Autoimmune thyroid disease: new models of cell death in autoimmunity

Autoimmunity to thyroid antigens leads to two distinct pathogenic processes with opposing clinical outcomes: hypothyroidism in Hashimoto's thyroiditis and hyperthyroidism in Graves' disease. The high frequency of these diseases and easy accessibility of the thyroid gland has allowed the identification of key pathogenic mechanisms in organ-specific autoimmune diseases. In early investigations, antibody- and T-cell-mediated death mechanisms were proposed as being responsible for autoimmune thyrocyte depletion. Later, studies on apoptosis have provided new insights into autoimmune target destruction, indicating the involvement of death receptors and cytokine-regulated apoptotic pathways in the pathogenesis of thyroid autoimmunity.     

Age-related prevalence of platelet-associated immunoglobulins G in nonthrombocytopenic patients with autoimmune thyroid disease and autoimmune polyglandular syndrome

OBJECTIVE: The prevalence of platelet-associated IgG (paIgG) in nonthrombocytopenic patients with autoimmune thyroid disease (AITD) alone or associated with autoimmune polyglandular syndrome (APS) has been studied. SUBJECTS: A total of 164 individuals were enrolled in this study: 81 patients with AITD alone, 33 patients with APS, and 50 healthy controls. RESULTS: The presence of paIgG was recorded in 41 of 81 patients with AITD (51%) as compared with 2 of 50 control subjects (4%, p < 0.0001). The prevalence of paIgG in patients with APS was higher even when compared with patients with AITD alone (25/33, 76%; p = 0.02). The presence of paIgG was not related to the functional thyroid parameters. The prevalence of paIgG was higher in the older than in the younger patients (75 vs. 47%, p = 0.0037). CONCLUSIONS: The results indicate that the prevalence of paIgG in patients with AITD is higher than previously thought, namely in elderly patients and in patients with APS, and not related to the thyroid function.     

Serum digoxin in patients with thyroid disease.

Serum digoxin concentrations were measured by radioimmunoassay in 17 hyperthyroid and 16 hypothyroid patients after a seven-day course of oral digoxin. The significantly higher levels of serum digoxin in patients with hypothyroidism and lower levels in those with hyperthyroidism were closely related to the measured changes of glomerular filtration rate and digoxin serum half time in these two groups. Differences in serum digoxin concentration contribute to the altered sensitivity to digoxin shown by patients with thyroid disease.     

Idiopathic heart block: association with vitiligo,thyroid disease,pernicious anaemia,and diabetes mellitus.

Out of 100 patients with chronic heart block 16 had one or more autoimmune disorders-namely, vitiligo (5,) hypothyroidism (4), Graves''s disease (1), pernicious anaemia (2), and diabetes mellitus (9). All these disorders occurred with greater frequency than normal and were more prevalent than in a group of hospital inpatients of comparable age. Autoantibodies were not increased. We suggest that among patients with idiopathic heart block there is a subgroup with multiple autoimmune disorders.     

Hirschsprung's disease prevalence in Europe: A register based study

Background: Hirschsprung's disease is a congenital gut motility disorder, characterised by the absence of the enteric ganglion cells along the distal gut. The aim of this study was to describe the epidemiology of Hirschsprung's disease, including additional congenital anomalies, total prevalence, trends, and association with maternal age. Methods: Cases of Hirschsprung's disease delivered during 1980 to 2009 notified to 31 European Surveillance of Congenital Anomaly registers formed the population‐based case‐series. Prevalence rates and 95% confidence intervals were calculated as the number of cases per 10,000 births. Multilevel Poisson regression was performed to investigate trends in prevalence, geographical variation and the association with maternal age. Results: There were 1,322 cases of Hirschsprung's disease among 12,146,210 births. The total prevalence was 1.09 (95% confidence interval, 1.03–1.15) per 10,000 births and there was a small but significant increase in prevalence over time (relative risk = 1.01; 95% credible interval, 1.00–1.02; p = 0.004). There was evidence of geographical heterogeneity in prevalence (p < 0.001). Excluding 146 (11.0%) cases with chromosomal anomalies or genetic syndromes, there were 1,176 cases (prevalence = 0.97; 95% confidence interval, 0.91–1.03 per 10,000 births), of which 137 (11.6%) had major structural anomalies. There was no evidence of a significant increased risk of Hirschsprung's disease in cases born to women aged ≥35 years compared with those aged 25 to 29 (relative risk = 1.09; 95% credible interval, 0.91–1.31; p = 0.355). Conclusion: This large population‐based study found evidence of a small increasing trend in Hirschsprung's disease and differences in prevalence by geographic location. There was also no evidence of an association with maternal age. Birth Defects Research (Part A), 100:695–702, 2014. © 2014 Wiley Periodicals, Inc.     

