Thyrotrophin augmentation after commencing thyroxine replacement in primary hypothyroidism

Prospective measurements of serum thyrotrophin and thyroxine concentrations were made in six patients with primary hypothyroidism treated consecutively with an incremental regimen of oral thyroxine. A fall in thyrotrophin occurred over several months, accompanied by a concurrent slow rise in serum thyroxine. Those patients with the highest initial values for thyrotrophin showed the typical curvilinear decline in thyrotrophin, whereas the remaining patients disclosed a transient rise in thyrotrophin for the first 3 months. This paradoxical rise was not associated with depression of cardiac output or glomerular filtration rate. The significance of thyrotrophin augmentation is uncertain, but it may be more common than generally appreciated. It did not occur in those patients with the most severe degrees of thyroid deficiency. Thyroxine exerts a dual action, and augmentation of thyrotrophin may reflect a dominant effect of increased protein synthesis, in contrast to negative feedback inhibition which suppresses thyrotrophin. These opposing actions are in competition at different dose levels of thyroxine, and may contribute not only to augmentation or suppression of thyrotrophin, but also to the curvi-linear pattern of fall. Such variations impair the utility of thyrotrophin as an index of euthyroidism.