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Circulating intercellular adhesion molecule-1(ICAM-1) in sera of patients with Graves' disease and Hashimoto disease.

OBJECTIVES: Intercellular adhesion molecule-1 (ICAM-1), a 80-110 kD glycoprotein, has been found to be a ligand for the lymphocyte function associated antigen-1 (LFA-1) molecule and has important roles in inflammatory and immune mediated mechanisms. ICAM-1 is expressed on thyroid follicular cells of patients with Hashimoto disease and cultured thyroid monolayer cells derived from the thyroid surgical specimen. In addition to the expression of ICAM-1 on the surface of cells, soluble variants of several adhesion molecules have been reported. METHODS: We evaluated the circulating ICAM-1 in sera of representative autoimmune thyroid disease, Hashimoto and Graves' disease, and analyzed correlations between circulating ICAM-1 and thyroid-directed autoantibodies. Sera were collected from 58 patients with autoimmune thyroid disease, 28 patients with Graves' disease and 30 patients with Hashimoto disease. Serum concentrations for circulating ICAM-1 were determined with sandwitch enzyme immunoassay. RESULTS: Compared with normal individuals, mean serum concentrations for circulating ICAM-1 were significantly elevated in patients with Hashimoto disease and antithyroperoxidase-positive Graves' disease. Patients with antithyroperoxidase-positive Graves' disease revealed significantly higher serum circulating ICAM-1 concentrations than antithyroperoxidase-negative Graves' disease. Circulating ICAM-1 showed significant positive correlation with serum titers of antithyroglobulin and antithyroperoxidase antibody (r = 0.44, n = 28, p = 0.009, and r = 0.55, n = 28, p = 0.001 respectively). There was a significant positive correlation between circulating ICAM-1 levels and serum antithyroperoxidase level in the group of autoimmune thyroid disease and also circulating ICAM-1 levels were significantly correlated with serum antithyroperoxidase antibody levels in antithyroperoxidase antibody-positive Graves' disease(r = 0.55, n = 28, p = 0.001) and in Hashimoto disease (r = 0.5, n = 30, p = 0.002). The thyrotropin binding inhibiting immunoglobulins(TBII) showed no significant correlation with circulating ICAM-1 levels. CONCLUSIONS: In the present study, high serum levels of ICAM-1 were associated with autoimmune thyroid disease. Graves' disease and Hashimoto disease and positively correlates with levels of antithyroperoxidase antibody.

Autoantibodies↗

[Hashimoto disease].

Hashimoto disease is a representative organ-specific autoimmune disease. It occurs very frequently in middle-aged women. Generally, the symptom is only diffuse and elastic hard goiters detected by careful plpation. Immunological tests frequently reveal anti-thyroglobulin antibody and anti-TPO antibody. Hypothyroidism develops in some patient along with progression of the disease. In some patient, on the other hand, a condition called destructive thyroiditis may develop during the course of the disease, in which the thyroid gland is transiently destroyed, accompanied by thyrotoxic state. In this state, namely painless thyroiditis, 123I-uptake ratio is extremely low and TSH-receptor antibody is generally not observed. The thyroid hormone is administered to patient with large goiter or hypothyroidism, and antiphlogistic analgesics or adrenocortical hormone with beta-blockers in case of destructive thyroiditis.

Female↗

A promoter polymorphism of the CYP27B1 gene is associated with Addison's disease, Hashimoto's thyroiditis, Graves' disease and type 1 diabetes mellitus in Germans.

