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Abstract Context Thyroid nodules, adenomas, and goiter have consistently been associated with thyroid cancer risk. Few studies have assessed whether thyroid dysfunction and thyroid autoimmunity influence this risk. Objective To examine thyroid cancer risk after diagnoses of a wide range of benign thyroid conditions. Design Hospital and cancer registry linkage cohort study for the years 1978 to 2013. Setting Nationwide (Denmark). Participants Patients diagnosed with hyperthyroidism (n = 85,169), hypothyroidism (n = 63,143), thyroiditis (n = 12,532), nontoxic nodular goiter (n = 65,782), simple goiter (n = 11,582), other/unspecified goiter (n = 21,953), or adenoma (n = 6,481) among 8,258,807 residents of Denmark during the study period. Main Outcome Measures We computed standardized incidence ratios (SIRs) for differentiated thyroid cancer, excluding the first 12 months of follow-up after benign thyroid disease diagnosis. Results SIRs were significantly elevated for all benign thyroid diseases apart from hypothyroidism. SIRs were higher for men than women and in the earlier follow-up periods. Elevated SIRs were observed for localized and regional/distant thyroid cancer. After excluding the first 10 years of follow-up, hyperthyroidism [n = 27 thyroid cancer cases; SIR = 2.00; 95% confidence interval (CI): 1.32 to 2.92], nontoxic nodular goiter (n = 83; SIR = 4.91; 95% CI: 3.91 to 6.09), simple goiter (n = 8; SIR = 4.33; 95% CI: 1.87 to 8.53), other/unspecified goiter (n = 20; SIR = 3.94; 95% CI: 2.40 to 6.08), and adenoma (n = 9; SIR = 6.02; 95% CI: 2.76 to 11.5) remained positively associated with thyroid cancer risk. Conclusions We found an unexpected increased risk of differentiated thyroid cancer, including regional/distant disease, following diagnosis of hyperthyroidism and thyroiditis that could not be solely attributed to increased medical surveillance. Hypothyroidism was less clearly associated with thyroid cancer risk. This large nationwide study provides strong evidence for an increased risk of differentiated thyroid cancer following diagnosis of hyperthyroidism and thyroiditis.

ObjectivesPrevious analyses of cataract in radiation-exposed populations have assessed relative risk; radiogenic excess additive risk (EAR), arguably of more public health importance, has not been estimated. Previous analysis of a large prospective cohort of US radiologic technologists (USRT) quantified excess relative risk of cataract in relation to occupational radiation dose. We aim to assess EARs of cataract.MethodsWe estimated EARs of cataract/cataract surgery in the USRT cohort using generalised additive models in relation to occupational radiation exposure, and assessed risk modification by a priori-selected cataract risk factors (diabetes, body mass index, smoking, race, sex, birth-year, ultraviolet B (UVB) radiation exposure).ResultsThere were 11 345 cataract diagnoses and 5440 of cataract surgery during 832 462 and 888 402 person-years of follow-up, respectively. Cumulative occupational radiation exposure was associated with self-reported cataract, but not with cataract surgery, with EAR/104 person-year Gy=94 (95% CI: 47 to 143, p<0.001) and EAR/104 person-year Gy=13 (95% CI: <0 to 57, p=0.551), respectively. There was marked (p<0.001) variation of EAR by age and by diabetes status, with risk higher among persons ≥75 years and diabetics. There were indications of elevated risk among those with higher UVB radiation (p=0.045), whites (p=0.056) and among those with higher levels of cigarette smoking (p=0.062). Elevated additive risk was observed for estimated occupational radiation eye-lens doses <100 mGy (p=0.004) with no dose–response curvature (p=0.903).ConclusionsThe elevated additive risks associated with low-dose radiation, if confirmed elsewhere, have important public health and clinical implications for radiation workers as well as regulatory measures.

