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PubMed1996

Guidelines for diagnosis and monitoring of thyroid disease: nonthyroidal illness.

On the basis of low specificity, poor positive predictive value, and cost, there is at present no basis for routine assessment of thyroid function in acutely hospitalized patients, unless clinical features suggest the possibility of thyroid dysfunction, or a patient's background increases the likelihood of thyroid dysfunction. When used in severely ill patients, estimates of both thyroxine (T4) and thyrotropin (TSH) show a high prevalence of abnormal results, but lack specificity and have poor positive predictive value for true thyroid disease. When thyroid function is tested in the critically ill, the positive predictive value for true thyroid disease of both free T4 and TSH measurements could be improved by using wider reference intervals than for unselected populations. The knowledge of nonspecific disease-related abnormalities of triiodothyronine, T4, and TSH is not currently likely to yield useful prognostic information or to alter management for individual patients. Thyroid testing should be readily available for any acutely ill patient with any clinical features that suggest thyroid dysfunction, and for groups at increased risk of thyroid dysfunction. An initial abnormal result for either TSH or free T4 estimate should be followed by combined analysis of free T4 and TSH with the best available methodology. Diagnosis of thyroid dysfunction should be based on the T4-TSH relation rather than either value alone. Persistence of an apparent diagnostic abnormality should be confirmed before therapy is commenced.

Humans↗
PubMed1991

Heterogeneity of autoantibodies against thyroid peroxidase in autoimmune thyroid disease: evidence against antibodies directly inhibiting peroxidase activity as regulatory factors in thyroid hormone metabolism.

The close relationship between thyroid microsomal antigen and thyroid peroxidase (TPO) is now well established. The present study evaluates the significance of autoantibodies against TPO (anti-TPO-Abs) in the various forms and stages of autoimmune thyroid disease with respect to a possible heterogeneous nature and particularly to their influence on TPO activity. When measured by a RIA using purified human TPO, anti-TPO-Abs were highly correlated with microsomal antibodies determined by enyzme-linked immunosorbant assay (r = 0.96; P less than 0.0001) and with the results of a TPO immunoprecipitation assay using crude microsomal preparations (r = 0.76; P less than 0.001). Relating the results of these assays to the reactivities of patients' sera with thyroid microsomes in immunoblot under nonreducing and reducing conditions, discordant results could be observed in a few cases. Further analysis of these data indicate a heterogeneous nature of anti-TPO-Abs, which react with at least two antigenic domains of the TPO molecule. The comparative analysis of patients with hyperthyroid Graves' disease, patients with Graves' disease in clinical remission, and patients with hypothyroid Hashimoto's thyroiditis revealed no significant differences in the antibody spectrum. When evaluating the direct influence of anti-TPO-Abs on the activity of TPO under a rigorous methodological approach, we found no significant inhibition of the enzymatic activity by any of the sera investigated from patients with autoimmune thyroid disease compared to that in sera from normal controls. In conclusion, the data indicate a heterogeneous nature of anti-TPO-Abs. The spectrum of antigenic epitopes recognized by anti-TPO-Abs seems not to be significantly different in the various forms and stages of autoimmune thyroid disease. The lack of an inhibitory effect of autoantibodies on TPO activity argues against direct binding of autoantibodies to the enzymatic sites of TPO and indicates that they are not important factors in producing thyroid dysfunction in autoimmune thyroid disease.

Adult↗
PubMed1997

Coexpression of CD40 and class II antigen HLA-DR in Graves' disease thyroid epithelial cells.

In Graves' disease, thyroid epithelial cells abnormally express HLA-DR Class II molecules in the vicinity of lymphocyte infiltrates, suggesting that lymphocyte proliferation is sustained by the appropriate presentation of antigenic material. The ability of thyroid epithelial cells to provide the necessary second signals has however not been documented. The expression of HLA-DR, CD40, CD40L, CD80, and CD28 was investigated on thyroid samples from 30 patients (Graves' disease, n = 16; benign toxic adenoma, n = 8; multinodular goiter, n = 6). Apoptotic cells were searched for using the TUNEL method. CD40 appeared to be coexpressed with HLA-DR in Graves' disease patients samples and in two control samples also containing lymphoid infiltrates. Almost no apoptotic cells were found. These data suggest that thyroid epithelial cells from Graves' disease patients have the ability to successfully present autoantigens. The near absence of apoptotic cells in surrounding lymphoid infiltrates is in keeping with this efficient provision of a rescue second signal.

