Incidence Of Differentiated Thyroid Cancer Research Articles

8578 Papillary Thyroid Carcinoma in Autonomous Nodule with Low Risk Characteristics in Adolescent

Abstract Disclosure: A. Aponte Velez: None. M.M. Mangual Garcia: None. Thyroid nodules in children are uncommon but are known to carry a greater risk of malignancy than adult thyroid nodules. Additionally, differentiated thyroid cancer (DTC) in children is more commonly found with extrathyroidal extension and metastases which makes the approach and treatment similar but with important differences. The incidence of DTC in children is increasing, making a personalized evaluation of thyroid nodules in pediatric patients even more valuable. Guidelines recommend evaluation of nodules based on sonographic characteristics rather than size of nodule. However, not having worrisome sonographic characteristics may not be as reassuring as in adult patients. A 13 year old female patient presented with a palpable non tender right sided solid thyroid mass. She had no family history of thyroid cancer or history of irradiation. Thyroid function tests were remarkable for TSH:0.017 and positive thyroid stimulating immunoglobulin. Thyroid Ultrasound findings described heterogenous parenchyma with multiple discrete lesions on right thyroid lobe with a dominant solid isoechoic nodule at upper lobe measuring 2.1 x 3.5 x 1.9cm and a smaller nodule in lower lobe. Thyroid scan demonstrated a large functional hot nodule occupying most of right thyroid lobe with suppression of rest of thyroid parenchyma. Ultrasound guided FNA was performed of this lesion and results were negative for malignancy. Patient underwent total thyroidectomy with pathology report revealing right thyroid nodule encapsulated classical variant of papillary thyroid carcinoma. No lymph node metastases were identified. Non neoplastic thyroid parenchyma revealed chronic lymphocytic thyroiditis. Patient underwent radioiodine therapy with Whole Body Scan post radioiodine therapy demonstrating focal increased radionuclide localization at in region of neck consistent with functional thyroid tissue. There was no evidence of metastatic disease. In children, risk of malignancy is underestimated in ultrasonography and cytology. In this patient, papillary thyroid carcinoma was identified despite being stratified as having low risk of malignancy based on ultrasonography characteristics, hyperfunctioning nodule in scintigraphy study along with negative FNA results. Hyperfunctional nodules are usually reassuring for low risk of malignancy but rarely DTC can be found as in our patient. Guidelines agree that FNA is not recommended in functional nodules as surgical resection is the main therapy in children. However, surgery may be deferred if subclinical hyperthyroidism and low risk sonographic characteristics are present such as in our patient. If surgery had been deferred, based on low risk of malignancy, the risk of progression of disease would have been higher. Prognosis of DTC in children is good but the recurrence rate along with morbidity at such a young age may improve with more studies of DTC in children. Presentation: 6/2/2024

In-utero and newborn factors and thyroid cancer incidence in adult women in the Sister Study cohort.

