Thyrotropin-secreting pituitary tumors: Clinical presentation, investigation, and management

Thyrotropin-secreting tumors, often macroadenomas, comprise approximately 0.5 to 1% of pituitary neoplasms. These tumors can often be distinguished from thyroid hormone resistance by an elevated α-subunit/thyrotropin (TSH) ratio and a blunted or absent response to thyrotropin-releasing hormone. Magnetic resonance imaging demonstrating a tumor should prompt removal. Surgery alone is curative in 35% of cases, and postoperative radiation therapy is helpful. Medical therapy with long-acting somatostatin analogues reduces serum TSH, free T₄, and tumor size. Abnormalities in a variety of molecular processes, cellular processes, or both have been described in pituitary tumors, including allelic deletions and loss of heterozygosity, mutations in G protein (G_sα) and the multiple endocrine neoplasia gene, overexpression of cyclin D₁ and Pit-1, hypermethylation of CpG islands of the retinoblastoma gene, and abnormal expression of the p53 and p16 tumor suppressor genes. Some alterations are observed in specific subtypes of pituitary tumors. Because TSH tumors have rarely been studied, much is yet to be learned about their molecular pathogenesis. Such information will permit targeted development of more specific and effective therapies for aggressive tumors.