Three patients who spontaneously developed persistent hypothyroidism during or following treatment with antithyroid drugs for Graves' hyperthyroidism.

Three patients with Graves' disease who spontaneously developed hypothyroidism after treatment with antithyroid drugs are described herein. Patient 1 developed a painful tender thyroid enlargement with a fever and accelerated erythrocyte sedimentation rate when she was receiving maintenance therapy with methimazole, and she progressed to persistent hypothyroidism with increased titers of antithyroglobulin and antimicrosomal antibodies and marked reduction of goiter size within the subsequent 2 months. Thyroid-stimulating hormone-binding inhibitory immunoglobulins (TBIIs) and thyroid stimulation-blocking antibody (TSBAb) were absent when she was hypothyroid. Hypothyroidism probably resulted from autoimmune thyroid destruction due to subacute aggravation of Hashimoto's thyroiditis. During the clinical course of patient 2, accelerated erythrocyte sedimentation rate and later transient increases of antimicrosomal and antithyroglobulin antibody titers were observed repeatedly (four times), and she finally fell into overt hypothyroidism. She also had negative results of tests for TBII and TSBAb. Her hypothyroidism appeared to result from repeated thyroid destruction due to aggravation of Hashimoto's thyroiditis. Patient 3 fell into hypothyroidism when receiving a small dosage of methimazole. The TBII and TSBAb were strongly active when she developed hypothyroidism, which thus seemed to be due to blocking antibody. Patients with Graves' hyperthyroidism may eventually progress to hypothyroidism later by several different mechanisms. Severe and sudden or slowly repeated thyroid destruction due to aggravation of Hashimoto's thyroiditis is one mechanism. Another may be the appearance of a blocking antibody to the TSH receptor.     

Hashimoto's Thyroiditis Presenting as Acute Painful Thyroiditis and as a Manifestation of an Immune Reconstitution Inflammatory Syndrome in a Human Immunodeficiency Virus-Seropositive Patient

Background: An immune reconstitution inflammatory syndrome (IRIS) may complicate immune restoration following start of antiretroviral therapy (ART) in human immunodeficiency virus (HIV)-infected patients. The occurrence of Graves' disease in the setting of an IRIS is well recognized. We hereby report a case of Hashimoto's thyroiditis, presenting as an acute painful thyroiditis, and as a complication of IRIS. Summary: A painful acute thyroiditis with thyrotoxicosis occurred in a 37-year-old HIV-infected woman 10 months after initiation of ART. This thyroiditis was associated with the appearance of a high titer of anti-thyroid peroxidase (anti-TPO) antibodies and was followed by persistent hypothyroidism, requiring thyroxine replacement therapy. Conclusions: Hashimoto's thyroiditis may present as an acute thyroiditis with thyrotoxicosis in HIV-infected patients after initiation of ART. Clinicians caring for HIV-infected patients should be aware of this possible association.     

Association of seasonal allergic rhinitis is high in Graves' disease and low in painless thyroiditis.

Hashimoto's thyroiditis is thought to be a T-helper cell type 1 (TH1)-dependent disease, but it is not clear whether Graves' disease is T-helper cell type 2 (TH2)-predominant or not. TH1-predominant diseases are infrequently and TH2-predominant diseases are frequently associated with allergic diseases. We examined the prevalence of seasonal allergic rhinitis to Japanese cedar pollen, a typical TH2-associated disease, in patients with Graves' disease (n = 126), painless thyroiditis (n = 46) and Hashimoto's thyroiditis (n = 88), and compared them to healthy controls (n = 766). Gender and age distribution were not different among patient groups and healthy controls, except for the higher age of patients with Hashimoto's thyroiditis. The prevalence of seasonal allergic rhinitis was significantly high in patients with Graves' disease (42.9%, p < 0.05) and low in patients with painless thyroiditis (13.0%, p < 0.01) but was not different in patients with Hashimoto's thyroiditis (26.1%) compared to that of healthy controls (32.6%). When patients with painless thyroiditis were included in Hashimoto's thyroiditis group, the prevalence of seasonal allergic rhinitis was 21.6% and significantly different from that of healthy controls (p < 0.05). These data indicate that Graves' disease is TH2 predominant and painless thyroiditis is a TH1-predominant disease. Our findings suggest that the shift from TH2 toward TH1 immunogenesis may be important for achieving earlier remission of Graves' disease.     

