How Much Should Thyroid Cancer Impact Plans for Pregnancy?

Since more than one third of all thyroid cancer diagnoses occur in patients aged <45 years with three-fourths of the diagnoses in women, pregnancy planning is a pertinent issue for a large number of thyroid cancer patients (1). For a young woman, the diagnosis and treatment of thyroid cancer can potentially alter or delay plans for conception. Factors that patients and physicians may consider when discussing family planning include the risk of cancer progression with pregnancy, the optimal timing of treatments, and the risk of treatments to the fetus and mother.

Since thyroid cancer is one of the two most commonly diagnosed cancers in the first year postpartum and there is a theoretical concern that high levels of human chorionic gonadotropin and estrogen can stimulate thyroid cancer growth, there has previously been concern that pregnancy leads to progression of thyroid cancer (2,3). Prior studies have identified a small number of patients with thyroid cancer who had progression of disease during pregnancy (4 –6). However, the study by Rakhlin et al. published in Thyroid utilizes response-to-therapy status to help put the risk of thyroid cancer progression in perspective (7). First, since the vast majority of all thyroid cancer patients have an excellent response to initial treatment, the fact that no progression or development of recurrence was noted in this subgroup should be encouraging for the overwhelming majority of patients and physicians. Second, even those patients with indeterminate or biochemical incomplete response continued to have no structurally identifiable disease after pregnancy. Finally, although 29% (11/38) of the patients with structural incomplete response to treatment had structural progression during pregnancy, only 8% (3/38) required additional therapy in the first year postpartum. It is not clear if pregnancy per se led to progression in these select patients or if these particular patients would have progressed with or without pregnancy. Not evaluated in the study by Rakhlin et al., but known from prior longitudinal data, is the fact that even with structural residual disease, the long-term prognosis of most thyroid cancer patients <45 years is still quite good, and in general, the 10-year disease-specific survival is 97–100% for all thyroid cancer patients diagnosed <45 years (1). Thus, evidence to date suggests that in the vast majority of patients, pregnancy will not impact thyroid cancer prognosis. Patients with residual structural disease will need close surveillance, but even in these patients, risk of death from thyroid cancer is very low and structural progression can typically be followed or, if needed, intervened upon postpartum.

Standard treatment for newly diagnosed differentiated thyroid cancer is typically surgery, sometimes followed by radioactive iodine and thyroid hormone suppression. Prior work has shown that surgical complications may be higher if thyroid surgery is performed during pregnancy (8). Surgery may also increase risk for fetal loss and altered organogenesis in the first trimester and for premature delivery in the third trimester. Thus, although there are infrequent scenarios where thyroid surgery should be performed during the second trimester, it is optimal to plan thyroid surgery prior to conception. However, if a small cancer is diagnosed during pregnancy, postponing surgery until the postpartum period is acceptable (9). Recent work has found that if papillary microcarcinomas are observed during pregnancy, an increase in size is only noted in 8%, and none of the 51 studied patients with papillary thyroid microcarcinomas developed nodal metastases (10).

Since all patients need thyroid hormone replacement post total thyroidectomy and 10–50% need it after hemithyroidectomy (11), most women with thyroid cancer are treated with thyroid hormone replacement before and during pregnancy. The majority of thyroid cancer patients need close to a 30% increase in levothyroxine dose with pregnancy (12,13). For optimal fetal and maternal outcome, the goal thyrotropin (TSH) is <2.5 mIU/L in treated hypothyroid patients (9), and goal TSH values may be lower in cancer patients. However, as long as TSH is within acceptable range prior to conception, the potential need for dose adjustments in levothyroxine should not deter conception. In addition, subclinical hyperthyroidism, which is the goal in some women with thyroid cancer, does not have detrimental effects on the mother or child during pregnancy (14).

Per the most recent American Thyroid Association guidelines, many low-risk thyroid cancer patients can forgo treatment with radioactive iodine (15). However, for those patients who are candidates for radioactive iodine, radioactive iodine is contraindicated during pregnancy, and it is recommended that conception be delayed for at least six months after treatment with radioactive iodine (16,17). This conservative recommendation of a six-month delay is based on a combination of factors, including not only the half-life of radioactive iodine but also the need to normalize thyroid hormone levels after thyroid hormone withdrawal for radioactive iodine treatment (16). Prior work has found that in patients who underwent surgery for thyroid cancer, treatment with radioactive iodine was associated with a significantly longer delay in childbearing (34.5 months vs. 26.1 months), and in subgroup analysis of women age 35–39 years, receipt of radioactive iodine was associated with a significantly decreased birth rate (18). It is possible that radioactive iodine directly affects reproductive health (19,20), but it is more probable that decisions to delay pregnancy lead to a decline in pregnancy rate in women aged ≥35 years. A prior survey study has shown that just under half of all endocrinologists prioritize patient desire for conception when deciding on whether to administer radioactive iodine (21). However, since in many scenarios radioactive iodine treatment can be avoided or delayed without risks of cancer progression, patient age and the desire for pregnancy should be a factor in determining whether and when to treat with radioactive iodine.

Given the overall excellent prognosis of most thyroid cancers, the lack of evidence that women with thyroid cancer are at significant risk with pregnancy, and the limited span in a woman's life for pregnancy, physicians and patients should not let a diagnosis of thyroid cancer drastically restrict pregnancy planning. When tailoring treatment to the patient, a woman's age, especially if approaching mid-30s, and her personal goals in life should factor into the thyroid cancer treatment and surveillance plan, including determining the need for and optimal timing of specific treatments and supporting plans for pregnancy post primary treatment. Physicians should try to minimize unnecessary pregnancy delays. The recent study by Rakhlin et al. (7) provides further data to help reassure patients and physicians. Patient reassurance and support is important, as in the vast majority of cases, diagnosis and treatment of thyroid cancer should not drastically alter life plans, including plans for pregnancy.