Thyroxine suppressive therapy in patients with nodular thyroid disease

PURPOSE: To review evidence about thyroxine suppressive therapy in patients with thyroid nodules, including the clinical importance and natural history of nodules and the effects and potential side effects of thyroxine therapy. DATA SOURCES: English-language articles published from 1986 to December 1996 were identified through searches of the MEDLINE database, selected bibliographies, and personal files. DATA EXTRACTION: Randomized, controlled trials and nonrandomized trials of thyroxine suppressive therapy for solitary and predominantly solid thyroid nodules were reviewed. In most studies, nodule cytology was evaluated by fine-needle aspiration biopsy. Therapy was considered suppressive if suppression was documented by thyroid-stimulating hormone-releasing hormone tests or sensitive thyroid-stimulating hormone assays. Response was defined as a decrease of 50% or more in nodule size or volume; most recent studies measured nodule size by ultrasonography. DATA SYNTHESIS: The evidence suggests that thyroxine suppressive therapy fails to shrink most nodules: Only 10% to 20% of nodules responded to this treatment. Fine-needle aspiration biopsy is more reliable in distinguishing benign from malignant nodules. Recent studies suggest that spontaneous decrease in size with complete disappearance of thyroid nodules is not uncommon. No data show that thyroxine therapy arrests further growth in most existing nodules or prevents the emergence of new nodules. Postoperative thyroxine therapy does not seem to prevent recurrence of thyroid nodules except in patients with a history of radiation therapy. Potential adverse effects of long-term suppressive therapy include osteoporosis and heart disease. CONCLUSIONS: Patients with cytologically benign nodules are best followed without thyroxine treatment. Most benign nodules remain stable in size and remain benign when monitored for a long time. For nodules that increase in size, biopsy should be done again or surgery should be performed.     

Management of thyroid nodules

Clinically apparent thyroid nodules occur in about 5 percent of the population. Because most patients with thyroid nodules present initially to their primary care physician, family physicians should have a thorough understanding of the diagnosis and treatment of thyroid nodules. The history and physical examination may be helpful in detecting thyroid nodules but are not useful in predicting malignancy. Furthermore, laboratory studies, ultrasonography and nuclear medicine scans do not reliably differentiate between benign and malignant thyroid nodules. In most cases, fine-needle aspiration biopsy can accurately identify malignant thyroid nodules. Fine-needle aspiration biopsy is safe and can be performed in an office setting.     

Possible relation of osteopontin to development of psammoma bodies in human papillary thyroid cancer

Fine-needle aspiration cytology (FNAC) is the most useful procedure for the evaluation of thyroid nodules. The requirement for repeated aspirations in the follow-up of benign nodular thyroid disease, however, is controversial. To determine the value of re-aspirations in benign nodular thyroid disease, we studied 457 fine-needle reaspirations performed on 216 patients (197 female, 19 male) aged 42.9+/-12 years with uninodular (n = 65) and multinodular (n = 151) thyroid disease. Two hundred fifty-seven of these were second, 137 were third, 46 were fourth, and 17 were fifth re-aspirations of the same nodule, performed in a mean follow-up time of 43.9+/-31 (3-156) months. FNAC results were benign in 407 (89%), insufficient for diagnosis in 31 (6.8%), suspicious in 16 (3.5%), and papillary carcinoma (PC) in 3 (0.7%). An initial benign diagnosis did not change after multiple aspirations in 213 (98.61%) of the cases. Three patients with initial aspirations read as benign had a diagnosis of PC from their second biopsies, (diagnosis confirmed at surgery). Re-examination of the initial FNAC revealed atypical features in 1 of the 3 patients. These 3 patients likely represent a false-negative result of the initial FNAC rather than benign nodular disease transformed to a malignant one during the follow-up period. In conclusion, a second aspiration of clinically suspicious nodules may correct a few initial false-negative results, but routine additional re-aspirations are not useful for clinically stable disease.     

