今日の臨床サポート 今日の臨床サポート

著者: 三宅成智 みはな耳鼻・甲状腺クリニック

監修: 森山寛1) 東京慈恵会医科大学附属病院

監修: 小島博己2) 東京慈恵会医科大学 耳鼻咽喉科

著者校正/監修レビュー済:2025/03/12
患者向け説明資料

改訂のポイント:
  1. 『甲状腺腫瘍診療ガイドライン2024』の発表に伴いコンテンツ内容を改訂した。また、甲状腺腫瘍のうち、悪性腫瘍についても当コンテンツ内に記載していたが別項(甲状腺癌)に譲るため記載を削除し、良性腫瘍についての記載を主とした加筆・修正を行った。

概要・推奨   

  1. 甲状腺腫瘍の診療は、①良悪性の鑑別、②甲状腺機能亢進症の有無の判定、が重要である。
  1. 甲状腺腫瘍では良悪性の判別が困難なことも多く、慎重な対応が求められる。
 

まとめ 

疾患情報(疫学・病態)  
  1. 甲状腺腫瘍には良性腫瘍、悪性腫瘍があり、良性腫瘍では主なものとして濾胞腺腫と腺腫様甲状腺腫がある。
  1. 慢性甲状腺炎(橋本病)により甲状腺の一部分が結節状となることがある(橋本病結節)。慢性甲状腺では乳頭癌や悪性リンパ腫が発生することもあり、鑑別には注意を要する。
  1. 甲状腺ホルモンを産生する腫瘍があり、自律性機能性甲状腺結節(auto-functioning thyroid nodule:AFTN)と呼称される。甲状腺機能亢進症の原因となるため、機能亢進と腫瘍があり疑われる場合には甲状腺シンチグラフィの検査適応がある。
  1. 腫瘍と混同しやすい疾患に、亜急性甲状腺がある。圧痛を伴う結節では、悪性腫瘍とともに鑑別診断として考える必要がある。経過中に甲状腺内で移動する、甲状腺機能の破壊性亢進といった特徴がある(FT3、FT4の上昇、Tg上昇など)。
  1. 濾胞腺腫は、濾胞上皮に由来し、通常は単発性である。
  1. 腺腫様甲状腺腫は結節性増殖が多発するのが特徴で、わが国の成人女性の数%と高い頻度で認める。
  1. 甲状腺腫瘍診療ガイドライン2018年版に示された甲状腺癌の危険因子は以下の通り。放射線被ばく(被ばく時年齢19歳以下、大量)(Grade A[1][2]、遺伝(Grade A)(代表的なものが多発性内分泌腫瘍症2型に属する髄様癌)[3]、体重の増加(Grade B[4]
  1. 甲状腺結節における悪性腫瘍の頻度:触診で甲状腺結節が発見された場合、癌の頻度は5~17.0%である。超音波検査で甲状腺結節が発見された場合、癌の頻度 2.6~8.3%である。
  1. 甲状腺結節の鑑別診断には、超音波検査がまずは推奨される。術前評価などを別として、CT、MRI、FDG-PET検査は推奨されない。
 