Autoimmune thyroid diseases in women with breast cancer and colorectal cancer

The aim of the study was to compare the prevalence of autoimmune thyroid diseases in three groups of women (66 with breast cancer (CaB), 68 with colorectal cancer (CaC) and 49 without oncological diseases as a control group). Serum levels of thyroid-stimulating hormone (TSH), free thyroxin (fT4), antibodies to thyroglobulin (TGB-ab) and thyroperoxidase (TPO-ab) and tumor markers CEA, CA 15-3 and CA 19-9 were investigated in all subjects by using the chemiluminiscence method. In contrast to Graves' disease (no observed case), autoimmune thyroiditis was diagnosed in 24.2 % women with CaB (4.5 % euthyroid and 19.7 % with subclinical or overt hypothyroidism), compared to 16.7 % in women with CaC (2.0 % euthyroid and 14.7 % with subclinical or overt hypothyroidism) and 16.2 % controls (4.0 % euthyroid and 12.2 % with subclinical or overt hypothyroidism). Serum levels of TGB-ab were higher in the group with breast cancer as compared to those with colorectal cancer and the control group (medians: 35.80 vs. 31.75 vs. 27.70, p<0.001). Similarly, the percentage of positive TGB-ab and TPO-ab serum levels was higher in women with breast cancer as compared to those with colorectal cancer and the control group. The results of the study support the controversial theory that there is an increased prevalence of autoimmune thyroiditis in women with breast cancer.     

Prevalence of coeliac disease in patients with thyroid autoimmunity.

The occurrence of autoimmune thyroid disorders among patients with coeliac disease (CD) is well documented, but the exact prevalence of CD among patients with autoimmune thyroid diseases (ATD) is as yet unclear. We screened 150 newly diagnosed patients with ATD by serum endomysial antibody detection (EmA). In 5 subjects (3.3%) EmA positivity was found; all underwent jejunal biopsy. On gluten-free diet an excellent clinical and histological response was recorded with an improvement of hypothyroidism and reduction of the thyroxine dosage. Our data suggest a significant high prevalence (3.3%) of CD in patients with ATD, in particular with Hashimoto's thyroiditis.     

Encephalopathy associated with autoimmune thyroid disease in patients with Graves' disease: clinical manifestations,follow-up,and outcomes

Background  

The encephalopathy associated with autoimmune thyroid disease (EAATD) is characterized by neurological/psychiatric symptoms, high levels of anti-thyroid antibodies, increased cerebrospinal fluid protein concentration, non-specific electroencephalogram abnormalities, and responsiveness to the corticosteroid treatment in patients with an autoimmune thyroid disease. Almost all EAATD patients are affected by Hashimoto's thyroiditis (HT), although fourteen EAATD patients with Graves' disease (GD) have been also reported.     

Remarkable prevalence of coeliac disease in patients with irritable bowel syndrome plus fibromyalgia in comparison with those with isolated irritable bowel syndrome: a case-finding study

Introduction

Irritable bowel syndrome (IBS) and fibromyalgia syndrome (FMS) are two common central sensitization disorders frequently associated in the same patient, and some of these patients with IBS plus FMS (IBS/FMS) could actually be undiagnosed of coeliac disease (CD). The present study was an active case finding for CD in two IBS cohorts, one constituted by IBS/FMS subjects and the other by people with isolated IBS.

Methods

A total of 104 patients (89.4% females) fulfilling the 1990 ACR criteria for FMS and the Rome III criteria for IBS classification and 125 unrelated age- and sex-matched IBS patients without FMS underwent the following studies: haematological, coagulation and biochemistry tests, serological and genetic markers for CD (i.e., tissue transglutaminase 2 (tTG-2) and major histocompatibility complex HLA-DQ2/HLA-DQ8), multiple gastric and duodenal biopsies, FMS tender points (TPs), Fibromyalgia Impact Questionnaire (FIQ), Health Assessment Questionnaire (HAQ), 36-Item Short Form Health Survey (SF-36) and Visual Analogue Scales (VASs) for tiredness and gastrointestinal complaints.

Results

As a whole, IBS/FMS patients scored much worse in quality of life and VAS scores than those with isolated IBS (P < 0.001). Seven subjects (6.7%) from the IBS/FMS group displayed HLA-DQ2/HLA-DQ8 positivity, high tTG-2 serum levels and duodenal villous atrophy, concordant with CD. Interestingly enough, these seven patients were started on a gluten-free diet (GFD), showing a remarkable improvement in their digestive and systemic symptoms on follow-up.

Conclusions

The findings of this screening indicate that a non-negligible percentage of IBS/FMS patients are CD patients, whose symptoms can improve and in whom long-term CD-related complications might possibly be prevented with a strict lifelong GFD.