Thyroid stimulation by placental factors

Abstract

There is now convincing evidence that the human placenta produces factors which have some role in regulating maternal thyroid function during normal pregnancy and are capable of inducing overt hyperthyroidism in some pregnant women and in patients with trophoblastic tumors. As far as the biochemical nature of these placental thyroid stimulators is concerned, a bulk of evidence indicates that hCG, which is abundant in the blood of pregnant women and patients with trophoblastic diseases and shares some structural similarities with human TSH, is the putative thyroid-stimulating factor. However, it is disturbing that most in vitro studies have failed to prove that hCG is truly capable of stimulating the human thyroid. Therefore, factors other than hCG have also to be considered, particularly some molecular variant forms of hCG with enhanced thyrotropic activity. Both the existence of tumor-associated hCG variants in patients with trophoblastic diseases and their ability to stimulate thyroid hormone release in human thyroid tissue have been demonstrated. To complicate things further, other variants of hCG have been identified and purified from pregnancy urine that have a thyroid inhibitory effect in human thyroid membranes. The variant forms of hCG have been shown to differ from the native hormone mainly in the carbohydrate moiety, with the more acidic, more glycosylated variants being the ones capable of stimulating the human thyroid and the more alkaline sialic acidic deficient variants on the other hand, being potent thyroid inhibitors. Future studies should reveal if the different thyroid stimulators and thyroid inhibitors may possibly interact with specific regions of the human TSH receptor that confer their respective functional activities.(ABSTRACT TRUNCATED AT 250 WORDS)

The Regulation of Thyroid Function in Pregnancy: Pathways of Endocrine Adaptation from Physiology to Pathology

“…It has since been amply confirmed that in various pathological conditions, such as molar pregnancy (104,105), other trophoblastic disease (choriocarcinoma) (106 -109), and cancers of various origins (110 -113), elevated hCG levels could induce hyperthyroidism, characterized by the rapid appearance of thyrotoxic symptoms and their even more rapid disappearance after the surgical removal of the mole or cure of the tumor. Taken together, these observations have led to the concept that a substance secreted during pregnancy, and at particularly high levels in moles and choriocarcinomas, could be responsible for hyperthyroidism.…”

Epidemiology of reproductive and hormonal factors in thyroid cancer: Evidence from a case‐control study in the Middle East

“…It has also been shown that serum human chorionic gonadotrophin, with its marked elevation in early pregnancy, may directly stimulate the thyroid gland through its TSH-like activity. 14 Moreover, oestrogen receptors have been demonstrated in thyroid cancers, particularly in well-differentiated carcinomas and oestrogen has been shown to promote thyroid tumors in animal models. 15,16 Based on the findings from descriptive and analytical epidemiology, laboratory and animal studies and individual case reports, there is sufficient evidence to suggest that hormonal and biochemical changes related to reproductive events and patterns could be relevant to the etiology of benign thyroid dysfunction or disease and neoplasia.…”

Associations of Serum Perfluoroalkyl Substances and Placental Human Chorionic Gonadotropin in Early Pregnancy, Measured in the UPSIDE Study in Rochester, New York

“… 95 Maternal PFHxS in pregnancy was negatively associated with thyroxine (T4) in 726 pregnancies, 90 and hCG regulates maternal thyroid hormone production in the first trimester. 96 , 97 …”