Adolescent↗
PubMed1992

Association of thyroid disease with acute leukemia.

The purpose of this paper is to evaluate the possible clinical association of autoimmune thyroid disease and acute leukemia. This study is a retrospective review of all adult patients with acute leukemia treated at our institutions from 1978-1989. Those with both leukemia and thyroid disease were evaluated and are presented. Twenty-seven of eight hundred seventy patients with acute leukemia had evidence of thyroid disease. This is a 3-fold increase in overall incidence. Twenty-one patients had acute myeloid leukemia, five had acute lymphoid leukemia, and one had accelerated chronic myeloid leukemia. Thyroid disease entities included toxic multinodular goiter (four patients), idiopathic hypothyroidism (eight patients), Graves' disease (eight patients), and Hashimoto's thyroiditis (seven patients). Whereas the association may have had a negative effect on elderly patients, those with Graves' disease and Hashimoto's disease appeared to have an improved outcome of the leukemia. There is an increased association of autoimmune thyroid disease and acute leukemia. Since thyroid hormones are important regulators of hematopoiesis and utilize receptors similar to those of differentiating factors such as retinoids, the association may be important for further study of mechanisms of growth regulations in leukemia.

Adult↗
PubMed1986

Autoimmune thyroid disease--a perspective.

Increasing evidence is accruing in favour of the view that autoimmune thyroid disease is due to an organ-specific defect in suppressor T lymphocytes that is genetically induced. While the initial evidence supporting this hypothesis was based on results with the migration inhibition factor test, subsequent investigations from our own and other laboratories have confirmed the presence of such an organ-specific suppressor T lymphocyte defect in autoimmune thyroid disease. Moreover, there is now good evidence that hyperthyroidism per se has an effect on suppressor T lymphocyte function and numbers, and this is superimposed on and is additive to the organ-specific defect while patients are hyperthyroid; this may well act as a self-perpetuating factor in continuing the disease. It has been proposed elsewhere that the expression of HLA-DR antigen on the cell membrane of the thyrocytes (possibly induced by viral infection) represents the initial inductive step in precipitating autoimmune thyroid disease in persons predisposed by virtue of having an immunoregulatory defect in the first place. However, there is now evidence that: (1) normal thyrocytes respond equally well to various stimuli in terms of DR expression when compared to Graves' or Hashimoto's thyrocytes; (2) supernatants from normal T lymphocytes will stimulate DR expression on thyrocytes at least as well as supernatants from Graves' T lymphocytes when stimulated by non-specific lectins; (3) conversely, Graves' T lymphocytes will stimulate thyroid DR expression more markedly than normal T lymphocytes when the lymphocyte-thyrocyte interaction is direct; (4) monocytes and helper T lymphocytes are essential for thyrocyte DR expression; (5) DR expression on thyrocytes does not lead to a self-perpetuating immune response. From all of these observations, it seems evident that DR expression is secondary to the primary immune assault in autoimmune thyroid disease, and is neither an initiating event, nor unique to autoimmune thyroid disease, nor a self-perpetuating phenomenon.

Autoantibodies↗
PubMed2005

High frequency of skewed X-chromosome inactivation in females with autoimmune thyroid disease: a possible explanation for the female predisposition to thyroid autoimmunity.

