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PubMed1978

Graft-versus-host reactions within the thyroid gland may evoke pari passu autoimmune thyroiditis.

Unilateral, intraorganal injection of parental lymph node cells into thyroid lobes of F1 hybrid rats elicited an intense, local graft-versus-host reaction within the injected lobes containing massive numbers of lymphocytes. Surprisingly, significant mononuclear cell infiltration was also seen within the contralateral (noninjected) thyroid lobes, even when the isthmus had been divided. The local graft-versus-host reaction spread from the injected gland to involve the regional lymph nodes and spleen. Migration of 51-cr-labeled donor lymph node cells was documented in these same tissue sites; lesser numbers of labeled cells were found in distant lymph nodes, including the contralateral cervical nodes. However, no significant label was found in the contralateral thyroid lobes. Microscopic evaluation of noninjected glands revealed intense infiltration of mononuclear cells around and within follicles, reminiscent of lesions induced by immunization with thyroid extract in Freund's complete adjuvant. The absence of donor cells in the inflammatory reactions within noninjected thyroid lobes raises the possibility of an autoimmune rather than graft-versus-host pathogenesis.

Autoimmune Diseases↗
PubMed2006

Individual thyroid dose estimates for a case-control study of chernobyl-related thyroid cancer among children of Belarus--part II. Contributions from long-lived radionuclides and external radiation.

Significant quantities of long-lived radionuclides were released to the environment during the Chernobyl nuclear power plant accident in 1986. These radionuclides contributed to radiation doses due to ingestion of contaminated foods and external exposure from the ground deposition that resulted. The contributions of these exposure pathways to thyroid doses received by subjects of an epidemiologic study of children from Belarus are evaluated and presented. The analysis shows that ingestion of the long-lived radionuclides, primarily radiocesium, typically contributed a small percentage of the total thyroid dose received by the study subjects. The median and mean fractional contributions were 0.76 and 0.95%, respectively. The contribution of external exposure to the thyroid dose was generally larger and more variable, with median and mean contributions of 1.2 and 1.8% of the total thyroid doses, respectively. For regions close to the reactor site, where radionuclide deposition was highest, the contributions of radiocesium ingestion and external exposure were generally lower than those of the short-lived radioiodine isotopes (132I and 133I) and their precursors (132Te). In other areas, the contributions of these two pathways were comparable to those of the short-lived radioiodines. For all subjects, intakes of 131I were the primary source of dose to the thyroid.

Adolescent↗
PubMed2004

Familial non-medullary thyroid cancer: a matched-case control study.

OBJECTIVES: Familial non-medullary thyroid cancer (FNMTC) is a newly recognized disease entity and can be distinguished from the more common sporadic non-medullary thyroid cancer. The purpose of this study was to determine some of the potential distinguishing features of FNMTC. STUDY DESIGN: Retrospective association study and matched-case control study. METHODS: Five hundred forty-three cases of well-differentiated follicular origin thyroid cancers were identified and collected in a database. Among this population, 24 cases of FNMTC were identified. A case of FNMTC was defined as a patient with the following two criteria: a well-differentiated follicular origin thyroid cancer and at least one first-degree relative with a well-differentiated epithelial origin thyroid cancer. The unmatched sporadic and FNMTC groups were compared using t test, Phi test, Cramer V test, and Pearson and Spearman correlation tests. Twenty-four FNMTC cases were matched to 24 sporadic cases based on age, gender, stage of disease at presentation, and tumor size. Clinicopathologic features, management, and outcome were analyzed statistically using a matched-proportional z test. Disease-free survival and disease-specific survival were analyzed using log-rank test and the Kaplan-Meier function. A P-value less than .05 was considered statistically significant. RESULTS: : There was no significant difference in ionizing radiation exposure, disease multifocality, surgical management, or recurrence between the sporadic and FNMTC patients. Although FNMTC patients tend to have improved disease-free survival and disease-specific survival, the difference was not significant at the 5% level. CONCLUSION: Although FNMTC is characterized by strong family history, these patients do not tend to have worse prognosis.

