Pregnancy as a risk factor for thyroid cancer progression.

PURPOSE OF REVIEW: The current review evaluates the impact of pregnancy on women with thyroid cancer in three different clinical situations: those with newly diagnosed differentiated thyroid cancer (DTC), those under active surveillance for papillary thyroid microcarcinomas (PMCs), and those with previously treated DTC. RECENT FINDINGS: Recent pregnancy is not associated with high-risk pathological features of DTC. In women with known PMCs under active surveillance, pregnancy does not increase the risk of disease progression. Thus, deferring surgery for newly diagnosed DTC or known PMCs until after delivery is safe for both mother and the unborn child. If a woman with previously treated DTC is planning pregnancy, response-to-therapy status is an excellent guide for predicting pregnancy-associated disease progression or recurrence. SUMMARY: Clinical studies consistently show that pregnancy is not associated with significant disease progression in newly diagnosed thyroid cancer, PMCs under active surveillance, or previously treated DTC.

Response to Therapy Status Is an Excellent Predictor of Pregnancy-Associated Structural Disease Progression in Patients Previously Treated for Differentiated Thyroid Cancer.

BACKGROUND: Pregnancy may be associated with an increased risk of recurrence/progression of differentiated thyroid cancer (DTC). However, it is unclear if the impact of pregnancy would differ based on pre-pregnancy response to therapy status. The objective of this study was to investigate the risk of recurrence/progression of DTC, applying the response to therapy assessments to pre-pregnancy status as recommended by the 2015 American Thyroid Association thyroid cancer guidelines. METHODS: This was a retrospective review of 235 women followed at Memorial Sloan Kettering Cancer Center for DTC who had a term pregnancy after initial treatment for DTC between 1997 and 2015. RESULTS: Structural disease recurrence/progression after pregnancy was documented in 5% (11/235) of the patients. When evaluated 3-12 months after delivery, patients who had an excellent, indeterminate, or biochemical incomplete response before pregnancy continued to show no evidence of structurally identifiable disease. Conversely, in women with a structural incomplete response to therapy prior to pregnancy, structural progression (defined as ≥3 mm increase in the size of known disease or identification of new metastatic foci) was identified after delivery in 29% (11/38). However, additional therapy was recommended during the first postpartum years in only 8% (3/38) of those patients who had a structural incomplete response to therapy prior to pregnancy, while the remainder (92%) continued to be followed with observation. CONCLUSION: None of the patients with an excellent, indeterminate, or biochemical incomplete response to therapy prior to pregnancy developed structurally identifiable disease after a full-term delivery. Even though structural disease progression was seen in almost a third of the patients with known structural disease prior to pregnancy, only a minority of these patients had changes sufficient to warrant additional therapy. These data confirm that pre-pregnancy response to therapy status is an excellent predictor of pregnancy-associated disease progression in women previously treated for DTC.

Antibodies against insulin measured by electrochemiluminescence predicts insulitis severity and disease onset in non-obese diabetic mice and can distinguish human type 1 diabetes status.

BACKGROUND: The detection of insulin autoantibodies (IAA) aids in the prediction of autoimmune diabetes development. However, the long-standing, gold standard 125I-insulin radiobinding assay (RBA) has low reproducibility between laboratories, long sample processing times and requires the use of newly synthesized radiolabeled insulin for each set of assays. Therefore, a rapid, non-radioactive, and reproducible assay is highly desirable. METHODS: We have developed electrochemiluminescence (ECL)-based assays that fulfill these criteria in the measurement of IAA and anti-insulin antibodies (IA) in non-obese diabetic (NOD) mice and in type 1 diabetic individuals, respectively. Using the murine IAA ECL assay, we examined the correlation between IAA, histopathological insulitis, and blood glucose in a cohort of female NOD mice from 4 up to 36 weeks of age. We developed a human IA ECL assay that we compared to conventional RBA and validated using samples from 34 diabetic and 59 non-diabetic individuals in three independent laboratories. RESULTS: Our ECL assays were rapid and sensitive with a broad dynamic range and low background. In the NOD mouse model, IAA levels measured by ECL were positively correlated with insulitis severity, and the values measured at 8-10 weeks of age were predictive of diabetes onset. Using human serum and plasma samples, our IA ECL assay yielded reproducible and accurate results with an average sensitivity of 84% at 95% specificity with no statistically significant difference between laboratories. CONCLUSIONS: These novel, non-radioactive ECL-based assays should facilitate reliable and fast detection of antibodies to insulin and its precursors sera and plasma in a standardized manner between laboratories in both research and clinical settings. Our next step is to evaluate the human IA assay in the detection of IAA in prediabetic subjects or those at risk of type 1 diabetes and to develop similar assays for other autoantibodies that together are predictive for the diagnosis of this common disorder, in order to improve prediction and facilitate future therapeutic trials.