CONTEXT: Autoimmune thyroid diseases (AITD) comprise Graves' disease (GD) and Hashimoto's thyroiditis (HT). They are characterized by loss of immunological self-tolerance and female preponderance. Theoretically, X chromosome inactivation (XCI) and resultant tissue chimerism could offer an explanation for the female predisposition to AITD. AIM: Our aim was to examine whether skewed XCI is associated with AITD. DESIGNS: We first conducted a classical case-control study of twin individuals with and without AITD, and then a case-control study of twin pairs discordant for AITD. PARTICIPANTS: Participants included 32 female twins with AITD and a control group of 96 healthy female twin individuals. METHODS: XCI analysis was performed by enzymatic predigestion of DNA with a methylation-sensitive enzyme followed by PCR of the polymorphic CAG repeat of the androgen receptor gene. The XCI pattern was classified as skewed when 80% or more of the cells preferentially inactivated the same X chromosome. MAIN OUTCOME MEASURES: We assessed the prevalence of skewed XCI. RESULTS: The frequency of skewed XCI in female twins with AITD, GD, and HT was 34, 37, and 31%, respectively, which was higher than the prevalence in the corresponding control populations, 11% (P = 0.003), 14% (P = 0.045), and 8% (P = 0.057), respectively. Similar results were found in twin pairs discordant for AITD. Overall, skewed XCI was associated with an increased risk of developing AITD, with an odds ratio of 9.0 (95% confidence interval, 1.64-49.4) (P = 0.022). CONCLUSION: These observations suggest a possible role of XCI in the etiology of AITD and may in part explain the female preponderance of AITD.

Adult↗
PubMed2003

Autoimmune thyroid diseases: etiology, pathogenesis, and dermatologic manifestations.

Autoimmune thyroid disease (AITD) including Graves' disease, Hashimoto's thyroiditis, and idiopathic hypothyroidism (atrophic Hashimoto's thyroiditis) is of vital concern to the dermatologist. This article reviews the cutaneous manifestations of Graves' disease and Hashimoto's thyroiditis. Recognition of dermatologic manifestations of AITD may alert practitioners to investigate for these disorders. The immune response involved in the pathogenesis of AITD is detailed. Current understanding of the role of genetic and environmental factors, antigens, and apoptosis are elaborated. The future holds exciting insight into the etiology, pathogenesis, and treatment of AITD.

Diagnosis, Differential↗
PubMed2001

Whole-blood proliferation assay for autoimmune thyroid disease: comparison to density-gradient separated-peripheral blood lymphocytes.

Autoimmune thyroid diseases feature prominent cellular infiltration of the thyroid gland as well as autoantibody production to thyroid antigens. The most common assay to evaluate cell-mediated immunity is based on incorporation of tritiated thymidine into proliferating T cells after stimulation by the test antigens. In the past, cell proliferation assays of thyroglobulin (Tg) using peripheral blood mononuclear cells (PBMC) of individuals with autoimmune thyroid diseases required large quantities of blood and specialized separation techniques, and have not yielded high counts or high stimulation indices. We therefore developed a proliferation assay using less than 5 mL of whole blood and compared proliferation of cells in whole blood to that using PBMCs separated by density gradient centrifugation. We also determined if responses could be enhanced by addition of interleukin-2 (IL-2) to the cultures. We found that an IL-2-stimulated proliferation assay to Tg using diluted whole blood is superior to the separated cell assay in detecting Tg-specific T-cell proliferation in autoimmune thyroid disease patients. Further refinement of this technique and larger trials may confirm its value for clinical investigation and special diagnostic applications.

Autoimmune Diseases↗
PubMed1997

Mild clinical expression of myasthenia gravis associated with autoimmune thyroid diseases.

