Resistance to thyroid hormone associated with autoimmune thyroid disease in a Turkish family

The syndrome of resistance to thyroid hormone (RTH) is characterized by impaired tissue responses to thyroid hormone. Hashimoto's thyroiditis is the most common thyroid autoimmune disease. We present a Turkish family with both RTH and Hashimoto's thyroiditis. RTH was detected through the presence of point mutation in thyroid hormone receptor (TR), and Hashimoto's thyroiditis was diagnosed due to the presence of thyroid autoantibodies. The proposita, her affected mother as well as her unaffected sister have thyroid autoantibodies consistent with Hashimoto's thyroiditis, and a heterozygous point mutation in exon 10 encoding the ligand (3,3',5-L-T3)-binding domain of the TRbeta gene was detected in both the proposita and the mother. The mutation is a replacement of cytosine for guanine in codon 453 (CCT->GCT) producing a missense mutation substituting a normal proline with an alanine (P453A), which reduces the affinity for T3 to 17% of that of the normal TRbeta. Both also have modest elevation of serum TSH levels. In severe RTH, marked elevation of thyroid hormone concentrations in the absence of suppressed TSH supports the laboratory diagnosis of RTH. However, when RTH is mild and associated with thyroiditis, even a modest thyroid gland insufficiency can obliterate the serum T4 and T3 elevations, typical of RTH. This will manifest as elevated serum TSH. Demonstration of TRbeta gene mutation is then necessary to establish the diagnosis. In addition, under these circumstances, treatment with thyroid hormone should be considered.     

Risk of thyroid cancer after childhood exposure to ionizing radiation for tinea capitis

BACKGROUND: The thyroid gland is known to be sensitive to the carcinogenic effect of ionizing radiation, especially in children. The role of potential modifiers of the risk and latency period effects needs further investigation. We examined the effect of low doses of ionizing radiation (4.5-49.5 cGy) on the risk of developing thyroid cancer after long latent periods of up to 54 yr after childhood exposure. METHODS: The study population included 10,834 individuals irradiated against tinea capitis in the 1950s and two matched nonirradiated groups (general population and siblings) for comparison. Cancer statistics and vital status data were obtained from national registries, updated to December 2002. Excess relative and absolute risks [excess relative risk per gray (ERR/Gy), excess absolute risk (EAR)] were estimated using Poisson regression for survival analysis. RESULTS: Within the study period, 159 cases of thyroid cancer were diagnosed. Total ERR/Gy and excess absolute risk per gray per 10(4) person-years for developing thyroid cancer reached 20.2 (95% confidence interval 11.8-32.3) and 9.9 (95% confidence interval 5.7-14.7), respectively. The risk was positively associated with dose and negatively associated with age at exposure. ERR/Gy was significantly elevated 10-19 yr after exposure, peaking at 20-30 yr, and decreasing dramatically (although still significantly elevated) 40 yr after exposure. CONCLUSIONS: Our findings agree with patterns of risk modification seen in most studies of radiation-induced thyroid cancer, although risk per unit dose seems higher. Our data show that 40 yr after irradiation, ERR decreases dramatically, although remaining significantly elevated. The hypothesis of different genetic susceptibility of the Jewish population deserves further exploration.     

Chronic unexplained anaemia in isolated autoimmune thyroid disease or associated with autoimmune related disorders

Objective The prevalence of chronic unexplained anaemia was analysed in patients with autoimmune thyroid disease (ATD). Design The presence of chronic unexplained anaemia, defined as anaemia not related to evident or occult bleeding and/or to erythropoietic disorders, was retrospectively assessed and compared in patients with nonautoimmune thyroid disease (NATD) and in patients with ATD. Subjects and measurements Biochemical and morphological parameters of anaemia were investigated and characterized in 1643 consecutive Caucasian outpatients with thyroid disease. In 991 patients, thyroid disease had a nonautoimmune origin. ATD was diagnosed in 652 patients (71 had Graves’ disease and 581 had Hashimoto's thyroiditis and its variants). In 145 patients ATD was associated with other autoimmune disorders. Results The presence of chronic unexplained anaemia was diagnosed in 123 patients (7·5%). Forty‐eight had a thalassaemic trait, representing 2·9% of the whole sample. A true chronic unexplained anaemia was recorded in 75/1643 (4·6%). The occurrence of unexplained anaemia was similar in patients with NATD (1·9%) and in those with isolated ATD (2·96%; P = NS) but increased in patients with ATD and autoimmune related disorders (ARD) compared to patients with isolated ATD and/or with NATD (28·3%; both P < 0·0001; RR = 9·56 and 14·75, respectively). Chronic unexplained anaemia was virtually absent in hyperthyroid patients and was more prevalent in hypothyroid than in euthyroid patients with ATD (P = 0·0047; RR = 2·104). Conclusions These results indicate that the increased frequency of chronic anaemia in patients with ATD is essentially due to the presence of concomitant autoimmune gastrointestinal diseases.     

