갑상선암 환자에서 진행성 대장 선종 혹은 대장암 발생의 상관관계

김다민 ( Da Min Kim ),김정하 ( Jung Ha Kim ),박준영 ( Jun Young Park ),전병우 ( Byung Woo Jun ),송림화 ( Lim Hwa Song ),정현애 ( Hyun Ae Jung ),김영호 ( Young Ho Kim ) 대한장연구학회 2011 Intestinal Research Vol.9 No.3

Background/Aims: Colorectal cancer and thyroid cancer are common diseases with relatively higher survival rates compared with other cancers. The number of patients identified with colorectal cancer or thyroid cancer who develop multiple primary malignancy during long-term follow-up is increasing with advances in diagnostic techniques and treatment modalities. However, the association between colorectal cancer and thyroid cancer is uncertain, and few data have been reported in Korea. This study examined the association between thyroid cancer and colorectal neoplasm. Methods: We retrospectively investigated 363 patients who underwent a colonoscopy, among patients diagnosed with thyroid cancer between January 2004 and December 2008 at Samsung Medical Center. The control group was comprised of 2,494 patients who underwent screening colonoscopy for the first time within the study period at the center for health promotion at Samsung Medical Center between March 2004 and December 2005. Results: The detection rates in patients with thyroid cancer were 4.7% (17/363) for advanced adenomas and 2.8% (10/363) for colorectal cancer. In the control group, it was 3.2% (79/2,494) for advanced adenomas and 0.3% (7/2,494) for colorectal cancer. A multivariate analysis revealed that the presence of thyroid cancer had an odds ratio of 1.893 (95% confidence interval, 0.868-4.128, P=0.109) in favor of finding at least one advanced colorectal neoplasm. Conclusions: The results indicate that thyroid cancer is not associated with advanced colorectal neoplasm. Survivors of thyroid and colorectal cancer live longer and hence are at risk for second primary cancers. Therefore, further studies that prospectively evaluate the association between thyroid cancer and colorectal advanced neoplasm are needed. (Intest Res 2011;9:206-210)

여포성 종양의 진단과 치료에 있어서의 문제점들

김원배 대한갑상선학회 2012 International Journal of Thyroidology Vol.5 No.2

Thyroid follicular adenoma and hyperplastic adenomatoid nodule may show overlapping cytologic pattern with thyroid follicular carcinoma and follicular variant of thyroid papillary carcinoma. Fine-needle aspiration cytology (FNAC) has limited role in differential diagnosis of those lesions showing high cellularity and absence of colloid. Those lesions are conventionally termed ‘follicular neoplasm’. As diagnostic hallmarks of follicular carcinoma (vascular- and capsular invasion) cannot be detected by cytology, verification by histology after surgery is mandatory. However, only 20% of patients with thyroid nodules diagnosed cytologically as ‘follicular neoplasm’are finally diagnosed as carcinoma after surgery. Therefore, there have been many trials to differentiate follicular adenoma (FA) from follicular carcinoma (FTC) in preoperative setting. Among those trials are 1) cell morphometry analysis by computer graphics, analysis of telomerase expression level, quantitation of specific protein markers, or intensive cytological analysis using FNAC specimens, 2) ultrasonographic evaluation,dynamic MRI, or MR spectroscopy for thyroid nodules and 3) gene expression profile analysis for thyroid nodules by microarray technique, all showing limited success or limitations hampering clinical application. Similarly,intra-operative frozen section analysis of thyroid nodule had been known to be of no diagnostic utility in a prospective, randomized trial. Current management strategy for ‘follicular neoplasm’ is initial surgery for diagnostic purpose to get pathologic diagnosis. If the nodule is diagnosed finally as FTC, completion thyroidectomy with or without radioactive iodine therapy is recommended in most cases. Minimally invasive FTC (without vascular invasion) is known to have excellent prognosis in most cases, so traditionally those patients had undergone unilateral operation without completion thyroidectomy. But, there had been reported cases showing distant metastasis and/or recurrence in patients with ‘minimally invasive FTC’. One of problems in diagnosis of ‘minimally invasive FTC’ is lack of international standardization for pathologic diagnosis. Optimal surgical extent for cases with FTC is not known yet. It might have been due to lack of risk stratification of patients which is unique to FTC (not well differentiated thyroid cancer as a whole), lack of biomarker predicting prognosis of FTC, and lack of controlled trial for management of patients with FTC. In near future, application of molecular diagnostic markers is expected to improve our management strategy for thyroid nodules diagnosed as ‘follicular neoplasm’, if molecular pathogenesis of FA and of FTC are comprehensively understood.

