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[Treatment of patient having thyroid nodules: dimension of disease, diagnostic choices and guide-lines].

UNLABELLED: The demand of nodule thyroid diagnosis has increased very much in the last years, because of large diffusion of medical information among the population, the increased use and improvement of medical technology that evidences more and more morphology alterations of the gland. The prevalence of palpable thyroid nodule is 2.1-4.2%, but when the ultrasonography is used the prevalence can reach in average 67%. The thyroid cancer however is a rare event: 1% of all malign tumours. The medium incidence is 2.1 for 100,000 men per year, and 5.19 for 100,000 women per year. pretest illness low probability presents a necessity of a very accurate diagnostic test. The introduction of FNA in the 70 has changed the diagnosis, and allowed to spare time and money. The patient with thyroid nodules should be evaluated by experienced physicians in the thyreopathy field, using efficient remote and family anamnesis, by an accurate palpation of the thyroid and the neck, cl AIM: ing necessary diagnostic controls. The physician should perform the FNA with a cytopathologist and should convey to him all the clinical and biotumoral information. He should be able to interpret correctly the results of the FNA and to suggest the diagnostic and therapeutical follow-up. This review reveals the best compromise between cost-effectiveness, based on the evidence results taken from international literature, taking into consideration various diagnostic opportunities at our disposal. Guide-lines for the treatment of patients with thyroid nodule are proposed.

Age Factors↗

Increased binding capacity of receptors for the epidermal growth factor in benign thyroid nodules and thyroid malignancies.

To determine the role of epidermal growth factor (EGF) receptors in thyroid tumorigenesis, EGF binding was compared in membranes from malignant and from benign thyroid tumors. Surgical specimens were obtained from 28 patients with thyroid carcinomas (3 papillary, 13 follicular, 6 undifferentiated, and 6 medullary carcinomas) and from 30 patients with benign thyroid tumors (15 scintigraphically functional and 15 nonfunctional nodules). In 30 cases normal tissue adjacent to the tumor was also obtained. EGF binding was seen to be increased not only in thyroid carcinomas but also in benign thyroid tumors, particularly in functional thyroid adenomas. The highest EGF binding was found in undifferentiated carcinomas. A direct comparison of the EGF binding characteristics in tumor and adjacent normal thyroid tissue revealed that the increased binding of EGF is due mainly to an increase in the number of binding sites rather than an alteration in receptor affinities. EGF binding capacities were 18.4 +/- 16.7 fmol/mg protein in thyroid carcinomas and 10.5 +/- 5.2 fmol/mg in the corresponding normal tissue (P < 0.05, Kd 0.84 +/- 0.26 nM, n = 11). In autonomously functioning thyroid adenomas binding capacities were 14.2 +/- 8.2 fmol/mg in the nodules and 8.9 +/- 4.8 fmol/mg in normal tissue (P < 0.01, Kd 0.73 +/- 0.62 nM, n = 15). In conclusion, EGF receptor levels are increased not only in malignant thyroid tumors but also in well-differentiated benign thyroid nodules.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

The frequency of cold thyroid nodules and thyroid malignancies in patients from an iodine-deficient area.

An analysis of thyroid cancer morbidity was carried out in two adjacent areas of Sicily differing in iodine intake. A consecutive series of 911 patients with "cold" nodules from an iodine-deficient area (IDA) and 2537 from a control area (CA) were examined by fine needle aspiration and selected for surgery and pathologic examination. Malignancies were found in 27 of the patients (2.96%) from the IDA and in 139 patients (5.48%) from the CA. Based on a population survey indicating that "cold" thyroid nodules were 2.5 times more frequent in the IDA with respect to the CA, we calculated a prevalence of 127 thyroid cancers per 10(5) inhabitants in the IDA versus 93 in the CA (P less than 0.001). Moreover, follicular and anaplastic carcinomas were three times more frequent in the IDA than in the CA (75 versus 24 cases per 10(5) inhabitants, respectively). These studies indicate that iodine deficiency may be one factor in the development of certain thyroid malignancies in man.

Adenocarcinoma↗

Radiation dose-response relationships for thyroid nodules and autoimmune thyroid diseases in Hiroshima and Nagasaki atomic bomb survivors 55-58 years after radiation exposure.