10560 Background: Thyroid cancer ranks as the fifth most common cancer in women globally, with 90% of cases classified as differentiated thyroid cancer (DTC). Currently, thyroid cancer etiology remains largely unknown, with childhood exposure to ionizing radiation and obesity among the few established modifiable risk factors. Considering that DTC is diagnosed at relatively younger ages compared to many other cancers, with higher incidence in females versus males, the current study aimed to investigate in-utero and newborn exposures in relation to adult female DTC incidence. Methods: From the Sister Study, a cohort of sisters of women with breast cancer living in the U.S. (including Puerto Rico), we included 47810 women who were cancer-free at baseline (2003–2009). At baseline, participants provided information on their birth and newborn characteristics, and characteristics of their parents before and during pregnancy. Using Cox proportional hazards regression models, we assessed the association between in-utero and newborn factors and self-reported DTC incidence during follow-up. The models were adjusted for attained age (timescale), race/ethnicity, BMI, smoking status, personal history of benign thyroid disease, educational level, household annual income, and Area Deprivation Index. Results: The median age at baseline of the study population was 55.4 (interquartile range [IQR]: 48.9-62.1). During follow-up (median: 13.1 years, IQR: 11.5-15), 233 women were diagnosed with DTC, with medical records available for 72% of cases. Factors associated with a higher incidence of DTC included gestational hypertension or hypertension-related disorders (15 exposed cases, HR= 1.87, 95%CI 1.10-3.16), and higher birth weight (for every additional kilogram HR=1.13, 95%CI 1.00-1.27). The HR for maternal pre-pregnancy or gestational diabetes was 2.33 (5 exposed cases, 95%CI 0.96-5.67). Conversely, being born at least two weeks before the due date was associated with a lower incidence (6 exposed cases, HR=0.35, 95%CI 0.15-0.79). These associations remained consistent when restricting to advanced-stage and large-sized DTCs. We observed no associations for participants’ birth order, time since last pregnancy of the participants' mother, multiple versus singleton birth, ever having been breastfed, parental smoking during pregnancy or age at delivery, maternal morning sickness, or paternal diabetes. Conclusions: In this study, maternal diabetes, maternal hypertension, and birth weight were associated with higher female DTC incidence while being born at least two weeks before the due date was associated with lower DTC incidence. These findings provide evidence that in-utero and newborn exposures may have a long-term influence on thyroid cancer development.

The relationship between thyroid peroxidase antibody and differentiated thyroid cancer: a systematic review and meta-analysis.

Thyroglobulin antibody (TgAb) has been found to be associated with the occurrence and development of differentiated thyroid cancer (DTC) for several years, but there is still controversy over whether thyroid peroxidase antibody (TPOAb) is related to differentiated thyroid cancer. We scrutinized relevant studies published up to July 2023 across four major databases including PubMed, Embase, Cochrane Library, and Web of Science, to examine the association between TPOAb and DTC. Clinical outcome measures include the incidence of DTC, tumor size, extrathyroidal invasion, lymph node metastasis, multifocality, recurrence and bilaterality. 12 original studies were included, involving a total of 20,330 subjects. Our analysis of the included studies revealed that TPOAb+ individuals exhibited a higher risk of developing DTC (OR=1.57 [95% CI: 1.00-2.45], p=0.049) than TPOAb- individuals. Furthermore, TPOAb+ DTC patients were more prone to present with bilateral (OR=1.40 [95% CI: 1.21-1.62], p<0.00001) and multifocal (OR=1.40 [95% CI: 1.23-1.60], p<0.00001) tumors than TPOAb- patients. Sensitivity analysis indicated a high sensitivity for these three findings. No significant differences in the risk of extrathyroidal extension and lymph node metastasis, recurrence rate, tumor size, were observed between TPOAb+ and TPOAb- DTC patients. The presence of TPOAb is correlated with an increase prevalence of DTC. However, its effectiveness as a prognostic marker for DTC patients warrants further investigation. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023448824.

Prepregnancy Body Mass Index and Risk of Differentiated Thyroid Cancer: A Prospective Cohort Study of More than 440,000 Danish Women.

Background: High body mass index (BMI) has previously been associated with increased risk of differentiated thyroid cancer (DTC); however, only few studies have investigated the association with BMI in a large cohort assessed at a young age and with sufficient data on confounding factors. We assessed the association between excess body weight and the risk of DTC and papillary thyroid cancer (PTC) in a large cohort of young Danish women with substantial confounder control. Methods: We included all parous Danish women registered with a prepregnancy BMI ≥18.5 kg/m2 during 2004-2016 in the Danish Medical Birth Registry in the study population. Cox proportional hazards regression models were used to estimate the hazard ratios (HRs) with confidence intervals (CIs) of DTC according to BMI. In subanalyses, we investigated PTC as a separate group. Analyses were adjusted for calendar time, education, smoking status, benign thyroid disease (BTD), type II diabetes, parity, and oral contraceptive use. In addition, we examined the association with increasing BMI stratified for previous BTD. Results: A total of 443,403 women were included in the study population, and the median age at baseline was 30.0 years. Altogether, 463 women were diagnosed with DTC during follow-up. Excess body weight was associated with a higher rate of DTC (overweight, BMI 25-29.9 kg/m2: HR = 1.54; CI 1.25-1.90. Obese, BMI ≥30 kg/m2: HR = 1.32; CI 1.00-1.75) compared with normal weight. Results were similar in PTC. In addition, we found an increased rate of DTC with increasing BMI, when investigating BMI as a continuous variable per 5 kg/m2 increase (HR = 1.17; CI 1.07-1.27). The results were similar in women without previous BTD. Conclusions: Our study confirms that excess body weight is associated with an increased incidence of DTC and PTC in women.

