Thyroid carcinoma

doi:10.1016/S0140-6736(03)12488-9

The Lancet

Volume 361, Issue 9356, 8 February 2003, Pages 501-511

https://doi.org/10.1016/S0140-6736(03)12488-9 Get rights and content

Summary

Thyroid carcinomas are fairly uncommon and include disease types that range from indolent localised papillary carcinomas to the fulminant and lethal anaplastic disease. Several attempts to formulate a consensus about treatment of thyroid carcinoma have resulted in published guidelines for diagnosis and initial disease management. Multimodality treatments are widely recommended, although there is little evidence from prospective trials to support this approach. Surgical resection to achieve local disease control remains the cornerstone of primary treatment for most thyroid cancers, and is often followed by adjuvant radioiodine treatment for papillary and follicular types of disease. Thyroid hormone replacement therapy is used not only to rectify postsurgical hypothyroidism, but also because there is evidence to suggest that high doses that suppress thyroid stimulating hormone prevent disease recurrence in patients with papillary or follicular carcinomas. Treatment for progressive metastatic disease is often of limited benefit, and there is a pressing need for novel approaches in treatment of patients at high risk of disease-related death. In families with inherited thyroid cancer syndromes, early diagnosis and intervention based on genetic testing might prevent poor disease outcomes. Care should be carefully coordinated by members of an experienced multidisciplinary team, and patients should be provided with education about diagnosis, prognosis, and treatment options to allow them to make informed contributions to decisions about their care.

Section snippets

Diagnosis

Patients with thyroid carcinoma (figure 1) usually present with a solitary thyroid nodule. Cytological examination of a fine-needle aspirate of the nodule is the appropriate initial diagnostic procedure.¹² Papillary, medullary, and anaplastic carcinomas can be readily diagnosed on the basis of the results of such examination. To distinguish between follicular carcinoma and benign follicular adenoma, histological examination needs to be done (figure 2) and show either invasion through the tumour

Differentiated thyroid carcinoma

Differentiated thyroid carcinoma is diagnosed in women twice as often as in men, with a median age at diagnosis of about 45 years. In regions of iodine insufficiency, follicular is more common than papillary thyroid carcinoma. External radiation, especially during early childhood, is associated with an excess relative risk for malignant disease of the thyroid of 3–9 per Gy.²⁵ Exposure to internal sources of radiation after the Chernobyl nuclear accident led to a 3–75-fold increase in the

Medullary thyroid carcinoma

Medullary thyroid carcinoma derives from the neuroendocrine C cells of the thyroid.¹²⁵ Sporadic disease accounts for 80% of all cases; the remainder of patients have inherited tumour syndromes such as multiple endocrine neoplasia type 2A (medullary thyroid carcinoma, multigland parathyroid tumours, and unilateral or bilateral phaeochromocytoma), type 2B (medullary thyroid carcinoma, phaeochromocytoma, mucosal neuromas, and marfanoid habitus), or familial medullary carcinoma.¹⁰ In type 2A, signs

Anaplastic thyroid carcinoma

Anaplastic thyroid carcinoma is associated with a disease-specific mortality of almost 100%.155, 156, 157, 158, 159, 160 Fewer than 10% of patients are younger than 50 years, and 60 to 70% are women.² About half of patients with anaplastic cancer have a previous or coexistent differentiated thyroid carcinoma, with evidence of dedifferentiation from more differentiated tumours often associated with loss of the TP53 tumour suppressor protein.¹⁶¹ Patients with anaplastic carcinoma usually present

Search strategy

MEDLINE database was searched for information about diagnostic and treatment of thyroid carcinoma published from 1966 to April, 2002. A review of reference lists expanded the searches. Recently published reports of consensus guidelines were used as an additional source of references, and these guidelines are cited wherever appropriate. The author's personal research and clinical experiences were incorporated in the final selection of references.

