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Evaluation of thyroid nodules challenges the most astute clinician. The history and the physical examination often identify those patients who require immediate surgical management. In other patients, time-honored thyroid function studies and thyroid scanning are helpful. Fine needle aspiration and computed tomography are also valuable in the diagnostic work-up.
BACKGROUND: Disorders of the thyroid are common in pregnancy. In particular, a thyroid nodule is frequently discovered before or during pregnancy. OBJECTIVE: To develop guidelines for the management of thyroid nodules during pregnancy. METHODS: We reviewed the cases of 40 pregnant patients with thyroid nodules evaluated during a 10-year period Cytological findings were compared with available histological findings, and concordance rates were determined. The rank sum test was used for statistical analysis. RESULTS: Fine-needle aspirations of thyroid nodules in 62% of patients were benign cytologically (25 patients). Of 8 patients with negative cytological results who had thyroidectomy, all had benign disease histologically (100% concordance rate). Cytological findings of papillary cancer (3 patients) strongly correlated with final histological diagnosis (100% concordance rate), whereas papillary cancer was confirmed histologically in only 2 of 4 patients with cytological findings suspicious for this disease (50% concordance rate). All 3 nodules with cytological findings suspicious for follicular neoplasm were benign adenomas histologically. Of 2 nodules suspicious for Hürthle cell neoplasm, l was Hürthle cell adenoma and the other was Hürthle cell carcinoma (100% concordance rate). Thyroidectomy during the second trimester of pregnancy or the early postpartum period was successful. CONCLUSIONS: The approach to thyroid nodules in pregnancy should be similar to that for nonpregnant patients. Thyroidectomy should be performed (1) during the second trimester for malignant lesions and cytological findings suspicious for papillary cancer and (2) in the postpartum period for cytological findings suspicious for follicular neoplasm.
A "cold" thyroid nodule basically always carries the risk of being "malignant". Scintigraphy and sonography can not differentiate between benign and malignant. The best means to discriminate the risk of "cold nodules" is by way of fine needle aspiration biopsy. In general the operative indication for "cold" nodules can be generous. In high suspicion the best surgical strategy is "hemithyroidectomy" as primary operation.
Thyroid nodules are commonly found in clinical practice, and their detection by either the physician or the patients always gives rise to concern as to the possible existence of a malignancy. Technological developments have had a major impact on the study and treatment of thyroid nodules. The application of fine-needle aspiration biopsies (FNAB) and the availability of high-resolution thyroid ultrasonography have modified thyroid nodule management even if important differences of opinion remain. This article describes the progress as well as contemporary controversies in thyroid nodule diagnosis and considers the effect these advances have had on the treatment of patients with nodular disease. It includes a brief description of the clinical importance of thyroid nodules, of the use and limitations of imaging studies in thyroid nodule diagnosis and of the usefulness, limitations, and impact of FNAB on nodule management.
Thyroid nodules are infrequently encountered in children. During the era of low-dose therapeutic irradiation, the incidence of malignancy in these lesions was 40% to 70%. Recent studies suggest that this incidence is declining, resulting in a concomitant relative increase in the proportion of benign nodular conditions. There is also a heightened awareness that secondary thyroid neoplasms may occur in children surviving primary malignant diseases. Records of 38 children treated surgically at Texas Children's Hospital between 1972 and 1984 have been reviewed to determine the incidence of benign vs. malignant pathosis and to study the role of prior irradiation or chemotherapy in the pathogenesis of thyroid disease. Benign conditions were diagnosed in 27 children (71%), with diffuse hyperplasia (10 children, 26%) and follicular adenoma (8 children, 21%) occurring most frequently. Thyroid carcinoma was diagnosed in the remaining 11 children (29%). All of these patients were euthyroid at presentation, none had received multimodal therapy for a prior malignant condition, and only one had a history of head and neck irradiation in infancy for a treatment of a benign condition (a congenital hemangioma). The clinical presentation, diagnostic evaluation, and surgical management of these patients are reviewed and closely parallel those of patients in other recently published series. No conclusions can be drawn regarding the development of thyroid neoplasia following multimodal therapy for primary disease; however, this incidence must be very low.
