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PubMed1999

Mitral valve prolapse in autoimmune thyroid disease: an index of systemic autoimmunity?

A coexistence of mitral valve prolapse (MVP) with autoimmune thyroid disease (AITD) has been described, but there are not sufficient data to explain this association. The aim of the present study was to investigate the prevalence of MVP in patients with AITD and to evaluate whether any correlation between MVP and certain immunological parameters exists. M-mode, two-dimensional Doppler echocardiography was performed in 29 patients with Graves' disease (GD), 35 with Hashimoto's thyroiditis (HT), 20 with nonautoimmune goiter, and 30 normal controls. Serum samples were examined for antinuclear antibodies (ANA), antibodies against extractable nuclear antigen (ENA), antiphospholipid antibodies (aCL), rheumatoid factor (RF), thyroid autoantibodies (TAAb), immunoglobulins and C3, C4. Eight of 29 GD patients and 8 of 35 HT patients had MVP, while none of the control group and 2 of 20 of the simple goiter group had MVP (p < 0.05). ANA were detected at low titers in 5 of 8 in MVP(+) GD versus 3 of 21 in MVP(-) GD (p < 0.05). In the HT group the MVP(+) patients had a significantly higher incidence of ANA and ENA, 5 of 8 and 2 of 8 versus 5 of 27 and 0 of 27 of MVP(-) patients, respectively, p < 0.05. A statistically significant higher incidence of aCL was found in HT MVP(+) patients. (3/8) versus HT MVP(-) 1/27, p < 0.05. RF levels (immunoglobulin A [IgA]) were significantly higher in MVP(+) patients. The association of MVP with nonorgan-specific autoantibodies indicates that MVP may also be an autoimmune disease. It is possible that patients with AITD who also have MVP may be at an increased risk to develop systemic autoimmunity.

Adult↗
PubMed1998

Stress protein expression in primary and immortalized cultures of human thyroid cells: a model system for the study of stress proteins in the pathogenesis of autoimmune thyroid disease.

Stress has, for many years, been linked to the onset of autoimmune disease and, in particular, autoimmune thyroid disease (AITD). Whilst the exact mechanism of this association is unknown, it is clear that episodes of stress can induce profound changes in the immune system. More specifically, recent studies from several laboratories have shown an association between the expression of stress proteins and, particularly, the Hsp70 family with AITD. Our own studies describe a thyroid-specific Hsp70 which shares antigenicity with the key thyroid autoantigen, thyroid peroxidase. Further studies on the molecular basis for this observation are, however, hampered by the lack of a suitably validated thyroid cell model. In this paper we compare the response of primary cultures of human thyrocytes to hyperthermia with the response seen in the immortalized human thyroid cell line HTori3. Both cell types responded in a broadly similar manner, synthesizing proteins from two of the major stress protein families, Hsp70 and Hsp90. In the primary human thyrocyte cultures the 70 kDa proteins showed a 7.5-fold increase and the 90 kDa proteins a 2.7-fold increase with hyperthermia whilst in the HTori3 cells the increases in response to hyperthermia were 10- and 6.5-fold, respectively. We also show a dose-dependent stress response in HTori3 cells cultured in the presence of arsenite ions. We conclude that the response of this highly differentiated and stable thyroid cell line to stress is similar to that seen in primary cultures of human thyroid cells and that these immortalized cells will afford a convenient and effective model for the further study of the role of stress in the pathology of AITD.

Arsenites↗
PubMed1989

Orocaecal transit time in health and in thyroid disease.

Altered bowel habit commonly occurs in thyroid disease. We measured orocaecal transit in healthy volunteers and in hyperthyroid and hypothyroid patients before and after treatment, using the lactulose hydrogen breath test incorporating a standard liquid meal to obtain a more physiological assessment. Mean transit time in 12 control subjects was 85 (8) minutes (mean (SE)) (mean coefficient of variation between replicate studies, 8.6% (3%)). In eighteen hyperthyroid patients transit was more rapid at 49 (4) minutes (p less than 0.01). Ten hypothyroid patients had a transit time similar to controls at 91 (9) minutes. Transit time returned to normal in thyrotoxic patients after treatment but in eight hypothyroid patients retested, it remained unchanged. Our findings suggest that (a) the inclusion of a liquid meal provides a reproducible method of measuring orocaecal transit using the lactulose hydrogen breath test, (b) rapid small bowel transit in thyrotoxicosis may be one factor in the diarrhoea which is a feature of the disease and (c) if altered gut transit is the cause of sluggish bowel habit in hypothyroidism, delay in the colon, and not small bowel, is likely to be responsible.

Adult↗
PubMed1996

Primary care diagnosis of thyroid disease.