Association of HLA antigen and restriction fragment length polymorphism of T cell receptor beta-chain gene with Graves' disease and Hashimoto's thyroiditis

HLA antigen phenotypes and BglII restriction fragment length polymorphism of T cell receptor beta-chain (TCR beta) gene were analyzed in 61 patients with Graves' disease and 50 patients with Hashimoto's thyroiditis. The antigen frequency of HLA-Bw46 in both Graves' disease (23.0%) and Hashimoto's thyroiditis (24.0%) was significantly higher than that in normal population (8.0%), with relative risks (RR) of 3.45 [corrected P (Pc) less than 0.009] and 3.66 (Pc less than 0.02), respectively. Significantly increased frequency of HLA-B51 antigen was also found in Hashimoto's thyroiditis (40.0% vs. 16.3% in controls; RR, 3.42; Pc less than 0.002). Hybridization of BglII-digested DNA with TCR beta probe revealed two alleles of 9.3 and 8.6 kilobases. The allele frequency of 8.6 kilobases in Graves' disease (79%) and Hashimoto's thyroiditis (76%) was significantly higher (P less than 0.01 and P less than 0.05, respectively) than that in controls (64%). The frequency of homozygous state 8.6/8.6 was significantly increased in both Graves' disease (62%) and Hashimoto's thyroiditis (60%) over that in controls (39%); the RR of 8.6/8.6 in Graves' disease and Hashimoto's thyroiditis were 2.55 (P less than 0.01) and 2.31 (P less than 0.05), respectively. These results indicate that in Japanese subjects at least two loci are involved in the susceptibility to Graves' disease and Hashimoto's thyroiditis, one related to HLA and another to TCR beta.     

Prevalence and Relative Risk of Other Autoimmune Diseases in Subjects with Autoimmune Thyroid Disease

Background

Common autoimmune disorders tend to coexist in the same subjects and to cluster in families.

Methods

We performed a cross-sectional multicenter study of 3286 Caucasian subjects (2791 with Graves' disease; 495 with Hashimoto's thyroiditis) attending UK hospital thyroid clinics to quantify the prevalence of coexisting autoimmune disorders. All subjects completed a structured questionnaire seeking a personal and parental history of common autoimmune disorders, as well as a history of hyperthyroidism or hypothyroidism among parents.

Results

The frequency of another autoimmune disorder was 9.67% in Graves' disease and 14.3% in Hashimoto's thyroiditis index cases (P = .005). Rheumatoid arthritis was the most common coexisting autoimmune disorder (found in 3.15% of Graves' disease and 4.24% of Hashimoto's thyroiditis cases). Relative risks of almost all other autoimmune diseases in Graves' disease or Hashimoto's thyroiditis were significantly increased (>10 for pernicious anemia, systemic lupus erythematosus, Addison's disease, celiac disease, and vitiligo). There was relative “clustering” of Graves' disease in the index case with parental hyperthyroidism and of Hashimoto's thyroiditis in the index case with parental hypothyroidism. Relative risks for most other coexisting autoimmune disorders were markedly increased among parents of index cases.

Conclusion

This is one of the largest studies to date to quantify the risk of diagnosis of coexisting autoimmune diseases in more than 3000 index cases with well-characterized Graves' disease or Hashimoto's thyroiditis. These risks highlight the importance of screening for other autoimmune diagnoses if subjects with autoimmune thyroid disease present with new or nonspecific symptoms.     

Changes in thyroid-stimulating immunoglobulins during antithyroid therapy

Thyroid-stimulating immunoglobulin (TSI) activity was measured by radioreceptor assay in sera from patients with Graves' disease, Hashimoto's thyroiditis, and thyroid cancer. In untreated Graves' disease (47 cases), TSI index was significantly lower [76.7 +/- 1.4 (SE)] than the average of a normal control group (30 cases; 94.4 +/- 1.9). In untreated Hashimoto's thyroiditis (25 cases), it was also significantly lower (83.0 +/- 2.4). In patients with thyroid cancer (19 cases), there was no significant difference from normal controls. After 131I treatment, the TSI index in Graves' disease decreased during 2--4 months, then increased and reached normal levels in 1 yr. During propylthiouracil treatment, the TSI index increased and reached a normal level in 5--6 months without the decreasing phase seen after 131I treatment. Free T4 index values were gradually decreased by both treatments. There was no significant relationship between TSI index and thyroid antibodies (microsomal antibodies and thyroglobulin antibodies) in untreated Graves' disease or Hashimoto's thyroiditis. It is concluded that 1) in the sera of patients with Graves' disease and Hashimoto's thyroiditis, there are immunoglobulin Gs that can displace TSH binding to thyroid membranes; 2) these immunoglobulins Gs are different from the classic antithyroid antibodies; and 3) 131T treatment of Graves' disease may enhance TSI production during the first 1--2 months after therapy.     