We studied for 5 yr a homogeneous group of 83 patients randomly assigned to a levothyroxine (L-T4) suppressive therapy or to a control group to evaluate changes in nodule or thyroid size, appearance of new nodules, and correlations with clinical parameters. In the control group, mean nodule volume increased significantly after 5 yr (2.12 +/- 1.46 vs. 1.46 +/- 0.77 mL), whereas in the treatment group it decreased, although not significantly (1.45 +/- 1.17 mL vs. 1.53 +/- 0.61 mL). Baseline nodule volume was not different in the two groups, but a significant difference was observed at 5 yr. After 5 yr, sonograms detected 12 new nodules in the control group (28.5%) and 3 (7.5%) in the treatment group. Nodule shrinkage was more frequent in patients with complete TSH suppression, but no correlation was found with other parameters. A significant increase in thyroid size was observed in the control group. In conclusion, long term TSH suppression induced volume reduction in only a subgroup of thyroid nodules, but effectively prevented the appearance of new lesions and increases in nodule and thyroid volume. As the changes in the natural history of nodular goiter are related to prolonged TSH suppression, which can induce unfavorable side-effects, L-T4 suppressive therapy should be reserved for small nodules in younger patients.
Thyroid follicular adenomas and adenomatous thyroid nodules are a frequent finding in geographical areas with iodine deficiency. They occur as hypofunctioning (scintigraphically cold) or hyperfunctioning (scintigraphically hot) nodules. Their predominant clonal origin suggests that they result from clonal expansion of a single cell, which is very likely the result of a prolonged increase in proliferation compared with non-affected surrounding cells. To test whether increased cell proliferation is detectable in cold thyroid nodules, we studied paraffin-embedded tissue from 40 cold thyroid nodules and their surrounding normal thyroid tissue for the occurrence of the proliferating cell nuclear antigen (PCNA) and Ki-67 (MIB-1 antibody) epitopes as markers for cell proliferation. All 40 thyroid nodules were histologically well characterized and have been studied for molecular characteristics before. The labeling index (number of labeled cells versus total cell number) for nodular and surrounding tissue was calculated. In 33 cold thyroid nodules a significant (p < or = 0.05) increase in the labeling index for PCNA was detectable. In 19 cold thyroid nodules a significant (p < or = 0.05) increase in the labeling index for Ki-67 was detectable. Moreover, surrounding tissues with lymphocyte infiltration showed a significantly higher labeling index for both PCNA and Ki-67 compared with normal surrounding tissue. These findings are first evidence that an increased thyroid epithelial cell proliferation is a uniform feature common to most cold nodules. However, the increase of proliferation markers shows a heterogeneity that is not correlated with histopathologic, molecular, or clinical characteristics.
BACKGROUND: The management of cystic thyroid nodules has not been standardized with respect to an initial fine-needle aspiration cytology (FNAC) cystic change result, which is defined as fluid aspiration and a smear with numerous macrophages but scant or no follicular cells. In the present study the physical characteristics of cystic thyroid nodules predictive of the pathology were investigated, and recommendations made on their management. METHODS: The aspiration results of 1436 thyroid nodules managed between 1998 and 2000 were investigated. A total of 157 patients who had a subsequent operation or follow-up data with reaspiration were the subjects of the present study. Age, sex, nodule characteristics and others were examined as possible predictors of cancer risk. RESULTS: The malignancy rate was 8.9%. Ten cases (71%) of malignancy were not cytologically diagnosed. Male sex and a nodule size of > or = 4 cm were found to be statistically significant predictors of malignancy. The malignancy rate was highest (100%) when a cystic lesion had malignant cytology on reaspiration and local invasion on radiology. CONCLUSIONS: When a cystic change is observed by initial FNAC of thyroid nodules, nodules of > or = 4 cm must be reaspirated and a firm cytologic diagnosis made to rule out malignancy. Nodules should be considered for surgery having taken into account other characteristics, in particular male sex and radiologic findings of local invasion.