Genome-Wide Association Studies of Autoimmune Thyroid Diseases, Thyroid Function, and Thyroid Cancer

황보율,박영주 대한내분비학회 2018 Endocrinology and metabolism Vol.33 No.2

Thyroid diseases, including autoimmune thyroid diseases and thyroid cancer, are known to have high heritability. Family and twin studies have indicated that genetics plays a major role in the development of thyroid diseases. Thyroid function, represented by thyroid stimulating hormone (TSH) and free thyroxine (T4), is also known to be partly genetically determined. Before the era of genome-wide association studies (GWAS), the ability to identify genes responsible for susceptibility to thyroid disease was limited. Over the past decade, GWAS have been used to identify genes involved in many complex diseases, including various phenotypes of the thyroid gland. In GWAS of autoimmune thyroid diseases, many susceptibility loci associated with autoimmunity (human leukocyte antigen [HLA], protein tyrosine phosphatase, non-receptor type 22 [PTPN22], cytotoxic T-lymphocyte associated protein 4 [CTLA4], and interleukin 2 receptor subunit alpha [IL2RA]) or thyroid-specific genes (thyroid stimulating hormone receptor [TSHR] and forkhead box E1 [FOXE1]) have been identified. Regarding thyroid function, many susceptibility loci for levels of TSH and free T4 have been identified through genome-wide analyses. In GWAS of differentiated thyroid cancer, associations at FOXE1, MAP3K12 binding inhibitory protein 1 (MBIP)-NK2 homeobox 1 (NKX2-1), disrupted in renal carcinoma 3 (DIRC3), neuregulin 1 (NRG1), and pecanex-like 2 (PCNXL2) have been commonly identified in people of European and Korean ancestry, and many other susceptibility loci have been found in specific populations. Through GWAS of various thyroid-related phenotypes, many susceptibility loci have been found, providing insights into the pathogenesis of thyroid diseases and disease co-clustering within families and individuals

Evaluation and Management of Bone Health in Patients with Thyroid Diseases: A Position Statement of the Korean Thyroid Association

홍아람,강호철 대한내분비학회 2023 Endocrinology and metabolism Vol.38 No.2

Thyroid hormones play an important physiological role in maintaining adult bone structure and strength. Consequently, thyroid dysfunction is related to skeletal outcomes. Overt hyperthyroidism is an established cause of high bone turnover with accelerated bone loss, leading to osteoporosis and increased fracture risk. Hyperthyroidism induced by thyroid-stimulating hormone-suppressive therapy in patients with differentiated thyroid cancer is a cause of secondary osteoporosis. In contrast, there is a lack of evidence on the negative impact of hypothyroidism on bone health. Considering the clinical updates on the importance of bone health in thyroid dysfunction, the Task Force from the Clinical Practice Guidelines Development Committee of the Korean Thyroid Association recently developed a position statement on the evaluation and management of bone health of patients with thyroid diseases, particularly focused on endogenous hyperthyroidism and thyroid-stimulating hormone-suppressive therapy-associated hyperthyroidism in patients with differentiated thyroid cancer. Herein, we review the Korean Thyroid Association’s position statement on the evaluation and management of bone health associated with thyroid diseases.

