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 »  Radiation and Pa...
 » Thyroid Autoimmunity
 »  Biological Link ...
 »  Dietary Iodine, ...
 »  Thyroiditis and ...
 »  References

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  Table of Contents  
Year : 2017  |  Volume : 54  |  Issue : 3  |  Page : 491-492

Papillary thyroid cancer: Why the increase and what can be done?

Professor (Retired), Government Medical College, Kozhikode, Kerala, India

Date of Web Publication24-May-2018

Correspondence Address:
K P Aravindan
Professor (Retired), Government Medical College, Kozhikode, Kerala, India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijc.IJC_221_18

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How to cite this article:
Aravindan K P. Papillary thyroid cancer: Why the increase and what can be done?. Indian J Cancer 2017;54:491-2

How to cite this URL:
Aravindan K P. Papillary thyroid cancer: Why the increase and what can be done?. Indian J Cancer [serial online] 2017 [cited 2022 Jun 26];54:491-2. Available from:

The article by Rao et al. in this issue of the journal highlights the clinicopathological profile of papillary thyroid cancer (PTC), the most common among thyroid malignancies.[1] This tumor is important in that its incidence is increasing rapidly around the world.[2] It is debatable whether the rise in incidence is due to increased detection of smaller clinically insignificant lesions or due to environmental factors.[3] It could also be a combination of both. Kerala has the highest incidence of this tumor in India. As per the Trivandrum cancer registry, in 1982–1986, thyroid cancer was placed fifth in 35- to 64-year-old women, accounting for 2.5% of cancers. By 2007–2011 it had become the second most common cancer, accounting for 10.2%. In the 15–34-year age group, it has replaced breast cancer (19.4%) to take the first place (35.6%).[4]

It has been argued that the increase in incidence is no mere diagnostic artifact because large tumors have also increased in number and that gender differences and birth cohort effects are present. In addition, thyroid cancer mortality has increased despite early diagnosis and better treatment.[1],[5]

If there are environmental factors in play in global increase in thyroid cancer, what are they? Among the potential risk factors for thyroid cancers, three have shown a rising trend in the recent decades. They are medical diagnostic radiation, iodine intake, and thyroid autoimmunity.

 » Radiation and Papillary Thyroid Cancer Top

The link between thyroid cancer and radiation is well-known.[6] There was a large increase in PTC among the cohort of children exposed to radiation after the Chernobyl accident.[7] Childhood exposure to diagnostic radiation has also increased in the past few decades, especially after the advent of computed tomography scan. It has been argued that this coincides with the rise in PTC incidence and that it could be a contributing factor.[8] Guidelines to limit excessive use of diagnostic radiation exposure in children need to be widely implemented.

High background radiation from thorium containing sand was considered a risk factor for cancer in the coastal areas of southern Kerala and parts of China. Studies from both these areas show no such causative link in existence.[9]

 » Thyroid Autoimmunity Top

Thyroid autoimmunity and chronic lymphocytic thyroiditis have shown a concomitant rise along with PTC over the years.[10] The possibility of autoimmune thyroiditis (AIT) as a predisposing factor for papillary thyroid carcinoma has been suggested.[11] The lymphocytic infiltration in PTC could either be a risk factor for papillary carcinoma or it could be a reaction to the tumor. In a study of papillary carcinoma of the thyroid, the grade of thyroiditis in the area within 2 cm and away from 2 cm did not show significant difference, indicating that lymphocytic thyroiditis is probably not a local immune response to papillary cancer.[12] This leaves the possibility that papillary carcinoma tends to develop in thyroids having lymphocytic thyroiditis.

 » Biological Link of Iodine and Thyroiditis Top

Enhancement of autoimmunogenic properties of thyroglobulin was first demonstrated by Roitt and Cooke.[13] Increased binding enhances stability of thyroglobulin and reduces its susceptibility to proteolytic cathepsins of thyroid, thus increasing auto-antigenicity.[14] It was also found that T cells from humans with chronic lymphocytic thyroiditis proliferate in the presence of iodinated thyroglobulin.[15] On adding iodine to drinking water, in non-obese diabetic NOD-H2 mice, the prevalence and severity of thyroid lesions increased markedly.[16] It was also shown that iodine intake significantly affected the incidence of spontaneous lymphocytic thyroiditis in young genetically predisposed rats.[17]