CONTEXT: Effects of irradiation on thyroid diseases such as thyroid nodules and autoimmune thyroid diseases have not been evaluated among people exposed to radiation more than 50 years in the past. OBJECTIVE: To evaluate the prevalence of thyroid diseases and their radiation-dose responses in atomic bomb survivors. DESIGN, SETTING, AND PARTICIPANTS: Survey study comprising 4091 cohort members (mean age, 70 [SD, 9] years; 1352 men and 2739 women) who participated in the thyroid study at the Radiation Effects Research Foundation. Thyroid examinations were conducted between March 2000 and February 2003. MAIN OUTCOME MEASURES: Prevalence of thyroid diseases, including thyroid nodules (malignant and benign) and autoimmune thyroid diseases, and the dose-response relationship of atomic bomb radiation in each thyroid disease. RESULTS: Thyroid diseases were identified in 1833 (44.8%) of the total participants (436 men [32.2% of men] and 1397 women [51.0% of women]) (P<.001). In 3185 participants, excluding persons exposed in utero, not in the city at the time of the atomic bombings, or with unknown radiation dose, the prevalence of all solid nodules, malignant tumors, benign nodules, and cysts was 14.6%, 2.2%, 4.9%, and 7.7%, respectively. The prevalence of positive thyroid antibodies, antithyroid antibody-positive hypothyroidism, and Graves disease was 28.2%, 3.2%, and 1.2%, respectively. A significant linear dose-response relationship was observed for the prevalence of all solid nodules, malignant tumors, benign nodules, and cysts (P<.001). We estimate that about 28% of all solid nodules, 37% of malignant tumors, 31% of benign nodules, and 25% of cysts are associated with radiation exposure at a mean and median thyroid radiation dose of 0.449 Sv and 0.087 Sv, respectively. No significant dose-response relationship was observed for positive antithyroid antibodies (P = .20), antithyroid antibody-positive hypothyroidism (P = .92), or Graves disease (P = .10). CONCLUSIONS: A significant linear radiation dose response for thyroid nodules, including malignant tumors and benign nodules, exists in atomic bomb survivors. However, there is no significant dose response for autoimmune thyroid diseases.

Aged↗

Optimal laboratory testing for diagnosis and monitoring of thyroid nodules, goiter, and thyroid cancer.

Optimal use of laboratory tests to diagnose and monitor patients with goiter, thyroid nodules, or thyroid cancer requires an appreciation of the pathophysiologic factors implicated in thyroid hyperplasia and neoplasia: growth factors (especially thyrotropin, TSH), growth-stimulating immunoglobulins, activating mutations of the TSH receptor, and other oncogenic transformations. In patients with diffuse goiter and thyroid nodules, serum TSH measurement in a highly sensitive assay excludes both primary hypothyroidism and common causes of thyrotoxicosis. In selected patients, screening for anti-thyroid peroxidase with or without anti-thyroglobulin antibodies can confirm the diagnosis of autoimmune thyroiditis. Serum calcitonin measurement is appropriate only when medullary thyroid carcinoma (MTC) is clinically suspected. Laboratory testing is essential in management of thyroid carcinoma patients after primary surgical therapy. Serum TSH measurement is vital to ensure that thyroxine replacement and TSH suppression are adequate in treatment of epithelial cancers. Serial monitoring of serum thyroglobulin (Tg) can detect tumor recurrence and quantify tumor burden. Interpretation of serum Tg results requires an appreciation of certain technical considerations (e.g., anti-Tg antibody interference) and the patient's concurrent TSH status. Periodic serum Tg measurements and 131I scans are complementary monitoring techniques. Serum calcitonin measurement and screening for ret protooncogene mutations are both valuable for identifying individuals with MTC.

Diagnosis, Differential↗

Meta- and reanalysis of gene expression profiles of hot and cold thyroid nodules and papillary thyroid carcinoma for gene groups.

CONTEXT: There are an increasing number of studies analyzing gene expression profiles in various benign and malignant thyroid tumors. This creates the opportunity to validate results obtained from one microarray study with those from other data sets. This process requires rigorous methods for accurate comparison. OBJECTIVE: The ability to compare data sets derived from different Affymetrix GeneChip generations and the influence of intra- and interindividual comparisons of gene expression data were evaluated to build multigene classifiers of benign thyroid nodules to verify a previously proposed papillary thyroid carcinoma (PTC) classifier and to look for molecular pathways essential for PTC oncogenesis. METHODS: Gene expression profile data sets from autonomously functioning and cold thyroid nodules and from PTC were analyzed by support vector machines. GenMAPP analysis was used for PTC data analysis to examine the expression patterns of biologically relevant gene sets. RESULTS: Only intraindividual reference samples allowed the identification of subtle changes in the expression patterns of relevant signaling cascades, such as the MAPK pathway in PTC. Using an artificial intelligence approach, the autonomously functioning and cold thyroid nodule multigene classifiers were derived and evaluated by cross-comparisons. CONCLUSION: We recommend defining classifiers within one generation of gene chips and subsequently checking them across different array generations. Using this approach, we have demonstrated the specificity of a previously reported PTC classifier on an independent collection of benign tumors. Moreover, we propose multigene classifiers for different types of benign thyroid nodules.