BACKGROUND: CYP27B1 hydroxylase catalyzes the conversion of 25 hydroxyvitamin D(3) (25OHD(3)) to 1,25(OH)(2)D(3), the most active natural vitamin D metabolite, which plays a role in the regulation of immunity and cell proliferation. We therefore investigated two single nucleotide polymorphisms in the CYP27B1 hydroxylase gene for an association with Addison's disease, Hashimoto's thyroiditis, Graves' disease and type 1 diabetes mellitus. METHODS: Patients with Addison's disease (n=124), Hashimoto's thyroiditis (n=139), Graves' disease (n=334), type 1 diabetes mellitus (n=252) and healthy controls (n=320) were genotyped for the promoter (-1260) C/A polymorphism and for the intron 6 (+2838) C/T polymorphism of the CYP27B1 gene. Patients and controls were compared using genotype-wise and allele-wise X(2) testing. RESULTS: A significant association was found between allelic variation of the promoter (-1260) C/A polymorphism and Addison's disease, Hashimoto's thyroiditis, Graves' disease and type 1 diabetes mellitus (P=0.0062, P=0.0173, P=0.0094 and P=0.0028 respectively). Significant differences were also observed for the intron 6 (+2838) C/T polymorphism (P=0.0058) in Hashimoto's thyroiditis but not for the other autoimmune endocrine diseases. CONCLUSIONS: The CYP27B1 promoter (-1260) C/A polymorphism appears to be associated with endocrine autoimmune diseases but the CYP27B1 intron 6 (+2838) C/T polymorphism appears to be associated only with Hashimoto's thyroiditis. These results imply a regulatory difference of the CYP27B1 hydroxylase to predispose to endocrine autoimmunity.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗

[A case of Turner syndrome complicated with Crohn's disease, erythema nodosum and Hashimoto disease].

A 26-year-old woman, who had had Turner syndrome from age 10 years old, had diarrhea, fever, joint pain, and erythema in the lower left leg. She was given a diagnosis of Crohn's disease, erythema nodosum, and Hashimoto disease. Systemic steroid therapy was very effective for both intestinal and skin lesions. It has been reported that half of inflammatory bowel disease patients with Turner syndrome have 46XiX (q) type chromosome abnormality, and this case also has this type of abnormality.

Adult↗

Hashimoto disease.

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Autoimmune Diseases↗

A case control study on psychiatric disorders in Hashimoto disease and Euthyroid Goitre: not only depressive but also anxiety disorders are associated with thyroid autoimmunity.

OBJECTIVE: To evaluate the association between mood and anxiety disorders in Hashimoto disease and Euthyroid Goitre in a case control study. METHODS: Cases included 19 subjects with Hashimoto disease in euthyroid phase, 19 subjects with euthyroid goitre, 2 control groups each of 76 subjects matched (4/1) according to age and sex drawn from the data base of a community based sample. Psychiatric diagnoses were formulated using the International Composite Diagnostic Interview Simplified, according to DSM-IV criteria. All subjects underwent a complete thyroid evaluation including physical examination, thyroid echography and measure of serum free T4 (FT4), free T3 (FT3), thyroid-stimulating hormone (TSH) and anti-thyroid peroxidase autoantibodies (anti-TPO). RESULTS: Subjects with Hashimoto disease showed higher frequencies of lifetime Depressive Episode (OR = 6.6, C.L. 95% 1.2-25.7), Generalized Anxiety Disorders (OR = 4,9 Cl 95% 1.5-25.4) and Social Phobia (OR = 20.0, CL 95% 2.3-153.3) whilst no differences were found between subjects with goitre and controls. CONCLUSION: The study seems to confirm that risk for depressive disorders in subjects with thyroiditis is independent of the thyroid function detected by routine tests and indicates that not only mood but also anxiety disorders may be associated with Hashimoto disease.

Journal Article↗

Computer analysis of echographic textures in Hashimoto disease of the thyroid.

Ultrasound B-scan images of the thyroid obtained from 10 patients with Hashimoto disease were digitized and processed by a computer method of image analysis that segments complex B-scan images into regions of homogeneous texture. The method was first applied to B-scan images of the normal thyroid and it consistently classified the normal tissue into a unique region. When applied to Hashimoto disease B-scan images, the same method segmented the thyroid into two regions. Detailed analysis of these regions revealed that their gray-level histograms were very different from that of the normal thyroid in eight cases. In two cases the histogram of one of the regions was similar to that of the previous eight cases, whereas the histogram and the tissue of the other region were similar to those of the normal tissue. This paper shows how these results can be interpreted according to the natural history of the Hashimoto disease.