Isolated thyroid nodule. Comparative value of cyto-puncture and scintigraphy

OBJECTIVES: Nodular thyroid disease, indicated by the presence of single or multiple nodules within the thyroid gland is a common clinical problem, the main question remains the malignancy. Radionuclide scanning, ultrasonography and fine needle aspiration biopsy have been helpful to distinguish benign from malignant nodules and to select patients for surgery. METHODS: We performed a prospective study to assess the comparative value of fine needle nonaspiration biopsy and thyroid scinti scan in the management of 412 patients operated for solitary thyroid nodule. RESULTS: Sensitivity and negative predictive values were the same for both methods, but specificity of cytology was greater than that of thyroid scinti scan (80.53% vs. 10.47%, p < 0.001). DISCUSSION: Thyroid radionuclide scanning remains valuable in the evaluation of a cytological benign solitary thyroid nodule when TSH value is low, in order to distinguish toxic adenoma from cold nodule in Graves' disease.     

Solitary thyroid nodules. Separating benign from malignant conditions

Although features found on history taking, physical examination, thyroid function tests, and imaging studies help categorize solitary thyroid nodules as benign or malignant, fine-needle aspiration biopsy is the diagnostic test of choice. Nodules found to be malignant on cytologic examination should be treated with surgery. Benign nodules may be followed clinically or treated with levothyroxine to suppress their growth. Intermediate nodules should be excised if there is clinical suspicion of malignancy. In suspect nodules, levothyroxine therapy with follow-up ultrasound assessment for size is appropriate. Nodules that do not shrink significantly within 6 months should be excised.     

Reliability of needle biopsy of solitary thyroid nodules in view of surgical indications

To evaluate the accuracy of fine-needle biopsy in the management of the solitary thyroid nodules, 320 biopsies without aspiration were performed in 212 patients, iteratively in 91 cases. Among the 212 initial biopsies, 93 smears were found presumably benign (43.9%), 6 malignant (2.8%), 49 benign implying cytologic control (23.1%), 24 suspicious with decision to operate (11.3%), 40 inadequate (18.9%). On 67 surgical indications (malignant or suspicious cytology, or clinical data), 59 operations were performed. The 11 diagnosed cancers (5.2% of the patients; 18.6% of the operations) correspond to six malignant and five suspicious cytologies at the first or second biopsy. On 145 cases without decision to operate, 125 were clinically surveyed, with sometimes another biopsy (mean survey: 27.6 months; range: 6-80 months), and it was never necessary to modify the initial expectancy attitude. Our results, rather similar to those related by most of the previous publications, confirm that the fine-needle biopsy is a reliable and effective means for the etiologic diagnosis of thyroid nodules and the indications for operative intervention. It spares many patients from a useless operation and is worthy to take a leading place in exploring these nodules.     

Solitary thyroid nodule in Khartoum

Ninety four patients with solitary and significantly dominant thyroid nodules were studied. Inadequate sampling was reported in 5 patients (5.9%). In the remaining 89 patients, 64 had simple goitre (72%), 12 follicular adenoma (13.5%), 12 were malignant nodules (6 follicular, 5 papillary and one anaplastic) (13.5%) and one patient had Hashimoto's thyroiditis. The incidence of malignancy in the clinically solitary nodules was 14% (10/70) compared to 10% (2/19) for the dominant nodules which increased to 16% (8/49) versus 10% (4/40) respectively after ultrasonography and histopathological confirmation of the nature of the gland. There is a low positive predictive value for follicular neoplasm with fine needle aspiration cytology (FNAC) (44%). This is due to the fact that reports of suspicious follicular pattern is agreed not to imply definite malignancy, however total lobectomy was done for those patients whereas terms like "not suspicious" and "highly suspicious" are considered to mean, benign and malignant respectively and in those latter groups the prediction was 100%. The study stresses the importance of FNAC techniques in reducing the surgical load with minimal false negative results, increasing the yield of carcinoma and projecting the importance of a significantly dominant nodule in endemic areas.     

