Serum cytokine levels in autoimmune and non-autoimmune hyperthyroid states.
(33/1222)
Although the role of interleukin-2 (IL-2) and interferon gamma (gammaIFN) is still poorly understood in hyperthyroid diseases, it is reasonable to assume that these cytokines may be present at higher levels in Graves' disease (GD) than in other primarily non-autoimmune thyroid diseases. In order to look for an easy method to distinguish GD from primarily non-autoimmune causes of hyperthyroidism, we compared 13 healthy individuals with 21 treated and untreated hyperthyroid GD patients and with 19 patients with hyperthyroidism due to other etiologies: 7 cases of multinodular goiter, 5 cases of excessive hormone replacement and 7 cases of amiodarone-associated hyperthyroidism. All patients presented low TSH levels and a dubious clinical thyroid state. We found a good correlation between TSH and serum IL-2 levels (r = 0.56; P<0.01). Serum IL-2 (P<0.01) and gammaIFN (P<0.01) levels were lower in the hyperthyroid group of patients than in control subjects, suggesting a depressed TH1 pattern in the T-cell subset of hyperthyroid patients. GD had normal IL-2 levels, while patients with other forms of thyrotoxicosis presented decreased IL-2 levels (P<0.05). There was no difference between treated and untreated GD patients. We suggest that the direct measurement of serum IL-2 level may help to confirm hyperthyroidism caused by GD. (+info)
Animal models of Graves' disease.
(34/1222)
Graves' disease (GD) is an autoimmune condition in which goitre and hyperthyroidism are induced by thyroid stimulating antibodies (TSAB) which mimic the action of thyrotrophin (TSH). The target of the autoimmune response is the thyrotrophin receptor (TSHR) and, since its cloning, a number of differing approaches have been adopted in an attempt to develop an animal model of GD. Methods in which synthetic peptides or fragments of the receptor produced in bacteria or insect cells have been injected into animals together with immunological adjuvants have had only limited success in inducing some of the signs and symptoms of GD. Genetic immunisation resulted in thyroiditis in the majority, but TSAB formation in only a minority, of treated inbred mice. Transfer of receptor in vitro primed T cells to syngeneic naive recipients, with priming either using a bacterial fusion protein or genetic immunisation, induced destructive thyroiditis in non-obese diabetic (NOD) mice but lymphocytic thyroiditis in BALBc mice. Furthermore, the orbits of 17/22 of the BALBc animals, but not the NOD animals, with thyroiditis had orbital changes similar to those seen in thyroid eye disease. TSAB and elevated thyroxine levels were induced in AKR/N mice injected with fibroblasts expressing the full length human TSHR and murine major histocompatibility complex (MHC) class II homologous to the recipient mice. No thyroiditis was induced but preliminary results from a different group using the same protocol suggest that receptor autoantibodies and thyroid dysfunction could be transferred using T cells primed in vitro with the receptor and MHC-II expressing cells. The majority of the studies described above have studied inbred mouse strains. In a novel departure, the NMR outbred strain has been treated by genetic immunisation with very promising results, including the induction of increased thyroxine levels in 4/30 female mice, accompanied by TSAB in addition to thyroiditis, and with signs of hyperactivity and orbital pathology. This review discusses the various protocols together with the information regarding the pathogenesis of GD which each has contributed, and concludes with an evaluation of how close we are to mimicking this polygenic, multifactorial disease. (+info)
Medical therapy of Graves' disease: effect on remission rates of methimazole alone and in combination with triiodothyronine.
