Hashimoto Goiter Research Articles

Significance of antibodies to thyroglobulin and thyroperoxidase as markers for the diagnosis of autoimmune thyroiditis

Thyroid gland lesions occupy a significant place in the group of autoimmune diseases. The most widespread lesion is autoimmune thyroiditis, also called Hashimoto's goiter after the Japanese scientist who first described this pathological process. According to some authors, autoimmune thyroiditis occurs in approximately 3–4 % of the population in the Russian Federation. Most often thyroid tissue lesion is observed in patients prone to the development of other autoimmune diseases. Hashimoto's thyroiditis is accompanied by the presence of high titers of antibodies to thyroglobulin and thyroperoxidase in 95 % of all cases. Constant inhibition of microsomal peroxidase by thyroperoxidase antibodies contributes to a decrease in the synthesis of thyroid hormones, resulting in the development of hypothyroidism. One of the leading diagnostic markers that make it possible to suspect the development of thyroiditis are antibodies to thyroglobulin and thyroperoxidase, which are specific immunoglobulins whose action is directed against the enzyme responsible for the formation of the active form of iodine. The damaging effect of these antibodies on biochemical structures, leading to a disruption in the production of thyroid hormones and the development of chronic autoimmune pathology of this organ, has been proven. A direct consequence of autoimmune thyroiditis is the development of a condition in which there is a decrease in the concentration of thyroxine and triiodothyronine. Hypothyroidism itself does not pose a direct danger to life, but can significantly reduce its quality, since thyroid hormones are actively involved in tissue metabolism processes, including oxygen metabolism.

Comparative Study between Dexmedetomidine Versus Dexamethasone as Adjuvants to Levobupivacaine for Cervical Plexus Block in Patients Undergoing Thyroid Operation. Prospective-Randomized Clinical Trial

Background: Thyroidectomy is the most common endocrine surgical procedure, and many challenges are encountered during the preoperative, intraoperative, and postoperative periods. After thyroidectomy, bilateral superficial cervical block is the most successful option reducing postoperative pain, analgesic needs and post-operative complications such as vomiting. Objective: Our study aimed to evaluate the analgesic effect, onset time of sensory block, duration time, postoperative visual analogue score (VAS) and complications of adding dexmedetomidine versus dexamethasone to levobupivacaine for cervical plexus block. Patients and Methods: A prospective-randomized clinical trial study that was conducted at Sohag University between April 2018 and March 2020. The study included fifty patients with (ASA) Class I or II, aged 30 to 60 years were scheduled for euthyroid surgeries (including thyroid adenoma, Hashimoto's goiter, and nodosity thyroiditis) Results: The addition of dexmedetomidine to levobupivacaine (group D) shortened the sensory block onset time compared to dexamethasone added to the levobupivacaine group (group S) (p < 0.05). The duration of analgesia of cervical plexus block in group (D) was significantly longer than that in group (S) (232.34 versus 303.55 min; p < 0.05). HR level in group (D) was significantly lower than that in group (S) (p < 0.05). Conclusion: The addition of 1 μg kg−1 dexmedetomidine to levobupivacaine for cervical plexus block (BSCPB) shortened the sensory block onset time and extended the duration of analgesia and increased the quality of analgesia more superior than the addition of dexamethasone.

English

OBJECTIVE: To evaluate the morphology of non-toxic goiter, the role of auto-immunity and lipid abnormalities in overt and sub-clinical hypothyroid goiter patients. METHODS: A descriptive observational study was undertaken amongst goiter patients without thyrotoxic features comprising 50 randomly selected cases within the range of 12-65years. Goiter patients with thyrotoxic features, acute illness and other visceral diseases were excluded. The patients were evaluated with thyroid function tests, USG-thyroid, FNAC-thyroid, anti-TPO and lipid profile after thorough clinical examination. RESULTS: In my study, most patients were female (with male: female ratio 1:5.25) and were middle aged (between age group 30-49years). Among all patients 60 %( i.e. 30) patients had Hashimoto's thyroiditis, 24% (i.e. 12) patients had diffuse colloid goiter and 16% (i.e. 8) patients had nodular goiter. 52% (i.e. 26) of all patients and 76.6% (i.e. 23) of Hashimoto's goiter patients were anti-TPO positive. Majority of colloid goiter (i.e. 66.7%) and nodular goiter (50%) patients were euthyroid but majority of Hashimoto's goiter patients were hypothyroid (65.38% overt and 33% sub-clinical). Majority of anti-TPO positive patients were hypothyroid (65.38% overt and 30.62% sub-clinical) and majority of anti-TPO negative patients (66.67%) were euthyroid. Within reference range of TSH, there was a linear increase in total serum cholesterol, LDL- cholesterol, triglyceride and decrease in HDL-cholesterol with increase in TSH. This lipid profile changes are mainly seen in Hashimoto goiter patients. CONCLUSION: this study emphasizes the role of auto-immunity in non-toxic goiter patients especially Hashimoto's thyroiditis patients and lipid profile changes in those patients.