1650P The interplay of peripheral circulating free DNA and platelet-to-lymphocyte ratio in patients with differentiated thyroid cancer with/without type 2 diabetes mellitus undergoing radioiodine therapy

Type 2 diabetes mellitus (T2DM) and differentiated thyroid cancer (DTC) are both endocrine system diseases. It has been found that DTC incidence in women with T2DM is constantly growing. T2DM is classified as a metabolic inflammatory disease with an altered number and function of immune cells, both innate and acquired immunity. Circulating cell-free (cf)DNA corresponds to cell-free circulating DNA fragments released in the bloodstream through inflammation, necrosis, apoptosis, or active secretion by nucleated cells such as lymphocytes.

Incidence and dynamic risk stratification in differentiated thyroid cancer in a high-resolution clinic, 2002–2017

ObjectiveWe evaluated the incidence, progression and the dynamic risk stratification in differentiated thyroid cancer (DTC) under follow-up in a high-resolution clinic (HRC). MethodsThis was a retrospective observational study on incident cases in the tumor registry from 2002 to 2017 and their evolution under follow-up in HRC. ResultsA total of 444 patients (78.5% women, 52.1±14.9 mean years old) were DTC diagnosed from 2002 to 2017. The incidence rate of DTC increased from 5.2 to 25.7×105 habitants/year in women and from 2.3 to 7.1×105 habitants/year in men (P<0.0001). This increased incidence was not associated with an increment in the incidental papillary microcarcinoma diagnosed (from 29.4% to 32%).In those patients undergoing follow-up at the HRC (84% papillary carcinomas), 65.7% were classified as being at a low risk of recurrence compared to 14.5% at high risk. Of those, 88.8% classified as making an excellent response at diagnosis remained disease-free at the final follow-up visit. However, those patients with an indeterminate or structurally incomplete response at diagnosis evolved to an excellent response in 55.8% and 42.9% of the cases, respectively, compared to 14.8% of those with a biochemically incomplete response (P<0.001) ConclusionsThe increased incidence of DTC is similar to results published previously in other countries. Dynamic risk stratification systems adequately classify DTC patients and assess diagnostic and treatment procedures, especially in low-risk subgroups.

A Search for Causes of Rising Incidence of Differentiated Thyroid Cancer in Children and Adolescents after Chernobyl and Fukushima: Comparison of the Clinical Features and Their Relevance for Treatment and Prognosis

The incidence of differentiated thyroid cancer (DTC) is steadily increasing globally. Epidemiologists usually explain this global upsurge as the result of new diagnostic modalities, screening and overdiagnosis as well as results of lifestyle changes including obesity and comorbidity. However, there is evidence that there is a real increase of DTC incidence worldwide in all age groups. Here, we review studies on pediatric DTC after nuclear accidents in Belarus after Chernobyl and Japan after Fukushima as compared to cohorts without radiation exposure of those two countries. According to the Chernobyl data, radiation-induced DTC may be characterized by a lag time of 4–5 years until detection, a higher incidence in boys, in children of youngest age, extrathyroidal extension and distant metastases. Radiation doses to the thyroid were considerably lower by appr. two orders of magnitude in children and adolescents exposed to Fukushima as compared to Chernobyl. In DTC patients detected after Fukushima by population-based screening, most of those characteristics were not reported, which can be taken as proof against the hypothesis, that radiation is the (main) cause of those tumors. However, roughly 80% of the Fukushima cases presented with tumor stages higher than microcarcinomas pT1a and 80% with lymph node metastases pN1. Mortality rates in pediatric DTC patients are generally very low, even at higher tumor stages. However, those cases considered to be clinically relevant should be followed-up carefully after treatment because of the risk of recurrencies which is expected to be not negligible. Considering that thyroid doses from the Fukushima accident were quite small, it makes sense to assess the role of other environmental and lifestyle-related factors in thyroid carcinogenesis. Well-designed studies with assessment of radiation doses from medical procedures and exposure to confounders/modifiers from the environment as e.g., nitrate are required to quantify their combined effect on thyroid cancer risk.