Algorithms↗

Interobserver variation for ultrasound determination of thyroid nodule volumes.

Thyroid ultrasound is used in the routine clinical assessment and the follow-up of thyroid disorders. The follow- up of patients with thyroid nodules is mostly based on thyroid nodule volume determinations performed by different observers. However, for the judgment of treatment effects there is uncertainty about the interobserver variation of thyroid nodule volume measurements by ultrasound because there are no prospective blinded studies available comparing the interobserver variation in thyroid nodule volume measurement. The aim of our study was therefore to determine the variation of thyroid nodule volume determinations for different observers. We conducted a prospective blinded trial. Our study population consisted of 42 probands (8 men, 34 women) with an uniform distribution of thyroid nodule sizes (25 uninodular and 17 multinodular thyroid glands). We compared the results of 3 ultrasonographers with certified experience in thyroid ultrasound. The interobserver variation for the determination of thyroid nodule volume (n = 38) was 48.96% for the ellipsoid method and 48.64% for the planimetric method. The interobserver variation for determining thyroid volume (n = 40) was 23.69% for the ellipsoid method and 17.82% for the planimetric method. A regression analysis revealed that the probability for the identification of the same nodule in nodular thyroids by all sonographers is 90%, if the nodule is at least 15mm in greatest diameter. Future investigations should not describe changes in nodule volume less than 50% as therapy effects because only volume changes of at least 49% or more can be interpreted as nodule shrinkage or growth. Reporting of nodule volume modification 50% or more and lack of information for ultrasound procedures introduce a bias in studies evaluating the effects of nodule treatments. The clinical interpretation of a shrinking/growing thyroid nodule based on volume determinations by ultrasound is not well established because it is difficult to reproduce a two-dimensional image plane for follow-up studies.

Adult↗

Evaluation of the thyroid nodule.

BACKGROUND: Thyroid nodules are common, yet treatment modalities range from observation to surgical resection. Because thyroid nodules are frequently found incidentally during routine physical examination or imaging performed for another reason, physicians from a diverse range of specialties encounter thyroid nodules. Clinical decision making depends on proper evaluation of the thyroid nodule. METHODS: The current literature was reviewed and synthesized. RESULTS: Current evidence allows the formulation of recommendations and a general algorithm for evaluating the incidental thyroid nodule. CONCLUSIONS: Only a small percentage of thyroid nodules require surgical management. Diagnosis and treatment selection require a risk stratification by history, physical examination, and ancillary tests. Nodules causing airway compression or those at high risk for carcinoma should prompt evaluation for surgical treatment. In nodules larger than 1 cm, fine-needle aspiration biopsy is central to the evaluation as it is accurate, low risk, and cost effective. Subcentimeter nodules, often found incidentally on imaging obtained for another purpose, can usually be evaluated by ultrasonography. Other laboratory and imaging evaluations have specific and more limited roles. An algorithm for the evaluation of the thyroid nodule is presented.

Biopsy, Fine-Needle↗

Natural history of benign solid and cystic thyroid nodules.

BACKGROUND: Thyroid nodules are common and most often benign. The natural history of benign thyroid nodules, however, is unclear. OBJECTIVE: To determine the natural history of cytologically benign thyroid nodules using ultrasonography. DESIGN: Retrospective case series. SETTING: Single tertiary care clinic. PARTICIPANTS: All patients referred to the Brigham and Women's Hospital Thyroid Nodule Clinic, Boston, Massachusetts, who had benign cytologic results on ultrasonography-guided fine-needle aspiration of a thyroid nodule between 1995 and 2000 and returned for a requested follow-up examination 1 month to 5 years later. MEASUREMENTS: Nodule dimensions were measured at both visits, and growth was defined as an increase in calculated volume of 15% or greater. These results were correlated with the time between examinations, age, sex, baseline serum thyroid-stimulating hormone concentration, and cystic content of each nodule. RESULTS: Nodule volume increased over time (P < 0.001). The estimated proportion of nodules with an increase in volume of 15% or greater after 5 years was 89%. Nodules with greater cystic content were less likely to grow than solid nodules (P = 0.01). Seventy-four of the 330 nodules were reaspirated on the second visit. Despite an average increase in volume of 69%, only 1 of 74 reaspirated nodules was malignant. CONCLUSION: Most solid, benign thyroid nodules grow. Therefore, an increase in nodule volume alone is not a reliable predictor of malignancy.

Biopsy, Needle↗