Papillary Thyroid Carcinoma and Pregnancy: What Impact on Prognosis? ()
1. Introduction
Differentiated papillary thyroid carcinoma (PTC) accounts for 80% of thyroid cancers and is most frequently found in women of childbearing age [1]. Its incidence is increasing during the last decades. Pregnancy is a favorable condition for the development of benign or malignant thyroid nodules, probably due to an imbalance in the iodine balance and the secretion of hormones with thyroid-stimulating activity [2] [3]. In particular, the increase in estrogen and HCG levels, which have a certain homology with TSHus, may be responsible for the rapid increase in the size of thyroid tumors during pregnancy [4].
Nevertheless, the impact of pregnancy on the prognosis of PTC remains a matter of debate. Some studies have suggested that pregnancy is a risk factor [5] [6]. Other retrospective series have reported that pregnancy has no significant impact on the prognosis of differentiated cancers [7] [8]. The first study to investigate the impact of pregnancy on the increase in papillary microcarcinoma size was conducted by Shindo et al. [9]. This study included nine patients with microPTC (tumor size ≤ 1) and suggested a risk of tumor enlargement during pregnancy. In contrast, a recent study of the same group of patients concluded that only 8% of the 51 patients showed an increase in tumor size of microPTCs, and no new cervical lymph node (LN) metastases were detected [10].
The main objective of the present study was to evaluate the effect of pregnancy on the course and prognosis of PTC in the short term through a prospective study.
2. Materials and Methods
2.1. Patients and Study Design
A prospective descriptive and analytical study was conducted in the Department of Diabetes Endocrinology at the Hassan II University Hospital in Fez. We included after consent, patients diagnosed with a well-differentiated papillary carcinoma of the thyroid and who presented a pregnancy during the year 2019 and 2020. The follow-up of these patients was continued until 1 year post-partum. Patients who had a miscarriage and those who were lost to follow-up were excluded from the study. Epidemiological, clinical, and paraclinical data were collected from the patients’ medical records
Our patients were classified according to the TNM classification of thyroid cancers UICC/AJCC2017, and according to the risk of relapse, they were divided into 3 groups: low, intermediate and high risk.
All Patients were followed up clinically, biologically by thyroglobulin, anti-Tg antibodies and TSHus, and radiologically by cervical ultrasound.
The prognostic factors studied were: the presence of distant metastases at the time of diagnosis, tumor stage, lymph node involvement, tumor size greater than 4 cm, multifocality, tumor capsule invasion and vascular invasion.
2.2. Definitions
Remission was defined by an undetectable Tg level (<1 ng/ml), negative anti-Tg antibodies and negative cervical imaging.
Persistent disease was defined by the presence of any of the following criteria:
1) Detectable Tg level > 1 ng/ml
2) Presence of a residue on cervical imaging
3) Presence of a focus of radioactive iodine uptake on whole body scan.
4) Persistent anti-Tg antibodies with a consistent upward trend.
2.3. Definition of Risk Groups
Risk of relapse according to the 2015 ATA classification:
Postpartum cancer progression was determined biologically by an increase in Tg levels of 20% or more, and radiologically by a 20% increase in a pre-pregnancy lesion, or the appearance of a new metastatic lesion.
Statistical analysis
The variables collected were analyzed descriptively: mean, standard deviation, for quantitative parameters and frequency, 95% confidence interval (CI) for qualitative parameters. Relationships between two variables were analyzed by chi-square test.
The relationship between clinical features and thyroid cancer progression was analyzed by the Pearson test. The factors identified as significant by univariate analysis were analyzed by linear regression.
P < 0.05 was considered statistically significant.
All statistical analysis was performed using SPSS version 21 software.
3. Results
3.1. Epidemiological, Anthropometric and Clinical Characteristics of Patients
We collected 26 patients. The mean age was 33.2 years ± 6.2. Most cases were sporadic, and a history of thyroid cancer was identified in only 3 patients (11.5%). The most frequent reason for initial consultation was a thyroid nodule in 86.3%. The diagnosis of PTC was made by cytopunction in 28% and by anatomopathological study of the thyroidectomy operation in the rest. All our patients underwent total thyroidectomy, lymph node dissection was performed in 13.8%, and supplementation with iratherapy was indicated in 67.8% before pregnancy. Contraception was indicated in all patients. The mean time between treatment and pregnancy was 2.3 years ± 1.4. All patients were undergoing thyroxine suppression therapy. The TSHus target was <0.1 in 44.3%, between 0.1 - 0.5 in 24.8% and between 0.5 - 2 in 30.9%, of cases.