Incidencia y estadificación dinámica del riesgo del carcinoma diferenciado de tiroides en una unidad de alta resolución. periodo 2002-2017

ObjectiveWe evaluated the incidence, progression and the dynamic risk stratification in differentiated thyroid cancer (DTC) under follow-up in a high-resolution clinic (HRC). MethodsThis was a retrospective observational study on incident cases in the tumor registry from 2002 to 2017 and their evolution under follow-up in HRC. ResultsA total of 444 patients (78.5% women, 52.1±14.9 mean years old) were DTC diagnosed from 2002 to 2017. The incidence rate of DTC increased from 5.2 to 25.7x105 habitants/year in women and from 2.3 to 7.1x105 habitants/year in men (P<0.0001). This increased incidence was not associated with an increment in the incidental papillary microcarcinoma diagnosed (from 29.4% to 32%).In those patients undergoing follow-up at the HRC (84% papillary carcinomas), 65.7% were classified as being at a low risk of recurrence compared to 14.5% at high risk. Of those, 88.8% classified as making an excellent response at diagnosis remained disease-free at the final follow-up visit. However, those patients with an indeterminate or structurally incomplete response at diagnosis evolved to an excellent response in 55.8% and 42.9% of the cases, respectively, compared to 14.8% of those with a biochemically incomplete response (P<0.001) ConclusionsThe increased incidence of DTC is similar to results published previously in other countries. Dynamic risk stratification systems adequately classify DTC patients and assess diagnostic and treatment procedures, especially in low-risk subgroups.

Predicting distant metastatic disease in differentiated thyroid cancer: a matched case-control study.

The occurrence of distant metastasis (DM) is the most important prognostic factor influencing survival outcomes in differentiated thyroid cancer (DTC). Identifying patients who are likely to develop DM and offering these cases more aggressive surgical approaches and I-131 therapy, is paramount to achieving the best possible outcomes. DM on presentation in DTC are uncommon, with an incidence of 1-9%. However, the incidence of DTC is rising and the disease affects a relatively young cohort of patients. The aims of this study were to investigate predictive factors in the development of DM by comparing a homogenous group of DTC patients with and without DM, and to illustrate the overall and disease-specific survival (DSS) rates of DTC patients presenting with DM. A matched case-control study of patients with DTC and DM was undertaken. The study group comprised a consecutive series of cases with DM treated in the period 1968-2014. Patients with DM at initial presentation were identified (DTC-DM group). A control group of patients without DM were matched based on age, gender, tumour size and histological subtype. The primary outcome measures were overall and disease-free survival. Secondary outcome measures were lymph node involvement (LNI), extra-thyroidal extension (ETE) of tumour and presence of BRAFV600E mutation identified on immunohistochemistry. A total of 2547 patients with DTC were reviewed and of these 83 (3.26%) had DM at initial presentation. At 5 and 10 years, the overall survival rates for DTC-DM patients were 89.6% and 64%, respectively. The 5 and 10 year DSS rates for DTC-DM cases were 90.2% and 67.3%, respectively. When compared to the DTC group, the DTC-DM group had significantly higher rates of ETE (63% vs. 29.5%, P < 0.0001) and LNI (32.5% vs. 18.8%, P = 0.044). Among patients with papillary thyroid cancer (PTC), the presence of BRAFV600E mutation was significantly associated with DM (62.2% vs. 36.8%, P = 0.028). ETE, LNI and BRAFV600E mutation in PTC are significant predictors for the development of distant metastatic disease.

