Ulla-Britt Ericsson

A high prevalence of thyroglobulin autoantibodies in adults with and without thyroid disease as measured with a sensitive solid-phase immunosorbent radioassay

Sera from 228 patients with thyroid disease and 140 healthy subjects without clinical or biochemical evidence of thyroid disease, were tested using a sensitive solid-phase immunosorbent radioassay (RIA) and a passive hemagglutination test (TRC test) for thyroglobulin antibodies (Tg-ab). With the RIA technique, Tg-ab was found in 27% of the controls (36% of the women and 15% of the men), whereas only 0.7% of them were Tg-ab positive with the TRC test. All individuals with primary hypothyroidism were Tg-ab positive with the RIA, compared with only 56% with the TRC test. Tg-ab (RIA) were found in 43/53 (81%) of the patients with toxic diffuse goiter, and in 30-40% of the patients with toxic nodular goiter, toxic adenoma, atoxic goiter, and thyroid carcinoma, the TRC test being positive in 10-17% of these patients. The high prevalence of Tg-ab in the healthy population suggests that subclinical thyroiditis is more frequent than has been assumed from antibody measurements made with less sensitive methods, and is in agreement with the prevalences reported from autopsy studies.

A compound follicular‐parafollicular cell carcinoma of the thyroid: A new tumor entity?

An unusual thyroid carcinoma is described, showing structural, histochemical and radioimmunologic features of both a follicular and a parafollicular cell carcinoma. Radioimmunoassay revealed high levels of thyroglobulin in the patients serum and in extracts from metastatic tumor tissue. Immunoreactive thyroglobulin was demonstrated histochemically in tumor cells. On scanning, pulmonary metastases showed uptake of 131I. Somatostatin and neurotensin immunoreactivity was also revealed histochemically in the tumor and a large proportion of the neoplastic cells were argyrophil. Serum calcitonin level was normal and no immunoreactive calcitonin was found in tumor tissue by radioimmunoassay or histochemically. Light microscopy showed cribriform patterns suggestive of follicular carcinoma as well as solid areas reminiscent of medullary carcinoma. Electron microscopy revealed two types of tumor cells. One type had electron dense granules resembling secretory granules characteristic of polypeptide hormone and/or monoamine producing endocrine cells. The other type had no such granules but showed a prominent vesicular rough endoplasmic reticulum similar to that seen in neoplastic follicular cells. The results suggest two alternative possibilities regarding the histogenesis of the tumor. One would be a mixed neoplasm, resulting from a coincidental malignant change in both follicular and parafollicular thyroid cells. The other, more likely alternative would be that the tumor cells are derived from a common stem cell with the potentiality of differentiating into both follicular and parafollicular adult cells. The finding that both thyroglobulin and somatostatin or neurotensin immunoreactivity occurred together in some tumor cells supports the latter possibility and suggests that at least some follicular and parafollicular cells may have a common precursor origin.

Prospectively measured triiodothyronine levels are positively associated with breast cancer risk in postmenopausal women

IntroductionThe potential association between hypo- and hyperthyroid disorders and breast cancer has been investigated in a large number of studies during the last decades without conclusive results. This prospective cohort study investigated prediagnostic levels of thyrotropin (TSH) and triiodothyronine (T3) in relation to breast cancer incidence in pre- and postmenopausal women.MethodsIn the Malmö Preventive Project, 2,696 women had T3 and/or TSH levels measured at baseline. During a mean follow-up of 19.3 years, 173 incident breast cancer cases were retrieved using record linkage with The Swedish Cancer Registry. Quartile cut-points for T3 and TSH were based on the distribution among all women in the study cohort. A Coxs proportional hazards analysis was used to estimate relative risks (RR), with a confidence interval (CI) of 95%. Trends over quartiles of T3 and TSH were calculated considering a P-value < 0.05 as statistically significant. All analyses were repeated for pre- and peri/postmenopausal women separately.ResultsOverall there was a statistically significant association between T3 and breast cancer risk, the adjusted RR in the fourth quartile, as compared to the first, was 1.87 (1.12 to 3.14). In postmenopausal women the RRs for the second, third and fourth quartiles, as compared to the first, were 3.26 (0.96 to 11.1), 5.53 (1.65 to 18.6) and 6.87 (2.09 to 22.6), (P-trend: < 0.001). There were no such associations in pre-menopausal women, and no statistically significant interaction between T3 and menopausal status. Also, no statistically significant association was seen between serum TSH and breast cancer.ConclusionsThis is the first prospective study on T3 levels in relation to breast cancer risk. T3 levels in postmenopausal women were positively associated with the risk of breast cancer in a dose-response manner.

