Abstract
Evidence from observational studies suggest a positive association between serum thyroid-stimulating hormone (TSH) levels and differentiated thyroid carcinoma. However, the cause–effect relationship is poorly understood and these studies are susceptible to bias and confounding. This study aimed to investigate the causal role of TSH in both benign thyroid nodules and thyroid cancer in up to 451,025 UK Biobank participants, using a genetic technique, known as Mendelian randomization (MR). Hospital Episode Statistics and Cancer Registry databases were used to identify 462 patients with differentiated thyroid carcinoma and 2031 patients with benign nodular thyroid disease. MR methods using genetic variants associated with serum TSH were used to test causal relationships between TSH and the two disease outcomes. Mendelian randomization provided evidence of a causal link between TSH and both thyroid cancer and benign nodular thyroid disease. Two-sample MR suggested that a 1 s.d. higher genetically instrumented TSH (approximately 0.8 mIU/L) resulted in 4.96-fold higher odds of benign nodular disease (95% CI 2.46–9.99) and 2.00-fold higher odds of thyroid cancer (95% CI 1.09–3.70). Our results thus support a causal role for TSH in both benign nodular thyroid disease and thyroid cancer.
Highlights
Thyroid cancer is the most common endocrine malignancy, with recent years seeing a significant increase in incidence (Kitahara & Sosa 2016)
In addition to ultrasonography and fine-needle aspiration biopsy, thyroid function tests including serum thyroid-stimulating hormone (TSH) level are recommended in the investigation of a thyroid nodule (Perros et al 2014, Haugen et al 2016)
The aim of this study was to test the hypothesis that elevated serum TSH has a causal role in the development of benign thyroid nodules and differentiated thyroid cancer, using genetic data from 451,025 participants in the UK Biobank
Summary
Thyroid cancer is the most common endocrine malignancy, with recent years seeing a significant increase in incidence (Kitahara & Sosa 2016). Ultrasonography and cytological analysis of fine-needle aspiration biopsy the true nature of the nodule remains indeterminate in up to 25% of cases and up to one-third of surgically excised nodules are benign (Bongiovanni et al 2012). There is, a need for better stratification of thyroid nodules according to risk of malignancy, and while recent years have seen the development of genomic tests to aid diagnosis (Nikiforov & Baloch 2019), these are yet to be widely used in clinical practice. In addition to ultrasonography and fine-needle aspiration biopsy, thyroid function tests including serum thyroid-stimulating hormone (TSH) level are recommended in the investigation of a thyroid nodule (Perros et al 2014, Haugen et al 2016).
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