Histomorphological aspects of the development of thyroid autoimmune diseases: consequences for our understanding of endocrine ophthalmopathy.

In this short review we will first evaluate the histomorphological aspects of the human and spontaneous animal thyroid autoimmune diseases. These diseases include Hashimoto goiter, primary myxedema, Graves' disease, and the spontaneous forms of thyroiditis in the Bio Breeding (BB) rat, the nonobese diabetic (NOD) mouse, and the obese strain (OS) of chicken. Based on sequential histomorphological events in the animal models of thyroid autoimmune disease, a mechanism for the pathogenesis of thyroid autoimmune disease is proposed. Since one of the human thyroid autoimmune diseases, specifically Graves' disease, is often associated with ophthalmopathy, the histomorphological aspects of the ophthalmopathic process are also evaluated to consider its possible autoimmune character.

Expression levels of the thyrotropin receptor gene in autoimmune thyroid disease: coregulation with parameters of thyroid function and inverse relation to major histocompatibility complex classes I and II.

Using a human TSH receptor (TSH-R) cDNA probe, we investigated TSH-R transcript levels in 13 human thyroid fragments by Northern blot analysis; 7 Graves' disease, 2 Hashimoto's disease, 3 endemic goiter, and 1 healthy thyroid gland were studied. TSH-R expression levels were variable, but displayed a close correlation to the expression of thyroid peroxidase (r = 0.703; P < 0.05), thyroglobulin (r = 0.817; P < 0.01), and the nuclear oncogene c-fos (r = 0.935; P < 0.001), but not c-myc. Overall, TSH-R transcript levels were low or absent in those thyroids in which expression of the major histocompatibility complex class I or II (MHC I or II) was high, thus establishing an inverse relation (MHC I, r = -0.791; P < 0.01; MHC II, r = -0.784; P < 0.01). In situ hybridization showed that apart from lymphocytes, thyroid cells themselves were the source of MHC II transcripts. gamma-Interferon expression was only detectable in 1 Hashimoto's goiter. Our findings suggest that next to lymphocyte infiltration, active regulatory events in the thyrocyte are responsible for the inverse relation between functional parameters (TSH-R, thyroid peroxidase, thyroglobulin, and c-fos) and immunological markers (MHC I and II).

Intrathyroidal HLA-DR-positive lymphocytes in Hashimoto's disease: Increases in CD8 and Leu7 cells

The peripheral and intrathyroidal HLA-DR-positive (DR +) lymphocyte subsets that were activated in vivo in patients with Hashimoto's disease (HD) were examined by two-color flow cytometry with monoclonal antibodies against CD3, CD4, CD8, Leu7, CD19, and HLA-DR antigens. The proportions of total DR + cells in peripheral lymphocytes and the proportions of DR + cells in the CD3 +, CD4 +, and Leu7 + lymphocytes were higher in patients with HD than in normal controls. Furthermore, the proportions of total DR + cells among intrathyroidal lymphocytes isolated from thyroid tissue of individuals with HD were higher than those in their peripheral lymphocytes. Interestingly, the proportions of DR + cells among the CD3 +, CD8 +, and Leu7 + lymphocytes in the thyroid were greatly increased. These data indicate that (i) CD3 + T, especially CD4 + T helper/inducer, lymphocytes and Leu7 + NK/K cells are activated in peripheral blood in Hashimoto's disease and that (ii) CD3 + T, especially CD8 + T suppressor/cytotoxic, lymphocytes and Leu7 + NK/K cells are predominantly activated in Hashimoto's goiter, suggesting an increase of cell-mediated cytotoxicity in the thyroid in Hashimoto's disease.

Intrathyroidal dendritic cells.

