Thyroidology最新文献

The aim of the present study was to examine the effects of melatonin (Mel) and of pinealectomy (PX) [in a long-term experiment in vivo - 10 weeks], as well as of Mel and N-acetylserotonin (NAc-5HT) [in experiments ex vivo in vitro and in vitro], on the rat thyroid growth processes. Additionally, the incubations in vitro of rat thyroid lobes with 3H-thymidine, in the presence of TSH, vasoactive intestinal polypeptide (VIP), VIP-antagonist ([4Cl-D-Ph6, Leu17]VIP), somatostatin (SS), all the substances used separately or jointly in combinations, were performed. It was shown that: (a) Mel--administered in late afternoon injections--decreased, while PX increased examined indices of thyroid growth in vivo, (b) Mel--administered in s.c. implanted pellets--reversed the inhibitory effect of Mel injections, (c) in experiments ex vivo in vitro and in vitro, the inhibitory effect of Mel revealed only for the lowest applied dose/concentration of the hormone, (d) NAc-5HT showed no effect, (e) VIP decreased 3H-thymidine incorporation into DNA of thyroid lobes in vitro and enhanced the inhibitory effect of SS on the process in question, (f) VIP-antagonist failed to reverse the inhibitory action of VIP on the thyroid growth.

The autoregulatory effects of iodide on thyroid growth and function are discussed to be mediated by iodinated derivatives of essential fatty acids (EFA), esp. iodolactones. We now reevaluated the effect of iodide on proliferation of isolated porcine thyroid follicles by determination of cell counts and investigated the effects of pretreatment of the follicles with arachidonic acid (AA, C 20:4 n6) in comparison to docosahexaenoic acid (DHA, C22:6 n3). Growth experiments were performed in multi-well culture plates and cell counts were determined after 6 d of incubation. EGF (5 ng/ml) significantly stimulated thyroid cell proliferation (151 +/- 6%; Mean +/- SD vs. basal control, 100 +/- 8%). 2.5 microM of iodide, added 24 h before EGF, had a weak stimulatory effect (168 +/- 9%) whereas higher concentrations of iodide (5-80 microM) exerted significantly dose-dependent inhibitory effects (117 +/- 1% at 80 microM of KI) which could be abolished with 500 microM of methimazole (155 +/- 11% at 80 microM of KI). Isolated porcine follicles showed a rapid uptake of EFA (25 microM) measured by specific tracer activity in the ethanol/acetic acid extracts of follicles (1.60 +/- 0.48 mumol EFA/ml follicle/24 h). Treatment with DHA (100 and 300 microM) significantly enhanced the inhibitory effect of 10 microM of iodide on thyroid follicle proliferation (84 +/- 2% and 45 +/- 4%) in contrast to follicles pretreated with AA (100 +/- 8% and 60 +/- 8%). These results demonstrate the biphasic effect of iodide on thyroid growth which can be abolished by inhibition of iodide organification with methimazole.(ABSTRACT TRUNCATED AT 250 WORDS)

Iodine administration, although efficient in goiter treatment or prevention, is also responsible for adverse effects such as cell necrosis or thyroiditis. These two effects were reproduced in iodide-treated goitrous mice. Morphological observations strongly suggest that thyroid cell death results from an excessive production of free radicals, which initiates lipid peroxidation. This hypothesis is strengthened by the facts that the thyroidal concentration of malonic dialdehyde, a stable product of lipid peroxidation, is increased, and that necrosis is partially prevented by free radicals scavengers. Epithelial necrosis is associated to an inflammatory reaction. The infiltrate is mainly made of cells expressing class II molecules of major histocompatibility complex (macrophages and dendritic cells), but also of T lymphocytes. However, this inflammation, which varies among mouse strains, is transient and it is not amplified or maintained by administration of cytokines, IFN gamma or TNF alpha, known to induce class II expression on thyrocytes.

During recent years several studies have been published comparing different ways of pharmacological treatment of a goiter due to iodine deficiency. These studies usually were performed with 300 to 500 micrograms of iodine, 100 to 150 micrograms levothyroxine, or a combination of in most cases 100 micrograms levothyroxine and 100 micrograms iodine. The largest data have been accumulated in 166 patients with in most cases diffuse goiter. Group A (n = 61) received 150 micrograms levothyroxine per day, group B (n = 50) 400 micrograms iodine per day and group C (n = 55) a combination of 75 micrograms levothyroxine and 200 micrograms iodine per day. During the eight months of therapy, in all three groups a significant and comparable mean decrease in goiter size was documented (-32.1% in group A, -37.3% in group B and -38.7% in group C [n.s. between the three groups]). Striking differences between the three groups are evident in the changes of basal and thyrotropin releasing hormone (TRH) stimulated thyrotropin (TSH). In group A, after eight months a sharp and significant decrease of TSH occurred (from 1.2 mU/l to 0.4 mU/l; mean; p < 0.05), while in group B TSH showed only a minor decrease (from 1.3 mU/l to 0.9 mU/l) and remained significantly higher compared to both, group A and C (p < 0.01). Similar changes were documented when the TSH after TRH administration was calculated. It is concluded, that all three therapeutic approaches are effective for goiter reduction.(ABSTRACT TRUNCATED AT 250 WORDS)

