very interesting study in mice that develop autoimmune thyroiditis when injected with thyroglobulin in complete Freund's adjuvant but a suppression of development of thyroiditis is effected when mice are orally administered with thyroglobulin at 4 intervals prior to immunization and 1 time afterwards. Feeding thyroglobulin only after immunization effects a reduction of 40 %. Also development of lymphnodes of orally tolerized animals is reduced. These lymphnodes do not react immunologically when challenged in vitro as compared to lymphnodes of non-tolerized mice. (Comment: This model resembles that in the human where development of diabetes mellitus type I may be postponed by prior injection with insulin.)

Rodien et al., Lyon Cedex and Marseille, France, investigated the antigen that causes antibody-dependent cell mediated-cytotoxicity (ADCC) that occurs in about 70% of patients with thyroiditis and 50 % of patients with Graves' disease. In their test system using affinity purified human thyroperoxidase (TPO) using porcine thyroid cells as targets, they found that TPO-Ab are the antibodies responsible for ADCC in autoimmune thyroid disease, pointing to the major role of TPO as an antigen in thyroid autoimmunity. This major role was detected in all patients with Graves' disease (n = 16) and with autoimmune thyroiditis (n = 14). No such role could be attributed to lactoperoxidase or thyroglobulin.

Zubaschev et al., Lubeck, Germany, reported further on their studies pertaining to the relationship between Yersinia enterocolitica (Y.e.) infection and autoimmune thyroid disease. They found positive T-cell responses to Y.e. in 75 % of patients with Graves' disease or Hashimoto's disease compared to 35% in normals. These findings are further evidence of a role of Y.e. in thyroid autoimmune diseases.

Simescu et al., Bucharest, Romania, and Bratislava, Slovakia, investigated ultrasonically the thyroid of 120 children performed by Merck Thyromobil since hypoechoicity of thyroid sonography has been assumed to correlate with autoimmune thyroiditis. Goiter prevalence was 20% and mean urinary iodine excretion was 5.08 ug/dl. Hypoechoicity was present in 10 children, however only 1 was positive for TPO-antibody. The authors concluded that hypoechoicity is not a criterium for autoimmune thyroiditis. (Comment: Although the authors may be right, a firm conclusion can only be drawn if autoimmune thyroiditis is classified according to histology and not by presence or absence of thyroid autoantibodies only.)

Reinhardt et al., Essen and Wuppertal, Germany, evaluated if administration of 250 ug iodine daily for a mean period of 6 months would affect thyroid function in 38 patients positive for serum anti-TPO levels and/or moderate to severe hypoechoicity on thyroid ultrasound. Thirty-seven similar patients served as controls. The study was performed in an area of modest iodine deficiency (urinary excretion 70.2 pg/g creatinine). In the iodine group 5 patients developed subclinical and 1 overt hypothyroidism, whereas only 2 patients in the control group became subclinically hypothyroid. One patient became hyperthyroid in the iodine group and none in the control group. The authors conclude that small amounts of iodine may induce abnormal thyroid function in patients with Hashimoto's thyroiditis in an iodine deficient area.

Kasagi et al., Kyoto, Japan, assessed the clinical significance of measurement of thyroglobulin (TG) and TPO antibodies in the diagnosis of Hashimoto's thyroiditis in 110 patients suspected of having the disease. The serum results were correlated with histology obtained by needle biopsy. On histological basis Hashimoto's thyroiditis was present in 38 patients. In these patients sensitivity, specificity, and accuracy for the presence of TG antibodies was 96 %, 96 % and 96 % respectively; for TPO antibodies 74%, 96% and 79%. TG antibodies were determined by a newly developed technique and appeared to be superior in establishing the diagnosis Hashimoto's disease over the presence of TPO antibodies. The results using the hemagglutination technique for anti-TG antibodies were disappointing. The authors conclude that using their TG-Ab, test unnecessary biopsies for establishing the diagnosis may be eliminated.

In another study also a new highly sensitive IRMA for TG antibody was tested by Barbesino et al., Pisa, Italy, in 23 patients with Hashimoto's thyroiditis with or without TPO-Ab, in 15 patients with nontoxic nodular goiter with TPO-Ab and in 20 patients with non-toxic nodular goiter without TPO-Ab. The prevalence of TG antibodies was 39% in Hashimoto's disease, 26% and 30% in the two other groups respectively. It should be noted that patients' sera were selected on the basis of a negative Tg-Ab result by passive agglutination or ELISA techniques and the results do indicate a much higher sensitivity of this newly developed IRMA in establishing the presence of TG antibodies.

Loviselli et al., Cagliari, Italy, studied the geographical distribution of TPO antibodies in 6507 schoolchildren (age 7-14 jaar) in 25 towns or villages from central and southern Sardinia, including several areas with mild to moderate iodine deficiency. They found that goiter prevalence ranged between 2.1 and 4.9% and that the presence of TPO antibody was independent of goiter formation and of any present iodine deficiency. The authors suggest that genetic and environmental factors other than iodine were involved, triggering autoimmunity because "hot spots" of TG-Ab prevalence was observed in some villages throughout the three provincies. Interestingly the same pattern of hot spots has been described in the same Sardinian regions for islet cell antibodies. Most patients with autoimmune thyroiditis have both antibodies against TPO and TG.