The presence, marker pattern, and ultrastructure of antigen-presenting dendritic cells were studied in normal thyroid glands from 9 subjects (6 obtained at surgery; 3 at autopsy) and in the thyroid glands form 13 patients with Graves' hyperthyroidism, 10 patients with simple nontoxic goiter, and 1 patient with Hashimoto's disease (all obtained at surgery). The immunohistochemical characterization of the cells was carried out using the monoclonal antibodies OKIa (class II MHC determinants), RFD1 and L25. These latter monoclonal antibodies react strongly with active dendritic cells in T-cell areas of secondary lymphoid organs (the interdigitating cells in lymph nodes and spleen). Antigen-presenting dendritic cells were defined as cells with an eccentric reniform nucleus, long cytoplasmic protrusions, and strong membrane-bound class II MHC positivity combined with little or no cytoplasmic acid phosphatase activity. According to these criteria normal human thyroid tissue contained a few dendritic cells; they were localized outside the thyroid follicles. These dendritic cells in normal thyroid tissue lacked the marker molecules identified by the monoclonal antibodies RFD1 and L25. In fact, the majority of the dendritic cells were strongly positive for the C3bi receptor (identified by the monoclonal antibody FK 24), which indicates a more monocyte/macrophage character of the cell. In Hashimoto's goiter, Graves' disease, and sporadic nontoxic goiter (which we consider an autoimmune thyroid disease) the numbers of dendritic cells were higher compared to those in the normal gland, and these dendritic cells were clearly positive for RFD1 and L25. The cells were often seen in contact with a few intrathyroidal lymphocytes, forming small lymphoid cell clusters. They were also found in the T-cell zones of larger well organized intrathyroidal lymphoid structures (focal thyroiditis). On ultrastructural examination the dendritic cells in Graves' glands, Hashimoto's goiter, and sporadic nontoxic goiter were similar to the interdigitating cells present in secondary lymphoid organs. The data suggest active involvement of dendritic cells in the immune process in the thyroids of patients with autoimmune thyroid disease.

T-suppressor cell defects in euthyroid nonendemic goitre.

Recently it has been suggested that a substantial number of nonendemic goitre cases can be considered as organ-specific autoimmune disorders of the thyroid. Circulating immunoglobulins, probably receptor autoantibodies, stimulating guinea pig thyroid growth in vitro (TGI) can be found in 2/3 of such patients. Defects in the regulatory balance between T-helper (Th) and T-suppressor (Ts) cells have been described in other thyroid autoimmune diseases, such as Graves' disease and Hashimoto goitre. Such defects are thought to play a role in the loss of control over thyroid autoantibody producing B cells. To investigate whether Ts cell defects can also be found in nonendemic euthyroid goitre, we studied their number and function in 15 of such patients. All patients were clinically euthyroid. Eleven were positive for TGI. Circulating T cells, Th cells and Ts/cytotoxic cells were enumerated using monoclonal antibody techniques (OKT3, Leu3a and OKT8, respectively). Suppressor cell function was assessed employing a proliferation assay in which a short-lived population of such cells was removed by a 24 h preculture. A significant difference was found between patients and controls regarding the Leu3a+/OKT8+ cell ratio: 2.74 (SD 0.94) in patients vs 1.75 (SD 0.38) in controls (P less than 0.01); the disturbed ratio was mainly due to a decrease in the percentage of OKT8+ cells. The functional Ts cell assay also showed a defect of patient lymphocytes: patient removal index (SRI) was 1.5 (SD 1.0) vs an index of 2.6 (SD 1.2) for healthy controls (P less than 0.05). A fair correlation between the numerical and functional data on Ts cells was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

The ultrastructure of thyroid in chronic autoimmune thyroiditis.

In an investigation of autoimmune thyroiditis, two cases of chronic asymptomatic thyroiditis, two cases of nodular goitre with focal thyroiditis and two cases of Hashimoto goitre were studied with the electron microscope. The ultrastructural observations were similar in the six cases. Cytological alterations of the follicle cells were found, some of which suggested an increased metabolic activity. Lymphocytes and plasmocytes established close relationships with the thyroid cells: emperipolesis was encountered.

MYXOEDEMA COMA

ABSTRACT Two fatal cases of myxoedema coma are reported. Case 1 was a woman who had, 4 months previously, undergone thyroidectomy and found to have Hashimoto's goitre. Case 2 was a 81-year-old widow with no previous history of thyroid disorder. Seventy cases reported in the literature are reviewed, and the symptoms and signs, autopsy findings, and treatment of myxoedema coma are discussed on the basis of 41 definite cases. It is apparent that cold was the most important precipitating factor, since nearly all the cases occurred during the winter months. Whether infection induces coma cannot be decided with certainty. There is no evidence that myxoedema coma is caused by or complicated by an accumulation of carbon dioxide, hypoglycaemia, or hypotension. All the patients had a low serum sodium, but normal serum potassium. Autopsy was carried out on 25 patients. A remarkable number showed signs of auto-immune thyroid disorder, 5 having Hashimoto's goitre, 4 severe lymphoid infiltration in the thyroid gland, and one Riedl's goitre. Thirteen out of 17 patients who survived or improved temporarily during treatment had been given 1-triiodothyronine (TIT). Out of the 24 patients who died only 9 had received TIT. The average dose was more than twice as high in 17 patients who survived or showed temporary improvement as in 24 patients who died. Warming was tried in a number of cases, but without any convincing effect. All the patients who survived had received steroid medication, and — in addition to TIT — steroid therapy seems to be indicated in the treatment of these patients.