Advancements in the treatment of differentiated thyroid cancer.

Derived from follicular epithelial cells, differentiated thyroid cancer (DTC) accounts for the majority of thyroid malignancies. The threefold increase in DTC incidence over the last three decades has been largely attributed to advancements in detection of papillary thyroid microcarcinomas. Efforts to address the issue of overtreatment have notably included the reclassification of encapsulated follicular variant papillary thyroid cancers (EFVPTC) to non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). In the last 5 years, the overall management approach for this relatively indolent cancer has become less aggressive. Although surgery and radioiodine ablation remain the mainstay of DTC therapy, the role of active surveillance is being explored. Furthermore, the most recent American Thyroid Association (ATA) guidelines offer flexibility between lobectomy and total thyroidectomy for thyroid nodules between 1 cm and 4 cm in the absence of extrathyroidal extension or nodal disease. As our understanding of the natural history and molecular underpinnings of DTC evolves, so might our approach to managing low-risk patients, obviating the need for invasive intervention. Simultaneously, advances in interventional and systemic therapies have greatly expanded treatment options for high-risk surgical candidates and patients with widespread disease, and continue to be areas of active investigation. Continued research efforts are essential to improve our ability to offer effective individualized therapy to patients at all disease stages and to reduce the incidence of recurrent and progressive disease.

Patients with chronic autoimmune thyroiditis are not at higher risk for developing clinically overt thyroid cancer: a 10-year follow-up study.

The association between chronic autoimmune thyroiditis (CAT) and differentiated thyroid cancer (DTC) remains controversial. The incidence of DTC increases when screening procedures are implemented, as typically occurs in CAT patients being routinely submitted to thyroid ultrasound (US). The aim of this study was to longitudinally evaluate the long-term development of DTC in patients with CAT. A retrospective longitudinal cohort study was designed. For the study, 510 patients with chronic autoimmune thyroiditis (CAT) with a 10-year follow-up were enrolled. Patients were divided in two groups according to the presence (CAT+ NOD+; n = 115) or absence (CAT+ NOD-; n = 395) of co-existent nodules at diagnosis. The main outcome measures were appearance of new thyroid-nodules and development of DTC during follow-up. During a 10-year median follow-up period, new thyroid-nodules were detected in 34/115 (29.5%) patients in the CAT+ NOD+ group and in 41/395 (10.3%) in the CAT+ NOD- group (P < 0.001). Logistic regression analysis showed that thyroid-volume at diagnosis and belonging to the CAT+ NOD+ group significantly predicted the appearance of a new thyroid nodule during follow-up, independently of baseline age and sex. Among the 75 patients experiencing the appearance of a new nodule, 27 (39%) met the criteria for fine-needle-aspiration-cytology (FNAC). A benign cytological diagnosis was rendered in all cases. In our series of CAT patients, the appearance of new thyroid-nodules was frequent, but none of them were found to be malignant. The presence of CAT appears to be associated with a negligible risk of developing clinically overt DTC.

Higher TSH Is Not Associated With Thyroid Cancer Risk in the Presence of Thyroid Autoimmunity.

Higher-but-within-normal thyrotropin (thyroid-stimulating hormone, TSH) is associated with higher risk for differentiated thyroid cancer (DTC) in surgical series. Our recent clinical observations suggest that this is not the case in the presence of autoimmune thyroid disease (AITD). We designed the present study to clarify this controversy. We analyzed our prospectively collected database of patients referred for thyroid surgery at 2 tertiary care referral centers in Greece and the United States. We collected data for preoperative TSH, postoperative pathology, and thyroid peroxidase (TPO) antibodies titers. Subjects were subdivided into 2 groups, those with AITD (i.e., lymphocytic thyroiditis) and non-AITD. We excluded subjects with Graves disease, abnormal TSH (< 0.40 or > 4.50 mIU/mL), or recent use of levothyroxine. We compared the serum TSH among different groups using the Mann-Whitney test. A total of 3973 subjects were screened; 1357 met exclusion criteria. After all exclusions, data from 1731 non-AITD subjects and 329 AITD subjects were included in the analysis. AITD subjects had higher TSH than non-AITD subjects (2.09 vs 1.48; P < 0.0001). TSH values were higher in DTC compared with benign histology only in non-AITD subjects (1.65 vs 1.40; P < 0.0001). Progressively higher TSH was associated with higher incidence of DTC only in non-AITD subjects (P < 0.0001). In AITD subjects, TSH was similar between groups with or without DTC (2.02 vs 2.14; P = 0.21). TSH concentrations are not associated with the risk of developing DTC in the presence of thyroid autoimmunity, even though this seems to be the case for all other patients.