問診・診察のポイント  
問診:
  1. 臨床経過(現病歴、既往歴)、検査歴、受診経緯、前医で受けた説明内容、家族歴

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文献 

Thompson DE, Mabuchi K, Ron E, Soda M, Tokunaga M, Ochikubo S, Sugimoto S, Ikeda T, Terasaki M, Izumi S.
Cancer incidence in atomic bomb survivors. Part II: Solid tumors, 1958-1987.
Radiat Res. 1994 Feb;137(2 Suppl):S17-67.
Abstract/Text This report presents, for the first time, comprehensive data on the incidence of solid cancer and risk estimates for A-bomb survivors in the extended Life Span Study (LSS-E85) cohort. Among 79,972 individuals, 8613 first primary solid cancers were diagnosed between 1958 and 1987. As part of the standard registration process of the Hiroshima and Nagasaki tumor registries, cancer cases occurring among members of the LSS-E85 cohort were identified using a computer linkage system supplemented by manual searches. Special efforts were made to ensure complete case ascertainment, data quality and data consistency in the two cities. For all sites combined, 75% of the cancers were verified histologically, 6% were diagnosed by direct observation, 8% were based on a clinical diagnosis, and 12.6% were ascertained by death certificate only. A standard set of analyses was carried out for each of the organs and organ systems considered. Depending on the cancer site, Dosimetry System 1986 (DS86) organ or kerma doses were used for computing risk estimates. Analyses were based on a general excess relative risk model (the background rate times one plus the excess relative risk). Analyses carried out for each site involved fitting the background model with no dose effect, a linear dose-response model with no effect modifiers, a linear-quadratic dose-response model with no effect modifiers, and a series of linear dose-response models that included each of the covariates (sex, age at exposure, time since exposure, attained age and city) individually as effect modifiers. Because the tumor registries ascertain cancers in the registry catchment areas only, an adjustment was made for the effects of migration. In agreement with prior LSS findings, a statistically significant excess risk for all solid cancers was demonstrated [excess relative risk at 1 Sv (ERR1Sv) = 0.63; excess absolute risk (EAR) per 10(4) person-year sievert (PY Sv) = 29.7]. For cancers of the stomach (ERR1SV = 0.32), colon (ERR1SV = 0.72), lung (ERR1SV = 0.95), breast (ERR1SV = 1.59), ovary (ERR1SV = 0.99), urinary bladder (ERR1SV = 1.02) and thyroid (ERR1SV = 1.15), significant radiation associations were observed. There was some indication of an increase in tumors of the neural tissue (excluding the brain) among persons exposed to the bombs before age 20. For the first time, radiation has been associated with liver (ERR1SV = 0.49) and nonmelanoma skin (ERR1SV = 1.0) cancer incidence in the LSS cohort. The present analysis also strengthened earlier findings, based on a smaller number of cases, of an effect of A-bomb radiation on salivary gland cancer.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID 8127952
Tronko MD, Howe GR, Bogdanova TI, Bouville AC, Epstein OV, Brill AB, Likhtarev IA, Fink DJ, Markov VV, Greenebaum E, Olijnyk VA, Masnyk IJ, Shpak VM, McConnell RJ, Tereshchenko VP, Robbins J, Zvinchuk OV, Zablotska LB, Hatch M, Luckyanov NK, Ron E, Thomas TL, Voillequé PG, Beebe GW.
A cohort study of thyroid cancer and other thyroid diseases after the chornobyl accident: thyroid cancer in Ukraine detected during first screening.
J Natl Cancer Inst. 2006 Jul 5;98(13):897-903. doi: 10.1093/jnci/djj244.
Abstract/Text BACKGROUND: The Chornobyl accident in 1986 exposed thousands of people to radioactive iodine isotopes, particularly (131)I; this exposure was followed by a large increase in thyroid cancer among those exposed as children and adolescents, particularly in Belarus, the Russian Federation, and Ukraine. Here we report the results of the first cohort study of thyroid cancer among those exposed as children and adolescents following the Chornobyl accident.
METHODS: A cohort of 32 385 individuals younger than 18 years of age and resident in the most heavily contaminated areas in Ukraine at the time of the accident was invited to be screened for any thyroid pathology by ultrasound and palpation between 1998 and 2000; 13 127 individuals (44%) were actually screened. Individual estimates of radiation dose to the thyroid were available for all screenees based on radioactivity measurements made shortly after the accident and on interview data. The excess relative risk per gray (Gy) was estimated using individual doses and a linear excess relative risk model.
RESULTS: Forty-five pathologically confirmed cases of thyroid cancer were found during the 1998-2000 screening. Thyroid cancer showed a strong, monotonic, and approximately linear relationship with individual thyroid dose estimate (P<.001), yielding an estimated excess relative risk of 5.25 per Gy (95% confidence interval [CI] = 1.70 to 27.5). Greater age at exposure was associated with decreased risk of radiation-related thyroid cancer, although this interaction effect was not statistically significant.
CONCLUSION: Exposure to radioactive iodine was strongly associated with increased risk of thyroid cancer among those exposed as children and adolescents. In the absence of Chornobyl radiation, 11.2 thyroid cancer cases would have been expected compared with the 45 observed, i.e., a reduction of 75% (95% CI = 50% to 93%). The study also provides quantitative risk estimates minimally confounded by any screening effects. Caution should be exercised in generalizing these results to any future similar accidents because of the potential differences in the nature of the radioactive iodines involved, the duration and temporal patterns of exposures, and the susceptibility of the exposed population.