Pediatric thyroid nodules: management in the era of fine needle aspiration

BACKGROUND/PURPOSE: Thyroid nodules are rare in children. The need to uncover malignancy is the most challenging dilemma in management. The aim of this report was to determine whether management of pediatric thyroid nodules has changed in the era of fine-needle aspiration (FNA) cytology. METHODS: Twenty-four children with thyroid nodules comprised the study group. Demographic characteristics, clinical manifestations, imaging results, FNA cytology results, surgical therapy, complications, and pathological reports were reviewed retrospectively. FNA cytology results were categorized as either benign, malignant, suspicious, or insufficient. RESULTS: Girls outnumbered boys (five to one) with a mean age of 14.9 years. Nineteen nodules were benign and five malignant. Malignancy was characterized by localized tenderness, multiglandular appearance, and fixation to adjacent tissues. Ultrasound scans and nuclear scans gave no clue toward management because cystic, hot, and warm nodules figured among malignant cases. FNA in 18 children achieved 80% accuracy, 60% sensitivity, 90% specificity, 75% positive, and 81% negative predictive value. Physical examination findings, persistence of the nodule, and progressive growth decided for surgery in most children. CONCLUSIONS: FNA is a safe adjunctive test that plays a minor role in the decision to withhold surgery. Its greatest strength is to resolve, in case of suspicious or malignant cytology, that a more radical procedure will be needed. Clinical judgement as determined by serial physical findings continues to be the most important factor in the management of thyroid nodules in children.     

Significance of nondiagnostic fine-needle aspiration of the thyroid

BACKGROUND: Fine-needle aspiration biopsy (FNAB) has been shown to be rapid and cost effective in the evaluation of thyroid nodules. The significance of nondiagnostic (unsatisfactory) FNAB is uncertain, however. METHODS: We reviewed 345 consecutive thyroid FNABs and identified 59 patients with initially unsatisfactory specimens. These patients had follow-up to determine whether their thyroid nodules proved to be malignant. RESULTS: Three patients (5.1%) were found to have organ-confined papillary carcinoma of the thyroid, the largest tumor mass measuring 1.2 cm. Six patients (10.2%) had benign adenomas. CONCLUSIONS: In most cases of initially nondiagnostic FNAB of a thyroid nodule, neoplasia is not found subsequently. A minority of cases may still harbor malignancy. None of our patients in whom repeated FNA was either nondiagnostic or suggestive of benign disease were ultimately found to have a malignancy.     

Bactericidal activity of a fermented hot-water extract from Stevia rebaudiana Bertoni towards enterohemorrhagic Escherichia coli O157:H7 and other food-borne pathogenic bacteria

AIMS: To evaluate the correlation of fine needle aspiration (FNA) cytology and frozen section biopsy in the diagnosis of thyroid nodules. METHODS: The medical records of 662 patients who underwent FNA cytology of the thyroid and thyroid surgery were analysed. Frozen section biopsies were taken from 586 of the 662 patients. The diagnostic correlations of FNA cytology, frozen section, and both FNA cytology and frozen section with definitive histological assessment were evaluated. RESULTS: Among the 662 patients who received FNA cytology, there were 356 cases (53.8%) diagnosed as benign, 114 cases (17.2%) as malignant, 148 cases (22.4%) as indeterminate, and 44 cases (6.6%) as unsatisfactory. The positive predictive value for the detection of malignancy by FNA cytology was 92.1% and the negative predictive value was 95.2%. The incidence of malignancy in the indeterminate cytological diagnosis was 23%. The diagnosis from frozen sections was benign in 445 cases (75.9%), malignant in 134 cases (22.9%), and deferred in 7 cases (1.2%). By frozen section, the positive and negative predictive values were 97% and 95.5%, respectively. Diagnostic accuracy up to 98% was achieved when FNA cytology and frozen section diagnoses were in agreement. No false positives were observed when FNA cytology and frozen sections were both positive for malignancy. When FNA cytology and frozen section diagnoses were discordant, frozen section showed a higher accuracy (78.9%) than FNA cytology (21.1%). In the face of an indeterminate or unsatisfactory cytological diagnosis, the diagnostic accuracy of frozen sections reached 92.6%. CONCLUSIONS: The results confirm that FNA cytology is a useful tool in the initial evaluation of thyroid nodules. Intraoperative frozen section is a valuable procedure to confirm the cytological diagnosis and identify malignancy in patients with indeterminate or unsatisfactory cytological diagnosis. With reliance on frozen sections as an intraoperative guide of thyroid surgery, the possibility of unnecessary extensive surgery and the need for the second operation are considerably lower.     