Adenocarcinoma, Follicular↗
PubMed1996

The T/ebp null mouse: thyroid-specific enhancer-binding protein is essential for the organogenesis of the thyroid, lung, ventral forebrain, and pituitary.

The thyroid-specific enhancer-binding protein (T/ebp) gene was disrupted by homologous recombination in embryonic stem cells to generate mice lacking T/EBP expression. Heterozygous animals developed normally, whereas mice homozygous for the disrupted gene were born dead and lacked the lung parenchyma. Instead, they had a rudimentary bronchial tree associated with an abnormal epithelium in their pleural cavities. Furthermore, the homozygous mice had no thyroid gland but had a normal parathyroid. In addition, extensive defects were found in the brain of the homozygous mice, especially in the ventral region of the forebrain. The entire pituitary, including the anterior, intermediate, and posterior pituitary, was also missing. In situ hybridization showed that the T/ebp gene is expressed in the normal thyroid, lung bronchial epithelium, and specific areas of the forebrain during early embryogenesis. These results establish that the expression of T/EBP, a transcription factor known to control thyroid-specific gene transcription, is also essential for organogenesis of the thyroid, lung, ventral forebrain, and pituitary.

Adrenal Cortex↗
PubMed1986

Microbial adjuvant and autoimmunity. IV. The induction of thyroid lesions in syngeneic X-irradiated mice by the transfer of spleen cells from mice immunized with thyroid extract and Klebsiella O3 lipopolysaccharide.

The role of humoral and cellular immune responses in the initiation and maintenance of autoimmune thyroiditis was investigated in mice immunized with syngeneic thyroid extract and Klebsiella O3 lipopolysaccharide (KO3 LPS) as an adjuvant. The transfer of spleen cells from hyperimmunized mice to 400R-irradiated syngeneic mice produced definite lesions in the thyroid glands, whereas the transfer of immune sera failed to do so. No lesions were induced in normal intact mice by the same transfer of sera and spleen cells from hyperimmunized mice. It was suggested that the induction of thyroiditis by immunization using KO3 LPS adjuvant is primarily due to cell-mediated immunity and that pretreatment of mice by X-irradiation is essential for production of the lesions. The role of X-irradiation in the induction of thyroiditis was discussed.

Adjuvants, Immunologic↗
PubMed1993

Suppression of autoimmune thyroid disease by FK 506: influence on thyroid-infiltrating cells, adhesion molecule expression and anti-thyroglobulin antibody production.

Autoimmune thyroid disease was induced in female PVG/c rats by neonatal thymectomy, followed by sublethal, whole body x-irradiation. Disease development, assessed by histological evidence of lymphocytic thyroiditis and circulating levels of anti-thyroglobulin antibodies, was reduced significantly by a 3-week course of FK 506 (0.5 or 1.5 mg/kg per day) commencing after the detection of autoantibody production. Thyroid-infiltrating mononuclear cells (MNC) in untreated rats stained predominantly for CD4+ and MHC class II antigen which was expressed widely on dendritic cells. Fewer infiltrating cells expressed TCR alpha/beta, CD5, CD8 or LFA-1 beta. Intercellular adhesion molecule-1 (ICAM-1) was observed on MNC, vascular endothelial cells and a minority of residual thyroid epithelial cells. FK 506 administration reduced markedly the incidence of infiltrating TCR alpha/beta +, CD5+, CD4+, CD8+, and LFA-1 beta + cells and the expression both of MHC class II antigens and ICAM-1 on MNC, endothelial cells and thyrocytes. Compared with normal PVG/c rats, there were reduced incidences of CD4+ CD8- and CD4- CD8+ lymphocytes and an elevation in the CD4+/CD8+ cell ratio in the spleens of animals with autoimmune thyroiditis. These changes were partially reversed by FK 506. Systemic drug levels estimated by enzyme immunosorbent assay were in excess of those known to blockade cytokine production by CD4+ T lymphocytes in vitro and some evidence of minor renal dysfunction was observed. The results are consistent with a therapeutic effect of FK 506 mediated via interference with CD4+ T lymphocyte function and adhesion molecule-dependent cytotoxic effector mechanisms.

