In the past 20-30 years, the epidemiology of thyroid nodular disease has changed remarkably owing to a striking increase in the number of thyroid nodules being diagnosed in the adult population.
In Italy, approximately 50% of all adults have one or more thyroid nodules, and the figure climbs as high as 75% in certain regions (1). The increasing prevalence of nodules is accompanied by a similar trend in thyroid cancer rates.
The increase is more marked in women than in men (8.1% versus 6.2% per year, respectively) (3). The same basic trend can be observed in other countries as well. (The exception is Sweden, where the incidence of thyroid cancer in both sexes has dropped by 18%). On the whole, however, is the exception: although in the geographic variability of the phenomenon with an average global increase of 58.1% with the exception of Sweden where a decrease of 18% is recorded for both genders (4).
The increase in thyroid cancer is due in large part to the diagnosis of localized, non-aggressive tumors. However, there are already signs of a parallel rise in the incidence of larger and more aggressive cancers, with local spread or even distant metastases at the time of diagnosis (5).
The incidence of tumours with diameters of > 6 cm has more than doubled (6). Thyroid cancer mortality rates are also showing a tendency to increase. In the past 15 years, rates in the United States have increased by about 0.8% per year (2). Today, thyroid cancer represents the fifth most frequent tumour in women in the United States. The increased incidence of thyroid cancer can be explained in part by the increasingly widespread use of modern diagnostic imaging technology and histopathological analysis (6).
The scenario in Italy
Italy is one of countries that have experienced the most marked increases in thyroid cancer incidence (7), with a predominance of papillary thyroid cancers and similar distributions in males and females (8). Incidence rates vary widely from region to region: between 2001 and 2005, the highest figures were recorded in Emilia-Romagna, in the province of Ferrara (37.5/100,000); the lowest were in Trentino Alto Adige (7.3/100,000) (8).
These differences have been attributed by some to regional differences in access to the health system, but roles have also been proposed for environmental factors (9).
The main environmental risk factor for thyroid cancer is exposure to ionizing radiation, especially during childhood (10). This exposure can be occupational or caused by atomic accidents. However, some studies suggest that the risk of thyroid cancer can also be increased by radiation exposure related to diagnostic tests (11) or to the natural radioactivity linked to peculiar geological factors (e.g., volcanic soil, geothermal areas) (9).
Iodine deficiency plays a major role in the pathogenesis of simple and nodular goitres, as shown by their decreased prevalence after the implementation of iodine supplementation campaigns (12). However, the relation between iodine deficiency and the incidence of thyroid cancer remains controversial.
The risk of thyroid cancer is more closely linked to genetic factors than that of any other tumour (13). Genetic and epigenetic factors and the iteration between these are involved in the carcinogenesis of benign nodules and carcinomas and influence tumoral aggressiveness (14). A different genetic substratum in the different populations (15) could contribute to the epidemiological heterogeneousness observed in the world. The genetic make-up could also represent the predisposing terrain on which environmental factors act.
Therefore, to provide “personalized therapy” for thyroid cancers, each patient has to be “profiled” from multiple points of view, identifying the diverse factors–environmental, genetic, epigenetic, nutritional, and socioeconomic to name a few—that may have contributed to the disease and/or are likely to affect its treatment.
Nonuniform distribution of resources and technology can also contribute to differences in the management of thyroid cancer, hindering widespread application of internationally recommended clinical protocols in daily practice.
The continuous interaction of all these elements yields a complex phenomenon, whose optimal management requires balanced collaboration by all parties involved (specialists and general practitioners, patients and their associations, the healthcare institutions). Diagnostic and therapeutic innovations can be an invaluable resource, but their indiscriminate use can increase healthcare costs without necessarily improving the quality of care.
Bibliography
- Durante C, Cava F, Paciaroni A, Filetti S. 2008 Benign thyroid nodules: diagnostic and therapeutic approach. Recenti Prog Med.;99(5):263-70.