Recent diagnostic advances include sensitive thyroid-stimulating hormone (TSH) assays, more accurate free thyroxine assays, and fine-needle aspiration biopsy. The workup of patients with suspected thyroid dysfunction generally begins with a TSH assay; guidelines are provided for subsequent thyroid tests. Aspiration biopsy is appropriate for those with a nodular goiter.

Autoantibodies↗
PubMed1996

[Molecular biology of thyroid diseases].

Recent developments in molecular biology and the accessibility of techniques for clinical research have led to a better understanding of the background of common thyroid diseases. The cloning and sequencing of the thyroid stimulating hormone receptor, thyroid peroxidase and thyroglobulin, and the characterization of the protein-DNA interaction during thyroid hormone action, as well as the discovery of intracellular signal transduction pathways were the most important steps which resulted in new diagnostic and therapeutic approaches. New explanations of thyroid autoimmune processes are being investigated.

Genes, Tumor Suppressor↗
PubMed2001

Lack of linkage and association between autoimmune thyroid diseases and the CTLA-4 gene in a large Tunisian family.

The autoimmune thyroid diseases (AITDs) including Graves' disease and Hashimoto's thyroiditis are inherited as complex traits. We have performed linkage and association studies to investigate the role of CTLA-4 gene in the AITDs development using the D2S311, D2S143, the intragenic CTLA-4 (AT)(n) microsatellite markers and the CTLA-4 (A/G) dimorphism in exon 1. Four extended pedigrees belonging to a large Tunisian family named Akr and including 154 individuals from which 20 were affected with Hashimoto's thyroiditis and 26 with Graves' disease, were used in this investigation. No evidence for linkage with none of the markers was found under neither dominant nor recessive models [Z=-7.14 and Z=-14.32 at theta=0.0, respectively for the CTLA-4 (AT)(n) marker]. A family-based association study on 51 nuclear families derived from the Akr pedigree was performed by the FBAT approach applied to the CTLA-4 (AT)(n) marker and the CTLA-4 (A/G) dimorphism. We found no association of individual alleles to disease for both markers. These results showed no evidence for the involvement of the CTLA-4 locus in the AITDs pathogenesis.

Abatacept↗
PubMed2002

Thyroid hormone autoantibodies in primary Sjögren syndrome and rheumatoid arthritis are more prevalent than in autoimmune thyroid disease, becoming progressively more frequent in these diseases.

To verify the greater prevalence of circulating thyroid hormone autoantibodies (THAb) in primary Sjogren syndrome (SS) vs Hashimoto's thyroiditis (HT) and Graves' disease (GD), we measured THAb in the serum of patients with these 3 diseases who were sampled from 1998-1999 (no.=20, 88, 25) and 1990-1992 (no.=13, 75, 31). Patients with rheumatoid arthritis (RA) (no.=23 and 16) and other collagenoses (no.=20 and 16) were also studied. A third series of patients with these 5 diseases was studied from 1975-1982, and data have been taken into account. THAb were detected using a specific radioimmunoprecipitation method, and their presence was correlated with the presence of TG antibodies (TGAb). We found that IgG antibodies against T3, T4 or both were present with these prevalences in the 1975-1982, 1990-1992 and 1998-1999 series: HT=1, 4, 20%; GD=2, 6, 32%; SS=20, 31, 50%; RA=0, 12, 26%; other collagenoses=0, 0, 0%. The majority of the Sjogren or arthritis cases positive for THAb were negative for TGAb, while the opposite was true for the 2 autoimmune thyroid diseases. We conclude that prevalence of THAb in the 2 non-thyroid autoimmune diseases is greater than in the 2 thyroid autoimmune diseases. In addition, prevalence of THAb is increasing over time regardless of disease. Molecular similarity between extra-thyroid connective proteins (specifically associated to primary SS and RA) and iodinated regions of TG, and an increased preponderance of environmental factors as triggers of autoimmune diseases might account for our findings.

Adult↗
PubMed2005

Association of a CTLA-4 3' untranslated region (CT60) single nucleotide polymorphism with autoimmune thyroid disease in the Japanese population.

