Does lats cause hyperthyroidism in Graves' disease?: (A review biased toward the affirmative)

Abstract

The long-acting thyroid stimulator (LATS) is now accepted as a feature of Graves' disease, and a great deal is known about its biochemical characteristics and its mode of action on the thyroid. Briefly, it is an IgG that directly influences thyroid gland function; its action involves stimulation of adenyl cyclase and enhanced production of 3′, 5′ cyclic adenosine monophosphate in the thyroid. It has an effect on at least one other extrathyroid tissue, adipose tissue, as shown by increased lipolysis in guinea pig epididymal fat that is incubated with LATS. While these facts are all well established, little is known about factors controlling the production of LATS, and its precise role in Graves' disease is much debated. The relationship of LATS to features of Graves' disease, apart from hyperthyroidism, is probably quite indirect; indeed, there may be in the syndrome one or more other immunoglobulins that have more significance than LATS has for pretibial myxedema (dermopathy) and ophthalmopathy. Although LATS is said to occur in a majority of patients with hyperthyroidism of Graves' disease when concentrates of IgG are tested, even tenfold concentration has failed to show 100% positive results. This fact has raised doubts about the colse pathogenetic relationship of LATS to hyperthyroidism. Moreover, a few patients have been reported to have LATS in blood but to have suppressible (with thyroid hormone) thyroid function. Therefore, LATS as the sole cause of hyperthyroidism is a theory that is now difficult to uphold. The existence of a permissive factor that facilitates its action on the thyroid is one postulate that may reconcile the apparent discrepancies.