Thyrotoxicosis usually develops as a primary disorder of the thyroid gland. Primary hyperthyroidism is characterized by clinical symptoms and signs of thyroid hormone excess, elevated circulating free thyroxine (T₄) or triiodothyronine (T₃) concentrations or both, and a suppressed serum level of thyrotropin (TSH). Rarely, thyrotoxicosis may result from primary TSH overproduction by the pituitary gland with secondary thyroid enlargement and hyperfunction. This is referred to as central hyperthyroidism.

There are two known causes of central hyperthyroidism: (1) TSH-producing pituitary tumors (TSHomas) and (2) the syndrome of pituitary resistance to thyroid hormone (PRTH). These disorders produce clinical manifestations of thyrotoxicosis with elevated serum free T₄ and T₃ concentrations but are distinguished by the critical finding of nonsuppressed (inappropriately normal or frankly elevated) serum TSH levels.

Central hyperthyroidism often has been misdiagnosed in the past, leading to inappropriate and frequently harmful therapeutic interventions. More recently, enhanced physician awareness and improved diagnostic tools have resulted in both types of central hyperthyroidism being diagnosed with increased frequency. This has been accompanied by major advances in our understanding of the pathophysiology of these entities and the development of more effective treatment modalities. This article reviews current concepts regarding the development, diagnosis, and management of TSHomas and the syndrome of PRTH.