Conflict of interest statement

The author has

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Comparison of Body Iodine Pool Assessment Methods Before Radioiodine Therapy
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El tratamiento con yodo radiactivo (RAIT) se recomienda para reducir el riesgo de recurrencia y de metástasis en personas con cáncer diferenciado de tiroides (CDT) de riesgo intermedio-alto. En la preparación para la RAIT, la estimulación de la tirotropina y la reducción en la reserva corporal de yodo son elementos importantes para contribuir al éxito de la terapia. Para ello, se pide a los pacientes que reduzcan la ingesta de este mineral antes de la RAIT, y puede evaluarse su reserva corporal midiendo su excreción por la orina (yoduria) antes del tratamiento. El objetivo de nuestro estudio ha sido comparar los métodos utilizados para medir la reserva de yodo corporal en la evaluación de la eficacia de la dieta con bajo contenido en yodo (RID) aplicada a la preparación del paciente para la RAIT.
Suspendieron la levotiroxina tres semanas antes de la RAIT y fueron controlados con una RID durante las dos semanas previas a la realización del tratamiento 80 pacientes con CDT. Tras dos semanas de RID, en todos se llevó a cabo una recolección de orina de 24 h el día previo a la fecha de administración de la RAIT. Los sujetos finalizaron dicha recolección en la mañana de la fecha de RAIT y suministraron una muestra puntual de orina. Se calculó la excreción estimada de creatinina en orina de 24 horas de los pacientes. La estimación de la excreción urinaria de yodo o yoduria (UIE) de 24 horas oras se determinó a partir del índice yodo/creatinina (I/C) obtenido en la muestra de orina puntual de los individuos. Se compararon los resultados de la yoduria de 24 horas, la concentración de yodo en la muestra puntual de orina, el cociente I/C en la muestra puntual de orina y la estimación de la yoduria de 24 horas en los pacientes.
En 99%, la eficacia de la RID fue suficiente según la yoduria de 24 horas obtenida previamente a la RAIT. La yoduria o UIE media de 24 horas fue de 48,81 mcg/d en las muestras de orina tomadas para evaluar su reserva corporal de yodo. Los valores de la concentración de yodo y el índice I/C, adquiridos ambos en la muestra puntual de orina de los pacientes, así como la yoduria estimada de 24 horas fueron todos ellos inferiores de forma estadísticamente significativa respecto a la yoduria real de 24 horas, que fue el método de referencia empleado (p 0,026 vs. < 0,001 vs. 0,041). Se detectó una correlación positiva moderada entre la yoduria de 24 horas y la concentración de yodo (r 0,440), el índice I/C, ambos en la muestra de orina puntual (r 0,493), y en la estimación de la yoduria de 24 horas (r 0,560). La correlación más estrecha se obtuvo con la yoduria o UIE estimada de 24 horas.
La estimación de la yoduria de 24 horas obtenida a partir del índice I/C de la muestra puntual de orina puede utilizarse de forma práctica y segura como alternativa a la determinación de la yoduria o UIE de 24 horas, que constituye el método de referencia para evaluar la reserva de yodo corporal.
Radioactive iodine therapy (RAIT) is recommended to reduce the risk of recurrence and metastasis in patients with intermediate-high risk differentiated thyroid cancer (DTC). In preparation for RAIT, stimulation of thyroid-stimulating hormone and reduction of body iodine pool are important for treatment success. For this purpose, patients are asked to reduce their iodine intake before RAIT, and the body iodine pool can be evaluated by measuring iodine excretion in urine before treatment. The aim of our study is to compare the methods used to measure the body iodine pool in the evaluation of the restricted iodine diet (RID) effectiveness applied in the RAIT preparation.
Eighty DTC patients discontinued levothyroxine three weeks before RAIT and followed up with a RID two weeks before treatment. After two weeks of RID, all patients collected their 24-hour urine the day before the RAIT date. Patients completed 24-hour urine samples on the morning of the RAIT date and also provided a spot urine sample. The estimated 24-hour creatinine excretion of the patients was calculated. Estimated 24-hour urinary iodine excretion (UIE) was calculated using the spot urine iodine/creatinine (I/C) ratio of the patients. 24-hour UIE, iodine concentration in spot urine, I/C ratios in spot urine and estimated 24-hour UIE of the patients were analyzed by comparing with each other.