A polymorphism within the vitamin D-binding protein gene is associated with Graves' disease but not with Hashimoto's thyroiditis

Graves' disease and Hashimoto's thyroiditis are common autoimmune thyroid disorders. Experimentally, 1,25(OH)(2) D(3) prevents Hashimoto's thyroiditis. Vitamin D serum levels in Graves' disease were found to be significantly lower than in nonautoimmune hyperthyroidism. The polymorphic vitamin D-binding protein (DBP) greatly facilitates vitamin D actions, and DBP alleles differ regarding their affinity for 1,25(OH)(2) D(3). Therefore, we investigated polymorphisms of the DBP gene for an association with thyroid autoimmunity. Families with an offspring affected by Graves' disease (95 pedigrees) or by Hashimoto's thyroiditis (92 pedigrees) encompassing 561 individuals of Caucasian origin were genotyped for three DBP polymorphisms [(TAAA)(N) in intron 8; StyI; and HaeIII in exon 11]. Indirect haplotyping and (extended) transmission disequilibrium testing were performed. There was a significant transmission disequilibrium of the intron 8 polymorphism in patients with Graves' disease (P < 0.03) but not of the exon 11 polymorphism. In contrast, neither the intron 8 nor the exon 11 polymorphism was associated with Hashimoto's thyroiditis. Maternal and paternal transmission as well as allele frequencies in DQ2(+) and DQ2(-) patients did not differ in either disease. Therefore, allelic variants of the DBP gene confer susceptibility to Graves' disease but not to Hashimoto's thyroiditis in our population. These findings support a role of the vitamin D endocrine system in thyroid autoimmunity.     

Hodgkin's disease and hyperthyroidism

In recent years we have had the occasion to observe hyperthyroidism in 6 patients with Hodgkin's disease. All patients had received Mantlefield irradiation and were disease-free when hyperthyroidism appeared. Hyperthyroidism allows three different pictures to be distinguished: 1 case report of Graves' disease without ophthalmopathy, 1 case report of Hashimoto's thyroiditis corresponding to a particular form called hashitoxicosis, and 4 case reports of atypical silent thyroiditis. Reports concerning case studies of postirradiation Graves' disease or Hashimoto's thyroiditis during Hodgkin's disease are only to be found exceptionally. Atypical silent thyroiditis was recently individualized, but no postirradiation case studies have been reported. It is suggested that these 6 cases represent a radiation-induced immune thyroid disease: physiopathology and predisposing factors are discussed.     

Production of 8-OHdG and cytochrome c by cultured human mononuclear cells in patients with autoimmune thyroid disease

Since oxidative stress is related to autoimmune thyroid disease, we studied the production of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and cytochrome c by culture of mononuclear cells from patients with Graves' disease and Hashimoto's thyroiditis. In patients with untreated Graves' disease, 8-OHdG and cytochrome c levels in culture supernatant of mononuclear cells were significantly higher than those of healthy control subjects, while the cytochrome c levels were significantly higher in patients with untreated Graves' disease and Hashimoto's thyroiditis than those of control subjects. Significant correlations between 8-OHdG and FT4, and cytochrome c were found. These results indicated that thyroid function has a potent influence on oxidative stress.     

Endothelin-1 levels in patients with disorders of the thyroid gland.