Animals↗
PubMed1979

Thyroid adenylate cyclase stimulating immunoglobulins in thyroid diseases.

The occurrence of serum immunoglobulins with capacity to stimulate thyroid adenylate cyclase (TSAb) was studied in seventy-two healthy volunteers and 120 unselected patients with various thyroid diseases. A high frequency of TSAb (82.5%, P less than 0.00006) was found in Graves' disease, while TSAb was present only in 13--20% of serum from patients with nontoxic nodular goitre, nontoxic diffuse goitre, toxic adenoma, toxic nodular goitre and myxoedema. These patients had low level of TSAb compared to patients with Graves' disease. In patients with Graves' disease there was no correlation between the level of TSAb and hormonal status except serum triiodothyronine (rs = 0.29, P less than 0.05), and no relation with eye involvement or presence of microsomal thyroid antibodies was found. The results indicate that the human thyroid adenylate cyclase assay system with 1 hour incubation periods is a sensitive method for detection of immunoglobulins with TSH-like capacity to stimulate the thyroid gland.

Adenoma↗
PubMed1980

On incubation of long acting thyroid stimulator with human thyroid and adrenal homogenates.

In view of the ability of long acting thyroid stimulator (LATS) containing sera and IgG samples to stimulate the adrenal cortex of the mouse, it was decided to study the effect of incubation of LATS containing IgG with human thyroid and adrenal homogenates. Whereas incubation with human thyroid gland abolished (loss greater than 80%) both the thyroid and adrenocortical stimulatory effects of LATS, incubation with human adrenal gland resulted in a minimal loss (20%) of both of these stimulatory activities; the magnitude of this loss was no greater than that attributable to non-specific absorption observed with liver and kidney homogenates by previous workers. It is suggested that a, human and mouse thyroid receptors for TSH/LATS are similar and that adrenocortical receptor for ACTH/LATS are different; and b, the inability of human adrenal homogenates to neutralize LATS explains the absence of hyperadrenocorticism in patients with Graves' disease.

Adrenal Glands↗
PubMed1994

Solid cell nests of the thyroid in medullary thyroid carcinoma.

Solid cell nests of the thyroid gland were studied in 44 patients with medullary thyroid carcinoma. In 10 (22.7%) patients, solid cell nests were revealed in the vicinity of tumour foci (five cases) or in the contralateral thyroid lobe and isthmus (four cases); in one case the location was indeterminate. In all seven cases in which immunohistochemical studies were carried out, solid cell nests showed negative staining for thyroglobulin, calcitonin and chromogranin A, findings which were distinct from those in medullary thyroid carcinoma. It is therefore suggested that solid cell nests of the thyroid are not precursors of this tumour.

Adolescent↗
PubMed1993

Feeding of rapeseed presscake meal to pigs: effects on thyroid morphology and function and on thyroid hormone blood levels, on liver and on growth performance.

Effects of feeding soybean meal (SBM) or a mixture of SBM and 5%, 10% and 15% of either 0- and 00-rapeseed presscake meal (RPM) on thyroid, liver and growth performance were studied in castrated boars. Goitrin (G) intake was closely correlated with total glucosinolate intake and blood thiocyanate concentration. In pigs fed 10% and 15% 0-RPM refused feed was enhanced and daily gain decreased. Liver weight and DNA/total liver increased with increasing G intake. Thyroid weights increased up to a G intake of 4.6 mmol/d and then decreased with higher G intake. DNA content/g dry matter (DM) increased continuously and total thyroidal DNA content up to a G intake of 4.6 mmol/l, indicating hyperplasia. Epithelial thickness increased up to a G intake of 13.3 mmol/d, whereas follicular area only up to an intake of 4.6 mmol G/d and then decreased, mirrored by a decrease of DM content. Thyroidal thyroxine (T4) and triiodothyronine (T3) content decreased with increasing G intake. Blood serum levels of T4 decreased with increasing G intake, whereas T3 levels only tended to decrease. Therefore, measured parameters differently reacted to different G intake. In groups fed high amounts of G, hyperplasia was not sufficient to maintain physiological circulating T4 levels, but enhanced thyroidal secretion T3 and/or extrathyreoidal T4 to T3 conversion obviously allowed maintenance of near normal circulating T3 concentrations and barely reduced growth rate despite marked hypothyroidism.

