Abstract
I read with interest the important article by Caturegli et al. (1) and the accompanying editorial by Weetman (2), and thank Prof. Weetman (2) for having cited the article on the increased local incidence and changed presentation of Hashimoto's thyroiditis (HT) over the 31-year period, 1975–2005, in the area of the Strait of Messina, Sicily, Italy (3).
That article (3) is now complemented by one (4) that shows the partial overlap in HT presentation between two bordering provinces (Messina and Catania), with an active volcano located in the Catania province. The incidence of HT has increased over the years in both provinces, but to a much greater extent in Messina than in Catania (4). In contrast, the incidence of thyroid cancer is moderately greater in Catania, with papillary thyroid cancer (PTC) being the leading histotype in both provinces (4). Thus, one implication from these findings (4) is the apparent protective effect of HT on the epidemiology of thyroid cancer in Messina compared with Catania. As mentioned in the Discussion (4), there was a striking parallelism between these two Sicilian cohorts of HT patients and two Turkish cohorts of HT patients (5,6). Different environmental factors acting in different areas of the same region or nation may explain those differences (4 –6).
Also pertinent to the relevant article by Caturegli et al. (1) is a forthcoming article (7) that complements a previous one (8) on the cytological diagnosis of HT in the province of Messina. Over the years 1988–2010, the diagnosis of PTC at fine-needle aspiration cytology (FNAC) increased from 0% (0/73) in 1988 to 2.0% (17/861) in 2010 with a peak of 2.7% (26/976) in 2006. Of the 11,258 adequate FNACs performed in the period 1988–2010, PTC (n=200) accounted for 1.8% of the diagnoses, while HT (n=700) accounted for 6.2% (7). A finding worthy of note is that the increased local incidence of PTC lagged behind the increased local incidence of HT by 5–6 years (7). The percentage of either lesion increased linearly over the 23 years, but HT with a much steeper trend (r=0.924, p<0.001) compared with PTC (r=0.396, p=0.062), and to a greater extent. Indeed, compared with the initial value in 1988, the highest number of HT patients (which was recorded in the year 2007) represented a 90-fold increase, while the highest number of PTC patients (which was recorded in the year 2006) represented only a 25-fold increase. Compared with the 5-year period, 1993–1997, in the predicted 5-year period, 2008–2012, PTC patients were 4.5 years younger (42.8 vs. 47.5), and males were relatively more represented (female-to-male ratio of 2:1 vs. 5:1). Previously (8), we had reported an age at FNAC and a female-to-male ratio of 51.5 years and 24:1, respectively; however, these two indices decreased to 46.6 years and to 8:1 in the years 2003–2005.
Unlike we did (3,4,7,8), Caturegli et al. (1) neither provided data on age and sex nor presented HT and PTC on the same graph, that is, on the same scale. This missing information precludes to appreciate the magnitude of the increased incidence and changed presentation of HT, and the chronological relationship between the increased incidence of PTC and the increased incidence of HT, at least over the last two or three decades. Furthermore, in their Figure 4, PTC cases are not represented also as a whole group to be compared with the HT cases as a whole group in their Figure 3. Nevertheless, the increased incidence in HT and PTC at thyroidectomy appears to have occurred between the mid and the late 1990s, which is in agreement with all of our data (3,4,7,8). Unfortunately, the data of Caturegli et al. (1) could not be incorporated in the very recent meta-analysis on the association between HT and PTC (9), but one can easily anticipate that those data (1) would have reinforced the conclusion of an association between these two thyroid diseases.
HT is the leading autoimmune disease and PTC is the leading thyroid cancer, with the incidence of either disease having increased significantly over the years. It may not be coincidental that both HT and PTC are heterogeneous, multifaceted diseases: HT is heterogeneous functionally, serologically, echographically, and genetically (HLA genotypes). PTC is heterogeneous in terms of focality (single or multiple), size (micro- or macrocarcinoma), histological variants, and molecular signatures. In the context of the interaction between endogenous and exogenous factors that trigger or may trigger thyroid diseases (10) and with both HT and PTC being under the influence of genetic and environmental factors, perhaps it is time to ask ourselves whether the heterogeneity in the features discussed above of the two diseases could reflect heterogeneous interplay between the two categories of factors. Clearly, identification of the environmental triggers might have prophylactic implications for such epidemiologically relevant diseases. This statement is in line with the conclusion by Caturegli et al. (1): “Advancement in the understanding of its [HT] pathogenesis and preoperative diagnosis will improve recognition and treatment of this disorder, and may one day lead to its prevention.”
Concomitant changes in these features for HT and PTC with changes in environmental influences (particularly those related to chemical pollutants) over given periods of time and investigating parallel cohorts of patients (HT alone, PTC alone, and HT coexisting with PTC) may prove key to shedding light on the mechanistic explanation for the association between the two diseases. Hopefully, this endeavor will be accomplished within the next few years, not the next 100 years.
Footnotes
Author Disclosure Statement
The author has nothing to disclose.