The endothelium derived peptide endothelin-1 (ET-1) is the major isoform of the endothelin peptide family, which is produced and secreted in the endothelial cell system. We measured plasma levels in patients with thyroid diseases and investigated associations between laboratory and clinical markers of thyroid metabolism and ET-1 plasma levels. ET-1 plasma levels were determined in patients with Graves' disease (n = 54), endemic goiter (n = 26), patients with Hashimoto's thyroiditis (n = 21) and compared to healthy controls (n = 60). ET-1 plasma levels were significantly elevated in patients with Hashimoto's thyroiditis (p < 0.0001) and in patients with Graves' disease (p = 0.003), when compared to healthy controls. In patients with endemic goiter, no significant differences were found compared to healthy controls (p = 0.298) and when compared to patients with Graves' disease (p = 0.16). We did not observe an association between ET-1 plasma levels and parameters of thyroid disease (e.g. thyroidea-stimulating hormone, thyroxine, volume of the thyroid). Furthermore, patients with and without endocrine thyroid disease showed no significantly different ET-1 plasma levels (p = 0.78). These data suggest that the autoimmunologically induced inflammatory response of the thyroid gland in Hashimoto's thyroiditis and Graves' disease is responsible for increased ET-1 plasma levels. Furthermore, our data do not support a role for ET-1 as a valid quantitative indicator for stage or progression in endemic goiter, Graves' disease or Hashimoto's thyroiditis.     

EVIDENCE FOR THYROID ANTIGEN-REACTIVE T LYMPHOCYTES INFILTRATING THE THYROID GLAND IN GRAVES''DISEASE

We have investigated the relative distribution and some in vitro functions of thyroid-infiltrating immunocompetent cells obtained at fine-needle aspiration biopsy in twelve patients with Graves' disease and thirteen patients with Hashimoto's thyroiditis. In both disorders the predominant (57--59%) thyroid-infiltrating cell was a small lymphocyte. Significant numbers of plasma cells (10%) were seen only in Hashimoto's thyroiditis. Mononuclear phagocytes (monocytes plus macrophages) were present in similar numbers (12--18%) in both disorders. In both Graves' and Hashimoto's disease there was a relative reduction of (thymus-dependent) lymphocytes in the thyroid gland as compared to the blood. Blood and thyroid-infiltrating T lymphocytes were tested for in vitro cell-mediated immunity (CMI) to thyroid antigen in the leucocyte migration inhibition test (LMT). CMI was readily demonstrated in the blood of most patients with Graves' and Hashimoto's disease. When the thyroid-infiltrating lymphocytes were tested for CMI in the LMT, only the infiltrating cells from patients with Graves' disease displayed CMI, whereas the thyroid-infiltrating lymphocytes in Hashimoto's disease were negative. Fractionation of the immunocompetent cells demonstrated that the thyroid antigen-induced LMT response of blood and thyroid-infiltrating lymphocytes in Graves' disease is a T lymphocyte-dependent phenomenon.     

TRACKING OF INDIUM-111-OXINE LABELLED LYMPHOCYTES IN AUTOIMMUNE THYROID DISEASE

Peripheral lymphocytes (approximately 10(8)) from 4 subjects affected by autoimmune thyroid disease (2 Hashimoto's thyroiditis, 1 primary myxoedema, 1 Graves' disease) and 4 normal subjects were labelled in vitro with 40 microCi of indium-111-oxine and, following autologous injection, the distribution of the cells in the body was investigated by gamma camera imaging. Lymphocytes in the thyroid were observed 24 h after injection in both patients with Hashimoto's thyroiditis and in the patient with primary myxoedema, but not in the patient with Graves' disease or in any of the controls. To our knowledge, this is the first report using this method to try and demonstrate lymphocytes in the thyroid gland, and supports the concept that cell-mediated immunity may be playing an important role in the pathogenesis of Hashimoto's thyroiditis and primary myxoedema.     

Comparison of thyroid antigens by the experimental production of precipitating antibodies to human thyroid fractions and the identification of an antibody which competes with long-acting thyroid stimulator (LATS) for thyroid binding

Antibodies were raised to various sub-cellular fractions of human thyroids, (of Graves' disease, Hashimoto's thyroiditis, and non-toxic goitre). With one exception it was found that antibodies to the Graves' thyroid fractions crooss-reacted with both the non-toxic goitre and Hashimoto's thyroiditis fractions. This exception was in the antiserum to the Graves' 105 000 x g pellet (Gr4) which contained an anr the Hashimoto's (/) thyroid preparations. The antibody-antigen between A-1 and Gr4 could be blocked by the addition of LATS (or TSH) to the antigen, thus suggesting that A- 1 might be a LATS-like immunoglobulin. These results suggest that the TSH receptor can be produced in vivo. Production of such an antibody to the TSH receptor would permit the development for the first time fo a good animal model of Graves' disease.     