Humans↗

Thyroxine replacement dose in patients with Hashimoto disease: a potential role for interleukin-6.

OBJECTIVE: To investigate the potential association between serum inflammatory cytokine levels and thyroxine replacement dose in patients with Hashimoto disease. PATIENTS AND METHODS: The study included 40 patients (12 men) with a mean age of 56.52+/-6.12 years who had hypothyroidism due to Hashimoto disease. Serum interleukin-1b (IL-1b), tumour necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) levels, as well as TSH, T(3) and T(4) were measured (ELISA). RESULTS: Serum IL-6 showed a significant positive correlation both with total thyroxine replacement dose (r=0.551, p=0.001) and with dose per kilogram of body weight (r=0.482, p=0.002). There was also a significant negative linear correlation between serum IL6 and T(3) (r=-0.322, p=0.043), as well as between serum IL6 and T(3)/T(4) ratio (r=-0.332, p=0.036). A further significant (r=0.419, p=0.007) positive association was demonstrated between IL6 and TNF-alpha. However, no association was found between T(3) or T(3)/T(4) ratio and TNF-alpha or IL1b. CONCLUSIONS: In patients with Hashimoto disease serum IL-6 levels are positively associated with thyroxine replacement dose and negatively associated with T(3) and T(3)/T(4) ratio. These results are possibly attributable to the inhibitory effect of IL6 on deiodination of T(3) and imply a role for IL6 in determining thyroxine replacement dose among these patients.

Dose-Response Relationship, Drug↗

[Hashimoto disease and hypothyroidism in child-bearing period--essential problem for woman and her child].

Hashimoto disease is the most frequent cause of women's hypothyroidism in the reproductive period. It can, both directly and indirectly, influence the fertility, pregnancy, and fetus development. Nevertheless congenital hypothyroidism is very occasionally the consequence of chronic autoimmune thyroiditis. The neonatal hypothyroidism screening makes the early thyroxin treatment possible and prevents the development of complications from central nervous system. The authors showed main problems of Hashimoto disease in women during pregnancy as well as pregestational and postgestational period. The reasons of congenital hypothyroidism taking into account both iodine deficiency and excess were also presented.

Congenital Hypothyroidism↗

[Slowly progressive IDDM with rheumatoid arthritis and Hashimoto disease in high elderly].

We report a 79-year-old woman case of slowly progressive IDDM (SPIDDM) with rheumatoid arthritis (RA) and Hashimoto disease. High titer of anti-glutamic acid decarboxylase antibody (GAD) with a value of 16,400 U/ml (normal value: less than 5 U/ml) and deteriorated secretion of insulin, and clinical course led to the diagnosis of SPIDDM. Both anti-islet cell and anti-insulin antibodies were negative. One year prior to the diagnosis, at 78 years of age, she was newly diagnosed with NIDDM and had been medicated with sulfonylurea and voglibose, resulting her glucose levels well-controlled. Four months before admission, a gradual increase of plasma glucose was noticed, while oral hypoglycemic agents were fully administrated. On admission, her glycemic control was revealed as follows; a fasting blood glucose level of 458 mg/dl and an HbA1 C level of 14.3%. Urinary CPR was 22.5 micrograms day. Her insulin secretion was proved not to be induced with intravenous glucagon injection. Hyperinsulinemic euglycemic glucose clamp test showed the normal glucose uptake ratio; 9.5 mg/kg/min. Moderate doses of subcutaneous insulin (20 units daily) were effective on her diabetes control. She was newly diagnosed with Hashimoto disease that required thyroid hormone replacement 50 micrograms per day after having developed NIDDM. High titer of anti-thyroglobulin antibody (46.9 U/ml) and anti-thyroid peroxidase antibody (81.5 U/ml) were observed. The patient had been medicated for RA with anti-inflammatory drugs since her early seventieth. Rheumatoid factor was elevated to 127.7 IU/L and, anti-nuclear antibody (x 80) and anti-DNA antibody (x 80) were present. It may be of interest that a specific phenotype of HLA; A24 (9) and DR9 recognized to be susceptible to IDDM was detected in the high-elderly onset SPIDDM. Taken together HLA typing with her history of both RA and Hashimoto disease, our case may provide the information to the mechanism of pathogenesis of SPIDDM. Furthermore, to out knowledge, this is the first case of SPIDDM in the aged; 75-year-old or more.

