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ORIGINAL ARTICLE
Year : 2020  |  Volume : 9  |  Issue : 2  |  Page : 132-138

Fine-needle aspiration of goiter (benign and non-neoplastic) with thyroid function abnormalities


1 Department of Pathology, Kasturba Medical College, Mangalore, Karnataka, India
2 Department of Pathology, AIIMS, Patna, Bihar, India

Date of Submission04-Dec-2014
Date of Decision28-Apr-2020
Date of Acceptance29-Apr-2020
Date of Web Publication18-Jul-2020

Correspondence Address:
Dr. Debarshi Saha
Department of Pathology, Kasturba Medical College, Mangalore (Manipal University), Light House Hill Road, Mangalore, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/JDRNTRUHS.JDRNTRUHS_270_14

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  Abstract 


Introduction: Thyroid nodule is the prime indication for FNA, which is also a cheap and effective investigation. The current study seeks an association between benign goiter and aberrant thyroid function tests (TFTs). Can thyroid FNA anticipate overt morbidity resulting from thyroid function abnormalities?
Materials and Methods: FNA records of 173 patients were studied along with the TFT results. A slide review was undertaken where the FNA impression did not correspond to the TFT.
Results: The female:male ratio was 149:24. Two (1.15%) had inadequate cellularity. Nearly 95/173 cases had abnormal TFTs. Multinodular goiter (126), Hashimoto's thyroiditis (43), and two and one cases of granulomatous and unclassified thyroiditis, respectively, constituted our diagnostic profile. Abnormalities in TFT did not correlate with age group, gender, or FNA diagnoses. However, hypothyroidism (clinical and subclinical) was significantly observed in Hashimoto's thyroiditis (HT) cases. Further, scant colloid and hurthle cell change were significantly correlated with HT. A histological correlation was obtained in 46 cases. Four neoplastic cases among which three papillary carcinomas arising in small focal areas within cysts were seen.
Conclusions: The major observation in this study is the subset of euthyroid and subclinically hypothyroid cases (23/43, 53.48%) of Hashimoto's thyroiditis (P = 0.0021). If treated with thyroxine replacement, overt hypothyroidism, particularly in pregnant women who are at risk of developing antithyroid antibodies, may be prevented. Besides, the inadequacy rate (1.15%) in the current study is low. False negatives 3/46 (6.5%), though available on a meager and selected subset of the patient population is still within the range of published data.

Keywords: Fine-needle aspiration, goiter, Hashimoto's thyroiditis, hyperthyroidism, hypothyroidism, multinodular goiter


How to cite this article:
Saha D, Krishnamurthy A, Kumar A, Sinha R, Kini J. Fine-needle aspiration of goiter (benign and non-neoplastic) with thyroid function abnormalities. J NTR Univ Health Sci 2020;9:132-8

How to cite this URL:
Saha D, Krishnamurthy A, Kumar A, Sinha R, Kini J. Fine-needle aspiration of goiter (benign and non-neoplastic) with thyroid function abnormalities. J NTR Univ Health Sci [serial online] 2020 [cited 2020 Aug 5];9:132-8. Available from: http://www.jdrntruhs.org/text.asp?2020/9/2/132/289887




  Introduction Top


Thyroid nodule (TN) remains the main indication of thyroid fine-needle aspiration (FNA), the aim being to distinguish neoplastic lesions from the non-neoplastic lesions and thereby reduce the number of diagnostic surgeries.[1] A goiter or TN may accompany thyroid function abnormalities and/or antithyroid antibodies. Though these conditions may be investigated by ultrasonogram scans, radioactive iodine uptake, and radionuclide scans, and serum thyroid antibody tests, they are expensive for the Indian population, except the plain ultrasonogram and thus, FNA offers itself as a cheap, affordable, and reliable diagnostic modality to an overwhelming majority of the patients. We have attempted to seek out whether any real associations between benign goiter and thyroid function abnormalities exist. By performing the FNA, a minimally invasive procedure and attempting to diagnose the condition by relating to the thyroid function tests (TFT), can we forestall substantial morbidity in some patients?


  Materials and Methods Top


The study was conducted at KMC hospitals Attavar and Ambedkar Circle, Mangalore. The data were collected for 5 months (March to July 2013) and 173 cases were obtained.