We evaluated the association of central versus overall adiposity on levels of thyroid stimulating hormone (TSH), free triiodothyronine (fT(3)), and free thyroxine (fT(4)) among euthyroid subjects taken from a cross-sectional, representative sample of the adult non-institutionalized U.S. population. The National Health and Nutrition Examination Survey 2007-2008 included 1,623 men and 1,491 women who were 20 years and older, with no history of thyroid or liver disease, kidney failure, diabetes, or thyroid function-altering prescription medication use (based on self-report), and having TSH, fT(3), and fT(4) levels between 0.5-4.49 mIU/L, 2.5-3.9 pg/mL, and 0.6-1.6 ng/dL, respectively. Associations between body mass index (BMI) and waist circumference (measures of overall and central adiposity, respectively) and TSH, fT(3), and fT(4) levels were estimated using multivariable linear regression models stratified by sex and adjusted for age, race, smoking status, and alcohol intake. An increase in serum TSH levels was observed for every 1-quartile increase in BMI in euthyroid men (3.8% [95% CI 0.8%, 6.8%]) and euthyroid women (4.0% [95% CI 1.6%, 6.5%]). Similar, albeit slightly weaker, associations were observed with waist circumference. We also found increases in fT(3) levels with every 1-quartile increase in BMI (1.0% in men and 1.3% in women) and waist circumference (1.2% in men and 1.2% in women). No associations were observed with fT(4.) Our results provide support that BMI and waist circumference are positively associated with levels of serum TSH and f T(3) but not fT(4) among euthyroid adults. Longitudinal studies are needed to define the temporality of these associations and their potential health implications.

Key Points The incidence of thyroid cancer has increased over the past several decades, which, in many countries around the world, has been largely driven by new cases of papillary thyroid cancer Increased opportunities for detection and diagnosis of small, indolent thyroid cancers seem to explain much, but not all, of the patterns in thyroid cancer incidence Results from epidemiological studies suggest that a substantial proportion of thyroid cancer diagnoses (>40% in the USA) could be attributable to environmental factors, such as obesity and cigarette smoking Clinical practice guidelines have recently changed in response to an increasing awareness of the potential for unnecessary diagnosis and treatment in a subset of patients Large-scale, prospective epidemiological studies and laboratory-based investigations are needed to identify modifiable risk factors for thyroid cancer and promising targets for thyroid cancer prevention The incidence of thyroid cancer has increased substantially in many countries over the past few decades. In this Review, Kitahara and Sosa describe the changing incidence of the disease and suggest possible explanations for the trends, emphasizing implications for patients and ongoing strategies to combat this growing public health issue. During the past few decades, the incidence of thyroid cancer has increased substantially in many countries, including the USA. The rise in incidence seems to be attributable both to the growing use of diagnostic imaging and fine-needle aspiration biopsy, which has led to enhanced detection and diagnosis of subclinical thyroid cancers, and environmental factors. The latest American Thyroid Association (ATA) practice guidelines for the management of adult patients with thyroid nodules and differentiated thyroid cancer differ substantially from the previous ATA guidelines published in 2009. Specifically, the problems of overdiagnosis and overtreatment of a disease that is typically indolent, where treatment-related morbidity might not be justified by a survival benefit, now seem to be acknowledged. As few modifiable risk factors for thyroid cancer have been established, the specific environmental factors that have contributed to the rising incidence of thyroid cancer remain speculative. However, the findings of several large, well-designed epidemiological studies have provided new information about exposures (such as obesity) that might influence the development of thyroid cancer. In this Review, we describe the changing incidence of thyroid cancer, suggest potential explanations for these trends, emphasize the implications for patients and highlight ongoing and potential strategies to combat this growing clinical and public health issue.

Objective: We examined the associations between cigarette smoking, alcohol intake, and thyroid cancer risk in a pooled analysis of five prospective studies. Methods: Data from five prospective U.S. studies were standardized and then combined into one aggregate dataset (384,433 men and 361,664 women). Pooled hazard ratios (HR) and 95 % confidence intervals (CI) for thyroid cancer were estimated from mutually adjusted models of cigarette smoking and alcohol intake, which were additionally adjusted for age, sex, education, race, marital status, body mass index, and cohort. Results: Over follow-up, 1,003 incident thyroid cancer cases (335 men and 668 women) were identified. Compared to never smokers, current smoking was associated with reduced risk of thyroid cancer (HR = 0.68, 95 % CI 0.55—0.85); this association was slightly stronger among non-drinkers (HR = 0.46, 95 % CI 0.29—0.74). No reduction in risk was observed for former, compared to never, smokers. Greater smoking intensity, duration, and pack-years were associated with further reductions in risk among former and current smokers. Alcohol intake was also inversely associated with thyroid cancer risk (≥7 drinks/week versus 0, HR = 0.72, 95 % CI 0.58—0.90, p trend = 0.002). Inverse associations with smoking and alcohol were more pronounced for papillary versus follicular tumors. Conclusion: The results of this pooled analysis suggest that both cigarette smoking and alcohol consumption are associated with reduced risks of papillary thyroid cancer and, possibly, follicular thyroid cancer.