Aged↗

[Two cases of hearing loss following Hashimoto disease].

UNLABELLED: Hearing loss accompanies some of thyroid gland diseases especially those with hypothyroidism. Some authors state it correlates with autoimmune background of certain thyroid gland disturbances. We present two cases of patients with Hashimoto disease accompanied by fluctuating cochlear hearing loss and peripheral vestibular loss in one of the cases. FIRST CASE: there was unilateral worsening of bilateral hearing loss diagnosed previously after gentamycine treatment in 16 year old female with Hashimoto disease. There was significant improvement confirmed in audiological tests when the child became euthyroid. Second case presenting hearing loss and vertigo: 16 year old female with hypothyroidism and diabetes mellitus type 1 with high blood concentration of anticytoplasmic immunoglobulins lasting for 2 years. Bilateral cochlear perceptive hearing loss was diagnosed. In summary an association of autoimmune process as well as thyroid hormones blood level with inner ear condition was suggested. Trying to find the reason of observed disturbances one should consider wide differential diagnostics in all the cases of perceptive seemingly idiopathic cochlear hearing loss. The presented problem needs to be further investigated in larger clinical material.

Adolescent↗

[A case of 'hallucination of soliloquy' with hypothyroidism induced Hashimoto disease. Meaning of psychopathological research about symptomatic psychosis].

We describe the first reported case of symptomatic psychosis with the 'hallucination of soliloquy.' A 48[correction of 40]-year-old woman with Hashimoto disease exhibited of compulsive checking, mysophobia, and excessive hand washing. When these obsessive-compulsive symptoms diminished, she began to suffer from the 'hallucination of soliloquy', the automatic flow of meaningless words inside her mind. As the 'soliloquy' increased, her mood became unstable and she attempted suicide by analgesic ingestion. After this, she was admitted to the psychiatric ward of a general hospital. The administration of clomipramine (150 mg daily) decreased the 'soliloquy' symptoms, but they did not resolve. When hypothyroidism became available, thyroid hormone treatment (levothyroxine at 50 mg daily) was started. Four weeks later, her 'soliloquy' symptoms had almost resolved and after three months in a stable state, thyroid hormone treatment was stopped and her 'soliloquy' symptoms soon reappeared. After thyroid hormone treatment was resumed, her 'soliloquy' symptoms disappeared immediately. Typical auditory hallucinations and delusions of reference were not observed throughout the clinical course. We speculate that the symptoms were symptomatic psychosis induced by hypothyroidism secondary to Hashimoto disease, because the changes of her hallucinations were related to free T3 values and the symptoms disappeared soon after starting thyroid hormone treatment. The main features of this case were 'soliloquy' alternating with obsessive-compulsive symptoms, but her 'soliloquy' symptoms were thought to be autochthonous ideas rather than obsessive thoughts. Furthermore, the symptoms in this case were different from schizophrenia, since there was no disturbance of communication, and she had the sensation of both speaking and hearing her own voice. The psychopathology of this 'hallucination of soliloquy' may be related to the theory of 'vocalization of background thinking' (N. Nakayasu). Detailed observation of patients with symptomatic psychosis and a psychopathological description of their symptoms may help to contribute to the etiologic elucidation and treatment of psychosis.

Female↗

Interphase ribosomal RNA cistron staining in thyroid epithelial cells in Grave's disease, Hashimoto's thyroiditis and benign and malignant tumours of the thyroid gland.