- Davies L, Welch HG. 2006 Increasing incidence of thyroid cancer in the United States, 1973-2002.JAMA.10;295(18):2164-7.
- Leenhardt L, Grosclaude P, Chérié-Challine L; Thyroid Cancer Committee. 2004 Increased incidence of thyroid carcinoma in France: a true epidemic or thyroid nodule management effects? Report from the French Thyroid Cancer Committee. Thyroid;14(12):1056-60.
- Kilfoy BA, Zheng T, Holford TR, Han X, Ward MH, Sjodin A, Zhang Y, 2008 International patterns and trends in thyroid cancer incidence, 1973-2002. Cancer Causes Control.;20(5):525-31
- Aschebrook-Kilfoy B, Grogan RH, Ward MH, Kaplan E, Devesa SS. 2013 Follicular thyroid cancer incidence patterns in the United States, 1980-2009.Thyroid;23(8):1015-21
- Morris LG, Myssiorek D. 2010Improved detection does not fully explain the rising incidence of well-differentiated thyroid cancer: a population-based analysis. Am J Surg.;200(4):454-61.
- McLeod DS, Sawka AM, Cooper DS. 2013 Controversies in primary treatment of low-risk papillary thyroid cancer. 23;381(9871):1046-57.
- Lise M, Franceschi S, Buzzoni C, Zambon P, Falcini F, Crocetti E, Serraino D, Iachetta F, Zanetti R, Vercelli M, Ferretti S, La Rosa F, Donato A, De Lisi V, Mangone L, Busco S, Tagliabue G, Budroni M, Bisanti L, Fusco M, Limina RM, Tumino R, Piffer S, Madeddu A, Bellù F, Giacomin A, Candela G, Anulli ML, Dal Maso L; AIRTUM Working Group. 2012. Changes in the incidence of thyroid cancer between 1991 and 2005 in Italy: a geographical analysis. ;22(1):27-34.
- Malandrino P, Scollo C, Marturano I, Russo M, Tavarelli M, Attard M, Richiusa P, Violi MA, Dardanoni G, Vigneri R, Pellegriti G. 2013 Descriptive epidemiology of human thyroid cancer: experience from a regional registry and the “volcanic factor”. Front Endocrinol (Lausanne). 4;4:65.
- Schlumberger M, Cailleux AF, Suarez HG, de Vathaire F. 1999 Irradiation and second cancers. The thyroid as a case in point. C R Acad Sci III. ;322(2-3):205-13
- Niemann T, Zbinden I, Roser HW, Bremerich J, Remy-Jardin M, Bongartz G. 2013 Computed tomography for pulmonary embolism: assessment of a 1-year cohort and estimated cancer risk associated with diagnostic irradiation. Acta Radiol. ;54(7):778-84.
- Zaletel K, Gaberscek S, Pirnat E. 2011Ten-year follow-up of thyroid epidemiology in Slovenia after increase in salt iodization. Croat Med J. 15;52(5):615-21.
- Goldgar DE, Easton DF, Cannon-Albright LA, Skolnick MH. 1994 Systematic population-based assessment of cancer risk in first-degree relatives of cancer probands. J Natl Cancer Inst. 1994 Nov 2;86(21):1600-8.
- Xing M, Alzahrani AS, Carson KA, Viola D, Elisei R, Bendlova B, 2013 Association between BRAF V600E mutation and mortality in patients with papillary thyroid cancer. JAMA;309(14):1493-501.
- Damiola F, Byrnes G, Moissonnier M, Pertesi M, Deltour I, Fillon A, Le Calvez-Kelm F, Tenet V, McKay-Chopin S, McKay JD, Malakhova I, Masyakin V, Cardis E, Lesueur F, Kesminiene A. 2013 Contribution of ATM and FOXE1 (TTF2) to risk of papillary thyroid carcinoma in Belarusian children exposed to radiation. Int J Cancer. 1;134(7):1659-68.