PubMed · 16776140
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Nobuyuki Takasu. 2006-05-28. [Subclinical hyperthyroidism/thyrotoxicosis].. https://pubmed.ncbi.nlm.nih.gov/16776140/
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Hyperthyrotropinaemia, in which normal levels of T4 occur in association with raised thyroid stimulating hormone (TSH), is usually picked up on neonatal screening. High TSH level can continue for a long time in some of the cases. There is no consensus concerning the follow-up or treatment plan for hyperthyrotropinaemia. In this study, results of a 4-year follow-up of 36 cases who had been medically treated are discussed. Low-dose (5 microg/kg/day) L-thyroxin treatment was carried out in 36 cases that had 5 mU/l or higher TSH and showed exaggerated response to TRH test. Dose was decreased to 2-3 microg/kg/day in 24 of these patients during 6 months follow-up. The drug was stopped in three cases because of the development of biochemical hyperthyroidism. Denver developmental assessment test was applied to all cases at the end of the third year. All patients showed a normal development in relation to their age. According to our results, cases with hyperthyrotropinaemia need to be followed regularly for a long time and a need for low-dose L-thyroxin treatment may exist at ages varying from patient to patient.
CONTEXT: Methimazole (MMI) and propylthiouracil (PTU) are widely used as antithyroid drugs (ATDs) for the treatment of Graves' disease. Both MMI and PTU reduce thyroid hormone levels by several mechanisms, including inhibition of thyroid hormone synthesis and secretion. In addition, PTU decreases 5'-deiodination of T(4) in peripheral tissues. ATDs may also interfere with T(3) binding to nuclear thyroid hormone receptors (TRs). However, the effect of ATDs on the transcriptional activities of T(3) mediated by TRs has not been studied. OBJECTIVE: The present study was undertaken to determine whether ATDs have an effect on the gene transcription regulated by T(3) and TRs in vitro. METHODS: Transient gene expression experiments and GH secretion assays were performed. To elucidate possible mechanisms of the antagonistic action of ATDs, the interaction between TR and nuclear cofactors was examined. RESULTS: In the transient gene expression experiments, both MMI and PTU significantly suppressed transcriptional activities mediated by the TR and T(3) in a dose-dependent manner. In mammalian two-hybrid assays, both drugs recruited one of the nuclear corepressors, nuclear receptor corepressor, to the TR in the absence of T(3). In addition, PTU dissociated nuclear coactivators, such as steroid receptor coactivator-1 and glucocorticoid receptor interacting protein-1, from the TR in the presence of T(3). Finally, MMI decreased the GH release that was stimulated by T(3). CONCLUSIONS: ATDs inhibit T(3) action by recruitment of transcriptional corepressors and/or dissociation of coactivators. This is the first report to show that ATDs can modulate T(3) action at the transcriptional level.
Hydrogen peroxide (H(2)O(2)) is necessary for thyroid hormone production and also for intracellular signalling purposes. Owing to its oxidative properties, however, it is harmful to cells, and deregulation of thyroid oxidative state has been implicated in the pathology of thyroid cancer. In this project, we studied the effects of H(2)O(2) on morphology and histochemical indicators of differentiated function (intracellular thyroglobulin), ability to generate NADPH (glucose-6-phosphate dehydrogenase (G6PD) activity) and vitality (apoptosis assay) in human thyroid epithelial cells. We further evaluated whether methimazole, an antithyroid drug reported to have antioxidative properties, could counteract the effects of H(2)O(2). Our data demonstrate tolerance to H(2)O(2) in concentrations less than 0.3mM and harmful effects at higher concentrations. 10mM methimazole sensitizes the cells towards H(2)O(2), possibly due to a dose-dependent inhibition of G6PD. Our data demonstrate the importance of this antioxidative system and point towards a relevant, but seldom recognized, influence of methimazole.