Animal Feed↗
PubMed1987

Effects of amiodarone and thyroid dysfunction on myocardial calcium, serum calcium and thyroid hormones in the rat.

1 Myocardial calcium content was found to be elevated and serum calcium reduced in hypothyroid rats. 2 Treatment of rats with amiodarone at either 30 mg kg-1 or 150 mg kg-1 daily did not result in any significant changes in myocardial or serum calcium. 3 The administration of amiodarone to hypothyroid rats attenuated the changes in serum but not myocardial calcium, suggesting that amiodarone may exert a thyroid hormone-like effect in the hypothyroid state. 4 The administration of amiodarone to thyroid hormone-treated rats resulted in attenuation of the effects on serum calcium and calculated intracellular calcium; this was consistent with an antagonistic interaction between amiodarone and thyroid hormones. 5 Administration of amiodarone resulted in significant changes in circulating thyroid hormone levels in the rat; triiodothyronine was reduced and basal thyrotrophin elevated compared to euthyroid controls. Serum thyroxine was not changed; this is in contrast to the effects in man. 6 Amiodarone does not exert its anti-arrhythmic action via changes in total myocardial calcium content in the euthyroid rat; nonetheless the described interactions between the drug and thyroid hormones may be involved in its mechanism of action.

Amiodarone↗
PubMed1998

Pattern of thyroid lesions and role of fine needle aspiration cytology (FNA) in the management of thyroid enlargement: a retrospective study from a teaching hospital in Riyadh.

The study aims to determine the cytological pattern of thyroid lesions, in addition to the utility and accuracy of fine needle aspiration (FNA) cytology as an initial diagnostic method in the investigation of these lesions among Saudi patients. Four hundred and seventy-nine (479) FNAs were performed on patients presenting with diffuse or nodular thyroid enlargement to the endocrinology clinic at King Khalid University Hospital in Riyadh during the period September 1993 to September 1996. The results of the FNA and the 125 histological diagnoses obtained from the subsequent partial and subtotal thyroidectomies were retrospectively and independently reviewed and compared by two cytopathologists. The results of the FNA cytological diagnosis showed that 372 patients (77.7%) had benign lesions, 24 (5%)) had lesions which were suspected of malignancy, 25 (5.2%) had malignant neoplasms, and 58 (12.1%) had FNAs which were inadequate for cytological assessment. Colloid and adenomatous nodules were the most common benign lesions reported (47.8%). Papillary carcinoma was the most common malignant neoplasm (4.2%). Despite the relatively limited number of patients who underwent surgery, cytohistopathology combined with statistical analysis of the results showed that our FNA accuracy rate is in the region of 94.4% with a sensitivity of 78% and a specificity of 100%. In addition, the negative predictive value (NPV) and the positive predictive value (PPV) of FNA thyroid cytology were 93% and 100% respectively. Our findings indicate that FNA cytology can be used effectively in the evaluation of both nodular and diffuse thyroid lesions whilst cytopathologist should be aware of the potential diagnostic pitfalls and the limitations of the procedure in the diagnosis of follicular, cystic, and small neoplasms, the positive identification of thyroiditis and most cases of neoplasia by itself provides justification for FNA.

Adult↗
PubMed1978

Atypical thyroid follicles arising from an ultimobranchial-like cyst in a postnatal canine thyroid gland.