하시모토 갑상선염의 동반 여부에 따른 갑상선 유두암의 초음파 소견

박준영,이태현,박동희 대한영상의학회 2010 대한영상의학회지 Vol.63 No.2

목적: 하시모토 갑상선염을 동반한 환자와 동반하지 않은 환자에서 발생한 갑상선 유두암의 초음파 소견을 비교하고자 한다. 대상과 방법: 갑상선 결절로 수술을 시행한 후 갑상선 유두암으로 진단받은 190명을 후향적으로 분석하였다. 하시모토 갑상선염이 동반된 유두암 환자군과 동반되지 않은 유두암 환자군의 초음파 소견을 비교하였다. 결과: 190명의 환자 중에 61명이 수술 후 하시모토 갑상선염으로 진단되었다. 하시모토 갑상선염을 동반한 유두암 환자군은 남자 3명, 여자 58명으로 여성에서 발생 빈도가 높았다(p=0.0026). 초음파 소견상 하시모토 갑상선염을 동반한 갑상선 유두암에서 거대석회화의 발생 빈도가 유의하게 높았으며(p=0.0009), 침상 경계, 현저한 저에코, 그리고 불규칙한 모양 등은 두 집단간에 유의한 차이점이 없었다. 석회화가 없는 경우 하시모토 갑상선염이 동반된 환자에서 초음파상 유두암을 발견하지 못하는 빈도가 높았다. 결론: 하시모토 갑상선염을 동반한 갑상선 유두암은 갑상선염이 없을 때보다 거대석회화가 많이 발생하며, 초음파상 석회화가 없는 경우 악성 결절을 발견하지 못하는 경우가 있기 때문에 하시모토 갑상선염이 있는 경우 세심한 검사가 필요할 것으로 생각한다. Purpose: This study was designed to compare the ultrasonographic features of papillary thyroid carcinoma with and without Hashimoto’s thyroiditis. Materials and Methods: This retrospective study included 190 patients with papillary thyroid carcinoma which was proven by neck surgery. The difference in the ultrasonographic findings between papillary thyroid carcinoma with Hashimoto’s thyroiditis and papillary thyroid carcinoma without Hashimoto’s thyroiditis were calculated statistically. Results: Hashimoto’s thyroiditis was diagnosed in 61 of 190 patients following neck surgery. The incidence of coexisting papillary thyroid carcinoma with Hashimoto’s thyroiditis was significantly higher in women (p=0.0026). In addition, the frequency of macrocalcification in patients with Hashimoto’s thyroiditis was also significantly higher (p=0.0009). Conversely,other ultrasonographic findings including the shape, margin, echogenicity and calcifications, for patients with papillary thyroid carcinoma with Hashimoto’s thyroiditis and papillary thyroid carcinoma without Hashimoto’s thyroiditis, were not statistically significant. We also found that patients with Hashimoto’s thyroiditis who showed no calcification on ultrasonography tended not to detect the papillary carcinoma at a higher frequency. Conclusion: On ultrasonography, macrocalcifications occurred more frequently in patients with Hashimoto’s thyroiditis than those without Hashimoto’s thyroiditis. Malignant thyroid nodules without calcifications in patients with Hashimoto’s thyroiditis more often could not be detected. Therefore, it is important carefully examine patients with Hashimoto’s thyroiditis.

갑상선 악성종양 및 양성종양에서 Fra - 1 표현에 대한 연구

김용현(Youg Hyun Kim),오정헌(Jeong Heon Oh),김난희(Nan Hee Kim),최경묵(Kyung Muk Choi),김상진(Sang Jin Kim),백세현(Sei Hyun Baik),최동섭(Dong Seop Choi),이응석(Eung Seok Lee) 대한내과학회 2000 대한내과학회지 Vol.59 No.4

Background : Differential diagnosis of thyroid nodule is important in deciding treatment modality and fine needle aspiration is a good method to do so. But, sometimes, it has limitation in use because of inadequate test material and difficulty in interpreting it. Among the study of oncogene and tumor suppresor gene on the origin of thyroid tumor, expression of Fra-1, one of AP-1 system, is increased in thyroid neoplasm. So there is a possibility that it would be used as a method for differential diagnosis of thyroid nodule. We tried to know whether presence or absence of Fra-1 expression can be used as a diagnostic method in differential diagnosis of thyroid nodule using immuno- histochemical(IHC) staining method.Methods : In 4 types of thyroid tumor that was confirmed by histologic diagnosis after operation(30 cases of papillary cancer, 10 cases of follicular cancer, 16 cases of follicular adenoma, 18 cases of adenomatous goiter), IHC staining method was performed to evaluate the expression of Fra-1.Results : In papillary and follicular thyroid cancer, the expression of Fra-1 was stronger than benign thyroid tumor, but there was no difference in Fra-1 expression between two types of carcinoma. Weak expression of Fra-1 was observed in all cases of follicular adenoma, and it was also weakly expressed in 6 out 18 cases of adenomatous goiter. Conclusion : The expression of Fra-1 was stronger in thyroid cancer than in benign thyroid adenoma, but it was impossible to differentiate thyroid cancer from benign thyroid adenoma by the presence or absence of Fra-1 expression using IHC staining method.(Korean J Med 59:398-403, 2000)

Update from the 2022 World Health Organization Classification of Thyroid Tumors: A Standardized Diagnostic Approach