Selenium is an essential trace element that is important for thyroid hormone metabolism and has antioxidant properties which protect the thyroid gland from oxidative stress. The association of selenium, as well as intake of other micronutrients, with thyroid cancer is unclear. We evaluated associations of dietary selenium, beta-carotene, calcium, vitamin D, vitamin C, vitamin E, folate, magnesium, and zinc intake with thyroid cancer risk in the National Institutes of Health - American Association of Retired Persons Diet and Health Study, a large prospective cohort of 566,398 men and women aged 50-71 years in 1995-1996. Multivariable-adjusted Cox proportional hazards regression was used to examine associations between dietary intake of micronutrients, assessed using a food frequency questionnaire, and thyroid cancer cases, ascertained by linkage to state cancer registries and the National Death Index. With the exception of vitamin C, which was associated with an increased risk of thyroid cancer (HR(Q5 vs Q1), 1.34; 95% CI, 1.02-1.76; P(trend), <0.01), we observed no evidence of an association between quintile of selenium (HR(Q5 vs Q1), 1.23; 95% CI, 0.92-1.65; P(trend), 0.26) or other micronutrient intake and thyroid cancer. Our study does not suggest strong evidence for an association between dietary intake of selenium or other micronutrients and thyroid cancer risk. More studies are needed to clarify the role of selenium and other micronutrients in thyroid carcinogenesis.

There are well-documented associations of glaucoma with high-dose radiation exposure, but only a single study suggesting risk of glaucoma, and less conclusively macular degeneration, associated with moderate-dose exposure. We assessed risk of glaucoma and macular degeneration associated with occupational eye-lens radiation dose, using participants from the US Radiologic Technologists Study, followed from the date of surveys in 1994–1998, 2003–2005 to the earliest of diagnosis of glaucoma or macular degeneration, cancer other than non-melanoma skin cancer, or date of last survey (2012–2014). We excluded those with baseline disease or previous radiotherapy history. Cox proportional hazards models with age as timescale were used. There were 1631 cases of newly self-reported doctor-diagnosed cases of glaucoma and 1331 of macular degeneration among 69,568 and 69,969 eligible subjects, respectively. Estimated mean cumulative eye-lens absorbed dose from occupational radiation exposures was 0.058 Gy. The excess relative risk/Gy for glaucoma was −0.57 (95% CI −1.46, 0.60, p  = 0.304) and for macular degeneration was 0.32 (95% CI −0.32, 1.27, p  = 0.381), suggesting that there is no appreciable risk for either endpoint associated with low-dose and low dose-rate radiation exposure. Since this is the first examination of glaucoma and macular degeneration associated with low-dose radiation exposure, this result needs to be replicated in other low-dose studies.

Abstract Context US papillary thyroid carcinoma (PTC) incidence recently declined for the first time in decades, for reasons that remain unclear. Objective This work aims to evaluate PTC incidence trends, including by histologic subtype and size, and noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Design This descriptive study uses US Surveillance, Epidemiology, and End Results–18 cancer registry data (2000-2017). Patients Participants included individuals diagnosed with PTC (2000-2017) or NIFTP (2016-2017). Results During 2000 to 2015, PTC incidence increased an average 7.3% per year, (95% CI, 6.9% to 7.8%) during 2000 to 2009, and 3.7% per year (95% CI, 0.2% to 7.3%) during 2009 to 2012, before stabilizing in 2012 to 2015 (annual percentage change [APC] = 1.4% per year, 95% CI, –1.8% to 4.7%) and declining in 2015 to 2017 (APC = –4.6% per year, 95% CI, –7.6% to –1.4%). The recent declines were observed for all sizes of PTC at diagnosis. Incidence of follicular variant of PTC (FVPTC) sharply declined in 2015 to 2017, overall (APC = –21.1% per year; 95% CI, –26.5% to –15.2%) and for all tumor sizes. Observed increases in encapsulated papillary carcinoma (classical PTC subtype) and NIFTP each accounted for 10% of the decline in FVPTC. Classical PTC incidence continuously increased (2000-2009, APC = 8.7% per year, 95% CI, 8.1% to 9.4%; 2009-2017, APC = 1.0% per year, 95% CI, 0.4% to 1.5%), overall and for all sizes except smaller than 1 cm, as did incidence of other PTC variants combined (2000-2017, APC = 5.9% per year, 95% CI, 4.0% to 7.9%). Conclusion The reasons underlying PTC incidence trends were multifactorial. Sharp declines in FVPTC incidence during 2015 to 2017 coincided with clinical practice and diagnostic coding changes, including reclassification of noninvasive encapsulated FVPTC from a malignant to in situ neoplasm (NIFTP). Observed increases in NIFTP accounted for 10% of the decline in FVPTC.