Increased thyroid blood flow in the hypoechoic lesions in patients with recurrent, painful Hashimoto's thyroiditis at the time of acute exacerbation

We report two cases with painful Hashimoto's thyroiditis, who developed recurrent fever and painful thyroid. Glucocorticoid treatment was transiently successful but tenderness in the thyroid gland and fever developed when glucocorticoid was tapered. One patient underwent total thyroidectomy uneventfully. As is well known, it is frequently difficult to make differential diagnosis between painful Hashimoto's thyroiditis and subacute thyroiditis particularly at the initial phase. Interestingly, color flow doppler sonography of patient 1 revealed an increased thyroid blood flow in the hypoechoic lesions at the time of acute exacerbation although the serum level of TSH was suppressed. In the other patient, thyroid blood flow was also increased mainly in the hypoechoic lesions when the serum level of TSH was moderately increased, and it disappeared completely after supplementation of prednisolone and L-T4. Since thyroid blood flow in subacute thyroiditis is always decreased, such an increased blood flow in the hypoechoic lesion may be one of clinical characteristics of painful Hashimoto's thyroiditis, and useful for differential diagnosis from subacute thyroiditis.     

Immune complex deposits in Graves' disease and Hashimoto's thyroiditis.

The thyroid glands of four patients with Graves' disease and five patients with Hashimoto's thyroiditis were investigated to demonstrate in vivo immune complex deposition. By electron microscopy, electron-dense deposits were observed in the follicular basal lamina--basement membrane--(FBL) often associated with lymphocytic and plasma cell infiltration. A positive correlation was obtained with all cases by immunofluorescent studies using anti-IgG, IgA, IgM, C3 and antithyroglobulin conjugated serums. The staining was of a granular pattern and coincided to the FBL region. No discrepancies were noted in electron microscopic and immunofluorescent observations between patients with Graves' disease and Hashimoto's thyroiditis, and the occasional observation of immune complexes in areas devoid of infiltrate in some patients with Graves' disease. Morphologically, the deposits were found to be similar to those described in the Obese Strain chickens with spontaneous autoimmune thyroiditis.     

Circulating activated T cell subsets in autoimmune thyroid diseases: differences between untreated and treated patients.

To investigate the relationships between lymphocyte subsets and thyroid function, peripheral blood lymphocytes were analysed with cell surface antigens of activated (HLA-DR+) T, helper T (CD4+ 2H4-, CD4+ 4B4+) and suppressor-inducer T (CD4+ 2H4+, CD4+ 4B4-) cells subsets in 56 patients with Graves' disease, 16 patients with Hashimoto's thyroiditis, 7 patients with typical subacute thyroiditis and 2 patients with the thyrotoxic phase of autoimmune thyroiditis. Both patients with Graves' disease and Hashimoto's thyroiditis had increased percentages of HLA-DR+ T (Ia+ CD3+) cells as well as HLA-DR+ helper-inducer T (Ia+ CD4+) cells, which seemed to be independent of treatments. The percentage of HLA-DR+ suppressor-cytotoxic T (Ia+ CD8+) cells was increased in euthyroid or hypothyroid patients with Graves' disease following treatment, but was normal in hyperthyroid patients. The percentages of Ia+ CD4+ cells and Ia+ CD8+ were also increased in patients with thyroiditis, whereas these abnormal values normalized in the remission phase. These findings suggest that an increase in Ia+ CD4+ cells characteristically occurs during immune system activation in patients with hyperthyroid Graves' disease, Hashimoto's thyroiditis and the thyrotoxic phase of subacute thyroiditis, whereas the activated CD8+ cells in Graves' disease are induced by antithyroidal therapy.     