PMID 16818853
Brandi ML, Gagel RF, Angeli A, Bilezikian JP, Beck-Peccoz P, Bordi C, Conte-Devolx B, Falchetti A, Gheri RG, Libroia A, Lips CJ, Lombardi G, Mannelli M, Pacini F, Ponder BA, Raue F, Skogseid B, Tamburrano G, Thakker RV, Thompson NW, Tomassetti P, Tonelli F, Wells SA Jr, Marx SJ.
Guidelines for diagnosis and therapy of MEN type 1 and type 2.
J Clin Endocrinol Metab. 2001 Dec;86(12):5658-71. doi: 10.1210/jcem.86.12.8070.
Abstract/Text This is a consensus statement from an international group, mostly of clinical endocrinologists. MEN1 and MEN2 are hereditary cancer syndromes. The commonest tumors secrete PTH or gastrin in MEN1, and calcitonin or catecholamines in MEN2. Management strategies improved after the discoveries of their genes. MEN1 has no clear syndromic variants. Tumor monitoring in MEN1 carriers includes biochemical tests yearly and imaging tests less often. Neck surgery includes subtotal or total parathyroidectomy, parathyroid cryopreservation, and thymectomy. Proton pump inhibitors or somatostatin analogs are the main management for oversecretion of entero-pancreatic hormones, except insulin. The roles for surgery of most entero-pancreatic tumors present several controversies: exclusion of most operations on gastrinomas and indications for surgery on other tumors. Each MEN1 family probably has an inactivating MEN1 germline mutation. Testing for a germline MEN1 mutation gives useful information, but rarely mandates an intervention. The most distinctive MEN2 variants are MEN2A, MEN2B, and familial medullary thyroid cancer (MTC). They vary in aggressiveness of MTC and spectrum of disturbed organs. Mortality in MEN2 is greater from MTC than from pheochromocytoma. Thyroidectomy, during childhood if possible, is the goal in all MEN2 carriers to prevent or cure MTC. Each MEN2 index case probably has an activating germline RET mutation. RET testing has replaced calcitonin testing to diagnose the MEN2 carrier state. The specific RET codon mutation correlates with the MEN2 syndromic variant, the age of onset of MTC, and the aggressiveness of MTC; consequently, that mutation should guide major management decisions, such as whether and when to perform thyroidectomy.

PMID 11739416
Renehan AG, Tyson M, Egger M, Heller RF, Zwahlen M.
Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies.
Lancet. 2008 Feb 16;371(9612):569-78. doi: 10.1016/S0140-6736(08)60269-X.
Abstract/Text BACKGROUND: Excess bodyweight, expressed as increased body-mass index (BMI), is associated with the risk of some common adult cancers. We did a systematic review and meta-analysis to assess the strength of associations between BMI and different sites of cancer and to investigate differences in these associations between sex and ethnic groups.
METHODS: We did electronic searches on Medline and Embase (1966 to November 2007), and searched reports to identify prospective studies of incident cases of 20 cancer types. We did random-effects meta-analyses and meta-regressions of study-specific incremental estimates to determine the risk of cancer associated with a 5 kg/m2 increase in BMI.
FINDINGS: We analysed 221 datasets (141 articles), including 282,137 incident cases. In men, a 5 kg/m2 increase in BMI was strongly associated with oesophageal adenocarcinoma (RR 1.52, p<0.0001) and with thyroid (1.33, p=0.02), colon (1.24, p<0.0001), and renal (1.24, p <0.0001) cancers. In women, we recorded strong associations between a 5 kg/m2 increase in BMI and endometrial (1.59, p<0.0001), gallbladder (1.59, p=0.04), oesophageal adenocarcinoma (1.51, p<0.0001), and renal (1.34, p<0.0001) cancers. We noted weaker positive associations (RR <1.20) between increased BMI and rectal cancer and malignant melanoma in men; postmenopausal breast, pancreatic, thyroid, and colon cancers in women; and leukaemia, multiple myeloma, and non-Hodgkin lymphoma in both sexes. Associations were stronger in men than in women for colon (p<0.0001) cancer. Associations were generally similar in studies from North America, Europe and Australia, and the Asia-Pacific region, but we recorded stronger associations in Asia-Pacific populations between increased BMI and premenopausal (p=0.009) and postmenopausal (p=0.06) breast cancers.
INTERPRETATION: Increased BMI is associated with increased risk of common and less common malignancies. For some cancer types, associations differ between sexes and populations of different ethnic origins. These epidemiological observations should inform the exploration of biological mechanisms that link obesity with cancer.