While investigating the intrinsic vasculature of the canine thyroid gland, atypical thyroid follicles were observed histologically, arising from a postnatal thyroid cyst of unknown origin, in stained sections of a male, 1-year-old, mesaticephalic dog. The animal was anesthetized, bled, killed by injection of Toxital directly into the heart, and perfused with 10% buffered neutral formalin solution. The thyroid tissue was fixed, embedded in paraffin, sectioned serially, and mounted on glass slides. Concordant with descriptions in the literature, this structure appeared to be a postnatal ultimobranchial-like cyst with direct connections to both ultimobranchial and mixed follicles. Seemingly, this observation has never been reported previously in the canine and would lend support to the hypothesis that ultimobranchial-like cysts may give rise to these atypical follicles. However, the authors are not totally convinced that all such thyroid cysts are solely ultimobranchial in orgin. A review of the literature supporting this contention is discussed.

Animals↗
PubMed1985

Thyroid dysfunction in patients on regular hemodialysis: evaluation of the stable intrathyroidal iodine pool, incidence of goiter and free thyroid hormone concentration.

Thyroid function tests and stable intrathyroidal iodine were evaluated in 17 patients on regular hemodialysis treatment (RHD). Triiodothyronine levels in the hypothyroid range, thyroxine levels in the low normal range, but normal levels of thyroid-stimulating hormone, free thyroxine and free triiodothyronine were found. Normal values of stable intrathyroidal iodine and a normal incidence of goiter for our region were also found. It is concluded that in patients on RHD: (1) free thyroid hormone levels are normal and probably represent the most meaningful way of evaluating thyroid function; (2) in our RHD population goiter is no more prevalent than in normal persons; (3) the iodine storage function of the thyroid is not always altered.

Adult↗
PubMed1968

In vitro stimulation by long-acting thyroid stimulator of thyroid glucose oxidation and 32P incorporation into phospholipids.

Long-acting thyroid stimulator (LATS) increased glucose oxidation and (32)P incorporation into phospholipids in in vitro experiments with dog thyroid slices. The time course of the response was different from that obtained with thyroid-stimulating hormone (TSH), but was very similar to the delayed effect observed in vivo. During a 45 min incubation, TSH, but not LATS increased glucose oxidation, whereas in longer experiments up to 6 hr, both substances augmented (14)CO(2) production. Amounts of pooled human gamma globulin equivalent to LATS were inactive. Although TSH stimulated (32)P incorporation into phospholipids during a 2 hr incubation, LATS was ineffective. In longer incubations, from 4(1/2) to 8 hr, LATS did increase (32)P incorporation. The stimulatory effect of LATS was not abolished by anti-TSH antibody capable of neutralizing human TSH. Effects of LATS were also obtained with beef and pig thyroid slices. In addition to stimulation of glucose oxidation in dog thyroid slices, LATS occasionally also stimulated glucose oxidation in dog spleen and liver slices. Despite a 54-fold increase in LATS concentration, a satisfactory dose-response curve could not be demonstrated when (14)CO(2) production was measured.

Animals↗
PubMed1977

Thyroid dysfunction in chronic renal failure. A study of the pituitary-thyroid axis and peripheral turnover kinetics of thyroxine and triiodothyronine.

