Endocrine Abstracts (2012) 28 PL6

The thyroid - too much and too little across the ages

Jayne Franklyn


School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, United Kingdom.


Thyroid dysfunction is common. Overt hyperthyroidism is associated with cardiovascular morbidity (especially risk of atrial fibrillation) and all cause and vascular mortality. Our recent studies suggest that excess vascular mortality associated with hyperthyroidism is reduced only by treatment with radioiodine given in sufficient doses to induce hypothyroidism. Subclinical hyperthyroidism is also associated with risk of AF, as well as mortality from all causes and vascular mortality. There is evidence, although less strong, that subclinical hyperthyroidism is associated with increased risk of osteporotic fracture of the hip. Evidence that subclinical hypothyroidism has adverse consequences is less abundant. Weak associations with coronary heart disease are only evident in those with serum TSH >10 mU/L. Our (relatively large) RCT of T4 treatment of subclinical hypothyroidism failed to show any beneficial effects on tests of mental function or well being. Mild thyroid deficiency may, however, be highly important in the context of pregnancy and fetal development. We have shown expression of thyroid hormone transporters in human fetal tissues from early on in fetal development. We have recently demonstrated that UK schoolgirls may be iodine deficient, which may in turn be associated with subtle changes in thyroid status relevant in pregnancy. We've also shown that the presence of thyroid autoantibodies in euthyroid women may be associated with adverse pregnancy outcomes, perhaps related to subtle changes in thyroid function within the reference range. Slightly high TSH is associated with increased likelihood of thyroid cancer in those presenting with thyroid nodules or goitre. This may be because TSH stimulates a variety of growth factors expressed in the thyroid. It also stimulates thyroidal expression of the oncogenes PTTG and PBF. We have studied the role of these oncogenes in the pathogenesis and progression of thryoid cancer in depth. Amongst other findings, we have shown that PBF is over-expressed in thyroid cancer and reduces function of the sodium iodide symporter - and hence affects uptake of iodine into the thyroid gland.This in turn could explain the sometimes reduced response to radioiodine therapy in some thyroid cancers, typically those with a poor prognosis. Understanding molecular mechanisms such as these remains one of the on-going challenges around better management of thyroid cancer.

Declaration of interest: There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Funding: No specific grant from any funding agency in the public, commercial or not-for-profit sector.

Partly supported by the Clinical Endocrinology Trust.

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