4 Discussion
Thyroid cancer is a disease which arises mostly in women, with a considerable proportion in the reproductive age.7 In this study we investigated the pregnancy outcomes and related risk factors in papillary thyroid cancer survivors. The major finding of this study is the higher proportion of maternal and fetal complications among pregnancies in papillary thyroid cancer survivors.
Previous studies rarely focused on the maternal and fetal outcomes of patients with thyroid cancer complicated with pregnancy, and the conclusions are not consistent. A retrospective study analyzing postoperative thyroid cancer survivors found no difference in pregnancy preeclampsia, gestational diabetes mellitus, cesarean section, postpartum hemorrhage, preterm delivery and low birth weight infants, but the incidence of implantation disease in the thyroid cancer group increased.4 A retrospective cohort study on a U.S. inpatient sample database, including 581 pregnant women diagnosed with thyroid cancer, showed a higher incidence of preeclampsia, cesarean section, midwifery, blood transfusion, deep vein thrombosis and prolonged hospital stay in the thyroid cancer group.5 Another study showed that maternal and fetal outcomes in 8 patients with thyroid papillary carcinoma complicated with pregnancy. Compared with the control group, the study group had no differences in abortion, live birth, cesarean section, and neonatal birth weight, but the incidence of neonatal low Apgar score increased.6 Our preliminarily study suggests that the incidence of complications during pregnancy, including gestational diabetes mellitus, cesarean section, postpartum hemorrhage and fetal malformation, is increased in patients with papillary thyroid carcinoma after treatment.
Thyroid hormone plays a key role in pregnancy maintenance and fetal development. The physiological requirement of thyroid hormone increases about 30%–50% after pregnancy gradually.8,9 A systematic review revealed that subclinical hypothyroidism in pregnancy is associated with multiple adverse maternal and neonatal outcomes, such as pregnancy loss, placental abruption, premature rupture of membranes and neonatal death.10 Studies showed that hyperthyroidism in pregnancy was associated with abortion, pregnancy induced hypertension, premature birth, low birth weight infants, fetal growth restriction and stillbirth.11 Another report confirmed that when TSH <1.2 mU/L, only 17.2% of women need to increase the dose of L-T4 during pregnancy.12 Because of the postoperative suppressive therapy, the growth of L-T4 in these survivors was limited in our study, which 14 patients with subclinical hyperthyroidism and 3 patients with subclinical hypothyroidism.
This study also found that the incidence of fetal malformations in the study group increased significantly (5.7% VS 1.5%). Whether it was directly related to thyroid cancer or not, our study has not yet reached a clear conclusion. The observation of this phenomenon highlight the need for a larger sample size and the design of a prospective cohort study to reveal whether there is an internal correlation.
Total or near total thyroidectomy is the standard treatment for patients diagnosed with thyroid cancer, followed by radioactive iodine administration as an adjunctive treatment in differentiated thyroid tumors. I-131 treatment can reduce the long-term incidence rate of differentiated thyroid cancer and may improve survival rate. Among patients treated with I-131, 30% are expected to have transient amenorrhea or irregular menstruation, which usually disappears within one year. Male patients can show transient spermatogenesis disorder associated with elevated FSH, which can be reversed within 18 months after I-131 treatment. However, the risk of persistent male or female gonadal dysfunction may increase in some patients after repeated or highly accumulated radioactive iodine treatment. The effects of I-131 in either parent, on subsequent pregnancy outcomes and offspring have not been recorded.13,14 Whether postoperative radiotherapy for thyroid papillary carcinoma can increase adverse outcomes in the mother and fetus and the occurrence of fetal malformation is still controversial.15,16 I-131 treatment is generally safe, but most authorities recommend avoiding pregnancy up to one year after I-131 treatment, to have allow for complete replacement of irradiated sperm and reverse transient ovarian injury. The average pregnancy time of patients in this study group after radioactive I-131 treatment was 2.5 years. The risk factor analysis did not suggest that thyroid cancer treatment could increase the incidence of adverse maternal and fetal outcomes and fetal malformations.
As a retrospective study, comprehensive evaluation of the clinicopathological data of this article is limited and it is difficult that measurements of thyroid function could cover the entire pregnancy. Due to the limited clinical data of this research, the existing conclusions need to be further verified by expanding samples.
In conclusion, the incidence of maternal and fetal complications during pregnancy, including gestational diabetes mellitus, cesarean section, postpartum hemorrhage and fetal malformation, was increased in patients in papillary thyroid cancer survivors. Therefore, we suggest that monitoring of these survivors should be strengthened and further investigation is needed.
