Physiopathology, Diagnosis, and Treatment of Secondary Hyperthyroidism

Abstract

Thyrotropin-secreting pituitary adenomas (TSHomas) are a rare cause of secondary hyperthyroidism and account for less than 2% of all pituitary adenomas. In the last 30 years, the recognition of TSHomas has been facilitated by the routine use of ultrasensitive TSH immunometric assays, i.e., methods clearly able to distinguish between TSH concentration in normal controls and undetectable TSH levels in hyperthyroid patients, as well as by the direct measurement of circulating free thyroid hormones (FT4 and FT3). TSHomas must be promptly diagnosed whenever measurable levels of TSH in the presence of high FT4 and FT3 concentrations are documented. As similar biochemical picture is found in patients with thyroid hormone resistance (RTH), a differential diagnosis between the two disorders must be performed. Therefore, a correct diagnosis is fundamental in order to prevent dramatic consequences, such as improper thyroidectomy in patients with secondary hyperthyroidism due to TSHoma or unnecessary pituitary surgery in patients with RTH. The differential diagnosis between TSHomas and RTH mainly rests on dynamic testing, such as T3 suppression test, TRH tests, as well as injection of long acting somatostatin for 2 or more months. First-line therapeutical approach to TSHomas remains pituitary neurosurgery, though in particular cases medical treatment should be considered. The medical treatment of TSHomas mainly rests on the administration of somatostatin analogs, such as octreotide and lanreotide, which are effective in reducing TSH secretion in the majority of patients with consequent normalization of FT4 and FT3 levels and restoration of the euthyroid state.