정찬권,Andrey Bychkov,Kennichi Kakudo 대한내분비학회 2022 Endocrinology and metabolism Vol.37 No.5

The fifth edition of the World Health Organization (WHO) histologic classification of thyroid neoplasms released in 2022 includes newly recognized tumor types, subtypes, and a grading system. Follicular cell-derived neoplasms are categorized into three families (classes): benign tumors, low-risk neoplasms, and malignant neoplasms. The terms “follicular nodular disease” and “differentiated high-grade thyroid carcinoma” are introduced to account for multifocal hyperplastic/neoplastic lesions and differentiated thyroid carcinomas with high-grade features, respectively. The term “Hürthle cells” is replaced with “oncocytic cells.” Invasive encapsulated follicular and cribriform morular variants of papillary thyroid carcinoma (PTC) are now redefined as distinct tumor types, given their different genetic alterations and clinicopathologic characteristics from other PTC subtypes. The term “variant” to describe a subclass of tumor has been replaced with the term “subtype.” Instead, the term “variant” is reserved to describe genetic alterations. A histologic grading system based on the mitotic count, necrosis, and/or the Ki67 index is used to identify high-grade follicular-cell derived carcinomas and medullary thyroid carcinomas. The 2022 WHO classification introduces the following new categories: “salivary gland-type carcinomas of the thyroid” and “thyroid tumors of uncertain histogenesis.” This review summarizes the major changes in the 2022 WHO classification and their clinical relevance.

Survival Comparison of Incidentally Found versus Clinically Detected Thyroid Cancers: An Analysis of a Nationwide Cohort Study

문신제,박영주,이은경,최훈성,Sue K. Park 대한내분비학회 2023 Endocrinology and metabolism Vol.38 No.1

Background: The true benefit of thyroid cancer screening is incompletely understood. This study investigated the impact of ultrasound screening on thyroid cancer outcomes through a comparison with symptomatic thyroid cancer using data from a nationwidecohort study in Korea. Methods: Cox regression analysis was performed to assess the hazard ratios (HRs) for all-cause and thyroid cancer-specific mortality. Considering the possible bias arising from age, sex, year of thyroid cancer registration, and confounding factors for mortality (including smoking/drinking status, diabetes, and hypertension), all analyses were conducted with stabilized inverse probability of treatment weighting (IPTW) according to the route of detection. Results: Of 5,796 patients with thyroid cancer, 4,145 were included and 1,651 were excluded due to insufficient data. In comparison with the screening group, the clinical suspicion group was associated with large tumors (17.2±14.6 mm vs. 10.4±7.9 mm), advanced T stage (3–4) (odds ratio [OR], 1.24; 95% confidence interval [CI], 1.09 to 1.41), extrathyroidal extension (OR, 1.16; 95% CI, 1.02 to 1.32), and advanced stage (III–IV) (OR, 1.16; 95% CI, 1.00 to 1.35). In IPTW-adjusted Cox regression analysis, the clinical suspicion group had significantly higher risks of all-cause mortality (HR, 1.43; 95% CI, 1.14 to 1.80) and thyroid cancer-specific mortality (HR, 3.07; 95% CI, 1.77 to 5.29). Mediation analysis showed that the presence of thyroid-specific symptoms was directly associated with a higher risk of cancer-specific mortality. Thyroid-specific symptoms also indirectly affected thyroid cancer-specific mortality, mediated by tumor size and advanced clinicopathologic status. Conclusion: Our findings provide important evidence for the survival benefit of early detection of thyroid cancer compared to symptomatic thyroid cancer.