The clinical presentation of autoimmune thyroid disease in men is associated with IL12B genotype

Background Common variants in the interleukin 12B (IL12B) gene are associated with predominantly inflammatory (Th1) or antibody‐mediated (Th2) immune responses. As Hashimoto’s disease and Graves’ disease are thought to arise from mainly Th1 and Th2 immune responses respectively, we hypothesized that IL12B genotype may influence the clinical presentation of autoimmune thyroid disease. Objective We tested for differences in IL12B genotype between Graves’ disease and Hashimoto’s disease. Patients We studied a discovery cohort of 203 Australian women and 37 men with autoimmune thyroid disease, a replication cohort of 100 European men and a cohort of 146 Chinese men. Intervention We analysed three IL12B variants: rs41292470, in the promoter; rs3212227, in the 3′ untranslated region and rs6887695, located 60 kilobases upstream from the coding region. Results In the discovery cohort, rs41292470 and rs3212227 genotypes did not differ significantly between Hashimoto’s disease and Graves’ disease. In Australian men (but not women), rs6887695 genotype differed between Hashimoto’s disease and Graves’ disease, with a minor allele frequency (MAF) of 14% and 41%, respectively (P = 0·034). This result was confirmed in the European men (MAF 24% and 41%; P = 0·013). On combined analysis of Australian, European and Chinese men (N = 285), the difference was highly significant (MAF 23% and 45%; P = 3 × 10^?5). In 233 men without thyroid disease, the MAF was 34%, significantly different from Graves’ disease (P = 0·005) and Hashimoto’s disease (P = 0·029). Conclusion In men with autoimmune thyroid disease, a common variant located upstream of the IL12B coding region may influence whether patients present with Graves’ disease or Hashimoto’s disease.     

Occupational exposure to non-ionizing radiation and an association with heart disease: an exploratory study

Exploratory analyses for dose-related exposure to non-ionizing radiation and adverse health effects among male physical therapists were done from a mail questionnaire survey. The cohort consisted of 3004 respondents who were stratified into subgroups according to exposure across and within the various types of non-ionizing radiation energy emitted from diathermy equipment. The radiation modalities considered were ultrasound, microwave, shortwave, and infrared. An association between heart disease and exposure to shortwave radiation was the only consistently significant finding when high and low exposure groups were compared.     

系统性红斑狼疮合并甲状腺疾病的临床特征分析

目的 调查系统性红斑狼疮（SLE）合并免疫性甲状腺疾病的年患病数,并探讨分析其临床特点.方法 回顾性调查2008年度武汉同济医院风湿免疫科住院的172例SLE病例,分析其中49例检测了甲状腺功能患者的临床资料,并分组比较SLE合并甲状腺疾病的临床特征.结果 SLE合并甲状腺功能减退症（甲减）组,17例;SLE合并甲状腺功能亢进症（甲亢）组,10例;病例对照组,22例.SLE合并甲状腺疾病的总体患病率约为15.7%,合并甲减和甲亢的患病率分别为9.89%和5.81%.多关节炎和抗ds-DNA抗体阳性检出率低是SLE合并甲减的主要特征,发热则在SLE合并甲亢的病人多见（P均＜0.05）.结论 SLE合并甲状腺疾病临床并不少见,它具有独特的临床特征,应注意监测其甲状腺功能.     