Aberrant tau phosphorylation and neurite retraction during NGF deprivation in PC12 cells

OBJECTIVE: To investigate the final results of cases with preoperative diagnoses of thyroid follicular neoplasms by fine needle aspiration cytology (FNAC). STUDY DESIGN: A retrospective review of 6,499 patients who received thyroid ultrasonography with FNAC at Chang Gung Memorial Hospital. Among 6,499 patients, 209 (3.2%) were diagnosed by FNAC as having follicular neoplasms, of which 84 received surgical treatment. Eighty-two of the 84 cases had a frozen section prepared during the operation. RESULTS: Thyroid malignancy was confirmed histopathologically in 164 cases. Among 84 thyroid follicular neoplasm patients, 21 cases were diagnosed as malignant tumors, including papillary thyroid carcinoma, follicular thyroid carcinoma, medullary thyroid carcinoma and Hürthle's cell carcinoma. Ultrasonography on these 21 patients revealed that 16 cases (76.2%) had low echo density in the thyroid nodule. The percentage was statistically significantly different from that in benign cases, 23.8% (P < .05). A higher incidence of malignancy was found in males, but the data did not reach statistical significance (P = .0586). CONCLUSION: Most of the follicular neoplasms revealed by FNAC were benign lesions. Low echo density on ultrasonography and male sex carried a higher risk of malignancy.     

Ultrasonic examination of the thyroid gland. Possibilities and limitations

In 440 patients with various thyroid disorders scintiphotography and ultrasonography were carried out. For ultrasonic examination both the A-mode and B-mode display technics were employed, included in the study were 324 patients with hypofunctioning solitary nodules; a histopathologic diagnosis could be obtained in 151 of these. The method proved to be especially valuable for differentiating between solid and cystic nodules. This is of practical importance because completely cystic nodules are nearly always benign and may be treated by thin needle puncture with aspiration of the cyst fluid. In addition, ultrasonography is of some value in making a better functional classification of nodules, better estimating the size of the thyroid and in the follow-up of patients with various thyroid disorders who are under treatment or untreated. Differentiating between benign and malignant solid nodules was not possible with the technic used. The examination can be safely carried out in pregnancy. The limitations of the technic are discussed.     

Seqalert--a daily sequence alertness server for the EMBL and SWISSPROT databases

OBJECTIVE: Fine-needle aspiration biopsy (FNAB) is the preferred diagnostic study for evaluating thyroid nodules. Despite its accuracy, many patients undergo thyroidectomy for benign nodules. This study was undertaken to identify risk factors that might increase the specificity of FNAB. METHODS: Medical records of 422 patients who underwent thyroid surgery between 1986 and 1996 were reviewed. All patients had FNAB prior to surgery. RESULTS: Of the 422 patients, 36% had benign cytology, 46% had indeterminate cytology, and 13% had cancer. In the indeterminate group, 29% of patients had cancer at surgery. Of patients with papillary cytology, 84% had malignancies. Five percent of FNABs were nondiagnostic. Neither age, gender, nor tumor size was associated with increased specificity of FNAB. CONCLUSION: There is no subpopulation of patients with indeterminate FNAB cytology at increased risk of having well-differentiated thyroid cancer.     

Telomerase activity in the differential diagnosis of papillary carcinoma of the thyroid

BACKGROUND: Although fine-needle aspiration (FNA) is 90% sensitive in the detection of papillary carcinoma (PC) of the thyroid, its specificity has been reported as low as 52%. Consequently, patients who have an FNA suspicious for PC may undergo operation for a benign process. The ribonucleoprotein telomerase has been noted to be activated in a wide variety of carcinomas. We examined 30 PCs for telomerase activity to determine whether this would be a useful adjunct to FNA in the diagnosis of lesions suspicious for PC. METHODS: Standard telomere repeat amplification protocol assays were performed on fresh frozen tissue samples from 30 PCs, 3 benign nodules, and 10 normal thyroids. RESULTS: Telomerase activity was documented in 20 of 30 (67%) of the PCs, 0 of 3 benign nodules, and 0 of 10 normal thyroids. In all, 11 of the 20 PCs had FNA cytology that was nondiagnostic of PC, and 2 of the benign nodules had FNA that was suspicious for PC. CONCLUSIONS: The telomerase assay appears useful in the distinction of benign from malignant thyroid lesions that have FNA suspicious for but not diagnostic of PC. On the basis of these findings, a prospective trial examining telomerase activity in FNAs suspicious for thyroid cancer has been initiated.     