Prospectively measured thyroid hormones and thyroid peroxidase antibodies in relation to breast cancer risk

Thyroid hormones influence both normal breast cell differentiation and breast cancer cell proliferation and stimulate the angiogenesis of certain cancer forms. Several cross‐sectional studies have measured thyroid hormones/autoantibodies in breast cancer ceases vs. controls, but it is difficult to determine the cause–effect direction in these studies. Only three prospective studies have reported on the subject so far. The aim of our study was to investigate prediagnostically measured levels of thyroid hormones, thyrotropin (TSH) and thyroid autoantibodies in relation to subsequent risk of breast cancer. The Malmoe Diet and Cancer study examined 17,035 women between 1991 and 1996. Blood samples were collected at baseline and free triiodothyronine (T3), free thyroxin (T4), TSH and thyroid peroxidase autoantibodies (TPO‐Ab) levels were measured in 676 cases and 680 controls. Relative risks with 95% confidence intervals were assessed using a logistic regression analysis adjusted for potential confounders. Free T4 levels were positively associated with a high risk of breast cancer, and the OR for women with free T4 levels above vs. below the median was 1.40 (1.10–1.77). This association was most pronounced in overweight women (1.51:1.07–2.12). Women with high levels of TPO‐Ab had a lower risk of breast cancer, but only the analysis of TPO‐Ab as a continuous variable reached statistical significance. Free T4 was in our study positively associated with a high risk of breast cancer. This association was most pronounced in overweight/obese women. Women with a high level of TPO‐Ab had a relatively low risk of breast cancer.

Salivary gland involvement in autoimmune thyroiditis, with special reference to the degree of association with Sjo¨gren's syndrome

From a total of 63 patients with autoimmune thyroiditis, 19 cases were further investigated to determine the degree of concomitant morphologic and functional salivary gland changes. For comparison, 21 of a total of 28 cases of primary Sjögrens syndrome were also examined. Of the 19 cases of autoimmune thyroiditis, 11 showed various degrees of salivary gland involvement on the basis of an analysis of lower lip salivary gland biopsy specimens, scintigraphy of the parotid, and unstimulated whole sialometry. Six of these cases fulfilled the criteria of primary Sjögrens syndrome. A remarkably high proportion of dark-staining acini was observed in the lower lip biopsy specimens of our patients with thyroiditis (8 of 19, 42%) and less among our patients with primary Sjögrens syndrome (5 of 21, 24%). We conclude that significant involvement of salivary glands may occur in cases of autoimmune thyroiditis, which indicates that common mechanisms may frequently be operative in the development of thyroid and salivary gland immune disease.

Triiodothyronine (T3) levels in relation to mortality from breast cancer and all-causes: a population-based prospective cohort study.

OBJECTIVE The potential association between thyroid hormones and breast cancer has been investigated in a large number of studies without conclusive results. This study investigated triiodothyronine (T3) levels in relation to breast cancer mortality in a population with no breast cancer patients at baseline. An additional aim was to study T3 levels in relation to mortality from other cancers and all-cause mortality. DESIGN AND METHODS This was a population-based prospective cohort study including 2185 women in whom T3 levels were measured as part of a preventive health project, i.e. before diagnosis in women who later developed breast cancer. Mean follow-up was 24.1 years and record-linkage to The Swedish Cause-of-Death registry identified 471 women who died: 26 out of breast cancer and 182 from other cancers. Mortality was assessed using a Coxs analysis, yielding hazard ratios (HRs), with 95% confidence intervals. Analyses of T3 as a continuous variable were repeated for pre- and peri/postmenopausal women separately. RESULTS T3 levels were positively associated with the risk of breast cancer-specific death in the age-adjusted analysis: HR for T3 as a continuous variable was 2.80 (1.26-6.25). However, the crude analysis did not reach statistical significance. Breast cancer mortality was even higher in postmenopausal women: 3.73 (1.69-8.22), but stratified analyses included few events. There were no statistically significant associations between T3 levels and deaths from other cancers, age-adjusted HR: 1.09 (0.72-1.65) or all-cause mortality (1.25:0.97-1.60). CONCLUSIONS This study, the first of its kind on prospectively measured T3 levels, indicates that T3 levels are positively associated with breast cancer-specific mortality and that this is not related to a general effect on all-cause mortality.