Thyroid function was evaluated in 46 patients with end-stage kidney disease and 42 normal subjects. Patients were studied before and after the institution of maintenance hemodialysis (HD) and after renal transplantation (RT). Serum total triiodothyronine concentrations (TT(3), ng/100 ml, mean+/-SD) were 63+/-17 and 83+/-22 in the non-HD and HD groups, respectively. Values from normal subjects were 128+/-25 and from RT patients 134+/-20. The TT(3) was in the hypothyroid range (<78 ng/100 ml; 2 SD below normal mean) in 80% of non-HD and 43% of HD patients. Mean serum total thyroxine concentration (TT(4)), although within the normal range, was lower than the control value. T(4)-binding globulin capacity was also slightly lower but the difference was not statistically significant. Among patients whose TT(4) was 1 SD below the normal mean, the free T(4) index was equally depressed, suggesting that factors other than decreased binding capacity might be responsible for the low TT(4). In addition, there was a 37% incidence of goiter. Mean serum thyroid-stimulating hormone (TSH) was not elevated and the TSH response to thyrotropin-releasing hormone (TRH) was distinctly blunted, suggesting the possibility of pituitary dysfunction as well. In vivo (125)I-l-T(4) and (131)I-l-T(3) kinetics during 0.2 mg/day of l-T(4) replacement showed marked reduction in T(3) turnover rate in the uremic patients, both before and during HD; the values (mug T(3)/day, mean+/-SD) for the different groups were as follows: normal, 33.8+/-6.1; non-HD, 13.5+/-2.6; HD, 12.9+/-3.1; and RT, 30.3+/-7.1. The low T(3) turnover rate was due to impaired extrathyroidal conversion of T(4) to T(3). The mean percent+/-SD of metabolized T(4) converted to T(3) was 37.2+/-5.8 in normal subjects, 15.7+/-3.1 in non-HD, 12.8+/-1.7 in HD, and 34.0+/-14.7 in RT patients. In contrast, thyroidal T(3) secretion rate was not different between the control and the three patient groups. Thus, it appears that uremia affects thyroid function at several levels: (a) subnormal pituitary TSH response to TRH; (b) possible intrathyroidal abnormalities as suggested by slightly decreased TT(4) and high incidence of goiter; and (c) abnormal peripheral generation of T(3) from T(4). Restoration of renal function with RT resulted in normalization of all parameters of thyroid function with the exception of blunted or absent TSH response to TRH. The latter may be a direct consequence of glucocorticoid administration.

Adult↗
PubMed1988

Short pulses of low dose thyrotropin-releasing hormone do not affect thyroid hormone secretion from perfused dog thyroid lobes.

Small amounts of TRH are present in the thyroid, and TRH has been shown in several studies to have a moderate direct inhibitory effect on TSH-stimulated thyroid hormone secretion. In a recent publication, however, data were presented to demonstrate that very low doses of TRH given in short pulses induce immediate increases in T4 secretion from the thyroid. This type of secretion had never been observed previously. We have tried to reproduce these results employing perfused dog thyroid lobes in which small and rapid variations in the release of hormones from the follicular cells are easily detected. TRH was infused in concentrations ranging from 1.7 X 10(-11) to 1.7 X 10(-8) M for 10-min periods. There was no effect on thyroid secretion of T4 and T3, nor did the infusion of 1.7 X 10(-9) M TRH for 160 min alter the T4 secretion induced by 4 microU/ml TSH.

Animals↗
PubMed1990

Changes in 127I mice thyroid follicle studied by analytical ion microscopy: a key for the comprehension of amiodarone-induced thyroid diseases.

Analytical ion microscopy was used to evaluate the quantitative changes in thyroid 127I mapping induced by amiodarone in relation to the iodine intake. Mice were maintained on a normal diet (NID), on a low iodine diet (LID) or on a high iodine diet (HID) during 3 months. They received daily ip injections of amiodarone or NaI during the last 10 days. Microanalysis of iodine was performed on thyroid sections. In NID mice, the cellular 127I concentration (mean +/- SE: 0.90 +/- 0.06 micrograms/mg) was lower than that of follicular lumina (6.99 +/- 0.17). Amiodarone increased cellular concentration (2-fold) and decreased follicular concentration; NaI induced the same results. In LID mice, both concentrations, which were decreased 60- to 70-fold in comparison with NID, were restored by amiodarone, while NaI enhanced follicular concentration more than amiodarone. In HID mice, the follicular concentration (1.5-fold higher than normal) returned to a normal range with amiodarone, but cellular concentration (2.5-fold lower than normal) remained low, while NaI increased the cellular concentration 3-fold. These data show that iodine released by amiodarone has a bioavailability different from that of NaI. They indicate that thyroid response to amiodarone is related to dietary iodine intake, which, in turn, determines autoregulatory mechanisms. They also raise the question of the possible existence of an intrinsic property of amiodarone which would explain the specificity of its activity on thyroid iodine organification and the development of amiodarone-induced human thyroid diseases.

Amiodarone↗