Browsing by Author "Stephenson, Alexandra"

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    Malignancy risk of hyperfunctioning thyroid nodules compared with non-toxic nodules: systematic review and a meta-analysis
    (2021-02-25) Lau, Lorraine W.; Ghaznavi, Sana; Frolkis, Alexandra D.; Stephenson, Alexandra; Robertson, Helen L.; Rabi, Doreen M.; Paschke, Ralf
    Abstract Background Hyperfunctioning or hot nodules are thought to be rarely malignant. As such, current guidelines recommend that hot nodules be excluded from further malignancy risk stratification. The objective of this systematic review and meta-analysis is to compare the malignancy risk in hot nodules and non-toxic nodules in observational studies. Methods Ovid MEDLINE Daily and Ovid MEDLINE, EMBASE, Scopus, and Web of Science databases were searched. Observational studies which met all of the following were included: (1) use thyroid scintigraphy for nodule assessment, (2) inclusion of both hyperfunctioning and non-functioning nodules based on scintigraphy, (3) available postoperative histopathologic nodule results, (4) published up to November 12, 2020 in either English or French. The following data was extracted: malignancy outcomes include malignancy rate, mapping of the carcinoma within the hot nodule, inclusion of microcarcinomas, and presence of gene mutations. Results Among the seven included studies, overall incidence of malignancy in all hot thyroid nodules ranged from 5 to 100% in comparison with non-toxic nodules, 3.8–46%. Odds of malignancy were also compared between hot and non-toxic thyroid nodules, separated into solitary nodules, multiple nodules and combination of the two. Pooled odds ratio (OR) of solitary thyroid nodules revealed a single hot nodule OR of 0.38 (95% confidence interval (CI) 0.25, 0.59), toxic multinodular goiter OR of 0.51 (95% CI 0.34, 0.75), and a combined hot nodule OR of 0.45 (95% CI 0.31, 0.65). The odds of malignancy are reduced by 55% in hot nodules; however, the incidence was not zero. Conclusions Odds of malignancy of hot nodules is reduced compared with non-toxic nodules; however, the incidence of malignancy reported in hot nodules was higher than expected. These findings highlight the need for further studies into the malignancy risk of hot nodules.
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    Thyroid Stimulating Hormone Receptor Mutations in Non-Autoimmune Hyperthyroidism
    (2020-08-24) Stephenson, Alexandra; Paschke, Ralf; Robbins, Stephen M.; Grewal, Savraj S.
    Non-autoimmune hyperthyroidism (NAH) is rare and occurs due to a constitutively activating thyroid stimulating hormone receptor (TSHR) germline mutation. Germline mutations in TSHR lead to sporadic and familial NAH (SNAH, FNAH) whereas somatic mutations lead to hot thyroid adenoma (HTA). The role and prevalence of TSHR mutations in NAH have been reported to vary significantly. Furthermore, the result of these mutations appears to vary across different reports. Most interestingly, there is also a proposed role for TSHR in thyroid carcinoma. This thesis seeks to determine the true prevalence of TSHR mutations in HTA (the subset of NAH where the most samples are available), explore the phenotype of germline NAH, provide an overview of all TSHR associated disorders and begin to unravel the role of TSHR in carcinoma. This is done in 4 chapters. The first uses targeted NGS technology to determine the true prevalence of TSHR mutations in NAH (specifically HTA). This found that TSHR is the sole gene responsible for the development of HTA (96% mutation positive in an optimal subset of samples). The second chapter explores the phenotype of germline NAH, the variability of presentation, the consequences of late diagnosis, and the possible role of TSHR in bone through literature review and two novel case reports. The third chapter is an all-encompassing look at disorders associated with the TSHR including thyroid carcinoma, as documented by the TSHR mutation database. Thyroid carcinoma is further explored in the fourth chapter which outlines preliminary results and background for a plan to further evaluate TSHR’s role in thyroid carcinogenesis. This thesis concludes that TSHR signaling is solely responsible for HTA, that NAH can have variable presentations and requires early total thyroidectomy, and that TSHR undeniably plays a role in thyroid carcinoma that warrants further exploration.