The etiology of the autoimmune thyroid diseases (AITDs), Graves' disease (GD) and Hashimoto's thyroiditis is largely unknown. However, genetic susceptibility is believed to play a major role. The cytotoxic T-lymphocyte antigen-4 (CTLA-4) gene, encoding a negative regulator of the T-lymphocyte immune response, had been reported to be associated and/or linked to AITD. Recently, AITD susceptibility in the Caucasians was mapped to the 6.1-kb 3'UTR of the CTLA-4 gene, in which the single-nucleotide polymorphism (SNP), CT60, was most strongly associated with AITD. In order to determine the association of the CTLA-4 gene with AITD in the Japanese, case-control association analysis for the CT60 of the CTLA-4 gene using 264 AITD patients and 179 healthy controls was done. The frequency of the disease-susceptible G allele of the CT60 of the Japanese control was higher than that of the Caucasians (72.6 vs. 52.3%). However, the G allele of the CT60 was associated with GD (84.0 vs. 72.6%, P=0.0008) and AITD (80.1 vs. 72.6%, P=0.009) in the Japanese. Furthermore, the G allele of the CT60 was associated with the increased risk for GD [P=0.004, odds ratio (OR)=2.0] and AITD (P=0.03,OR=1.6) in a recessive model. These results suggested that the CTLA-4 gene is involved in the susceptibility for GD and AITD in the Japanese.

3' Untranslated Regions↗
PubMed1992

Isolated IgA deficiency accompanied by autoimmune thyroid disease.

Selective immunoglobulin (Ig) A deficiency is reported to occur in 1 in 16,000 in Japan and has been reported to be complicated with various autoimmune diseases. A 49-year-old woman was diagnosed as having autoimmune thyroid disease. Her serum IgA, IgM and IgG were revealed to be 4.1, 154 and 1930 mg/dl, respectively. Severe skin eruption which occurred with 30 mg/day of methimazole (MMI) or 300 mg/day of propylthiouracil (PTU), was relieved by reducing MMI to 15 mg/day and administering anti-allergic drugs. Although the influence of IgA deficiency on autoimmunity and allergy still remains unclear, this is a report of IgA deficiency associated with autoimmune thyroid disease.

Autoimmune Diseases↗
PubMedDate not supplied

[Present strategies in the diagnosis and treatment of thyroid diseases].

AIM: Selective and critical presentation of the present exploring methods concerning surgical thyroid diseases and accomplishing a pre-surgical diagnosis as accurate as possible. Depending of the diagnosis--choosing the most appropriate surgical strategy according to the newest concepts in thyroid pathology. MATERIALS AND METHOD: Clinical-statistic study, carried out retrospectively over 1,108 patients having various surgical thyroid maladies hospitalized in 1980-1999 period. There have been operated 1,058 cases. Demographic structure as regards sex, F/M was 9.07/0.93 for goiters, whereas for thyroid cancer it was 3/1. RESULTS: Nodular goiters are the most frequent (77.31%), with a pathology benign majority (91.30%). The fundamental problem is the pre-surgical establish malign lesions that require a complex therapeutic protocol comparing to benign nodules. Benign lesions 91.30%, carcinomas 5.48%, others 3.21%. All types of thyroidectomies have been made: T.ST 69.37%, T.T for benign and malign lesions 7.65% and other procedures. Thyroid specific morbidity is 4.25%, whereas unspecific is 8.69%. The 0.08% mortality (1 case), virtually null, place the result between the best of the kind. CONCLUSIONS: Pre-surgical diagnosis, as accurate as possible, based on the clinic exam using the vacuum punction with a fine needle, finally confirmed by the paraffin exam, provided the choice of an optimal surgical strategy, followed by an appropriate post-surgical protocol. Total thyroidectomy is the preferred procedure is most of the thyroid cancer forms and in benign diseases is highly recommended (multi-nodular goiters, hyperthyroid, Basedow disease, cancer).

Adult↗
PubMed1990

Familial occurrence of multiple sclerosis with thyroid disease and systemic lupus erythematosus.

Multiple sclerosis (MS) has some features which suggest it is an autoimmune disease. Autoimmune diseases frequently occur in families, and patients and families often have more than one type of autoimmune disease. However, there are few reports of MS occurring in patients or families with other autoimmune conditions. It is difficult to make a separate diagnosis of MS in a patient who has a systemic autoimmune disease such as systemic lupus erythematosus (SLE) or Sjögren's syndrome, because these diseases can affect the nervous system directly. However, it is possible to make independent diagnoses of MS and an autoimmune disease confined to another single organ in the same patient, or diagnoses of MS and SLE (or other autoimmune diseases) in different family members. Here we describe clinically definite MS in 2 sisters, one of whom had Graves' disease, and the other of whom had a daughter with SLE and with a high titre of anti-thyroid antibodies. Other female family members over 4 generations had histories of thyroid disease, MS and Addison's disease. Available family members were HLA typed. The MS patients were positive for HLA DR2. All but one of the affected family members were related to the proband on the maternal side, and all of these affected females shared an HLA haplotype. However, this haplotype was also present in unaffected individuals. Thus HLA type alone cannot account for the familial occurrence of these disorders. We conclude that, in this family, MS, like autoimmune thyroid disease and SLE, may be an autoimmune disease developing in genetically predisposed individuals.