Analyzing the relationship between differentiated thyroid cancer and thyroid autoimmunity: an exploratory study from tertiary care center in South India

Background: Differentiated thyroid cancer (DTC) is the most common endocrine malignancy. There is a rising incidence of DTC over the past few decades. This dramatic increase in incidence may be due to increased detection rate or because of factors like thyroid stimulating hormone (TSH) or thyroid autoantibodies which remains unclear. Our study aims to analyze the association between DTC and thyroid autoimmunity.Methods: This was a retrospective study over 1 year conducted at the department of endocrine surgery, Madras medical college, a tertiary care center in South India. During the study period, 364 total thyroidectomies were performed which includes 292 benign and 72 malignant cases. Among malignancies, 15 non-DTC cases were excluded from the study. Finally, we included 57 patients with DTC and 114 patients with benign disease (randomly chosen age and sex-matched controls) for analysis. Demographic data, TSH levels, antithyroglobulin (anti-TG), and anti-thyroid peroxidase (anti-TPO) antibody levels, histopathology were recorded and analyzed.Results: Histopathological examination revealed 47.4% of DTC and 63.2% of benign cases has associated thyroiditis. In our study elevated anti-TPO and anti-TG antibodies were not significantly associated with DTC (anti-TPO positivity 75.4% in DTC group vs. 74.6% in benign group, p=0.90, anti-TG antibody positivity 66.7% in DTC vs. 67.5% in benign group, p=0.90). Also, no significant association established between elevated TSH and DTC.Conclusions: Association between thyroid autoantibodies and DTC has been evaluated in several studies with inconsistent results. The present study did not show any significant associations between elevated thyroid autoantibodies, TSH levels, and DTC.

Clinical management of papillary thyroid microcarcinoma

Papillary thyroid microcarcinoma(PTMC)of the thyroid is defined as papillary thyroid carcinoma measuring<1 cm. The incidence of differentiated thyroid cancer is increasing greatly. However, roughly half of this increase is attributable to the identification of PTMC. Serum thyroid stimulating hormone, thyroid ultrasound and ultrasound guided thyroid fine needle aspiration cytology(FNAC)are still the cornerstone for its diagnosis. The active surveillance approach in which active treatment is delayed until the cancer shows signs of substantial progression could be considered in selected patients with low-risk PTMC. Active surgery is still the first line treatment for other PTMC patients, although thermal ablation may be an alternative option for low-risk patients with PTMC. (Chin J Endocrinol Metab, 2018, 34: 353-358) Key words: Papillary thyroid microcarcinoma; Active surveillance; Thermal ablation

Anaplastic Thyroid Cancer in Sicily: The Role of Environmental Characteristics.