Myasthenia gravis (MG) may occur in association with autoimmune thyroid diseases (AITD). The aim of this study was to evaluate the features of MG associated with AITD compared to those of MG without AITD. A total of 129 MG patients (34 men and 95 women; age range, 11-81 yr) were subdivided into: group A, 56 MG patients with AITD [25 with autoimmune thyroiditis and 31 with Graves' disease (GD)]; group B, 21 MG patients with nonautoimmune thyroid diseases; and group C, 52 MG patients without thyroid disease. The severity of MG was ranked according to the Osserman score. Laboratory evaluation included assays for antithyroid and antiacetylcholine receptor (AchRAb) antibodies. Ocular MG (Osserman's class 1) was more frequent in group A (41.0%) than in group B (14.2%; P < 0.03) or C (21.4%; P < 0.03). Severe generalized MG (classes > or = 2B) was more frequent in groups B (57.1%; P < 0.03) and C (51.9%; P < 0.02) than in group A (28.5%). GD patients with clinical evidence of ophthalmopathy had a higher frequency (P = 0.05) of ocular MG (57.8%) than GD patients without clinical ophthalmopathy (16.6%). Thymic disease was less frequent in group A (26.7%) than in group B (71.4%; P = 0.001) or C (59.7%; P = 0.001). The prevalence of thymic hyperplasia was 17.8%, 38.0%, and 40.3% in groups A, B, and C, respectively; the prevalence of thymoma was 8.9%, 33.4%, and 19.4%. When only patients with generalized MG were considered, thymic disease was less frequent (P < 0.02) in group A (40.6%) than in the remaining groups (69.4%). AchRAb was more frequent in groups B (57.1%) and C (57.6%; P < 0.03) than in group A (35.7%). In conclusion, MG associated with AITD has a mild clinical expression, with preferential ocular involvement and lower frequency of thymic disease and AchRAb. This supports the hypothesis that ocular and generalized MG are separate diseases with different spectra of associated diseases. Nonautoimmune thyroid diseases have no influence on the features of MG. The association of ocular MG and AITD might be due to a common autoimmune mechanism and/or a peculiar genetic background.

Adolescent↗
PubMed1981

Correlation between thyroid peroxidase activity and histopathological and ultrastructural changes in various thyroid diseases.

A morphological and biochemical study was performed on thyroid tissue with various thyroid diseases. The thyroid peroxidase (TPO) activity of normal thyroid tissues ranged from 2.6 to 7.0 mGU/mg DNA. The activity was low in adenomas and extremely low in carcinomas, and there was no significant relationship between the histological subclassification of follicular adenomas (simple, colloid, oxyphil) and TPO activity. The activity was various in the cases of chronic thyroiditis, ranging from non-detectable to 9.8 mGU/mg DNA, and the TPO activity showed a close correlation with the degree of lymphoid cell infiltration of the diseases. In the seven cases of Graves' disease, the values were high, though the elevation was not so remarkable in three cases which had already been euthyroid or slightly hypothyroid after long-term treatment. By means of subcellular fractionation, more than 50% of peroxidase activity was shown to be localized in the microsomal pellets, and this result well coincided with the electron microscopic findings of prominent development of rER.

Adenoma↗
PubMed1999

Lack of association between a polymorphism of human thyrotropin receptor gene and autoimmune thyroid disease.

A polymorphism in codon 52 of the human thyrotropin receptor results in a proline to threonine substitution in the extracellular domain of the receptor, but the association with autoimmune thyroid disease has been uncertain and there is no report the prevalence of this polymorphism in Orientals. To investigate this polymorphism and the association with autoimmune thyroid disease, we studied 113 normal unrelated individuals, 142 autoimmune thyroid disease patients including 112 Graves' disease and 30 Hashimoto's thyroiditis in the Thai population. We screened genomic DNAs of these subjects for the presence of A253 by PCR amplification using a degenerate oligonucleotide primer which produces a Tth111 I restriction site only in the presence of A253. The variant allele was present in 5.3 per cent of normal and 3.5 per cent of autoimmune thyroid disease, 2.7 per cent of Graves' disease and 6.7 per cent of Hashimoto's thyroiditis. The allele distribution in autoimmune thyroid disease patients did not differ significantly from that observed in controls. No association was found between this TSH-R polymorphism and the occurrence of autoimmune thyroid disease.

Adult↗
PubMed1976

Binding of thyroid microsomes by lymphocytes from patients with thyroid disease and normal subjects.

Lymphocytes that could bind 125I-labelled thyroid microsomal membranes (ABL) were present in the peripheral blood of patients with various types of thyroid disease as well as in normal healthy subjects. In patients with anti-thyroid cytoplasmic antibodies the number of ABL was about three times normal (11-21 +/- 0-60 compared with 3-26 +/- 0-18 per 10(4) lymphocytes). In contrast, in patients with thyroid disease without anti-thyroid cytoplasmic antibodies, the number of antigen-binding lymphocytes was not significantly greater than in the normal controls (3-94 +/- 0.14 per 10(4) lymphocytes). The binding of thyroid microsomes by antigen-binding lymphocytes could be blocked by thyroid microsomes but not by thyroid mitochondrial membranes, thyroglobulin or liver microsomes.