(35/1222)
In a prospective, randomized study of 135 newly diagnosed patients with hyperthyroidism due to Graves' disease we compared the effect on remission rates of additional triiodothyronine (T3) with conventional antithyroid drug therapy. To this end 114 patients were followed for at least 12 months (15.7+/-4.9, mean+/-s.d.) after the discontinuation of any therapy. After return of thyroid function to normal (8.5+/-7.4 weeks, mean+/-s.d.) patients were maintained on antithyroid medication for 9.0+/-2.5 months. They were then randomly assigned to one of three groups: group 1 (n=44) stopped methimazole, groups 2 (n=39) and 3 (n=31) continued with exogenous T3 (not exceeding 75 microgram/day in any patient) for a further 6 months either with (group 2) or without (group 3) a fixed dose of 10mg methimazole daily. The T3 dose was kept variable to keep TSH suppressed (<0. 1mU/l), which could be achieved in 82% of patients on 100% of their monthly visits. No serious side-effect requiring the discontinuation of the study occurred in any patient. Total T3, TSH-receptor antibodies and some previously suggested potential predictors of relapse including thyroid size by ultrasound, 24h urinary iodine excretion, history of cigarette smoking and ophthalmopathy were determined at the outset of the study and subsequently every 6 months (and total T3 every 4 weeks). No significant difference (P>0.05, Chi square) was seen in relapse of hyperthyroidism after a mean follow-up of 16 months (range: 12-31 months; groups 1:52%, 2:44% and 3:42%) in an area of low-to-moderate iodine intake (prevalence of 24h urinary iodine excretion <100 microgram/24h: 17 and 25% at two different measurements respectively). Concomitantly, no predictor of recurrence of disease could be identified, irrespective of treatment modality. (+info)
Serum leptin levels and bioelectrical impedance assessment of body composition in patients with Graves' disease and hypothyroidism.
(36/1222)
We investigated whether thyroid status modulates serum leptin concentrations and body composition as determined by bioelectric impedance analysis (BIA). The percent body fat mass (%FM) in male Graves' disease was significantly lower than that in age- and sex- matched normal subjects, at the levels of 11.4+/-6.4% (mean+/-SD) vs 19.9+/-9.2% for men (n=12, P<0.05) but not for women (22.6+/-7.6% vs 24.9+/-13.1%, n=28). In contrast, in female hypothyroidism (n=11) %FM was significantly higher than that in normal subjects (32.9+/-11.5%, P<0.01). Among other body composition parameters, the percentage of body water (%BW), and lean body mass (LBM) were significantly lower in hypothyroid patients, and the ECM (extracellular mass)/BCM (body cell mass) ratio was significantly (P<0.0001) increased in Graves' disease which was the result of marked depletion of BCM with concomitant expansion of ECM. The serum leptin levels were significantly decreased in male Graves' patients (2.3+/-0.7 ng/ml, P<0.05), whereas in female Graves' patients (8.8+/-5.9 ng/ml) and patients with hypothyroidism (9.5+/-7.6 ng/ml), the levels were not different from those of normal controls matched for BMI or %FM. There was a positive correlation between serum leptin levels and %FM in female Graves' patients (r=0.635, P=0.001) and in hypothyroid patients (r=0.801, P=0.014) but not in male Graves patients. There was no significant relationship between serum leptin levels and thyroid hormones, TRAb, or TSAb. In euthyroid obese subjects there was a positive relationship between serum leptin levels and serum TSH levels (r=0.37, P<0.01). These results suggest that hyperthyroidism is characterized by the decreased fat mass and serum leptin levels in men, but female patients appear to be resistant to the effect of thyroid hormones. Together with previous reports, thyroid status has a minor role in the regulation of serum leptin levels. (+info)
Human thyrotropin-releasing hormone-associated peptide 3 (hTAP-3) in serum.
(37/1222)
Human thyrotropin-releasing hormone (TRH)-associated peptide 3 (hTAP-3), one of the cryptic peptides resulting from the proteolytic processing of preproTRH to produce TRH, was measured in human plasma from normal, hyperthyroid, and hypothyroid subjects. The dilution curve of hTAP-3 immunoreactivity in the serum paralleled the standard curve of the radioimmunoassay. HPLC analysis revealed a single strong immunoreactive peak, which corresponded to the authentic peptide, hTAP-3. The half-life of hTAP-3 in serum was approximately 3.5 min, and the addition of aprotinin and EDTA completely prevented its degradation. In hyperthyroid patients, plasma concentrations of hTAP-3 were significantly higher than those in the control group and hypothyroid patients, but no correlation was found between its level and that of thyroid hormone. These findings indicate the existence of intact hTAP-3 in the human serum and increases in plasma hTAP-3 levels in hyperthyroid patients, suggesting that blood hTAP-3 may be derived from the peripheral organs rather than the hypothalamus. (+info)
A case of ectopic thyroid in lateral neck associated with Graves' disease.
