Inappropriate Secretion of TSH Syndrome

The syndrome of inappropriate secretion of TSH was the term originally coined to indicate two forms of central hyperthyroidism, i.e. thyrotropin (TSH)-secreting pituitary adenomas (TSHomas) and resistance to thyroid hormone action (RTH). Both forms are characterized by high levels of free thyroxine (FT4) and free triiodothyronine (FT3) in the presence of measurable TSH concentrations, a biochemical picture which is in contrast to primary hyperthyroidism where TSH levels are always undetectable. Patients with TSHoma are clinically hyperthyroid, while RTH patients are generally euthyroid (so-called generalized RTH). However, in a minority of RTH thyrotoxic patients, features have been described with such individuals being deemed to have predominant central or pituitary resistance. Although incidence of inappropriate secretion of TSH is generally low, it is essential to rule out the likely causes of discordance in the TSH/T4 (thyroxine) relationship. The distinction between TSHoma and PRTH can be difficult since both conditions do not present significant differences in age, sex, gender or concentrations of TSH, FT4 and FT3. The failure to recognize them as different entities may have deleterious consequences, such as thyroid ablation in patients with central hyperthyroidism, or unnecessary pituitary surgery in those with PRTH. The objective of this review is to properly characterize them with a history of an affected first-degree relative, biochemical dynamic tests, pituitary imaging and genetic testing, according to what has been reported in international literature, and to analyze biochemical difficulties in choosing the best biochemical tools for that purpose, taking into account that no individual biochemical test can validate the differential diagnosis that must be based on a combination of: serum SUα, SUα/TSH ratio, TSH response to TRH, TSH response to suppression with LT3, and genetic analysis. Rev Argent Endocrinol Metab 50:253-264, 2013 No financial conflicts of interest exist.