PMID 18280327
日本内分泌外科学会 甲状腺腫瘍診療ガイドライン作成委員会編. 甲状腺腫瘍診療ガイドライン2024. 内分泌外会誌, 2024; 41(Suppl2).
日本超音波医学会用語・診断基準委員会編:甲状腺結節(腫瘤)超音波診断基準.超音波医学 2011;38 (1): 27-30.(説明:1991年に公示されたBモードによる甲状腺結節の超音波診断基準の改訂版).
Bongiovanni M, Spitale A, Faquin WC, Mazzucchelli L, Baloch ZW.
The Bethesda System for Reporting Thyroid Cytopathology: a meta-analysis.
Acta Cytol. 2012;56(4):333-9. doi: 10.1159/000339959. Epub 2012 Jul 25.
Abstract/Text OBJECTIVE: We aimed to investigate the validity of the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) through meta-analysis.
STUDY DESIGN: All publications between January 1, 2008 and September 1, 2011 that studied TBSRTC and had available histological follow-up data were retrieved. To calculate the sensitivity, specificity and diagnostic accuracy, the cases diagnosed as follicular neoplasm, suspicious for malignancy and malignant which were histopathologically confirmed as malignant were defined as true-positive. True-negative included benign cases confirmed as benign on histopathology. The nondiagnostic category was excluded from the statistical calculation. The correlations between the 6 diagnostic categories were investigated.
RESULTS: The publications review resulted in a case cohort of 25,445 thyroid fine-needle aspirations, 6,362 (25%) of which underwent surgical excision; this group constituted the basis of the study. The sensitivity, specificity and diagnostic accuracy were 97, 50.7 and 68.8%, respectively. The positive predictive value and negative predictive value were 55.9 and 96.3%, respectively. The rates of false negatives and false positives were low: 3 and 0.5%, respectively.
CONCLUSIONS: The results of meta-analysis showed high overall accuracy, indicating that TBSRTC represents a reliable and valid reporting system for thyroid cytology.

Copyright © 2012 S. Karger AG, Basel.
PMID 22846422
Yousef A, Clark J, Doi SA.
Thyroxine suppression therapy for benign, non-functioning solitary thyroid nodules: a quality-effects meta-analysis.
Clin Med Res. 2010 Dec;8(3-4):150-8. doi: 10.3121/cmr.2010.881. Epub 2010 Aug 25.
Abstract/Text Levothyroxine (LT4) suppressive therapy for solitary thyroid nodules is not popularly advocated presently because its clinical efficacy and safety are currently considered controversial. This meta-analysis aims to address efficacy issues by using rigorous methods to arrive at a pooled estimate. On the basis of the analysis, it is estimated that LT4 therapy is clearly associated with up to a two-fold increase in the chance of nodule reduction. This translates to a number needed to treat (NNT) of 6 or a 50% decrease in the risk of cancer given nodule reduction. Keeping this definition of efficacy in mind and a low incidence of adverse events with low level LT4 suppression, such an intervention might be appropriate in patients selected on the basis of a low risk for adverse effects.