Propylthiouracil and carbimazole associated-antineutrophil cytoplasmic antibodies (ANCA) in patients with Graves' disease

OBJECTIVE: Propylthiouracil treatment of Graves' disease has been postulated to provoke antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. We aimed to investigate whether carbimazole therapy was also associated with increased risk of ANCA. DESIGN: The occurrence of ANCA and the relationship to thionamide treatment was investigated in a cross-sectional study in a consecutive series of 407 patients' with Graves' disease, 200 with Hashimoto's thyroiditis and 649 normal euthyroid subjects. MEASUREMENTS: ANCA was measured by indirect immunofluorescence (IIF) and enzyme-linked immunosorbent assay (ELISA) for proteinase 3 and myeloperoxidase-ANCA. RESULTS: The prevalence of ANCA, as measured by IIF, was increased in the Graves' disease cohort (19.9%) compared with euthyroid controls (4.6%; P < 0.001). The prevalence of MPO-ANCA (measured by ELISA) was also increased in Graves' disease (P = 0.019). ANCA prevalence was more strongly associated with propylthiouracil treatment than carbimazole (P = 0.0265), although risk of ANCA was also higher in Graves' patients treated with carbimazole than controls (RR 2.2, P < 0.0001). ANCA positivity was not increased in patients with Hashimoto's thyroiditis. CONCLUSION: This study revealed a high prevalence of ANCA in treated patients with Graves' disease but not in those with Hashimoto's thyroiditis. Furthermore, within the Graves' disease population, ANCA development was associated with propylthiouracil usage to a greater extent than carbimazole. These findings suggest that the altered immune environment associated with autoimmune thyroid disease is not sufficient to develop ANCA but treatment with thionamides is important in promoting ANCA development.     

Increased levels of serum interleukin-18 in Graves' disease.

We have previously reported that serum soluble interleukin-2 receptor (sIL-2R) and IL-12 levels were significantly increased in hyperthyroid Graves' disease. In this study, we investigated serum IL-18 levels in patients with either Graves' disease or Hashimoto's thyroiditis. The serum IL-18 levels in Graves' disease were significantly increased in the hyperthyroid state and were decreased during treatment with methimazole or propylthiouracil. On the other hand, the levels in Hashimoto's thyroiditis in the hypothyroid state showed no significant differences from those in healthy subjects. When liothyronine sodium was administered orally to healthy subjects, serum IL-18 levels were not changed. Positive correlations between serum IL-18 and IL-12, IL-12 and sIL-2R, and sIL-2R and IL-18 levels were noted in Graves' disease. These results suggest that Th1 cytokines might play an important regulatory role in Graves' disease.     

Autoantibody tests in autoimmune thyroid disease: a case-control study.

Both positive antinuclear antibody (ANA) and anti-DNA antibodies have been reported in patients with autoimmune thyroid disease. We sought to determine the frequency of ANA and other autoantibodies in autoimmune thyroid disease versus control subjects. We measured ANA by 2 methods (mouse liver, HEp-2), anti-dsDNA, anti-Ro, anti-La, anti-Sm, anti-RNP, and anticardiolipin in 26 patients with Hashimoto's thyroiditis, 26 patients with Graves' disease, and 26 control patients. Positive ANA by either method were more common in patients with Graves' disease than in controls (p = 0.002 and 0.05). Although common (46.2%), ANA by HEp-2 method was not found significantly more often in patients with Hashimoto's thyroiditis than in controls. Evidence for systemic autoimmune diseases was not found: patients with autoimmune thyroid did not have autoantibodies other than ANA and did not differ from controls in rheumatologic symptoms. Positive ANA using the widely accepted HEp-2 method were commonly found in both Graves' disease and Hashimoto's thyroiditis. No evidence of subclinical systemic autoimmune disease was found, either by specific autoantibody tests or by increased frequency of rheumatologic symptoms or signs.     

Increase in antideoxyribonucleic acid antibody titer in postpartum aggravation of autoimmune thyroid disease

Serum antidouble stranded DNA antibody levels were measured during pregnancy and after delivery in women who had postpartum exacerbations of Graves' and Hashimoto's diseases. The changes in serum anti-DNA antibody levels closely paralleled those in the serum free T4 index, significantly increasing in the thyrotoxic phase 3-8 months postpartum in women with postpartum exacerbations of thyrotoxicosis due to Graves' disease and 1-3 months postpartum in women with postpartum destructive thyrotoxicosis of Graves' and Hashimoto's diseases. No change in anti-DNA antibody level was found in women with no postpartum exacerbations of thyroid diseases, nor could we demonstrate significant increases in serum anti-DNA antibody titers in patients with thyrotoxicosis due to subacute thyroiditis or in normal pregnant and postpartum women. The changes in serum anti-DNA antibody titers may reflect some generalized immunological abnormality in women who have postpartum exacerbations of Graves' or Hashimoto's diseases.