Thyroid function on trophoblastic neoplasias

Abstract

Molar pregnancy has been repeatedly reported to be associated with hyperthyroidism. After removal of the molar tissue the patient's hyperthyroidism disappears. This fact suggests that the molar tissue produces a specific thyrotropin. But the control mechanism of the thyroid function under such conditions remains to be clarified. To throw some light on this problem, the author measured the serum levels of thyrotropins (human chorionic thyrotropin : hCT and human pituitary thyrotropin : hTSH) and performed TRH infusion test and various thyroid function tests (T3, T4 ETR, PBI, BMR, T3-RSU, radioiodine uptake and TBG) on the patients with hydatidiform mole and trophoblastic neoplasias. In molar pregnancy, an abnormally large amount of hCT was demonstrated as compared with normal pregnancies of similar gestational age, and the serum levels of hCT found to be correlated with the hCG serum levels (P<0.01). hCT became undetectable nearly five days after molar evacuation, and the time required for the disappearance of hCT after molar evacuation was longer than that of normal delivery. The base line levels of serum hTSH were statistically indistinguishable among women with molar pregnancies and those with normal pregnancies and nonpregnant subjects. The TSH response to TRH infusion in cases of molar pregnancy was somewhat blunted as compared with those of normal pregnancy of similar gestational age. The mean net increase (_??_ TSH) to TRH stimulation was smaller than that of normal pregnant women, but the serum hCT level did not change after the TRH infusion either in molar or normal pregnancy. From the above data, the following items could be extracted : the increase in thyrotropic activity in plasma of the patients with hydatidiform moles is due to the accelerated production of a kind of thyrotropin (hCT) by molar tissue like as in hCG; such hCT is independent of the pituitary TSH, and consequently of TRH stimulation; although it remains to be shown whether or not such hCT from hydatidiform moles is identical with hCT from normal trophoblast, the molecular size seems to be larger than hCT from normal trophoblast since the disappearance time is longer. All patients with hydatidiform moles should have hyperthyroidism if judged by T3 T4, PBI, BMR and radioiodine uptake, but practically, these patients show little or no clinical symptoms of hyperthyroidism. Since T4 levels correlated with serum hCT levels (P<0.01), it is obvious that the elevated thyroid function is due to the increased hCT produced by the molar tissue. But the degree of the clinical symptom is modified by steroid hormones which influence TBG-binding capacity and by other factors. The production and secretion of hTSH by the pituitary is also controlled by the “cross-auto feed-back mechanism” of hCT or the “negative feed-back mechanism” of free thyroid hormone which is stimulated by hCT. As a conclusion, high serum hCT levels, high thyroid hormone levels, and modified clinical symptoms by increased binding capacity of TBG and by suppression of hTSH secretion by two feed-back mechanisms, are the characteristics of molar pregnancy. And, in place of hypothalamic-pituitary-thyroid axis, molar trophoblast-thyroid axis is proposed to be acting as a dominant regulating mechanism for thyroid function in molar pregnancy.Some hydatidiform moles develop into choriocarcinoma or chrioademoma destruence. Changes in hormone production taking place during such developments have not been studied serially. According to the author's study, like as in hydatidiform moles, hCT is also secreted by these chorionic neoplasias, but serum hCT levels were lower than in moles. In these case, mild hyperthyroidism was noted and slight suppression of hTSH secretion was observed.