PMID 20739581
Bandeira-Echtler E, Bergerhoff K, Richter B.
Levothyroxine or minimally invasive therapies for benign thyroid nodules.
Cochrane Database Syst Rev. 2014 Jun 18;2014(6):CD004098. doi: 10.1002/14651858.CD004098.pub2. Epub 2014 Jun 18.
Abstract/Text BACKGROUND: Thyroid nodules (TN) are common in the adult population. Some physicians use suppressive levothyroxine (LT4) therapy to achieve a reduction in the number and volume of TN. In addition, minimally invasive treatments, such as percutaneous ethanol injection (PEI) sclerotherapy, laser photocoagulation (LP), and microwave (MW), radiofrequency (RF) and high-intensity focused ultrasound (HIFU) ablation, have been proposed, especially for pressure symptoms and cosmetic complaints, as an alternative to surgery. However, the risk to benefit ratio of all treatments for benign TN is currently unknown.
OBJECTIVES: To assess the effects of LT4 or minimally invasive therapies (PEI, LP, and RF/HIFU/MW ablation) on benign TN.
SEARCH METHODS: We identified studies from computerised searches of The Cochrane Library, MEDLINE, EMBASE and LILACS (all performed up to April 2014). We also searched trial registers, examined reference lists of included randomised controlled trials (RCTs) and systematic reviews, and contacted study authors.
SELECTION CRITERIA: We included studies if they were RCTs of LT4, PEI, LP, RF, HIFU or MW therapy in participants with an established diagnosis of benign TN. We excluded trials investigating the prevention of recurrence of thyroid disease after surgery, irradiation or treatment with radioiodine.
DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data, assessed studies for risk of bias and evaluated overall study quality utilising the GRADE instrument. We assessed the statistical heterogeneity of included studies by visually inspecting forest plots and quantifying the diversity using the I² statistic. We synthesised data using random-effects model meta-analysis or descriptive analysis, as appropriate.
MAIN RESULTS: Thirty-one studies randomised 2952 outpatients to investigate the effects of different therapies on benign TN. Studies on LT4, PEI, LP and RF ablation therapy randomised 2083, 607, 192 and 70 participants, respectively. We found no RCTs of HIFU or MW ablation therapy in benign TN. The duration of treatment varied according to the applied therapies: up to five years for LT4 and one to three PEI ablations, one to three LP sessions and one or two RF sessions. Median follow-up was 12 months for LT4 and six months for minimally invasive therapies. Evidence was of low-to-moderate quality, and risk of performance and detection bias for subjective outcomes was high in most trials.No study evaluated all-cause mortality or health-related quality of life. Only one LT4 study provided some data on the development of thyroid cancer, reporting no abnormal cytological findings. One LP study provided limited information on costs of treatment.LT4 compared with no treatment or placebo was associated with a nodule volume reduction of 50% or more in 16% compared with 10% of participants after 6 to 24 months of follow-up (risk ratio (RR) 1.57 (95% confidence interval (CI) 1.04 to 2.38); P = 0.03; 958 participants; 10 studies; moderate-quality evidence). Pressure symptoms or cosmetic complaints were not investigated in LT4 studies. LT4 therapy was generally well tolerated: three studies provided quantitative data on signs and symptoms of hyperthyroidism, which were observed in 25% of LT4-treated versus 7% of placebo-treated participants at 12 to 18 months of follow-up (269 participants; 3 trials; low-quality evidence).PEI compared with cyst aspiration only was associated with a nodule volume reduction of 50% or more in 83% compared with 44% of participants after 1 to 24 months of follow-up (RR 1.83 (95% CI 1.32 to 2.54); P = 0.0003; 105 participants; 3 studies; low-quality evidence). Improvements in neck compression symptoms after 6 to 12 months of follow-up were seen in 78% of participants receiving PEI versus 38% of those in comparator groups. No reliable summary effect estimate could be established, RR ranged from 1.0 to 3.06 in favour of PEI (370 participants; 3 trials; low-quality evidence). In all trials, participants experienced periprocedural cervical tenderness and light-to-moderate pain usually lasting from minutes to several hours. As a result of the PEI procedure, 26% of participants reported slight-to-moderate pain compared with 12% of those receiving cyst aspiration only (RR 1.78 (95% CI 0.62 to 5.12); P = 0.28; 104 participants; 3 studies; low-quality evidence).One study comparing LP with LT4 showed a nodule volume reduction of 50% or more in favour of LP after 12 months of follow-up in 33% of LP participants versus 0% of LT4 participants, respectively (62 participants; 1 trial; low-quality evidence). A total of 82% of LP-treated versus 0% of untreated participants showed improvements in pressure symptoms after 6 to 12 months of follow-up (RR 26.65 (95% CI 5.47 to 129.72); P < 0.0001; 92 participants; 3 trials; low-quality evidence). Around 20% of LP-treated participants reported light-to-moderate cervical pain lasting 48 hours or more (97 participants; 3 trials; low-quality evidence).One trial with 40 participants, comparing RF with no treatment, resulted in a mean nodule volume reduction of 76% in the RF group compared with 0% of those in the no-treatment group at six months of follow-up (low-quality evidence). These RF-treated participants had fewer pressure symptoms and cosmetic complaints after 12 months of follow-up compared with untreated participants (a 2.8 decrease versus a 1.1 increase on a six-point scale, respectively, with higher values indicating more severe symptoms; low-quality evidence). All participants complained of pain and discomfort during RF, which disappeared when the energy was reduced or turned off (low-quality evidence).
AUTHORS' CONCLUSIONS: No study evaluated all-cause mortality, health-related quality of life or provided systematic data on the development of thyroid cancer. Longest follow-up was five years and median follow-up was 12 months. Nodule volume reductions were achieved by PEI, LP and RF, and to a lesser extent, by LT4. However, the clinical relevance of this outcome measure is doubtful. PEI, LP and RF led to improvements in pressure symptoms and cosmetic complaints. Adverse events such as light-to-moderate periprocedural pain were seen after PEI, LP and RF. Future studies should focus on patient-important outcome measures, especially health-related quality of life, and compare minimally invasive procedures with surgery. RCTs with follow-up periods of several years and good-quality observational studies are needed to provide evidence on the development of thyroid cancer, all-cause mortality and long-term adverse events.

PMID 24941398
薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、渡邉裕次、井ノ口岳洋、梅田将光および日本医科大学多摩永山病院 副薬剤部長 林太祐による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、 著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※同効薬・小児・妊娠および授乳中の注意事項等は、海外の情報も掲載しており、日本の医療事情に適応しない場合があります。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適応の査定において保険適応及び保険適応外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適応の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
三宅成智 : 特に申告事項無し[2025年]
監修:森山寛 : 特に申告事項無し[2025年]
監修:小島博己 : 特に申告事項無し[2025年]

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