(38/1222)
Thyroid follicles in the lateral position of the neck are usually thought to represent the metastasis of thyroid carcinoma. Here we present a case of a 28-year-old woman with accessory ectopic thyroid associated with Graves' disease. Despite a history of Graves' disease poorly controlled with large dose propylthiouracil she was found to be pregnant and artificial abortion was planned. Thyroid scintigraphy was carried out, which indicated an uptake into the region above the left lobe as well as into both lobes of the thyroid gland. In order to control hyperthyroidism and to exclude the possibility of metastasis, total thyroidectomy with tumor resection was performed before the artificial abortion. Pathological examinations of the thyroid gland indicated findings compatible with Graves' disease. The lateral neck mass was revealed to be composed of nonneoplastic thyroid tissue, showing similar histological findings to those of the goiter, which were consistent with Graves' disease. Taken together with several previous reports, it appears that there are some cases with lateral ectopic thyroid tissue, whose pathogenetic mechanism remains to be elucidated. (+info)
Familial dysalbuminemic hypertriiodothyroninemia in a Japanese kindred.
(39/1222)
A 56-year-old Japanese housewife had been diagnosed as having Graves' disease and was treated with methimazole. When she was referred to our hospital, the serum T3 level was high irrespective of high TSH level. High serum T3 levels were also observed in two out of her three sisters. Electrophoresis revealed that binding of 125I-T3 to serum albumin was markedly increased whereas the binding of 125I-T4 to serum albumin was slightly increased in the three sisters whose serum T3 levels were high. These data indicate that the presence of an albumin variant is the cause of hypertriiodothyroninemia in this family. (+info)
Soluble L-selectin levels in type I diabetes mellitus: a surrogate marker for disease activity?
(40/1222)
L-selectin (CD62L) is a cell adhesion molecule which plays a key role in the initiation of leucocyte migration from blood vessels to sites of local inflammation. The aim of this study was to investigate T-lymphocyte expression of CD62L antigen and serum levels of soluble L-selectin (sL-selectin) in subjects with clinical and preclinical type I diabetes to determine whether they could provide surrogate markers for disease activity. CD62L selectin expression on memory T lymphocytes was studied by cytometric analysis in 22 patients with newly diagnosed type I diabetes, 20 first-degree relatives of patients with type I diabetes, 14 patients with Graves' disease, and 22 healthy controls. sL-selectin levels were measured by enzyme-linked immunosorbent assay (ELISA) in enlarged groups of subjects in these categories, as well as in patients with long-standing type I diabetes, treated Graves' disease and type II (non-insulin dependent) diabetes. L-selectin levels were also related to islet autoantibodies, human leucocyte antigen (HLA) genotype and L-selectin T668C gene polymorphisms. L-selectin expression on memory T lymphocytes was reduced in newly diagnosed diabetes and islet autoantibody positive siblings compared with controls. sL-selectin levels were significantly raised in newly diagnosed type I diabetes compared with controls, with intermediate levels in family members, both with and without islet autoantibodies, and in long-standing type I diabetes. Levels were also raised in patients with untreated Graves' disease. Patients with type II diabetes had sL-selectin levels which did not differ from controls. sL-selectin levels correlated with the presence of diabetes-associated HLA alleles in both family members and controls; levels also fell with increasing age in family members. Multiple regression analysis showed that HLA genotype and age were independent determinants of sL-selectin levels. sL-selectin levels are raised at the time of diagnosis of type I diabetes and Graves' disease and appear to be modulated by disease activity, but levels are determined predominantly by HLA-associated genetic susceptibility and age. sL-selectin may provide a late marker of autoimmune destruction of islets and sequential measurement may be useful in monitoring disease activity and the effect of interventions preceding type I diabetes. (+info)