According to the 2017 UICC/AJCC TNM, our patients were classified according to tumor stage into stage I in 75%, and stage II in 25% (Table 1). Concerning the risk of recurrence, the patients were divided into 3 risk groups: low risk (30.9%), intermediate risk (24.8%), and high risk (44.3%) (Figure 1). 66.3% of the patients were declared cured before conception, 12.8% had persistent disease, and 20.9% had a pregnancy before the efficacy assessment. The mean thyroglobulin level of our patients was 4.03 ng/ml ± 3.28.
3.2. Study of Prognostic Factors
The postpartum evaluation did not show any recurrence in patients declared cured before conception. In the 2 patients with persistent disease, cervical ultrasound did not show any increase in the size of the thyroid residue. Recurrence was noted in only 17.8% of cases.
We studied the clinical, paraclinical and therapeutic factors that could influence the prognosis of the disease. Our study showed a significant correlation between recurrence and the presence of unfavorable histological signs (p = 0.02), and the initial thyroglobulin level (p = 0.01). However, pregnancy was not an influencing factor (p = 0.41) (Table 2).
4. Discussion
The impact of pregnancy on the prognosis of PTC is variable among studies. The effect of estrogen and HCG on both benign and malignant thyroid pathology has
![]()
Table 1. The staging of patients according to the 2017 UICC/AJCC TNM classification of thyroid cancers.
![]()
Table 2. Multivariate study of factors influencing prognosis.
![]()
Figure 1. Distribution of patients by risk groups.
long been suggested [4] [11]. A recent study has shown that estrogen can alter the proliferation of thyroid cancer cells and potentially enhance the action of certain carcinogens [12]. The actions of estrogens are probably mediated by nuclear and membrane estrogen receptors (ER), in particular ER-alpha [13]. According to the results of a study, these receptors were present in papillary differentiated thyroid carcinoma in pregnant women (DTC), and absent in nulliparous women, explaining the more aggressive behavior of DTC in association with pregnancy [14]. Nevertheless, our study did not demonstrate this association (p = 0.41). Our results were in agreement with those of several series: for example, Leboeuf et al., who explored the impact of pregnancy in 36 patients followed for DTC for an average of 04 months after delivery, concluded that pregnancy is not a risk factor for DTC recurrence in women in remission [15]. Another study conducted by Budak et al. comparing the relapse rate between 2 groups of pregnant and non-pregnant women, concluded that there was no significant difference between the 2 groups [16]. In addition, Yasuhiro et al. in a series including 50 pregnant patients concluded that pregnancy and delivery was associated with an increase in size of papillary thyroid microcarcinomas (PMCs) in only 8% of the 51 pregnancies/delivery cases. None of the patients developed nodal metastasis during pregnancy [17].
Our study showed in bivariate analysis that the risk of recurrence was correlated with tumor stage (p = 0.01), the presence of unfavorable histological signs (p = 0.02), and the initial thyroglobulin level (p = 0.01). On the other hand, in multivariate analysis, the association was significant for the presence of unfavorable histological signs (p = 0.02), and for the initial thyroglobulin level (p = 0.01). These same prognostic factors have been identified by several studies [17] [18] [19] [20] [21]. Age is controversial prognostic factors [19] [22], Nevertheless, our study did not show a significant association. Other factors have been reported in the literature, namely tumor size > 4 cm, extrathyroidal extension, presence of lymph node invasion, multifocality, adjuvant treatment with radioiodine [23] [24].
Concerning hormone suppressive therapy, several lines of evidence indicate that suppressive l-T4 treatment decreases the risk of progression in patients with persistent disease, and reduces the rates of recurrence in high-risk cancer patients. However, in other subgroups of thyroid cancer patients, the use of L-T4 therapy is not associated with any significant improvement in recurrence or survival rates [25], in our series this association was not demonstrated (p = 0.09).
However, it is very important to note that careful monitoring of these patients should be recommended even if there is no effect of pregnancy on the prognosis of the disease.
5. Conclusions
The identification of poor prognostic factors at the time of initial management is essential in order to identify high-risk patients and to adapt the therapeutic strategy.
Our study shows that the risk of recurrence of PTC is correlated with the presence of unfavorable histological signs and the initial thyroglobulin level. However, pregnancy does not seem to be a risk factor.
The Limitations of the Study
Our study has some limitations, including the small sample size and the short duration of patient follow-up.