Autoantibodies↗
PubMed2001

Serial STIR magnetic resonance imaging correlates with clinical score of activity in thyroid disease.

PURPOSE: To assess the correlation between inflammatory activity in extraocular muscles measured with serial short tau inversion recovery (STIR) sequence magnetic resonance imaging (MRI) scans and clinical disease activity in thyroid eye disease. METHODS: In this retrospective study, 22 patients with thyroid eye disease who had undergone serial MRI scans using the STIR sequence were assessed. The signal intensity ratio (SIR) of the most inflamed extraocular muscle was compared with the Mourits score (a clinical measure of thyroid eye disease activity). RESULTS: The SIR value has previously been shown to correlate with clinical activity of thyroid eye disease. In a particular patient the SIR value increases in proportion with the clinical features of the disease as assessed by the Mourits rating system. When the change in STIR sequence MRI is compared with the change in Mourits score rating for a given patient the correlation is highly significant (p < 0.001). CONCLUSIONS: This study confirms that serial STIR sequence MRI scans correlate with clinical disease activity. Inflammatory activity in the most inflamed muscle (as measured by SIR) reflects overall disease activity. SIR values obtained from MRI scans provide a useful measure of disease activity and may help in the monitoring and treatment of this condition.

Female↗
PubMed2000

Demystifying autoimmune thyroid disease. Which disorders require treatment?

The term "autoimmune thyroid disease" encompasses all of the autoimmune thyroid conditions, including Hashimoto's thyroiditis, Graves' disease, most cases of silent thyroiditis, and postpartum thyroiditis. Extrathyroidal manifestations (e.g., ophthalmopathy, dermopathy) can occur in Graves' disease and, less commonly, Hashimoto's thyroiditis. Spontaneous hypothyroidism is common in patients with Hashimoto's thyroiditis, and when it develops, life-long therapy with levothyroxine is needed. In the United States, most adult patients with Graves' disease are initially or eventually treated with radioiodine thyroid ablation. For transient thyroiditis involving hypothyroidism or hyperthyroidism, short-term or symptomatic therapy is adequate.

Autoimmune Diseases↗
PubMed2005

Thyroid dysfunction in the offspring of mothers with autoimmune thyroid diseases.

UNLABELLED: An integrated three-compartment thyroid model exists during gestation: pregnancy influences thyroid function in several ways, the placenta plays an active role in TRH-thyroid and iodide transport and metabolism, and the fetus develops its own hypothalamic-pituitary-thyroid axis. This commentary reviews some basic and new data, especially in the maternal-offspring relationship in the case of maternal autoimmune thyroid diseases. CONCLUSION: The careful control of maternal autoimmune thyroid disease is essential in order to avoid pathological changes in the offspring.

Female↗
PubMed2003

[Early complications in surgical treatment of thyroid diseases: analysis of 2100 patients].

