Proposing a causal link between thyroid hormone resistance and primary autoimmune hypothyroidism

SummaryResistance to thyroid hormone (RTH) is a rare, inherited condition. It is characterised by raised circulating fT4 and TSH levels. The literature contains a number of descriptions of the finding of thyroid autoantibodies in patients with RTH. Until now, this has been attributed to the coincidental development of primary autoimmune thyroiditis as a second unrelated pathology. Our hypothesis is that the chronic TSH elevation in RTH stimulates lymphocytes to produce the pro-inflammatory cytokine TNF-α. TNF-α, in turn mediates thyroid cell destruction by binding to its receptors on thyrocytes, or indirectly by potentiating antibody formation or cytotoxic T lymphocyte production.