OBJECTIVES: Thyroid nodules constitute a very common clinical problem and the differential diagnosis includes thyroid cancer. As thyroid cancer is rare, it is important to know the prevalence of thyroid nodules in cohorts strongly predisposed to this problem to be able to measure its impact on the health care system, and to devise appropriate diagnostic strategies. The aim of this study was to determine the prevalence of thyroid nodules in women 40 year-old or older by echography. METHODS: Between August 1996 and December 1997, 207 women, 40 year-old or older, were consecutively evaluated by thyroid echography in the Radiology Division of the Hospital de Clínicas de Porto Alegre. Patients who came to the Division to be submitted to thyroid echography were excluded. The mean age of patients studied was 54.7 years (median: 53, range: 40-86 years). One hundred and twenty three patients (54.9%) had a normal thyroid and eighty-two had an abnormal gland (39.6%). Thyroid nodules were detected in seventy-three women (35.3%) and these were larger than 1 cm in 35 women (16.9%). Women without thyroid nodules were younger (53.1 +/-10.7 years) than women with thyroid nodules (58.2 +/-10.6 years) p=0.001; and the prevalence of any thyroid nodule (p=0.001) or nodules larger than 1 cm (p=0.007) increased with age. CONCLUSIONS: Thyroid nodules are very common in women 40 year-old or older, their prevalence increases with age in this cohort and these nodules are potentially palpable (larger than one cm) in one of six women in this age group It is important to have these data in mind when ordering thyroid echographic studies in women 40 year-old or older.
Factors contributing to the development of thyroid neoplasia remain poorly understood. Recent evidence indicates that overexpression of the inducible cyclooxygenase, COX-2, is important in the pathogenesis of epithelial carcinomas. These studies were undertaken to evaluate whether COX-2 is up-regulated in human thyroid neoplasia. Benign (n = 14), and malignant (n = 14) thyroid nodules were analyzed for expression of COX-2 mRNA by quantitative RT-PCR. Immunoblotting and immunohistochemistry were performed on representative samples. Three human thyroid cancer cell lines were similarly analyzed for COX-2 expression. Levels of COX-2 mRNA were significantly increased in thyroid nodule samples compared with adjacent thyroid tissue in the malignant specimens but not in the benign specimens. Additionally, COX-2 mRNA levels were significantly increased in malignant nodule samples compared with benign nodule samples. COX-2 protein expression was higher in 8 of 10 thyroid nodules compared with the adjacent tissue. Immunohistochemical analysis localized expression of COX-2 to the malignant epithelial cells. Immunofluorescence demonstrated COX-2 protein expression in all three thyroid cell lines. Finally, COX-2 expression could be detected by RT-PCR in fine needle aspiration specimens of thyroid nodules. These data indicate that COX-2 is up-regulated in human thyroid cancer, but not in benign thyroid nodules, and suggest that COX-2 expression may serve as a marker of malignancy in thyroid nodules.
To investigate further the relationship between thyroid hormones and thyroglobulin (TG) secretion, total and free thyroid hormone levels, TSH and its response to TRH and serum TG concentrations were determined in 61 patients with solitary autonomous thyroid nodules. Thyroid function varied widely from euthyroidism to clearcut thyrotoxicosis. Serum TG levels were significantly higher in patients than in normal controls. Individually they were above the normal range (greater than 50 ng/ml) in 95% of the patients, as well as in those with normal total and/or free thyroid hormone levels. Patients with high total and/or free thyroid hormone levels had higher TG concentrations than euthyroid patients. TG concentrations were significantly correlated with FT3 values. They were higher in patients in whom TSH was unresponsive to TRH than in the responsive groups. TG was also slightly higher in patients with hot nodules than in those with warm nodules. These data seem to indicate that TG is secreted along with thyroid hormones in the absence of any stimulatory action. It also is a sensitive index of thyroid hyperfunction. Twenty patients were controlled 6 months after nodulectomy. TG levels, though significantly lower than in the preoperative state, were still higher than in normal subjects. This increase was attributed to persistent hyperthyroidism in two patients only. The observation that the increase in TSH after TRH stimulation in post-operative patients was greater than that found in normal controls led us to believe that in most cases the high TG levels after surgery are due to stimulation of the normal thyroid tissue by rebound TSH secretion.