Diagnostic ionizing radiation exposure in a population-based cohort of patients with inflammatory bowel disease

OBJECTIVE:  For diagnosis, assessing disease activity, complications and extraintestinal manifestations, and monitoring response to therapy, patients with inflammatory bowel disease undergo many radiological studies employing ionizing radiation. However, the extent of radiation exposure in these patients is unknown.
METHODS:  A population-based inception cohort of 215 patients with inflammatory bowel disease from Olmsted County, Minnesota, diagnosed between 1990 and 2001, was identified. The total effective dose of diagnostic ionizing radiation was estimated for each patient. Linear regression was used to assess the median total effective dose since symptom onset.
RESULTS:  The number of patients with Crohn's disease and ulcerative colitis was 103 and 112, with a mean age at diagnosis of 38.6 and 39.4 yr, respectively. Mean follow-up was 8.9 yr for Crohn's disease and 9.0 yr for ulcerative colitis. Median total effective dose for Crohn's disease was 26.6 millisieverts (mSv) (range, 0–279) versus 10.5 mSv (range, 0–251) for ulcerative colitis ( P < 0.001). Computed tomography accounted for 51% and 40% of total effective dose, respectively. Patients with Crohn's disease had 2.46 times higher total effective dose than ulcerative colitis patients ( P = 0.001), adjusting for duration of disease.
CONCLUSIONS:  Annualizing our data, the radiation exposure in the inflammatory bowel disease population was equivalent to the average annual background radiation dose from naturally occurring sources in the U.S. (3.0 mSv). However, a subset of patients had substantially higher doses. The development of imaging management guidelines to minimize radiation dose, dose-reduction techniques in computed tomography, and faster, more robust magnetic resonance techniques are warranted.     

Disease associations with autoimmune thyroid disease.

Autoimmune thyroid disease (AITD) is common and occurs frequently in conjunction with other diseases. Many putative disease associations have been suggested for AITD but the validity of these associations is not clear in all cases. It is important to define disease associations correctly because this may offer a means to rationally screen for true associations, may shed light on shared pathophysiologic mechanisms and may be important if the associated disease impacts on patient management. This review has examined the evidence base for a large number of the suggested associations.     

A nine-year evaluation of emergency department personnel exposure to ionizing radiation

Emergency department personnel experience potential occupational hazards from exposure to ionizing radiation (x-rays). To assess this risk, ionizing radiation exposure was analyzed during a nine-year period for 128 ED personnel. The group consisted of 21 physicians, 92 nurses, and 15 ancillary personnel. Exposure was measured for both penetrating and nonpenetrating radiation using standard film dosimeter badges. Film badge use compliance was 66.7% for physicians, 86.2% for nurses, and 86.7% for ancillary personnel. Penetrating radiation exposure averaged 0.12 mrem/month for physicians, 0.70 mrem/month for nurses, and 0 mrem/month for ancillary personnel, all less than the average natural background exposure. We concluded that if standard radiation precautions are taken, the occupational risk from ionizing radiation exposure to personnel in the ED is minimal, and that routine monitoring of radiation exposure of ED personnel is unnecessary.     

Solar radiation is inversely associated with inflammatory bowel disease admissions

Objective: To explore the associations between latitude and solar radiation with inflammatory bowel disease admission rates in Chile, the country with the largest variation in solar radiation in the world.

Patients and methods: This is an ecological study, which included data on all hospital-admitted population for inflammatory bowel disease between 2001 and 2012, according to different latitudes and solar radiation exposures in Chile. The data were acquired from the national hospital discharge database from the Department of Health Statistics and Information of the Chilean Ministry of Health.

Results: Between 2001 and 2012 there were 12,869 admissions due to inflammatory bowel disease (69% ulcerative colitis, 31% Crohn’s disease). Median age was 36 years (IQR: 25–51); 57% were female. The national inflammatory bowel disease admission rate was 6.52 (95% CI: 6.40–6.63) per 100,000 inhabitants with increasing rates over the 12-year period. In terms of latitude, the highest admission rates for pediatric ulcerative colitis and Crohn’s disease, as well as adult ulcerative colitis, were observed in the southernmost region with lowest annual solar radiation. Linear regression analysis showed that regional solar radiation was inversely associated with inflammatory bowel disease admissions in Chile (β: ?.44, p?=?.03).

Conclusions: Regional solar radiation was inversely associated with inflammatory bowel disease admission rates in Chile; inflammatory bowel disease admissions were highest in the southernmost region with lowest solar radiation. Our results support the potential role of vitamin D deficiency on inflammatory bowel disease flares.     

Determination at the molecular level of a B-cell epitope on thyroid peroxidase likely to be associated with autoimmune thyroid disease.