In 99% of the patients, RID efficiency was sufficient according to 24-hour UIE before RAIT. The mean 24-hour UIE was 48.81 micrograms/day (mcg/day) in 24-hour urine samples taken from the patients to evaluate the body iodine pool. The patients’ iodine concentrations in spot urine, I/C ratios in spot urine, and estimated 24-hour UIE were all statistically significantly lower than actual 24-hour UIE, which was the reference method (p: 0.026 vs <0.001 vs 0.041). Moderate positive correlation between 24-hour UIE and iodine concentration in spot urine (r: 0.440), I/C ratio in spot urine (r: 0.493), and estimated 24-hour UIE (r: 0.560) found. The strongest correlation was obtained with the estimated 24-hour UIE.
The estimated 24-hour UIE obtained by using the I/C ratio in spot urine can be used practically and safely as an alternative to UIE in 24-hour urine, which is the gold standard method for evaluating body iodine pool.
A diagnostic model based on DNA methylation haplotype block characteristics for identifying papillary thyroid carcinoma from thyroid adenoma
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Papillary thyroid carcinoma (PTC) is the most prevalent form of thyroid cancer. Methylation of some genes plays a crucial role in the tendency to malignancy as well as poor prognosis of thyroid cancer, suggesting that methylation features can serve as complementary markers for molecular diagnosis. In this study, we aimed to develop and validate a diagnostic model for PTC based on DNA methylation markers. A total of 142 thyroid nodule tissue samples containing 84 cases of PTC and 58 cases of thyroid adenoma (TA) were collected for reduced representation bisulfite sequencing (RRBS) and subsequent analysis. The diagnostic model was constructed by the logistic regression (LR) method followed by 5-cross validation and based on 94 tissue methylation haplotype block (MHB) markers. The model achieved an area under the receiver operating characteristic curve (AUROC) of 0.974 (95% CI, 0.964-0.981) on 108 training samples and 0.917 (95% CI, 0.864-0.973) on 27 independent testing samples. The diagnostic model scores showed significantly high in males (P = 0.0016), age ≤ 45 years (P = 0.026), high body mass index (BMI) (P = 0.040), lymph node metastasis (P = 0.00052) and larger nodules (P = 0.0017) in the PTC group, and the risk score of this diagnostic model showed significantly high in recurrent PTC group (P = 0.0005). These results suggest that the diagnostic model can be expected to be a powerful tool for PTC diagnosis and there are more potential clinical applications of methylation markers to be excavated.
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A total of 97 PTC cN0 nodules with CLNM pathology data (pN0, with CLNM, n = 59; pN1, without CLNM, n = 38) in 85 patients were divided into a training set (n = 69) and a validation set (n = 28). For each lesion, 321 radiomic features were extracted from nonenhanced, arterial and venous phase CT images. Minimum redundancy and maximum relevance and the least absolute shrinkage and selection operator were used to find the most important features with which to develop a radiomics signature in the training set. The performance of the radiomics signature was evaluated by receiver operating characteristic curves, calibration curves and decision curve analysis .
Three nonzero the least absolute shrinkage and selection operator coefficient features were selected for radiomics signature construction. The radiomics signature for distinguishing the pN0 and pN1 groups achieved areas under the curve of 0.79 (95% CI 0.67, 0.91) in the training set and 0.77 (95% CI 0.55, 0.99) in the validation set. The calibration curves demonstrated good agreement between the radiomics score-predicted probability and the pathological results in the two sets (p= 0.399, p = 0.191). The decision curve analysis curves showed that the model was clinically useful.
This radiomic signature could be helpful to predict CLNM status in cN0 PTC patients.
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SeminarThyroid carcinoma