The records of FNA diagnoses of the thyroid were checked. All the non-neoplastic and benign lesions were considered for the study. The clinical findings and the results of the TFTs were noted. A review of the slides was undertaken when thyroid function discrepancy was noted. The data analysis was performed using SPSS version 13. This study was fully approved by our institutional review board.

Thyroid FNA was performed without dermal anesthesia by aspirating blindly on the nodule or diffusely enlarged nodular/smooth thyroid gland with a 23-24-gauge needle. At least two and at most, three aspirations were performed. The material obtained was dropped consecutively on rows of glass slides near the frosted end and immediately was smeared by sliding another glass slide on it, similar to making a peripheral smear. The slides destined for Papanicolaou stain were immediately dropped in a Coplin jar with 100% methanol in it. The air-dried smears were stained with May-Grunwald-Giemsa.

Since the Papanicolaou Society of Cytopathology Task Force on Standards of Practice does not specify the number or cluster or tissue fragments of thyroid follicular cells, we accepted five to six clusters of cells with more than 10 cells per cluster to be adequate.[2],[3] The additional criteria used were 1) a clean background 2) cells not entangled in blood so that visibility is not interfered with. Carnoy solution was used if the smears were very bloody.[1]

Ethical Clearance

Ethical approval for this study was obtained from the ethics committee of Kasturba medical college, Mangalore under the Manipal University vide number 'ICMR STS 2013- 00005' in May, 2013.


  Results Top


A total of 173 patients, who had their FNAs and TFTs conducted at KMC, Ambedkar Circle were included in the survey that included three cases of granulomatous thyroiditis (GT), 43 (24.85%) cases of Hashimoto's thyroiditis (HT), 126 (72.83%) cases of multinodular goiter (MNG), and 1 case of unclassified thyroiditis.

The age range of the patients involved in the study was 20 years to above 60 years [Table 1]. Of these, 149 (86.1%) were females and 24 (13.8%) were males. Around 54 patients belonged to the age group of 41 to 50 years, the highest of all age groups (significant, χ2 = 16.855, P = 0.0021). The mean age of the patients in this study was 42 ± 12.85 (S.D) years. For the males, the mean age was 48 ± 14 (S.D) years; for the females, the mean age was 41 ± 12.26 (S.D) years.
Table 1: Shows the Number of Patients in Each Age Groups

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Around 148 (85.5%) of the lesions were cellular, 23 (13.3%) were low to moderate and 2 (1.2%) were minimally cellular.

The general observations in MNG cases were of thyroid follicular cell sheets [Figure 1]a and [Figure 1]b along with variable amounts of colloid. Most of the aspirates demonstrated thin colloid, only a handful revealed thick material [Figure 1]c. Most of these cases displayed colloid or hemosiderin-laden macrophages, but a few, despite extensive Search failed to exhibit any. An impression of colloid goiter was conferred upon these cases. A small number of aspirates also illustrated large sheets with a microfollicular pattern [Figure 1]d but with scant, colloid, and few foamy cells in the background; the suggestion of hypercellular nodule in colloid goiter was provided in these cases.
Figure 1: (a and b) Nodular colloid goiter with follicular cell sheets. MGG ×100 (1A), MGG ×400 (1b). (c) An abundant thick colloid, MGG ×100. (d) Hyperplastic nodule in MNG, MGG ×100

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The cases of HT [Figure 2]c and [Figure 2]d were difficult to diagnose in a small subset of patients. Particularly, when the smears showed streaked lymphocytes with colloid in the background and follicular cells in the foreground, they were confounded with smearing artifacts [Figure 2]a and [Figure 2]b. Plasma cells, even if occasional, could be appreciated in full-blown HT, though they were absent in lymphocytic thyroiditis.
Figure 2: (a) Follicular cells entangled in colloid infiltrated with lymphocytes in Hashimoto's thyroiditis, PAP ×100. (b) Lymphocyte streaking in Hashimoto's thyroiditis, PAP ×100. (c) Follicular cells infiltrated and surrounded by lymphocytes and reactivated lymphoid cells in Hashimoto's thyroiditis, PAP ×100. (d) Hurthle cell change in Hashimoto's thyroiditis, PAP ×400

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Amongst the patients surveyed, 18 (10.4%) had high, 3 (1.7%) had low, and 152 (87.9%) had normal T3 levels; 10 (5.8%) had high, 18 (10.4%) had low, and 145 (83.8%) had normal T4 levels.