갑상선 질환이 없던 여성에서 우연히 발견된 갑상선 결절의 의의

김은경,박정수,정웅윤,오기근,이종태,유형식 대한영상의학회 2002 대한영상의학회지 Vol.46 No.4

Purpose: To determine the prevalence of thyroid nodules discovered incidentally at ultrasonography and to reassess their significance. Materials and Methods: During a six-month period and using a high-frequency transducer, 1033 subjects with suspected breast disease underwent a prospective study of the thyroid. We determined the prevalence of thyroid nodules according to age, and the malignancy rate. Results: Focal thyroid nodules were detected in 291 women (28.2%), their prevalence increasing with age (p< 0.01). The nodules, totalling 337, were single in 260 cases (89.3%) and multiple in 31 (10.7%); 271 were less than 1 cm in diameter, 53 were 1-2 cm, and 13 were more than 2 cm [mean, 7.1(range, 2-34) mm]; 126 (37.4%) were pure cysts, 62 (18.4%) were mixed, and 149 (44.2%) were solid. Of the 149 solid nodules, 139 were hypoechoic. Eighty women (with 106 nodules) underwent fine-needle aspiration bipsy, and 35 (with 45 nodules) underwent surgery. It was discovered, finally, that 29 women (2.8%) had 35 malignancies, of which 33 were papillary carcinomas and two were carcinomas which had metastasized from a breast malignancy. Eleven women (37.9%) had extrathyroidal invasion and 6 (20.7%) had cervical lymph node metastasis despite incidentaloma. Conclusion: The prevalence of incidentally found thyroid nodules was 28.2%. Since the malignancy rate of these was relatively high, at 10.4%, the clinical significance of this finding should be reassessed. 목적: 갑상선 초음파 검사로 우연히 발견되는 갑상선 결절의 빈도를 알아보고, 이의 의의를 평가하고자 한다. 대상과 방법: 6개월 동안 유방암 검진을 위해 내원한 1033명을 대상으로 갑상선 초음파 검사를 시행하였다. 나이에 따른 갑상선 결절의 비율과 악성율을 알아보았다. 결과: 291명(28.2%)에서 갑상선 결절이 발견되었으며 나이가 증가할수록 많이 관찰되었다(p<0.01). 갑상선 결절은 단일인 경우가 260예(89.3%), 다발성인 경우가 31예(10.7%)로 발견된 결절은 모두 337개였다. 271개는 1 cm이하였고 1-2 cm이 53개, 2 cm이상은 13개였다. 초음파 소견상 126예(37.4%)는 낭성, 62예(18.4%)는 혼합형, 149예(44.2%)는 고형이었다. 고형 중 139예는 저에코 결절이었다. 80명의 106개의 병변에서 세침흡인검사를, 35명의 45개 결절에 대해서는 수술을 시행하였다. 29명(2.8%)의 35개 결절에서 악성으로 확인되었고 33개는 유두상암이었고, 2개의 병변은 유방암으로부터 전이된 병변이였다. 29명 중11예(37.9%)에서 피막외침윤이 있었고, 6예(20.7%)에서 경부임파절 전이가 관찰되었다. 결론: 갑상선 초음파 검사를 통해 발견된 우연종의 빈도는 28.2%였고 이중 악성율은 10.4%로 높았기 때문에 임상적 중요성은 재평가되어야 한다.

Effect of thyroid-stimulating hormone suppression on quality of life in thyroid lobectomy patients: interim analysis of a multicenter, randomized controlled trial in low- to intermediate-risk thyroid cancer patients(MASTER study)

Ja Kyung Lee,Eu Jeong Ku,Su-jin Kim,Woochul Kim,Jae Won Cho,Kyong Yeun Jung,Hyeong Won Yu,Yea Eun Kang,Mijin Kim,Hee Kyung Kim,Junsun Ryu,June Young Choi 대한외과학회 2024 Annals of Surgical Treatment and Research(ASRT) Vol.106 No.1

Purpose: Current clinical practices favor less or no thyroid-stimulating hormone (TSH) suppression for low- to intermediate-risk thyroid cancer patients who receive thyroid lobectomy. The association of TSH suppression on healthrelated quality of life (HR-QoL) in patients after thyroid lobectomy is not well studied. This study aimed to evaluate the effect of TSH suppression on patient HR-QoL after thyroid lobectomy. Methods: This study included patients enrolled in an ongoing, multicenter, randomized controlled study investigating the effects of TSH suppression. Patients were randomized to either the low-TSH group (TSH target range, 0.3–1.99 μIU/mL) or the high-TSH group (TSH target range, 2.0–7.99 μIU/mL). The HR-QoL, hyperthyroidism symptom, and depression symptom questionnaires performed preoperatively and 2 weeks and 3 months postoperatively were evaluated. Results: Total of 669 patients (low-TSH group, 340; high-TSH group, 329) were included. Although total HR-QoL score changes were not different between the 2 groups, the high-TSH group had a significantly higher score in the physical domain at postoperative 3 months (P = 0.046). The 2 groups did not have significant differences in hyperthyroidism and depression scores. Conclusion: In the short-term postoperative period, the physical HR-QoL scores in thyroid lobectomy patients were better when they did not receive TSH suppression. This study suggests the importance of considering HR-QoL when setting TSH suppression targets in thyroid lobectomy patients.