Aim-To evaluate the expression of ribosomal cistrons in human thyroid epithelial cells (TECs) of patients with Grave's disease, Hashimoto's thyroiditis and benign and malignant tumours of the thyroid gland.Methods-TEC nucleoli were investigated in fine needle biopsy specimens from 10 controls, 39 patients with Grave's disease, 15 with Hashimoto's thyroiditis, 56 with benign, and 15 with malignant tumours of the thyroid. A one step silver staining method was applied. In most cases serum concentrations of thyroxine and triiodothyronine as well as goitre size were determined. In every case 100 TECs were evaluated for the mean numbers of nucleoli and for the average number of argyrophilic nucleolar organiser regions (AgNORs) per nucleus.Results-NORs were activated in all patients, but not in controls. The numbers of AgNORs in patients with Grave's disease were closely correlated with thyroxine or triiodothyronine, or both, concentrations and with the size of the thyroid. In patients with Hashimoto's thyroiditis about 30% of TECs nucleoli did not contain AgNORs, whereas others were heavily impregnated with silver. Compared with controls and benign tumours, the nucleoli of carcinomatous TECs were larger and irregular in shape. The mean number of AgNORs per nucleus in malignant cells was higher than that in their benign counterparts.Conclusions-The mechanism by which NORs are activated in TECs varies depending on the type of lesion. The higher AgNOR score in TECs from malignant tumours can be used to distinguish them from their benign counterparts.

Journal Article↗

Common and unique susceptibility loci in Graves and Hashimoto diseases: results of whole-genome screening in a data set of 102 multiplex families.

The autoimmune thyroid diseases (AITDs), comprising Graves disease (GD) and Hashimoto thyroiditis (HT), develop as a result of a complex interaction between predisposing genes and environmental triggers. Previously, we identified six loci that showed evidence for linkage with AITD in a data set of 56 multiplex families. The goals of the present study were to replicate/reject the previously identified loci before fine mapping and sequencing the candidate genes in these regions. We performed a whole-genome linkage study in an expanded data set of 102 multiplex families with AITD (540 individuals), through use of 400 microsatellite markers. Seven loci showed evidence for linkage to AITD. Three loci, on chromosomes 6p, 8q, and 10q, showed evidence for linkage with both GD and HT (maximum multipoint heterogeneity LOD scores [HLOD] 2.0, 3.5, and 4.1, respectively). Three loci showed evidence for linkage with GD: on 7q (HLOD 2.3), 14q (HLOD 2.1), and 20q (LOD 3.3, in a subset of the families). One locus on 12q showed evidence of linkage with HT, giving an HLOD of 3.4. Comparison with the results obtained in the original data set showed that the 20q (GD-2) and 12q (HT-2) loci continued to show evidence for linkage in the expanded data set; the 6p and 14q loci were located within the same region as the previously identified 6p and 14q loci (AITD-1 and GD-1, respectively), but the Xq (GD-3) and 13q (HT-1) loci were not replicated in the expanded data set. These results demonstrated that multiple genes may predispose to GD and HT and that some may be common to both diseases and some are unique. The loci that continue to show evidence for linkage in the expanded data set represent serious candidate regions for gene identification.

Chromosome Mapping↗

[A case of mononeuropathy multiplex associated with anti-GM1 and -SGLPG antibodies in a patient with ongoing Hashimoto disease].

We reported a case of mononeuropathy multiplex associated with anti-GM1 and -SGLPG antibodies in a patient with ongoing Hashimoto disease. A 56-year-old woman was admitted with asymmetrical patchy sensory and motor disturbance in the extremities. Muscle atrophy and weakness in the left palm and bilateral tibialis anterior muscles were also noted. Deep tendon reflexes were normal in all the extremities. Superficial and deep sensations were reduced in the hands and feet bilaterally, and the distribution of sensory loss was irregular. Her serum was positive for antinuclear antibody, rheumatoid factor, anti-RNP antibody, and anti-SS-A antibody. Serial electrophysiological studies suggested that the predominant process was axonal degeneration of the sensorimotor nerves. On sural nerve biopsy, there were no findings of vasculitis but severe axonal degeneration was observed. Thin-layer chromatography with immunostaining revealed anti-GM1 and -SGLPG antibodies. Treatment with corticosteroids was successful. In this case, the anti-GM1 antibody may have played a role in the pathogenesis of mononeuropathy multiplex associated with autoimmune disease.

Autoantibodies↗