Comparison of intraoperative cytology with frozen sections in the diagnosis of thyroid lesions

We retrospectively studied the usefulness of intraoperative cytology (IOC) and frozen section (FS) in the rapid diagnosis of 68 thyroid lesions. In 14 cases of papillary thyroid carcinoma, IOC correctly diagnosed 13 cases, while FS correctly diagnosed 11 cases. There was no significant difference in sensitivities, and both methods had similar specificities. In 21 cases of colloid nodule, IOC was slightly more sensitive than FS; IOC correctly diagnosed 16 cases, while FS correctly diagnosed 15 cases. However, the specificity of IOC was only 71%, but was 98% for FS. Of 17 follicular adenomas, FS diagnosed 16 as follicular neoplasms and misdiagnosed only 1 as a colloid nodule. By contrast, IOC misdiagnosed 9 follicular adenomas as colloid nodules, most of which were macrofollicular variants with abundant colloid. Of 11 follicular carcinomas, FS diagnosed all as follicular neoplasms, while IOC misdiagnosed 3 as colloid nodules. While IOC is not as accurate as FS in the diagnosis of colloid nodules and follicular neoplasms, it is highly sensitive and specific in the diagnoses of papillary carcinoma and performance of the technique is rapid and easy. In an intraoperative setting, IOC is a useful adjunct to FS in screening thyroid nodules for the presence of papillary carcinoma.     

The food-service industry, dietary guidelines and change

This study was aimed at assessing the clinical usefulness of measuring the contrast enhancement (CE) of solitary pulmonary nodules (SPN) in distinguishing benign from malignant lesions. We used spiral CT to study prospectively 35 pulmonary lesions presenting as SPNs < 30 mm phi; we evaluated the CE of the nodules 120 minutes after the administration of 100 mL of nonionic contrast material (= 30 grams of iodine), at 2 mL/s. The final diagnosis of the 35 SPNs was made at surgery (27 cases); positive sputum cytology (2 cases), 12 months' follow-up (5 cases) or fine-needle aspiration biopsy and 6 months' follow-up (1 case). Thus, 25 of 35 SPNs proved malignant (11 adenocarcinomas, 5 squamous cell carcinoma, 2 large cell carcinomas, 2 carcinoids, 1 small cell carcinoma, 2 cases with positive sputum cytology, 2 metastases) and the extant 10 of 35 proved benign. Malignant nodules enhanced markedly more (mean value: 36.8 HU) more than benign lesions (mean value: 18.6 HU). CE exceeded 20 HU in 23/25 malignant nodules and did not in 2/25; it did not exceed 20 HU in 6/10 benign nodules and did in 4/10. With 20 HU as the threshold value for a positive test (malignancy), sensitivity was 92%, specificity 60% and accuracy 83%; positive and negative predictive values were 85% and 75%, respectively. In conclusion, CE evaluation is a sensitive, although not very specific, indicator of malignancy in SPNs.     

Ultrasonographically-guided fine-needle aspiration cytology in the diagnosis of colonic lesions