Adult↗
PubMed1997

Sarcoid reaction in thyroid diseases: report of a case of thyroid carcinoma demonstrating sarcoid reaction in regional lymph nodes.

We describe an extremely rare case of thyroid carcinoma accompanied by sarcoid reaction in regional lymph nodes. The patient, a 40-year-old woman, was found to have anterior neck swelling during a routine medical examination. Physical examination revealed a bad movable and firm nodule measuring 3.5 x 2.5 cm in the right thyroid lobe. Examination of a fine-needle aspiration cytology of the nodule suggested papillary carcinoma of class V. Right lobectomy and isthmectomy with neck dissection were performed. Histopathological examination of the resected specimens revealed papillary carcinoma accompanied by metastatic foci in right perithyroidal lymph nodes and non-caseous sarcoid-like granulomas in pretracheal, right upper internal deep cervical and submandibular lymph nodes. We concluded that these granulomas were due to a sarcoid reaction associated with thyroid carcinoma, after performing examinations to rule out the possibility of systemic sarcoidosis.

Adult↗
PubMedDate not supplied

An introduction to benign thyroid disease: pathophysiologic, epidemiologic aspects and diagnostic methodology.

The role of preoperative noninvasive diagnostic procedures in the management of benign thyroid diseases is critically reviewed and on the basis of a series of more than 13,000 thyroid nodules, sequentially examined, the role of preoperative fine needle aspiration (FNA) cytology in discriminating benign from malignant lesions, is assessed. Retrospective studies were performed to determine the diagnostic accuracy of FNA adopted as routine preoperative screening procedure as compared to intraoperative frozen section (FS) analysis. US-guided FNA was shown to be more accurate allowing the preoperative identification of occult or minimal carcinoma: in fact about 3% of malignant thyroid nodules were detected. Moreover, the operation time is reduced, and unnecessary surgical treatments for benign lesions are eliminated, preventing the need of two-stage cancer surgery. FNA is a cost-effective diagnostic tool with about 20% reduction in the cost of care of patients with thyroid nodules. Most recent methods of molecular biology which seem promising in thyroid tissue sampled by FNA to detect malignant lesions missed by conventional cytology and included in the generic category of "follicular proliferation", are analyzed.

Biopsy, Needle↗
PubMed1990

Surgical strategy in thyroid disease.

Over the past 8 years, 311 patients have undergone surgical treatment by the senior authors for thyroid disease. Over 80% of the cases were performed by the head and neck surgical service at Olive View County Hospital, Sylmar, Calif, with the remainder performed at UCLA-affiliated institutions. This service is an important source of thyroid surgical training for UCLA head and neck residents who rotate through this major affiliate. The purpose of this communication is to review our experience with these cases; to describe our overall surgical strategy; and to detail the specifics of our surgical procedure, which we have developed to safely train residents in the treatment of these challenging cases. This article deals with the specific problems of preservation of the recurrent nerve, the parathyroid glands, and the techniques for reimplantation of injured parathyroid glands; the management of larger, substernal thyroid glands; and our techniques for partial thyroid surgery. In addition, the difficult decisions in the management of thyroid cancer, such as completion thyroidectomy; the management of lymph node mestastases; and how tracheal, esophageal, or laryngeal invasion should be managed are discussed. An initial section describing the general preoperative examination of these patients is also included, so that the proper surgical strategy can be developed prior to entering the operating room.

Adult↗
PubMed1991

The effect of lithium therapy on parameters thought to be involved in the development of autoimmune thyroid disease.

This study has considered the effects of primary affective disorders and lithium therapy on a number of factors thought to be important in the development of autoimmune thyroid disease. These factors were examined in (a) controls with no history of any such disorders; (b) patients with primary affective disorders treated with drugs other than lithium and (c) patients with primary affective disorders treated with lithium alone. Eight of 40 patients who were receiving lithium therapy were found to be positive for thyroid microsomal and/or thyroglobulin antibodies, compared to only 3/40 patients who were receiving some other form of treatment for their depression. Peripheral blood mononuclear cells from patients receiving lithium were found to have significantly reduced numbers of suppressor/cytotoxic T cells (P less than 0.05). In addition, suppressor T cells from these patients showed a significantly reduced response to stimulation with concanavalin A (P less than 0.01). These effects were greatest in patients found to be antibody positive. Increased B cell activity, as measured by increased IgG and IgM release following mitogen stimulation, was seen in patients receiving lithium and in those patients receiving other forms of treatment for their depression. This would suggest that the increase is a feature of primary affective disorders and is not due specifically to lithium treatment. It would appear from this study that lithium therapy induces antibody formation in susceptible individuals and this may ultimately lead to the development of thyroid disease.

Adult↗