In a panel of 13 mouse monoclonal antibodies generated against native (nondenatured) human thyroid peroxidase (TPO), only 1 (monoclonal antibody 47) recognized TPO protein fragments expressed in a human TPO cDNA sublibrary. Determination of the nucleotide sequences of 18 clones recognized by monoclonal antibody 47 localized its epitope to 9 amino acids (residues 713-721) in the human TPO protein. On Western blot analysis, only TPO monoclonal antibody 47 recognized the 933-amino acid TPO molecule after denaturation and reduction of the latter, supporting the concept that the major part of the epitope is represented by a continuous portion of the TPO sequence. The binding of TPO monoclonal antibody 47 to native TPO is inhibited by immunoglobulin G in the serum of patients with autoimmune thyroid disease. The epitope for monoclonal antibody 47 defined in the present study is, therefore, part of or in the vicinity of an epitope for autoimmune thyroid disease-associated TPO antibodies.     

Antibodies to membrane antigens in autoimmune thyroid disease

The possibility that sera from patients with autoimmune thyroid diseases contain autoantibodies to thyroid membrane proteins distinct from microsomal antigen and the TSH receptor has been investigated using (a) solid phase assay system based on human thyroid membranes and 125I-labelled protein A and (b) immunoprecipitation of detergent solubilized 125I-labelled thyroid membranes followed by gel electrophoresis and autoradiography. In the solid phase assay binding to membranes showed a highly significant correlation with binding to microsomes (r = 0.82; P less than 0.001; N = 82) indicating that the interaction between the serum and the membranes was due principally to microsomal antibody binding to microsomal antigen contaminating the membrane preparations. However, there were some discrepancies suggesting that an additional antigen-antibody system was involved. This possibility was then investigated using immunoprecipitation of 125I-labelled thyroid membranes. A labelled protein with mol wt 54 K was specifically immunoprecipitated (relative to normal pool serum) by 3 out of 4 sera from patients with Graves' disease who showed high binding to thyroid membranes. A further 4 sera from such patients with low membrane binding affinity failed to immunoprecipitate the 54 K protein. Sera from some patients with Hashimoto's disease and some patients with rheumatoid arthritis and one patient with Addison's disease also immunoprecipitated the 54 K protein from solubilized thyroid membranes. These studies suggested that antibodies interacting with the 54 K protein contributed to the discrepancies between thyroid membrane and microsome binding. However, the 54 K protein was also immunoprecipitated from detergent solubilized membranes prepared from human placenta, skeletal muscle and adrenal tissue.(ABSTRACT TRUNCATED AT 250 WORDS)     

Chronic neutropenia associated with autoimmune disease

Chronic neutropenia with autoimmune diseases is associated mainly with rheumatoid arthritis (RA), as Felty's syndrome or large granular lymphocyte (LGL) leukemia, and with systemic lupus erythematosus (SLE). Recent advances have allowed better understanding regarding the mechanism of neutropenia and improved options for treatment. Target antigens for antineutrophil antibodies have been identified for both Felty's syndrome and for SLE. The role of soluble Fas-ligand (FasL) in inducing apoptosis of neutrophils has been clarified for LGL leukemia and increased neutrophil apoptosis has been described in neutropenic patients with SLE. The role of immune complexes in affecting neutrophil traffic and function continues to be studied. Treatments of neutropenia have included methotrexate, cyclosporine A, and granulocyte colony-stimulating factor (G-CSF) as well as granulocyte-macrophage colony-stimulating factor (GM-CSF). The efficacy of both GM- and G-CSF in reversing neutropenia and decreasing the risk of infections in Felty's syndrome and SLE has been well documented. Of concern, however, have been flares of symptoms or development of leukocytoclastic vasculitis in some patients following the use of these cytokines. Recent results suggest that in these patients G-CSF should be administered at the lowest dose effective at elevating the neutrophil count above 1,000/microL.     

Crohn's disease associated with autoimmune neutropenia

We report a 29-year-old woman with a 20-year history of Crohn's disease and neutropenia. Because of repeated complications of Crohn's disease, she has undergone three intestinal resections and also has had recurrent skin abscesses, sinusitis, and pneumonia. Persistent neutropenia has been noted throughout the course of her disease, and antineutrophil antibodies have been detected in her serum and that of her younger brother, who also has Crohn's disease and neutropenia. We discuss autoimmune neutropenia in the context of other autoimmune manifestations of Crohn's disease and speculate as to its possible contributory role in the pathogenesis of Crohn's disease.