The role of hCG in regulation of the thyroid gland in normal and abnormal pregnancy

Abstract

There is strong evidence that at least some forms of hCG can interact with and stimulate the thyroid both in vitro and in vivo. Changes in thyroid tests are sufficiently common in normal pregnancy for us to regard them as physiologic. The evidence that hCG is the agent responsible for these changes remains largely circumstantial but is now supported by an increasing body of evidence from laboratory studies. Trophoblastic tumors secrete variant forms of hCG that can stimulate the thyroid, but we do not know if they have any role in the extreme examples of thyroid stimulation encountered in normal pregnancy. Preparations of hCG from pregnancy urine bind to thyroid membranes from a wide variety of species, but they do not activate adenylate cyclase in all assay systems. The enzyme in human thyroid cells or membranes is, at best, only weakly stimulated by hCG. There are ample in vitro data that hCG can stimulate the thyroid, but studies using human thyroid cells have yielded conflicting results. The most direct evidence comes from the study of thyroid tests in normal pregnancy. In early pregnancy, when hCG concentrations are highest, free thyroid hormones are increased and serum TSH concentration is decreased. An inverse correlation exists between serum hCG and TSH concentrations, but hCG generally correlates poorly with individual thyroid tests. An activity in pregnancy serum related to hCG is able to stimulate FRTL-5 cells and may account for the changes in thyroid function observed in pregnancy. Structural considerations, along with data from biologic assays and sensitive thyroid function tests, suggest that hCG has significant thyroid-stimulating activity. This information suggests that the thyroid may be under dual control from both hCG and TSH in early pregnancy.