To establish patterns predictive effects on the thyroid, animals have been treated with reference compounds directly acting on the thyroid hormone formation (such as methimazole, ethylenethiourea) as well as liver enzyme inducers leading to an increased excretion of thyroid hormones and therewith to a secondary response of the thyroid (such as aroclor 1254 and boscalid). Here we present the plasma metabolite changes which form the patterns for direct and indirect effects on the thyroid. It is possible to identify metabolites which are commonly regulated irrespective of an indirect or direct effect on the thyroid as well as groups of metabolites separating both MoAs. By putting the metabolite regulations in the context of affected pathways helps to identify thyroid hormone inhibiting MoAs even when the hormone levels are not consistently changed. E.g., direct thyroid hormone synthesis inhibitors affect some enzymes in the urea cycle, increase the 蠅-oxidation of fatty acids and decrease glutamate and oxoproline levels, whereas indirect thyroid hormone inhibiting compounds interact with the lipid mediated and liver metabolism.