Summary

Section snippets

Diagnosis

Differentiated thyroid carcinoma

Medullary thyroid carcinoma

Anaplastic thyroid carcinoma

Search strategy

Eur J Cancer

Lancet

Semin Nucl Med

Endocrinol Metab Clin North Am

Am J Hum Genet

Surgery

Eur J Cancer

Am J Med

Endocrinol Metab Clin North Am

Surgery

Surg Oncol Clin N Am

Surg Clin N Am

Surg Oncol Clin N Am

Endocrinol Metab Clin North Am

Surgery

Epidemiology of thyroid cancer

Prognostic factors for thyroid carcinoma: A population-based study of 15,698 cases from the Surveillance, Epidemiology and End Results (SEER) program 1973–1991

Cancer

Distant metastases in papillary thyroid carcinoma: 100 cases observed at one institution during 5 decades

J Clin Endocrinol Metab

An audit of management of differentiated thyroid cancer in specialist and non-specialist clinic settings

Clin Endocrinol (Oxf)

Guidelines for the management of thyroid cancer in adults

AACE/AAES medical/surgical guidelines for clinical practice: Management of thyroid carcinoma

Endocr Pr

NCCN practice guidelines for thyroid cancer, version 2001

Guidelines for diagnosis and therapy of MEN type 1 and type 2

J Clin Endocrinol Metab

Treatment guidelines for patients with thyroid nodules and well-differentiated thyroid cancer

Arch Intern Med

Usefulness of fine-needle aspiration in the diagnosis of thyroid carcinoma: a retrospective study in 37,895 patients

Cancer

Fine-needle aspiration biopsy of the thyroid: an appraisal

Ann Intern Med

Diagnosis of “follicular neoplasm”: a gray zone in thyroid fine-needle aspiration cytology

Diagn Cytopathol

Indeterminate fine-needle aspiration biopsy of the thyroid. Identification of subgroups at high risk for invasive carcinoma

Surgery

Clinical features associated with an increased risk of thyroid malignancy in patients with follicular neoplasia by fine-needle aspiration

Thyroid

Randomized prospective evaluation of frozen-section analysis for follicular neoplasms of the thyroid

Ann Surg

The value of frozen section examinations in determining the extent of thyroid surgery in patients with indeterminate fine-needle aspiration cytology

Arch Otolaryngol Head Neck Surg

Fine-needle aspiration cytology of the thyroid: an appraisal

Cancer

Thyroid incidentalomas. Prevalence by palpation and ultrasonography

Arch Intern Med

Thyroid incidentalomas: management approaches to nonpalpable nodules discovered incidentally on thyroid imaging

Ann Intern Med

Radiation and thyroid cancer

Post-Chernobyl thyroid carcinoma in Belarus children and adolescents: comparison with naturally occurring thyroid carcinoma in Italy and France

J Clin Endocrinol Metab

Familial papillary thyroid carcinoma: genetics, criteria for diagnosis, clinical features, and surgical treatment

World J Surg

Is familial non-medullary thyroid carcinoma more aggressive than sporadic thyroid cancer? A multicenter series

Surgery

Molecular pathogenesis of tumors of thyroid follicular cells

Proximity of chromosomal loci that participate in radiation-induced rearrangements in human cells

Science

Genetic and epigenetic alterations of the cyclin-dependent kinase inhibitors p15INK4b and p16INK4a in human thyroid carcinoma cell lines and primary thyroid carcinomas

Cancer

Mechanisms of aneuploidy in thyroid cancer cell lines and tissues: evidence for mitotic checkpoint dysfunction without mutations in BUB1 and BUBR1

Clin Endocrinol (Oxf)

The RAS oncogene induces genomic instability in thyroid PCCL3 cells via the MAPK pathway

Oncogene

PAX8-PPARgamma1 fusion oncogene in human thyroid carcinoma [corrected]

Science

branded from the start-distinct oncogenic initiating events may determine tumor fate in the thyroid

Mol Endocrinol

An expanded view of risk-group definition in differentiated thyroid carcinoma

Surgery

Seminar
Thyroid carcinoma