 » Dietary Iodine, Thyroid Autoimmunity, and Cancer Top

It was observed that there was an increase in the prevalence of AIT with increasing iodide intake in China in cohorts from three regions with different levels of iodine intake.[18] Similar findings were reported in small-scale comparative epidemiologic studies by Laurberg et al.[19] and Sczaboles et al.[20] High iodine intake may trigger and exacerbate AIT increasing the likelihood of overt hypothyroidism.[18],[21] The administration of iodized oil to patients with nontoxic goiter in an iodine-replete area was accompanied by the development of abnormal levels of thyroid autoantibodies and increase in thyroid lymphocytic infiltration.[22]

 » Thyroiditis and Papillary Thyroid Cancer After Salt Iodization Programs Top

Increase in AIT and PTC has been observed in many studies. In studies done over many phases of iodine prophylaxis, in Salta, Argentina, it was seen that increased iodine intake is associated with an increased incidence of PTC and AIT.[23] A former iodine-deficient goiter endemic region in Austria during a period of 1984–2001 after the introduction of iodine prophylaxis (1991) noted increased incidence of thyroid carcinoma.[24] A host of studies from China indicate increase in the two diseases after iodized salt was introduced.[25],[26],[27] There are similar studies from Sri Lanka,[28] Slovenia,[29] and Iran.[30]

Even in the post-iodization phase, goiter has persisted in India with a prevalence of 23% according to a country-wide study in 2003. The median urinary iodine excretion (UIE) in goitrous subjects (2–53 mmol/L) was significantly higher than in controls (2–24 mmol/L; P < 0.001).[31] We now realize that there are factors other than iodine deficiency responsible for goiters in India.

It is increasingly becoming evident that diseases due to excess of iodine may be becoming a public health problem calling for a fresh calibration of strategy. It is suggested that although iodine supplementation should be implemented to prevent and treat iodine deficiency disorders, supplementation should be maintained at a safe level. Levels that are more than adequate (median UIE 200–299 μg/L) or excessive (median UIE >300 μg/L) do not appear to be safe, especially for susceptible populations. Supplementation programs should be tailored to each particular region. Generally, no iodine supplementation should be provided for regions in which iodine intake is sufficient, whereas salt in regions in which iodine intake is deficient should be supplemented with iodine according to the degree of iodine deficiency.