Anaplastic thyroid cancer (ATC) is a rare but extremely aggressive cancer of the thyroid, contributing up to 30-40% of thyroid cancer-specific mortality. We analyzed ATC characteristics and survival rates in Sicily to evaluate the possible influence of environmental factors. With this aim, data regarding ATC incidences in urban/rural and industrial, iodine-deficient, and volcanic vs control areas were compared in Sicily as well as ATC data from Sicily and USA. Using the Sicilian Register of Thyroid Cancer (SRTC) database incidence, age, gender, tumor size and histotype, extrathyroidal extension, stage, and coexistence with pre-existing differentiated thyroid cancer (DTC) were evaluated in different areas of Sicily and also compared with Surveillance Epidemiology and End Results data in USA. Forty-three ATCs were identified in Sicily in the period 2002-2009. In our series only age <70 years at diagnosis (p = 0.01), coexistence with DTC (p = 0.027) and tumor size ≤6 cm (p = 0.012) were significant factors for increased survival at univariate analysis (only age at multivariate analysis). No difference in ATC incidence was found in urban vs rural areas and in iodine-deficient and industrial vs control areas. By contrast, in the volcanic area of Sicily, where DTC incidence is doubled relative to the rest of the island, also ATC incidence was increased. ATC data in Sicily were similar to those reported in the same period in the USA where overall survival rate at 6 and 12 months, however, was smaller. The similar ATC data observed in Sicily and USA (having different genetic background and lifestyle) and the increased ATC incidence in the volcanic area of Sicily paralleling the increased incidence of papillary thyroid cancer are compatible with the possibility that casual additional mutations, more frequent in a background of increased cell replication like DCT, are the major causes of ATC rather than genetic background and/or direct environmental influences.

Initial attributable cost and economic burden of clinically-relevant differentiated thyroid cancer: A health care service provider perspective

BackgroundRapid rise in differentiated thyroid cancer (DTC) may impose a heavy economic burden on future healthcare. We aimed to calculate the average first-year monetary cost/patient for DTC and estimate the projected cost burden on our local healthcare system. MethodsMedical records of 270 clinically-relevant DTC patients were reviewed to calculate the amount of services utilized during the first-year. Only direct costs were included with estimates derived from government gazette. Cancer incidences were derived from the territory-wide cancer registry. Total annual cost equaled to the incidence multiplied by the cost/patient. ResultsThe average first-year cost of DTC was USD11,560/patient. Initial surgery accounted for 66.9% of total cost. Male and female annual percentage increases for DTC were 4.86% and 4.28%, respectively. Female DTC is projected to surpass rectal cancer in 2019 (20.4/100,000 vs. 20.0/100,000) and colon cancer (47.2/100,000 vs. 46.8/100,000) in 2039. However, the projected incidence of DTC in 2026 would still be about one fourth that of CRC (19.5/100,000 vs. 83.2/100,000). ConclusionsThe average first-year monetary cost of DTC care was relatively low. Initial surgery accounted for most of the cost. Despite a rapid incidence rise, the projected first-year cost for DTC is unlikely to impose substantial economic burden on our local future healthcare system.

Letter: Diagnostic Whole-Body Scan May Not Be Necessary for Intermediate-Risk Patients with Differentiated Thyroid Cancer after Low-Dose (30 mCi) Radioactive Iodide Ablation (Endocrinol Metab 2014;29:33-9, Eon Ju Jeon et al.).

The initial treatment of differentiated thyroid cancer (DTC) is thyroidectomy, followed by remnant ablation with radioiodine (I-131). However, substantial uncertainty persists over the indications and optimal dose for I-131. In addition, the usefulness of a follow-up diagnostic I-131 whole-body scan (WBS) performed within 6 to 12 months after initial therapy is controversial [1]. Although a diagnostic WBS is not recommended for low-risk patients, it may be of value in the follow-up of patients with high or intermediate risk [2]. Since incidence of DTC and patients who undergo remnant ablation has been increasing rapidly, these issues are interesting and important to clinicians. Jeon and Jung [3] demonstrated that a postablation diagnostic I-131 WBS in intermediate-risk patients with DTC may not be necessary. Although the authors suggested their study results carefully, in my opinion, below mentioned point need to be emphasized. According to this study, among 255 intermediate-risk patients, 233 had no I-131 uptake in the thyroid bed, and 22 had I-131 uptake on the thyroid bed. On diagnostic WBS, the group showing uptake had significantly higher lymph node metastasis and on average had stimulated thyroglobulin (TG) levels below 2 ng/mL in the absence of TG antibodies. Among the 22 patients showing uptake in the thyroid bed, only five revealed stimulated TG levels above 2 ng/mL. Stimulated TG levels alone did not represent thyroid uptake in a significant portion of patients, and alone was not sufficient to screen patients. Although the recurrence of thyroid cancer was not statistically different between the group with no uptake and the group with uptake in the thyroid bed, the duration of follow-up was short. Moreover, only one among four patients with recurrence showed stimulated TG levels above 2 ng/mL and diagnostic WBS showed no uptake in three patients with DTC recurrence. Prospective, long-term studies on whether patients with or without a thyroid remnant in diagnostic WBS show different prognoses and outcomes will provide important information about this issue. Long-term follow-up data from 17 patients with thyroid bed uptake in this study is expected to provide important information despite the small number of patients. In real practice, the recommended preparatory low-iodine diet before diagnostic WBS is very stressful and bothersome for patients. Therefore, these results by Jeon and Jung [3] will be very valuable data in establishing an evidence-based follow-up strategy for DTC.