Hurthle cell changes were present among the aspirates of 69 patients with HT (n = 32, 46.37%), MNG (n = 35, 50.72%), and GT (n = 2, 1.15%) cases.

HT (n = 43) was significantly associated with Hurthle cell change (χ2 = 23.81, P < 0.0001). This has a margin of error 7.5%, confidence level 90% and response distribution of 40%.

Around 163 patients showed colloid (112 abundant, 4 moderate, 36 scant, 4 thick, and 5 thick blobs of colloid in their aspirates) while 10 did not. Scant to absent colloid was found in 46 aspirates with 33 HT cases, 9 MNG, 2 GT, and 1 unclassified thyroiditis and significantly associated with HT (χ2 = 25.68, P < 0.0001). Again, 37 of these 46 cases showed good cellularity in the aspirates (χ2 = 29.76, P < 0.0001). These two values had a margin of error 8%, confidence level 90%, and a response rate of 70–80%.

Levels of TSH did not show any relationship to FNA diagnoses as a whole [Table 2]. Nearly 84/126 of MNG cases had associated normal levels of TSH (P < 0.0001). Besides, 22 and 20 cases, respectively of 126 MNG cases were hypothyroid and hyperthyroid, respectively, and could not be significantly correlated (P = 0.15 and 0.20, respectively). No significant correlation between the various FNA diagnoses and the levels of T3 (Fishers's exact test, P = 0.195) or T4 [Table 3] could be established. [Table 4] correlates FNA diagnoses with the type of colloid present in the aspirates. Concerning thick and thick blobs of colloid, FNA diagnoses had a highly significant correlation. T3 (Fisher's exact test, P = 0.823; Fisher's exact test, P = 0.823) or T4 (Fisher's exact test, P = 0.592; χ2 = 0.244, P = 0.885) levels did not correlate significantly with the various age groups and gender of the patients, respectively. TSH levels too did not significantly correlate with age groups (χ2 = 6.069, P = 0.639) or gender (χ2 = 4.377, P = 0.122).
Table 2: Shows the Correlation Between FNA Diagnoses and Levels of TSH in Each Category

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Table 3: shows the Relation Between Various FNA Categories and T4

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Table 4: Shows Various FNA Diagnostic Categories and Type of Colloid in Aspirates

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Around 54.87% (95/173) of the total patients surveyed had abnormal TFT [Table 5]. An abnormal TFT did not correspond to any benign pathology under study significantly. The patients diagnosed as HT [Table 6] were either hypothyroid (subclinical or clinical, n = 25), hyperthyroid (n = 6), or had a normal TFT (n = 12). With respect to hypothyroidism, HT correlated significantly (χ2 = 14.535, P = 0.0007). The subclinically hypothyroid and euthyroid cases were 23 (53.48%) and significantly correlated to HT (χ2 = 12.3, P = 0.0021). This had a margin of error 9%, confidence level 90%, and a response rate of around 60%. The mean age of the HT cases was 38 ± 12.32 years.
Table 5: Shows FNA Diagnostic Categories Belonging to Either Normal or Abnormal TFTS

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Table 6: Shows the Thyroid Function Status in HT patients

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Perhaps, due to the benign nature of the lesions, the histological correlation was available in only 46 cases. Out of the 44 cases, four (4/46, 8.7%) were neoplastic. Three of them were papillary carcinomas in MNG. All of them were cystic and the carcinomas occupied a focal area (approx. 0.5 cm) in the wall of the cyst. Thus, the false-negative rate was (3/46, 6.5%), though this is not the actual false-negative rate since histopathological diagnoses of all the cases were not available. The fourth one was a follicular adenoma, although a toxic one in a background of HT; the TFT had also revealed hyperthyroidism.