 » References Top

Rao R, Giriyan SS, Rangappa PK. Clinicopathological profile of papillary carcinoma of thyroid: A 10-year experience in a tertiary care institute in North Karnataka, India. Indian J Cancer 2017;54:514-8.  Back to cited text no. 1
  [Full text]  
Pellegriti G, Frasca F, Regalbuto C, Squatrito S, Vigneri R. Worldwide increasing incidence of thyroid cancer: Update on epidemiology and risk factors. J Cancer Epidemiol 2013;2013:965212.  Back to cited text no. 2
Kitahara CM, Sosa JA. The changing incidence of thyroid cancer. Nat Rev Endocrinol 2016;12:646-53.  Back to cited text no. 3
Hospital based cancer registry. Regional cancer centre, Thiruvananthapuram 1982-2011. at [Last accessed on 01.03.2018].  Back to cited text no. 4
Pai SA. Increase in thyroid cancer incidence in Kerala-real or artificial? News from here and there. Natl Med J India 2017;30:180-1.  Back to cited text no. 5
Sinnott B, Ron E, Schneider AB. Exposing the thyroid to radiation: A review of its current extent, risks, and implications. Endocr Rev 2010;31:756-73.  Back to cited text no. 6
Cardis E, Hatch M. The Chernobyl accident-An epidemiological perspective. Clin Oncol (R Coll Radiol) 2011;23:251-60.  Back to cited text no. 7
Baker SR, Bhatti WA. The thyroid cancer epidemic: Is it the dark side of the CT revolution? Eur J Radiol 2006;60:67-9.  Back to cited text no. 8
Nair RR, Rajan B, Akiba S, Jayalekshmi P, Nair MK, Gangadharan P, et al. Background radiation and cancer incidence in Kerala, India-Karanagappally cohort study. Health Phys 2009;96:55-66.  Back to cited text no. 9
Caturegli P, De Remigis A, Chuang K, Dembele M, Iwama A, Iwama S. Hashimoto's thyroiditis: Celebrating the centennial through the lens of the Johns Hopkins hospital surgical pathology records. Thyroid 2013;23:142-50.  Back to cited text no. 10
Boi F, Pani F, Mariotti S. Thyroid autoimmunity and thyroid cancer: Review focused on cytological studies. Eur Thyroid J 2017;6:178-86.  Back to cited text no. 11
Treasily A. Mast cells and inflammation in papillary carcinoma of thyroid. Thesis submitted to Kerala University of Health Sciences for MD (Pathology); 2014.  Back to cited text no. 12
Roitt IM, Cooke A. The role of autoantigen in autoimmunity. Immunol Lett 1987;16:259-63.  Back to cited text no. 13
Lamas L, Ingbar SH. The effect of varying iodine content on the susceptibility of thyroglobulin to hydrolysis by thyroid acid protease. Endocrinology 1978;102:188-97.  Back to cited text no. 14
Rasooly L, Rose NR, Saboori AM, Ladenson PW, Burek CL. Iodine is essential for human T cell recognition of human thyroglobulin. Autoimmunity 1998;27:213-9.  Back to cited text no. 15
Rose NR, Rasooly L, Saboori AM, Burek CL. Linking iodine with autoimmune thyroiditis. Environ Health Perspect 1999;107(Suppl 5):749-52.  Back to cited text no. 16
Allen EM, Appel MC, Braverman LE. The effect of iodide ingestion on the development of spontaneous lymphocytic thyroiditis in the diabetes-prone BB/W rat. Endocrinology 1986;118:1977-81.  Back to cited text no. 17
Teng W, Shan Z, Teng X, Guan H, Li Y, Teng D, et al. Effect of iodine intake on thyroid diseases in China. N Engl J Med 2006;354:2783-93.  Back to cited text no. 18
Laurberg P, Pedersen KM, Hreidarsson A. Thyroid disorders in mild iodine deficiency. Thyroid 2000;10:951-63.  Back to cited text no. 19
Szabolcs I, Podoba J, Feldkamp J, Dohan O, Farkas I, Sajgó M, et al. Comparative screening for thyroid disorders in old age in areas of iodine deficiency, long-term iodine prophylaxis and abundant iodine intake. Clin Endocrinol (Oxf) 1997;47:87-92.  Back to cited text no. 20
Bournaud C, Orgiazzi JJ. Iodine excess and thyroid autoimmunity. J Endocrinol Invest 2003;26 (2 Suppl):49-56.  Back to cited text no. 21
Papanastasiou L, Alevizaki M, Piperingos G, Mantzos E, Tseleni-Balafouta S, Koutras DA. The effect of iodine administration on the development of thyroid autoimmunity in patients with nontoxic goiter. Thyroid 2000;10:493-7.  Back to cited text no. 22
Harach HR, Ceballos GA. Thyroid cancer, thyroiditis and dietary iodine: A review based on the Salta, Argentina model. Endocr Pathol 2008;19:209-20.  Back to cited text no. 23
Gomez Segovia I, Gallowitsch HJ, Kresnik E, Kumnig G, Igerc I, Matschnig S, et al. Descriptive epidemiology of thyroid carcinoma in Carinthia, Austria: 1984-2001. Histopathologic features and tumor classification of 734 cases under elevated general iodination of table salt since 1990: Population-based age-stratified analysis on thyroid carcinoma incidence. Thyroid 2004;14:277-86.  Back to cited text no. 24
Zhao H, Tian Y, Liu Z, Li X, Feng M, Huang T. Correlation between iodine intake and thyroid disorders: A cross-sectional study from the South of China. Biol Trace Elem Res 2014;162:87-94.  Back to cited text no. 25
Luo Y, Kawashima A, Ishido Y, Yoshihara A, Oda K, Hiroi N, et al. Iodine excess as an environmental risk factor for autoimmune thyroid disease. Int J Mol Sci 2014;15:12895-912.  Back to cited text no. 26
Dong W, Zhang H, Zhang P, Li X, He L, Wang Z,et al. The changing incidence of thyroid carcinoma in Shenyang, China before and after universal salt iodization. Med Sci Monit 2013;19:49-53.  Back to cited text no. 27
Fernando RF, Chandrasinghe PC, Pathmeswaran AA. The prevalence of autoimmune thyroiditis after universal salt iodisation in Sri Lanka. Ceylon Med J 2012;57:116-9.  Back to cited text no. 28
Zaletel K, Gaberscek S, Pirnat E. Ten-year follow-up of thyroid epidemiology in Slovenia after increase in salt iodization. Croat Med J 2011;52:615-21.  Back to cited text no. 29
Soveid M, Monabbati A, Sooratchi L, Dahti S. The effect of iodine prophylaxis on the frequency of thyroiditis and thyroid tumors in Southwest, Iran. Saudi Med J 2007;28:1034-8.  Back to cited text no. 30
Marwaha RK, Tandon N, Gupta N, Karak AK, Verma K, Kochupillai N. Residual goitre in the postiodization phase: Iodine status, thiocyanate exposure and autoimmunity. Clin Endocrinol (Oxf) 2003;59:672-81.  Back to cited text no. 31

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