BACKGROUND: Many different neoplastic and hyperplastic thyroid diseases present with clinically apparent thyroid nodules. Clonality analysis indicates whether a nodule arises from the polyclonal proliferation of a group of cells or forms a clone from a genetically altered cell and thus provides objective information on the origin of the thyroid nodules. Clonality was studied in thyroid nodules using the polymerase chain reaction (PCR) assay in the X-linked human androgen receptor (HUMARA) gene by random X chromosome inactivation in women. METHODS: DNA samples were obtained from 28 nodules in 21 women. All nodules and non-tumour thyroid tissues were fractioned selectively under a cryostat. Genomic DNA was isolated and digested with HhaI. PCR amplification of the HUMARA locus was performed using PCR mixtures containing [alpha-32P]2'-deoxycytidine 5'-triphosphate. The PCR products were analysed by denaturing gel electrophoresis. RESULTS: The HUMARA alleles were heterogeneous in 18 of 21 patients. Among the 23 nodules from 18 patients, all of the eight papillary thyroid carcinomas were monoclonal. Two solitary nodules from follicular adenomas were monoclonal. Of the 13 follicular nodules from nodular goitres, ten were polyclonal and three were monoclonal. The monoclonal follicular nodules were larger in size (3.5 versus 2.0 cm, P< 0.05) and had a tendency towards more cystic changes than polyclonal nodules. CONCLUSION: PCR-based clonality study of thyroid nodules may help to distinguish hyperplastic from neoplastic nodules.
We investigated the outcome of long standing palpable solitary thyroid nodules by surveying 441 patients and examining 140 patients who had untreated thyroid nodules for 15 +/- 4.5 years. In our clinical survey, the most common outcome was disappearance of the thyroid nodule (38.3%). Also a significant number of patients (36.3%) underwent surgery in other hospitals. Five (1.1%) patients died of thyroid cancer. When thyroid nodules were re-examined, most nodules indeed decreased in size or disappeared; however, 13% of nodules increased in size. Ultrasound of the nodules showed that most solitary nodules were multiple and partially cystic and solid. There was an increased incidence of calcification in long standing nodules. Thyroid cancer was found by fine needle aspiration biopsy in 26.3% of enlarging nodules and 6.4% of nodules without changing size. The risk of cancer decreased when the size of the nodule decreased. A total of 15 patients with suspicion of malignancy underwent surgery. Surgical procedures were lobectomy, near total thyroidectomy, or resection of nodules with or without modified neck dissection. Seven patients had papillary carcinoma and 2 patients with benign cytology had microscopically evident papillary carcinoma. In our study, the majority of palpable solitary thyroid nodules tended to decrease in size; these nodules do not require treatment. Enlarging solid nodules are a definite risk for thyroid cancer. If the size of the nodule remains the same, judicious approach with fine needle aspiration biopsy is needed.
Thyroid nodule is defined as "hot" on the bous it scintigraphic appearance. It can be defined like benign nodule with autonomous functionality. On scintiscan it shows high captation because there's an increase of production and secretion of thyroid hormones with total inhibition of TSH and suppression of extranodular tissue. Generally the treatment of hot thyroid nodule was surgical or with radio-metabolic therapy. Percutaneous ethanol injection (PEI) in the treatment of hot thyroid nodules has been suggested recently. The aim of our study was to value therapeutic effects of PEI under guidance by means of ultrasound in patients with hot nodules in toxic or pretoxic phase. 36 patients with autonomous thyroid nodules of 1.8-6 cm in diameter received sterile ethanol at 95% that has been injected with a 22-gauge needle and a probe with a guide device. The administrated dose varied from 1.2 to 1.5 ml for cc of tissue in 5-12 sessions. Ethanol injection was performed in a single site in nodules with diameter < 3 cm and in double sites in nodules with diameter > 3 cm. The patients were checked after treatment and then 3 and 6 months. Our experience confirms an excellent response to PEI in these patients. In fact after therapy symptoms of hyperthyroidism and hormonal levels become normal; no patient has even reached the range of subclinical or clinical hypothyroidism. Scintigram showed that previously suppressed thyroid tissue resumed functioning; at ultrasound all nodules had shrunk: thyroglobulin levels increased during treatment because ethanol induces coagulative intranodular necrosis with release in systemic circulation of this glycoprotein.(ABSTRACT TRUNCATED AT 250 WORDS)
The thyroid nodule is a topic in clinical medicine which remains controversial because any thyroid disease can virtually turn up a thyroid nodule. The reliability of the diagnostic techniques for making the distinction between a benign and a malignant lesion varies. The various techniques for the assessment of a solitary nonfunctional thyroid nodule are described and their comparative values in establishing the nature of the nodule, identifying patients with low likelihood of malignancy--making it possible to defer surgery or to avoid it altogether--are analyzed. According to the results and for several reasons, controversy over the best approach of solitary cold nodule management can remain. We propose an alternative approach and provide a personal guideline for the use of these tests.