Objectives There have been few studies of work history and mortality risks in medical radiation workers. We expanded by 11 years and more outcomes our previous study of mortality risks and work history, a proxy for radiation exposure. Methods Using Cox proportional hazards models, we estimated mortality risks according to questionnaire work history responses from 1983 to 1989 through 2008 by 90 268 US radiological technologists. We controlled for potential confounding by age, birth year, smoking history, body mass index, race and gender. Results There were 9566 deaths (3329 cancer and 3020 circulatory system diseases). Mortality risks increased significantly with earlier year began working for female breast (p trend=0.01) and stomach cancers (p trend=0.01), ischaemic heart (p trend=0.03) and cerebrovascular diseases (p trend=0.02). The significant trend with earlier year first worked was strongly apparent for breast cancer during baseline through 1997, but not 1998–2008. Risks were similar in the two periods for circulatory diseases. Radiological technologists working ≥5 years before 1950 had elevated mortality from breast cancer (HR=2.05, 95% CI 1.27 to 3.32), leukaemia (HR=2.57, 95% CI 0.96 to 6.68), ischaemic heart disease (HR=1.13, 95% CI 0.96 to 1.33) and cerebrovascular disease (HR=1.28, 95% CI 0.97 to 1.69). No other work history factors were consistently associated with mortality risks from specific cancers or circulatory diseases, or other conditions. Conclusions Radiological technologists who began working in early periods and for more years before 1950 had increased mortality from a few cancers and some circulatory system diseases, likely reflecting higher occupational radiation exposures in the earlier years.

Thyroid cancer incidence has increased significantly over the past three decades due, in part, to incidental detection. We examined the association between randomization to screening for lung, prostate, colorectal and/or ovarian cancers and thyroid cancer incidence in two large prospective randomized screening trials. We assessed the association between randomization to low-dose helical CT scan versus chest x-ray for lung cancer screening and risk of thyroid cancer in the National Lung Screening Trial (NLST). In the Prostate Lung Colorectal and Ovarian Cancer Screening Trial (PLCO), we assessed the association between randomization to regular screening for said cancers versus usual medical care and thyroid cancer risk. Over a median 6 and 11 years of follow-up in NLST and PLCO, respectively, we identified 60 incident and 234 incident thyroid cancer cases. Cox proportional hazards regression was used to calculate the cause specific hazard ratios (HR) and 95% confidence intervals (CI) for thyroid cancer. In NLST, randomization to lung CT scan was associated with a non-significant increase in thyroid cancer risk (HR = 1.61; 95% CI: 0.96-2.71). This association was stronger during the first 3 years of follow-up, during which participants were actively screened (HR = 2.19; 95% CI: 1.07-4.47), but not subsequently (HR = 1.08; 95% CI: 0.49-2.37). In PLCO, randomization to cancer screening compared with usual care was associated with a significant decrease in thyroid cancer risk for men (HR = 0.61; 95% CI: 0.49-0.95) but not women (HR = 0.91; 95% CI: 0.66-1.26). Similar results were observed when restricting to papillary thyroid cancer in both NLST and PLCO. Our study suggests that certain medical encounters, such as those using low-dose helical CT scan for lung cancer screening, may increase the detection of incidental thyroid cancer.