PubMed Health⌕ Search

PubMed · 9532338

Thyroxine suppression therapy in Graves' disease.

Abstract

A recent Japanese report of a novel 'block-and-replace' regime for Graves' hyperthyroidism in which thyroxine was continued alone after the combination therapy was stopped was associated with a negligible relapse rate of less than 2%. Such a finding has the potential to revolutionize the management of Graves' disease but a similarly large study from Scotland failed to confirm any benefit from the new treatment. Apart from obvious differences in race and dietary iodine there is no adequate explanation for the discrepant results. In all studies reporting a fall in thyrotropin (TSH) receptor antibodies (TRAb) and/or relapse rates following conventional or novel 'block-and-replace' regimes, serum TSH concentrations were often elevated in the control groups treated with antithyroid drugs alone. Theoretically, this could lead to continued expression of thyroid cell surface antigen, increased production of TRAb and an adverse effect on remission rates. This, however, fails to explain the extraordinary low remission rates of the original study from Japan and, in the meantime, there is no good reason to adopt the novel regime, at least in Caucasians.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

A Toft. 1997. Thyroxine suppression therapy in Graves' disease.. https://doi.org/10.1016/s0950-351x(97)80753-7

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

L-thyroxin treatment in infants with hyperthyrotropinaemia: 4-year experience.

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.

Antithyroid Agents↗

Barriers in the quest for quality drug information: salutary lessons from TGA-approved sources for thyroid-related medications.

Product information (PI) for thyroid-related medications endorsed by the Therapeutic Goods Administration, as reproduced in the commonly used compilation publications June 2006 MIMS (Monthly index of medical specialties) annual, MIMS Online and the Australian prescription products guide 2006, was evaluated to see whether it reflects contemporary therapeutic practice. Compared with current medical literature, these PI-based sources provide inadequate, inaccurate or outdated therapeutic directives. Examples include: Incorrect advice that thyroxine therapy should always begin at very low dosage. Failure to recommend increased thyroxine dosage early in pregnancy (thus placing the offspring of women being treated for hypothyroidism at risk of impaired fetal brain development). Incorrect and potentially unsafe advice to treat thyrotoxicosis with stable iodide in late pregnancy. Failure to advise serial adjustment of antithyroid drug dosage until after a patient becomes euthyroid (this can result in iatrogenic thyroid dysfunction). Outdated advice that antithyroid drugs are not compatible with breastfeeding. Recent initiatives to upgrade consumer medicine information (CMI) appear to accept PI-based sources as a reliable benchmark for CMI. That inference is not warranted for thyroid-related medications. Accountability for the updating of clinical information in PI needs to be defined, and the process for updating PI may need to be modified. Quality drug information, both PI and CMI, depends on fluent, evidence-based collaboration between suppliers, regulators, prescribers, specialist clinicians and consumers.

Antithyroid Agents↗

Antithyroid drugs inhibit thyroid hormone receptor-mediated transcription.

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.

Antithyroid Agents↗