Thyroid nodules are common. Most are benign lesions since clinically important thyroid carcinoma is a relatively rare disease. The most sensitive and specific test for the diagnosis of thyroid cancer is fine-needle aspiration biopsy, but its diagnostic accuracy depends upon whether or not one excises all suspicious nodules, thus including them as correctly diagnosed. Nevertheless, fine-needle aspiration biopsy is the most sensitive, specific, and cost-effective test for thyroid cancer. Therapy depends upon the cause of the thyroid nodule.
Thyroid nodularity is a common finding. The incidence of thyroid cancer in the general population is estimated at 0.1%. Thyroid nodules are evaluated by palpation, ultrasonography, radionuclide scintigraphy and fine-needle aspiration cytology. Routine thyroid scintigraphy is made by using Tc-99m-pertechnetate or the I-131 and I-123 scintigraphic method. Tc-99m-tetrofosmin accumulates in the myocardium, skeletal muscle, liver, spleen breast tissue, kidney and normal and pathological thyroid tissue. We investigated 36 patients (28 females and 8 males) with solitary and/or multiple thyroid nodules. All the patients were euthyroid, and their thyroid nodules were diagnosed by palpation and ultrasound examination. Thyroid scintigraphy was applied by Tc-99m-pertechnetate, then thyroid fine-needle aspiration biopsy was performed. Finally, Tc-99m-tetrofosmin scintigraphy was carried out. Five patients (14.8%) had differential thyroid carcinoma, 23 (63.8%) had thyroid adenoma, 1 (0.02%) had Riedel's thyroiditis and 7 (19.4%) had follicular cyst. We detected 80% uptake in the early phase and 100% in the late phase by Tc-99m-tetrofosmin scintigraphy in the differentiated thyroid carcinoma group. In summary, we claim that Tc-99m-tetrofosmin may be an important scintigraphic method to identify thyroid malignancy from benign thyroid pathologies.
OBJECTIVE: To evaluate the value of immunostaining using the monoclonal antibody (MoAB47) against thyroperoxidase (TPO) in distinguishing between benign and malignant tumour cells in fine needle aspiration cytology (FNAC) samples obtained from a solitary cold nodule of the thyroid gland for the purpose of strengthening the indication for thyroid surgery. DESIGN: A prospective, immunocytochemical study of FNACs taken from patients with solitary cold thyroid nodules who presented to Rigshospitalet, Copenhagen, Denmark, during the period April 1993 to May 1996. The first sample series was taken perioperatively in order to test the utility of the method. In the second part of the study samples were obtained preoperatively by ultrasonic guided aspiration. Tissue sections from the nodules obtained during a subsequent operation served as controls. PATIENTS: One hundred and eighty-one patients, 150 women and 31 men, were studied. The age range was 14-89 years with a median age of 44 years. Fifty-seven patients were excluded from the study for various reasons leaving us with a total of 124 nodules from 124 patients for final evaluation. METHODS: FNAC cells and corresponding nodular tissue were stained by immunocyto- and immuno-histochemistry using MoAb47 and by routine staining methods. Samples were considered benign if 80% or more of the epithelial-looking cells of both the FNACs and the histological tissue sections of the nodule were stained by TPO. Consequently, samples were considered malignant if more than 20% of the epithelial-looking cells failed to stain for TPO. Routinely stained tissue cells and sections served as diagnostic controls. RESULTS: A pattern with negative TPO staining was found in all lesions which, by conventional histological staining, were subsequently proven to be malignant. A universal and reliable, positive TPO staining pattern was found in all subsequently proven benign lesions, with the exception of one out of 26 follicular adenomas. This gave the method a sensitivity of 1.0 (negative TPO staining = malignancy in 27 out of 27) and a specificity of 0.99 (positive TPO staining = benign lesion, in 96 out of 97). Positive and negative predictive values were 0.96 and 1.00 respectively. CONCLUSION: Thyroperoxidase immunostaining of fine needle aspirates from solitary, scintigraphically cold nodules of the thyroid gland has proved to be an important and reliable diagnostic tool for distinguishing between benign and malignant nodules. Thus, patients might be spared further surgery if not otherwise indicated.