Hashimoto's thyroiditis, primary myxedema and Graves' disease are thyroid disease that are due to autoimmune reactions towards thyroidal antigens such as thyroid peroxidase (TPO), thyroglobulin (Tg) and the TSH receptor. Thyrocyte destruction in Hashimoto's thyroiditis and primary myxedema is caused by TPO- and Tg-specific lymphocytes and autoantibodies, thyrocyte stimulation in Graves' disease is caused by antibodies stimulating the TSH receptor, thyroid atrophy in primary myxedema is caused by antibodies blocking the TSH receptor, or a yet unknown thyroid growth receptor. The above listed thyroid autoimmune diseases are familial (genetically determined), and due to defects in the immunoregulatory mechanisms that should normally control excessive thyroid autoimmune reactivity. This control towards thyroidal antigens (tolerance) can be broken by professional antigen presenting cells, such as the dendritic cells. It is now known that thyroid autoimmune diseases are indeed initiated by dendritic cells: dendritic cells are present in low number in normal thyroids, but accumulate very early in thyroids that are later affected by thyroid autoimmune disease. Dendritic cells are also present in the normal anterior pituitary and in this gland they are known as the (folliculo) stellate cells, the regulators of growth and function of the surrounding pituitary-endocrine cells. It is discussed whether the influx and clustering of dendritic cells in the thyroid observed during early autoimmune thyroid disease is meant for the regulation of growth and function of the thyrocytes thus linking a putative early endocrine disturbance to the initiation of thyroid autoimmune disease.

Basic fibroblast growth factor (bFGF), insulin like growth factor I and II and transforming growth factor beta (TGF-beta) are assumed to be of importance in the paracrine and autocrine regulation of thyroid growth and function. Using in vitro cultures of isolated intact porcine thyroid follicles, we here present data that support a possible autocrine action of bFGF on proliferation, a possible explanation for the observed potentiation of EGF-stimulated growth by IGF-I, and results on the release and regulation of release of TGF-beta. For growth experiments, thyroid follicles (2 x 10(5) cells) were incubated for 6 days followed by cell counting. For the analysis of EGF binding sites, follicles were preincubated with and without IGF-I (10 ng/mL) for 48 h at 37 degrees C, incubated with 125I-EGF (5 nCi/well) and unlabeled EGF (0.1-500 ng/mL) for 24 h at 4 degrees C (2 x 10(5) cells/well); binding characteristics were calculated from Scatchard analysis. The TGF-beta bioactivity in untreated and acid treated media conditioned with thyroid follicles for 3 days (2 x 10(7) cells) was analyzed with a bioassay using mink lung epithelial cells. Basic FGF (0.1-1 ng/mL) dose-dependently stimulated the proliferation of thyroid follicles up to 135.0 +/- 6.1%; this effect was additive with IGF-I (10 ng/mL) but not with EGF (2 ng/mL). The IGF-I (10 ng/mL) just moderately increased proliferation (128.3 +/- 16%), but potentiated EGF (1 ng/mL)-stimulated growth (from 183.0 +/- 11.0% to 314.0 +/- 3.0%).(ABSTRACT TRUNCATED AT 250 WORDS)

Selenium supply appears to be insufficient in several regions of Europe as indicated by analysis of plasma and tissue selenium content and measurements of selenium dependent glutathione peroxidases (GPx). Selenium deficiency alters both thyroid hormone synthesis and tissue specific activation by 5'deiodinase isoenzymes. Human and rat Type I 5'deiodinase have been identified as selenoprotein containing selenocysteine in its active site. Regulation of selenium dependent expression of Type I 5'deiodinase occurs at the transcriptional and posttranscriptional level and a cellular hierarchy of selenite incorporation was found for Type I 5'deiodinase over GPx in LLC-PK1 kidney cells. The role of other newly discovered selenoproteins for thyroid hormone synthesis, activation, and action has to be investigated.

The author points out that natural history of sporadic nontoxic goiter (SNG) is characterized by increasing thyroid volume, nodularity and autonomy of function leading to hyperthyroidism in 13-16% of the patients after a medium follow-up of circa 12 years. Successively, the author reports and discusses the effectiveness and the outcome of the therapeutical modalities used for SNG: thyroidectomy, thyroid hormones and radioactive iodine.

Iodine deficient goiters were studied by immunohistochemistry and showed extensive presence and typical arrangement of dendritic cells, known to have excellent antigen presenting capacity. These cells were positive for all MHC-class II epitopes and for ICAM-1. Epithelial follicle lining cells were also seen to be class II positive but lacked ICAM-1. Thyroglobulin seemed not to be iodinated at the C-terminal hormogenic site, as shown by reactions with monoclonal antibodies. Iodine therapy, as well as thyroxine therapy were effective in reducing thyroid size. Both forms of therapy were found to decrease the pretreatment levels of circulating thyroid growth stimulating immunoglobulins (TGI).