BACKGROUND: The use of fine-needle aspiration cytology (FNAC) in the diagnosis of colonic lesions was investigated. METHODS: Some 22 patients (median age 71 years) with a colonic lesion identified on abdominal ultrasonography underwent ultrasonographically-guided FNAC using a 21-G needle. The sample was checked immediately by a cytopathologist for adequacy. RESULTS: Eighteen patients had colonic carcinoma; aspiration cytology detected malignant epithelial cells consistent with colonic carcinoma in 17 patients and severely dysplastic cells in one patient. The sensitivity and specificity of ultrasonographically-guided FNAC in the diagnosis of colonic carcinoma was 94 and 100 per cent respectively. The remaining four patients had a diagnosis of ileocaecal tuberculosis, ileocaecal Crohn's disease, and metastatic adenocarcinoma in the liver with no identifiable primary (two patients). One demonstrated granulomata, grew acid-fast bacilli and the patient was treated for tuberculosis. One had inflammatory cells and the patient was found to have Crohn's disease on histology. The remaining two patients had confirmed metastatic adenocarcinoma in the liver on aspiration cytology but suspected colonic lesions were found to be benign on cytological examination and no primary lesion was subsequently demonstrated. There were no complications of FNAC and patients complained of minimal discomfort. There has been no evidence of tumour recurrence with a median follow-up of 12 (range 1-25) months. CONCLUSION: Ultrasonographically-guided FNAC is a valid method for the diagnosis of colonic tumours.     

Usefulness of color echo Doppler with power Doppler in the diagnosis of hypoechoic thyroid nodules: work in progress

The aim of this study was twofold: first, to improve the predictive value of ultrasonography (US) in differentiating benign from malignant thyroid nodules and, second, to investigate whether color Doppler and power Doppler can distinguish different morpho-hemodynamic patterns of hypoechoic thyroid nodules according to their vascularity. Twenty-nine patients with hypoechoic thyroid nodule(s) were entered into this work in progress. Three typical power Doppler patterns were recorded and compared with color Doppler patterns and with cytologic and/or histologic findings. Power Doppler patterns were classified as follows: type A, a perilesional vascular halo; type B, a peri- and intralesional vascular halo, subdivided into: 1) with moderate intralesional vascularization, homogeneous structure and regular vessel caliber and 2) with rich intralesional vascularization, anarchical structure and winding vessel caliber and flow; type C, a perilesional vascular halo with a characteristic peripheral large afferent vessel characterized by winding caliber and flow. Of 29 patients, 21 had type A power Doppler (benign nodular goiter at cytology, in 4 of them with regressive phenomena); seven patients had type B power Doppler patterns-4 had a subtype 1 pattern (3 with nodular hyperplasias and 1 with a papillary adenoma), 3 had a subtype 2 (two had a follicular adenoma and one had a final diagnosis of angioinvasive follicular carcinoma). The patient with undifferentiated carcinoma had a type C power Doppler pattern. In conclusion, according to our early results, PD seems to be more sensitive and reliable than CD in the screening of thyroid nodules, and to yield better vascular information.     

Predictive value of fine-needle aspiration of the thyroid in the classification of follicular lesions

BACKGROUND: Fine-needle aspiration has been less valuable in the diagnosis of follicular lesions than for other neoplasms of the thyroid. It has been observed that follicular carcinoma is found in microfollicular, but not macrofollicular lesions, and this has served as a guide to management for many surgeons. The authors attempted to determine what cytologic parameters might usefully distinguish these types of follicular lesion. METHODS: The histologic findings and cytology of 56 thyroid lobectomies for follicular lesions that had adequate preoperative fine-needle aspiration of the thyroid (FNAT) were reviewed. Histologic specimens were classified into macrofollicular, mixed, and microfollicular groups. Cytologic features examined included the presence of colloid, irregularity of cell arrangements within groups, the presence and size of flat and folded cell sheets, three-dimensional clusters, and microfollicles and macrofollicles. RESULTS: Of the histologic specimens, 15 were preponderantly (> 70%) microfollicular, 19 were mixed, and 22 were predominantly (> 70%) macrofollicular. Three cytologic features were useful in their distinction: none of the predominantly microfollicular but 24% of the mixed and predominantly macrofollicular had abundant colloid (P = 0.048). Likewise, none of the predominantly microfollicular but 27% of the mixed and predominantly macrofollicular had large follicles (P = 0.026). Finally, 73% of the predominantly microfollicular but only 37% of the mixed and predominantly macrofollicular showed irregularity or crowding of cells in groups (P = 0.018). CONCLUSIONS: Used in combination, abundant colloid, regular spacing, and large follicles are helpful in distinguishing macrofollicular and mixed lesions from microfollicular ones, which have a higher malignant potential.