A 51-year-old female patient with long-standing hyperthyroidism due to a thyrotropin-secreting pituitary adenoma is reported, who became thyrotoxic again shortly after successful pituitary surgery. Functional testing and scintigraphy suggested the diagnosis of autonomous functioning thyroid nodules, which was confirmed by pathological examination of the resected thyroid tissue. This is the first report revealing the transition from a pituitary-dependent to a thyroid-dependent hyperthyroidism. Autonomous functioning thyroid nodules are, however, considered an intrinsic thyroid defect. In similarity with other disorders, in which trophic hormones may induce an autonomous secretion by the target gland, this report opens the possibility that a humoral factor may play a role in the development of autonomous functioning thyroid nodules.