  Discussion Top


This study was conducted to emphasize thyroid function disorders in patients suffering from goiter. The malignant diseases were excluded because it was immaterial whether they suffered from TFT abnormalities. However, false negatives exist on FNA diagnoses ranging from 2 to 7%.[4] In a landmark study by Raab et al., a false positive diagnosis was made in 25% and false negative in 9.9% on the FNA of the thyroid.[5] The current study obtained a histological diagnosis in only 46/173 (26.6%) cases and a false negative was seen in 3/46 (6.5%), but this may not be significant because an extremely low fraction of the study population was available for correlation.

As borne out by many studies in thyroid cytology in the past,[6],[7] the patient distribution too in this study was heavily skewed towards the female gender. The age group of 41–50 years had more patients than the rest of the groups and this was significant. The mean age of the cases in the present study (42 ± 12.85) was almost comparable to that of Stai et al. (47 ± 14)[7] but more than that of Kini et al. (31.63).[6] However, for the HT patients the mean age was 38 ± 12.32 years in the current study, approximately 61/2 years greater than and 9 years less than that of the studies done by Kini and Stai et al., respectively.[6],[7]

MNG claimed a large majority of the patients distantly followed by that of HT in the current study, 72.83% and 24.85%, respectively as opposed to 19.8% and 69.2%, correspondingly in the study done by Kini et al.[6] The cases showing features of both MNG and HT in the current study were categorized into either one depending upon the predominant pattern.

Most of the aspirates were cellular in the current study. The average rate of inadequate aspirate was 17%.[5] A recent report also puts the inadequacy at 10.4%.[8] Two (1.15%) aspirates in the study had very few cells, yet diagnoses were attempted and given as MNG. Their histopathological diagnoses were not solicited. High cellularity in the aspirates was significantly associated with scant colloid in the present study, the importance of which is still not appreciated.

Scant to absent colloid was seen in 46 cases. Around 33 cases of HT were significantly associated with scant colloid (P < 0.0001), though other studies have not mentioned such an association. About 32 of 43 patients with HT had Hurthle cells (P < 0.0001, highly significant). Out of 69 cases with Hurthle cells, the majority (35, 50.72%) are claimed by the MNG category. Association of Hurthle cells with HT is a well-known diagnostic criterion and is reported to be so by Kini and Stai et al.[6],[7] In our study, lymphocytic thyroiditis and Hashimoto's thyroiditis were considered as one entity since the management of both is the same.[6]

T3 and T4 levels were disregarded to determine the prevalence of HT [7] and also in the medical management of minimally enlarged thyroid with HT, wherein TSH levels were deemed essential.[6] Likewise, we too have not found any significant correlation of either T3 or T4 with age groups, gender, or FNA impression in the current study.

Though TSH levels did not correlate significantly in general with age groups, gender, or FNA impression; HT correlated significantly with hypothyroidism (P = 0.0007). Clinical and subclinical hypothyroidism is distinguished by elevated TSH levels above and below 10 μIU/mL, respectively [6] based on NHANES III study normative data for TSH distribution.[9] Subclinical hypothyroidism is determined by TSH levels between 5 and 10 μIU/mL, with normal T3 and T4 levels.[6],[7] Of the 43 cases in our study, 14 (32.6%) were clinically hypothyroid and 11 (25.6%) suffered from subclinical hypothyroidism in contrast to 46 (45.1%) and 9 (8.8%) out of 102 patients, respectively in the study by Stai et al.[7] Besides, the patients with normal TSH levels in our study (n = 12,28%) is appreciably less than that in the study by Stai et al. (n = 47,46.1%).[7] However, the studies by Kini [6] or Stai et al.[8] did not report any Hashitoxicosis, while our study had six (14%) patients with cytologic evidence of HT and thyrotoxicosis. The usual clinical course in these patients, who are mostly females between the 3rd to 6th decade, is to ultimately culminate in clinical hypothyroidism.[10] The number of euthyroid and subclinically hypothyroid HT cases (23,53.48%) is significant (P = 0.0021) in the current study. Though the effects of treating subclinical hypothyroidism are hitherto untested as prospective clinical trials are unavailable, yet potential benefits of treatment are worth mentioning. Evolution to absolute hypothyroidism and thereby its consequent morbidity may be halted; serum lipid profile, the normalization of which depends on adequate thyroid hormone levels may improve, and thus chances of cardiovascular complications may be reduced and psychiatric and cognitive abnormalities resulting from mild hypothyroidism may be negated.[6] The euthyroid and subclinically hypothyroid patients are the main beneficiaries of anticipatory thyroid hormone replacement therapy. Clinically, these euthyroid patients should be observed for signs of progression to overt hypothyroidism. Sporadic incidence of such cases developing antithyroid antibodies particularly in childbearing women in pregnancies is noteworthy.[6] Since hypothyroidism in the mother produces miscarriage, fetal, and neonatal death [7] and low intellect in the progeny, cytologically proven euthyroid, or subclinical hypothyroid HT cases need observation and follow-up and if pregnant, need supplemental thyroxine to prevent potential mishaps associated with hypothyroidism.