Kobe et al., Kobe, Japan, studied the clinical features and thyroid function in 401 patients with autoimmune thyroiditis (AIT) of whom 97% had both antibodies (group A), 18% only TG-Ab (group B) and 3% only TPO-Ab (group C). Thus, thyroid volume was 42 and 57 ml in groups A and B respectively, and significantly smaller in group C, being 27 ml. Nodularity in group A, B, and C was 9%, 53%, and 20%. Hypoechoicity was 69%, 26%, and 0% respectively, and the incidence of hypothyroidism was 58%, 23%, and 45% respectively. It is concluded that patients with isolated TG-Ab frequently have nodularity (mostly adenomatous), while hypothyroidism is less frequent and the incidence of AIT with only TPO Ab is rare.

Smyth et al., Dublin, Ireland, studied the possible relationship between TPO antibodies in 150 consecutive patients with breast cancer and in 50 patients with benign breast disease. The prevalence was 36% and 24% respectively, as opposed to 15% in controls. Thyroid volume as measured by ultrasound was enlarged in 37%, 26%, and 7% respectively. The demonstration of a high prevalence of TPO Ab as well as thyroid enlargement in patients with breast disease may reflect common growth stimulators of receptor sites. (Comment: It would be very interesting to know if specific types with regard to histology of breast tumors and progesteron or estrogen receptor density are linked to the presence of AIT and also if prognosis in general is dependent on the presence of AIT.)

Lotz et al., Rome, Italy, studied lipoprotein A (LP[A]) concentrations in 30 male and 29 female euthyroid subjects who were positive for thyroid autoantibodies. These subjects were screened out of 428 male and 162 female blood donors. A significantly increased mean concentration of LP(A) was found in antibody positive males versus controls: 20 mg/dl versus 13 mg/dl. No increased LP(A) was found in the antibody positive females. (Comment: Since thyroid function was not different in the studied groups, the question should be raised if the presence of thyroid autoimmunity points to an autoimmune genesis of increased LP(A) in males which effect is apparently suppressed in females presumably effected by female hormones?)

Huan et al., Taipe, Taiwan, investigated prospectively the prevalence of thyroid autoantibodies in 130 patients with chronic hepatitis C and compared the results with those in 143 patients with chronic hepatitis B. Antimicrosomal antibodies and anti TG antibodies were essayed using hemagglutination tests. They found a prevalence of these antibodies in 27% versus 7% in hepatitis C and B respectively. The results indicate that thyroid autoimmunity is more prevalent in patients with hepatitis C than in those with hepatitis B.

Centanni et al., Rome, Italy, studied the prevalence of achlorhydric atrophic gastritis (AAG) based on hypergastrinemia and pentagastrin-resistent achlorhydria and confirmed by histology obtained by gastroscopy in 40 patients with high levels of anti-TPO antibodies. They diagnosed 21/40 subjects (52.5%) as having AAG. Four of them were euthyroid, 2 hyperthyroid, and 15 hypothyroid. In those with AAG 55% showed a high level of anti-parietal cells antibodies. It is concluded that AAG is often associated with autoimmune thyroid disease and that screening for AAG in patients with high antiTPO levels is advisable. (Comment: The relationship between autoimmune thyroid disease and abnormalities in vitamine B12 resorption is known for a long time. The authors agree that in patients with thyroid autoimmunity serum vitamine B12 should be measured as a minimal routine.)

Takagi et al., Isumo, Japan, studied the presence of hyperprolactinemia and pituitary enlargement (MRI) in 3 groups of patients with Hashimoto's thyroiditis (HT). Group A had normal TSH and FT4 (n = 62), group B increased TSH and normal FT4 (n = 28), and group C elevated TSH and subnormal FT4 (n = 24). The prevalence of hyperprolactinemia was 9.7%, 7.1%, and 37.5% respectively. Upon T4 treatment in 6/9 patients in group C, prolactin decreased gradually and in 3 of the 4/9 patients who had also pituitary enlargement, the size decreased as well during T4.

Verbruggen et al., Brussels, Belgium, studied basal serum calcitonin and calcium stimulated calcitonin secretion in 4 groups with increasing severity of autoimmune atrophic thyroiditis, divided in 4 groups. Group I normal basal and TRH stimulated TSH (n = 11), group II normal basal but increased TSH after TRH (n = 11), group III increased basal TSH (n = 14), and group IV clinically hypothyroid with increased basal TSH and subnormal FT3 and FT4. Basal calcitonin was normal in the 4 groups as compared to controls, but calcium stimulated calcitonin was significantly lower in all groups, whereas that in group IV was even significantly lower as compared to the other patients groups. It is concluded that C cells are probably involved in the autoimmune process.

Drexhage et al., Rotterdam, The Netherlands, investigated the prevalence of bipolar psychosis in 375 psychiatric patients 2-3 weeks after hospitalization. They found that these affective disorders were found/developed equally frequent in cases with subclinical autoimmune thyroiditis (presence of serum TPO antibodies) as in controls. However, the character of the disorder differed, in that rapid cycling was more frequently present in the TPO positive patients. This fact was irrespective of a normal or an increased serum TSH.