Differentiated thyroid cancer in Greece: 1963-2000. Relation to demographic and environmental factors

Thyroid cancer (TC) is a relatively rare neoplasia, accounting for 0.35%-0.38% of total deaths due to cancer in Greece. Environmental/nutritional factors are considered to play a role in its pathogenesis. The aim of this retrospective review of patients' histories from three of the largest specialized centers in southern Greece, from 1963 to 2000, was to assess associations of differentiated TC (DTC) with demographic and environmental factors. The total number of DTC cases was 610 (119 men or 19.5%, and 491 women or 80.5%), of which 442 cases (72%) were papillary DTCs (pure papillary type: 54.5% and mixed papillary-follicular type: 45.5%), 90 cases (15%) were of the pure follicular type, while 78 cases (13%) were classified as suspicious lesions, requiring follow-up, but not definitively carcinomas. The mean age (+/-SD) at diagnosis for all groups was 42.3+/-1.3 years. Fifty percent of the patients were living in Athens at the time of diagnosis. The diagnosis was delayed in patients living in villages compared to those living in cities (mean age +/-SD): 43.7+/-14.1 years and 40.9+/-13.8 years, respectively; p<0.05, t-test). Patients who were born in iodine-sufficient areas (n=162/193, 84%; X(2)=5.09, P=0.02) had papillary carcinoma more frequently compared to patients who were born in previously iodine-deficient areas (n=159/214, 74%). During the observation period (1963-2000) there appeared to be three different trends in the incidence of newly diagnosed cases: a random variation during the first nine years and a steady increase during the second two decades (starting before the Chernobyl nuclear accident) followed by a significant decline during the last few years. We suggest that the observed variations in the incidence of DTC could be related to the availability of diagnostic tools as well as to increased awareness.

DIFFERENTIATED THYROID CANCER MAY HAVE GENETIC DETERMINANTS. 587

The etiology of differentiated thyroid cancer (DTC) is unknown, but there are several risk factors including female sex, exposure to ionizing radiation, and previous malignancy. Recent studies have suggested a role for altered oncogene expression [e.g. c-myc, ras, and papillary thyroid cancer gene (PTC)] in DTC. None has been abnormal in the majority of patients although PTC may be present in more aggressive tumors. To seek supporting evidence for the possible role of such genetic factors in pediatric patients with DTC, we reviewed 120 records of patients with DTC from the Department of Defense (DoD) Centralized Tumor Registry. All were diagnosed between 1953-1994 and ≤ 21 yr of age. Of these, 100 were papillary, 19 follicular, and 1 mixed papillary/follicular. Of note, 88.3% were Caucasian, 4.2% Black and 7.5% of other races. Although the exact racial distribution of all DoD pediatric patients is not known for this time period, we did compare this distribution to that of 18,832 representative DoD pediatric admissions for 1995. This was 69% Caucasian, 23% Black, and 8% other races and differed significantly from that of patients with DTC diagnosed in the 1990s (86.5% Caucasian; CI 73.6-93.9%, p<0.0005). When the data were stratified by decade of diagnosis, the incidence of DTC was greater in Caucasians from each decade. These differences support the hypothesis that there are genetic determinants in the etiology of DTC in children.