Screening for HT may also be done by anti-TPO antibodies along with TFT. However, 18.7% in the overt hypothyroid cases and 50% in the euthyroid and subclinically hypothyroid cases reported negative for this antibody in the study done by Stai et al.[7] Moreover, in a study by Rago et al., moderate to severe lymphocytic infiltration was found in thyroid gland histology of 52.4% (64/122) of patients have elevated levels of thyroid antibodies (TPOAb or thyroglobulin antibody, TgAb) and 11.8% (53/448) of the patients with negative thyroid antibodies and this correlation was statistically significant.[11] Conversely, a large number of patients also failed to show substantial lymphocytic infiltration in follicular epithelium even with a raised level of thyroid antibodies.[11] Thus, testing for antithyroid antibodies should be viewed as an ancillary test procedure rather than an essential one. It was also hypothesized that cytological evidence of HT heralds positive clinical diagnosis.[7]

Some authors believe that TNs with high TSH levels portend an increased risk of differentiated thyroid cancer.[12] Rago et al. in their study of 570 indeterminate nodules on cytology concluded that clinical and pathological measures of thyroid autoimmunity concurred with each other but association with malignancy lacked sufficient proof.[11] The incidence of thyroid carcinomas could not be linked to circulating TgAb, TPOAb, or extranodular lymphocytic infiltration on histology.[11] Therefore, we support the hypothesis that the risk of thyroid malignancy in HT is unfounded; irrefutable evidence of such an association is still needed though arguments in favor of carcinogenesis due to continued inflammation [7] that is tempting and may seem credible to some authors.

Thick blobs of a colloid are significantly associated with MNG or HT in the current study. Comparable studies have not been found in this aspect. It can, however, be claimed with little reservation that thick blobs of colloid on smears should indicate a diagnosis of MNG or HT, rather than any other forms of thyroiditis.

Previous studies done by Stai et al. and Kini et al. revealed unexpectedly high numbers of HT patients on cytology,[6],[7] surprisingly, a large majority of the patients in the current study suffered from MNG. Stai et al. had drawn a parallel prevalence between HT and diabetes mellitus type II (DM2).[7] In the face of such high numbers of MNG cases from an iodine sufficient area in the current study, its prevalence might be comparable to that of DM2. This observation is perplexing as traditional reason dictates iodine deficiency to instigate the MNG process. A familial, metabolic, or HLA association may not be unlikely.

Small papillary carcinomas in cysts may be aspirated by ultrasound guidance to curtail false negatives.[13] Even if technical aspects like inadequate cellularity daunt positive expectation of minimizing false negatives, lack of standardization of diagnostic categories, which is a pathologists' problem, plays ornery to arriving at a precise impression.[5] Cytologists use diverse norms for various diagnostic classes like atypical and follicular lesions or neoplasm.[5] Unanimous guidelines to reach a transparent set of diagnoses are eagerly awaited, which is concordant with both the clinician's deduction and pathologist's reasoning.


  Conclusion Top


The majority of the benign goiter cases in the present study consisted of MNG cases. HT was significantly associated with hypothyroidism. The major observation in this study is the subset of euthyroid and subclinically hypothyroid cases (23/43, 53.48%) of HT (P = 0.0021), who should be the main beneficiaries of anticipatory thyroid hormone replacement therapy leading to obviation of the deleterious effects of frank hypothyroidism. Antithyroid antibodies are an unreliable measure of this condition and hence, FNA is the sole diagnostic modality in these patients.