Thyroid gland surgery today is not saddled with high incidence of main complications. Miscellaneous surgical institutions with different surgical approach, operative technique and radicality have published reports with great discrepancy in incidence of complications, analyzing them with different methods of diagnosis and result evaluation. In the same way it is well known that higher latitude of operative procedure gave better control of thyroid diseases, but it can be accompanied with more complications. All of that motivate us to analyze complications of operative treatment in our patients under well known criteria, with hypothesis that higher radicality of operative procedure do not increase incidence of complications, and that this incidence is in correlations with results published in world literature. Aim of this nonrandomized study was to analyze results of operative treatment for huge number of consecutively operated patients in our teaching hospital, to analyze and compare results according to group of diseases and operative procedures, and to compare final results with results published in the world literature. Complications of operative treatment were analyzed retrospectively for period 1988-1997 (Group I) and prospectively in period 1998-2002 (Group II). Operations were performed by 20 surgeons and 20 young surgeons during their education. We have analyzed only complications during first 30 days after operation. In Group I there was 1425 patients with 1451 operations (192 thyroid malignancies, 247 hyperthyreosis, 98 reoperations, 13% thyroidectomies and 14.8% lobectomies), with complication rate of 14.3%. Most common complication was recurrent laryngeal nerve injury in 9.3% patients or 6.3% according to number of exposed nerves (nerve at risk), then postoperative hypocalcemia with rate of 4.7% (persistent in 1.3%). In Group II in 675 patients there was 687 operations (96 thyroid malignancies, 111 hyperthyreosis, 35 reoperations, 36.6% thyreoidectomies and 25% lobectomies), with complication rate of 10.7%. Most common postoperative complication was hypocalcemia with 5% rate (persistent in 0.7%), then recurrent laryngeal nerve injury in 4.4% patients or 2.9% according to number of exposed nerves. Incidence of recurrent laryngeal nerve injury in Group II is less frequent than in Group I, highly statistically significant (p < 0.01), while for other complications there is no statistically significant difference. Totally for both groups there was 0.7% tracheotomies, postoperative bleeding in 1.1% of patients, wound hemathoma in 0.5%. wound infections in 0.9%, pneumonia in 0.5%, mortality 0.5% and most common cause of death (8/11) was problem with respiration, Airway obstruction. In Group II complications were less frequent in total thyroidectomies in relation to lobectomy with contra lateral subtotal lobectomy. In both groups and totally incidence of complications was higher in reoperations, in patients with more extensive operative procedure, in malignant diseases and hyperthyreosis. In thyroid gland surgery more extensive operative treatment with improved operative technique (micro dissection, recurrent laryngeal nerve visualization and parathyroid gland preservation), in our teaching hospital, do not have influence on incidence of postoperative complications, even recurrent laryngeal nerve injury was significantly less frequent. This results are in correlation with published results of similar hospitals around the world.

Adolescent↗
PubMed1999

Follow-up evaluation and clinical course of patients with benign nodular thyroid disease.

Reliance on fine-needle aspiration biopsy (FNAB) in determining which patients with a thyroid nodule can be observed depends on a low false-negative rate. The purpose of this study was to determine the false-negative rate of FNAB, the utility of routine repeat FNAB, and the clinical course of patients with benign nodular thyroid disease. The records of all patients with nodular thyroid disease evaluated between June 1990 and May 1998 were reviewed. Patients with a benign FNAB were identified, and nodule size, substernal extension, the results of repeat FNAB, clinical course, histologic diagnosis, and length of follow-up were determined. Of the 341 patients referred with nodular thyroid disease, 121 had a benign FNAB. In 80 patients with a mean nodule size of 3.5 +/- 1.6 cm, clinical follow-up was recommended. The mean duration of follow-up was 20.5 months for 74 patients, and 6 patients were lost to follow-up. Nodule resolution was observed in 7 patients. Repeat FNAB was performed in 45 patients and was benign in 39 (87%), nondiagnostic in 2 (4%), cellular in 3 (7%), and malignant in 1 (2%). Thyroidectomy was performed in the patients with the cellular and malignant aspirates, and the pathology was adenomatous hyperplasia (2), follicular adenoma (1), and papillary carcinoma (1). Thyroidectomy was performed for increasing nodule size and/or compressive symptoms in 41 patients with a mean nodule size of 5.7 +/- 1.9 cm, 19 of whom had substernal extension (P < 0.05). Pathology included benign disease in 39, papillary cancer in 1, and lymphoma arising in Hashimoto's thyroiditis in 1 patient. Given that repeat FNAB was of value in only 1 patient and the false-negative rate for FNAB was only 2.5 per cent, the routine use of repeat FNAB in patients with benign nodular thyroid disease may not be justified. Development of compressive symptoms and diagnosis of unsuspected malignancy in patients with nodule enlargement, including lymphoma in patients with Hashimoto's thyroiditis, underscores the importance of long-term follow-up.

Adenoma↗