Noonan's Syndrome and Autoimmune Diseases

Noonans syndrome (NS) is a relatively common disease with an estimated incidence between 1/1,000 and 1/2,500 live births. NS is characterised by dysmorphic facies, short stature, chest deformity, ear abnormalities, cryptorchidism, ocular abnormalities, cubitus valgus, webbed neck, cutaneous and hair abnormalities, cardiovascular anomalies and delayed psychomotor development. The diagnosis rests solely on clinical criteria. Children with NS have a large number of potential health problems of which it is essential to be aware. Reports of autoimmune thyroiditis have been published. The aim of the present investigation was to study the prevalence of markers of autoimmune diseases, such as thyroglobulin antibodies (Tg-Ab) and antibodies to thyroid peroxidase (TPO-Ab) as well as IgA-antiendomysium antibodies (EMA) and IgA-antigliadin antibodies (AGA) in children with NS. As part of a Swedish multicenter trial to promote growth in patients with NS, Tg-Ab, TPOAb, AGA and EMA were measured in serum samples from 30 children, 16 girls and 14 boys, with NS, age range 3-20 years (mean age 12 years). All patients were diagnosed by one experienced clinician (O.W.) and evaluated according to the scoring system by Dunca et al.. The control group comprised 386 schoolchildren, 199 girls and 187 boys, aged 11-13 years (mean 12 years). Tg-Ab were detected in 20% (6/30) and TPOAb in 10% ( 5 / 3 0 ) of the patients, as compared to 14% (54/386) and 6% (22/386) of the controls

Gliadin Antibodies in Adult Insulin-Dependent Diabetes - Autoimmune and Immunogenetic Correlates

Gliadin antibody (GA) tests used in screening for coeliac disease (CD) frequently yield positive GA results without accompanying CD in cases of diabetes mellitus type 1 (DM-1). To enlighten this phenomenon we screened 848 DM-1 patients for IgA- and IgG-GA. Subsequently, 16 out of 19 high titre GA patients (6 with CD) were compared with 37 low titre DM-1 patients matched for sex, age and disease duration, for autoimmune and immunogenetic markers. Chronic thyroiditis and thyroid peroxidase (TPO) antibody positivity were more frequent in the GA-positive than in the GA-negative sub-group (38 vs. 2.7%, p=0.003, and 69 vs. 27%, p<0.001, respectively). The tissue transglutaminase (tTg) IgA titres correlated with CD but not with GA. tTg IgG titres were lower in GA-positive individuals (p = 0.0012). GA-positivity correlated with a higher titre of factor XIII IgA antibodies (p < 0.001). GA-positive DM-1 patients were characterised by a distinct immunogenetic profile; the risk of HLA DQB1*02 was lower among GA-positive patients than among GA-negatives (OR 0.4, preventive fraction 0.43). All CD patients were HLA DRBl*03-DQBl*02-positive, but none of the five patients with normal biopsies. GA-positive patients instead had HLA DRB1 * 13 in 37.5% as compared to 8.6% in GA-negative (OR 6.4, etiologic fraction 0.32). Thus, the occurrence of positive GA in DM-1 is correlated to TPO antibody positivity, thyroiditis and factor XIII IgA antibodies, but inversely correlated to tTg IgG, and seems to be associated with another HLA haplotype than that previously found to be associated with CD

Effect of therapy on the serum thyroglobulin concentration in patients with toxic diffuse goiter, toxic nodular goiter and toxic adenoma

Serum thyroglobulin (S-Tg) was measured in 104 patients with thyrotoxicosis, 59 of whom had toxic diffuse goiter (Graves’ disease), in 30 with toxic nodular goiter and in 15 with toxic adenoma. Before treatment, most patients had increased S-Tg concentrations, regardless of what type of thyrotoxicosis they had. After therapy the course of the S-Tg varied, two major patterns being observed: the S-Tg concentration increased in some patients but decreased in others, although no relationship could be found between these patterns and the outcome of therapy, the presence or absence of thyroglobulin antibodies (Tg-ab) or changes in the Tg-ab titer. However, the median pretreatment concentrations of S-Tg were significantly higher in patients with toxic nodular goiter and toxic adenoma than in those with toxic diffuse goiter (p < 0.001 and p < 0.05, respectively), but did not differ significantly between patients with toxic nodular goiter and toxic adenoma. The lowest posttreatment S-Tg concentrations were found after surgery, irrespective of type of thyrotoxicosis. The median pretreatment and posttreatment S-Tg concentrations in patients with toxic diffuse goiter who relapsed, did not differ from those patients in remission. This was also true of patients with toxic nodular goiter. In both groups, however, there was a tendency towards higher pretreatment S-Tg values in patients who subsequently relapsed. Serial determinations of S-Tg, on the other hand, are of limited value in predicting the risk of recurrence, independent of which type of thyrotoxicosis is involved.