HT was also significantly associated with scant colloid (P < 0.0001) and Hurthle cell change (P < 0.0001). Thick blobs of colloids were significantly associated with MNG and HT. Besides, high cellularity of the aspirates correlated significantly with scant to absent colloid (P < 0.0001), though the diagnostic implication of such an observation is yet to be pondered into. In contrast to the existing studies, the current study had a very low rate of inadequate cellularity (1.15%), but the diagnosis was attempted in both. False negatives 3/46 (6.5%), though available on a meager and selected subset of the patient population is still within the range of published data.

Though changes relating to both multinodular goiter and Hashimoto's thyroiditis are found in thyroid parenchyma adjacent to thyroid epithelial malignancies, it has not yet been categorically proven that Hashimoto's thyroiditis is associated with or gives rise to such carcinomas.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Papanicolaou Society of Cytopathology Task Force on Standard of Practice (Suen KC, Chair). Guidelines of the papanicolaou society of cytopathology for the examination of fine needle aspiration specimens from thyroid nodules. Mod Pathol 1996;9:710-5.  Back to cited text no. 1
    
2.
Goellner JR, Gharib H, Grant CS, Johnson DA. Fine needle aspiration of the thyroid, 1980-1986. Acta Cytol 1987;31:587-90.  Back to cited text no. 2
    
3.
Esmaili HA, Taghipour H. Fine-needle aspiration in the diagnosis of thyroid disease: An appraisal in our institution. ISRN Pathology. Volume 2012, Article ID 912728, 4 pages. doi: 10.5402/2012/912728.  Back to cited text no. 3
    
4.
Gharib H, Goellner JR. Fine-needle aspiration biopsy of the thyroid: An appraisal. Ann Intern Med 1993;118:282-9.  Back to cited text no. 4
    
5.
Raab SS, Vrbin CM, Grzybicki DM, Sudilovsky D, Balassanian R, Zarbo RJ, et al. Errors in thyroid gland fine-needle aspiration. Am J Clin Pathol 2006;125:873-82.  Back to cited text no. 5
    
6.
Kini U, Buch A, Bantwal G. Role of FNA in the medical management of minimally enlarged thyroid. Diagn Cytopathol 2006;34:196-200.  Back to cited text no. 6
    
7.
Staii A, Mirocha S, Todoreva-Koteva K, Glinberg S, Jaume JC. Hashimoto thyroiditis is more frequent than expected when diagnosed by cytology which uncovers a preclinical state. Thyroid Res 2010;3:11.  Back to cited text no. 7
    
8.
Yang J, Schnadig V, Logrono R, Wasserman PG. Fine needle aspiration of thyroid nodules: A study of 4703 patients with histologic and clinical correlations. Cancer 2007;111:306-15.  Back to cited text no. 8
    
9.
Hollowell JG, Staehling NW, Flanders WD, Hannon WH, Gunter EW, Spencer CA, et al. Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National health and nutrition examination survey (NHANES III). J Clin Endocrinol Metab 2002;87:489-99.  Back to cited text no. 9
    
10.
Nayak B, Hodak SP. Hyperthyroidism. Endocrinol Metab Clin N Am 2007;36:617-56.  Back to cited text no. 10
    
11.
Rago T, Coscio GD, Ugolini C, Scutari M, Basolo F, Latrofa F, et al. Clinical features of thyroid autoimmunity are associated with thyroiditis on histology and are not predictive of malignancy in 570 patients with indeterminate nodules on cytology who had a thyroidectomy. Clin Endocrinol (Oxf) 2007;67:363-9.  Back to cited text no. 11
    
12.
Heymart MR, Repplinger DJ, Leverson GE, Elson DF, Sippel RS, Jaume JC, et al. Higher serum thyroid stimulating hormone level in thyroid nodule patients is associated with greater risks of differentiated thyroid cancer and advanced tumor stage. J Clin Endocrinol Metab 2008;93:809-14.  Back to cited text no. 12
    
13.
Tambouret R, Szyfelbein WM, Pitman MB. Ultrasound-guided fine-needle aspiration biopsy of the thyroid. Cancer 1999;87:299-305.  Back to cited text no. 13
    


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]



 

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