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PubMed2006

Large needle aspiration biopsy and galectin-3 determination in selected thyroid nodules with indeterminate FNA-cytology.

Thyroid fine-needle aspiration biopsy (FNA)-cytology is widely used for the preoperative characterisation of thyroid nodules but this task is difficult for follicular lesions, which often remain undefined. We propose a strategy for improving the preoperative characterisation of selected follicular thyroid proliferations, which is based on large needle aspiration biopsy (LNAB) and galectin-3 expression analysis. Eighty-five thyroid specimens were obtained by LNAB (20-gauge needles) from thyroid nodules with indeterminate follicular FNA-cytology. Aspirated material was processed as a tissue microbiopsy to obtain cell blocks for both cyto/histo-morphological evaluation and galectin-3 expression analysis, by using a purified monoclonal antibody to galectin-3 and a biotin-free immunoperoxidase staining method. Preoperative diagnosis was compared to the final histology. LNAB and cell-block technique allow a preliminary distinction between nodules with a homogeneous microfollicular/trabecular structure, as frequently observed in tumours, and lesions with mixed normo-micro-macrofollicular architecture, as observed in goitre. Furthermore, LNAB provides optimal substrates for galectin-3 expression analysis. Among 85 cases tested, 14 galectin-3-positive cases were discovered preoperatively (11 thyroid cancers and three adenomas confirmed at the final histology), whereas galectin-3-negative cases were 71 (one carcinoma and 70 benign proliferations at the final histology). Sensitivity, specificity and diagnostic accuracy of this integrated morphologic and phenotypic diagnostic approach were 91.6, 97.2 and 95.3%, respectively. In conclusion, LNAB plus galectin-3 expression analysis when applied preoperatively to selected thyroid nodules candidate to surgery can potentially reduce unnecessary thyroid resections.

Adult↗

PubMed1996

[Comparative yield of fine needle biopsy and cytology of solid thyroid nodules].

BACKGROUND: The correct management of thyroid nodules requires an accurate histological diagnosis to discard carcinoma. AIM: To assess the diagnostic value of fine needle aspiration biopsy of thyroid nodules as compared to cytology of the same sample and surgical biopsy. PATIENTS AND METHODS: One hundred and forty three thyroid nodules were punctured with a 21 G needle under continuous aspiration obtaining a sample for cytological and histological diagnosis. Fifty patients were subjected to a thyroidectomy. RESULTS: The age of studied patients ranged from 12 to 78 years old and 94% were female. Mean nodule diameter was 2.7 +/- 1.4 cm. Two percent of procedures were complicated with local hematomas, that subsided spontaneously. A diagnosis of cancer was reached in 16% of all patients and 46% of operated patients. Cytology had a 50% sensitivity, 87.5% specificity, a 89.4% positive predictive value and a 87.5% negative predictive value. The figures for fine needle aspiration biopsy were 82.6, 100, 100 and 87% respectively. CONCLUSIONS: Fine needle aspiration biopsy has a better diagnostic accuracy than cytology and is a simple and safe procedure.

Adolescent↗

PubMed2006

Is fine-needle aspiration (FNA) of multiple thyroid nodules justified?

BACKGROUND: The clinical management of patients with solitary thyroid nodule is well established; however, the evaluation of patients with multiple thyroid nodules is controversial. The aim of this study was to assess if there is a correlation between the risk of malignancy and number of thyroid nodules. DESIGN: The study cohort included 2,884 patients (2,410 females and 474 males) with 3,274 thyroid nodules that underwent FNA under ultrasound guidance between November 1997 and April 2004. Multiple thyroid nodules were aspirated in 360 patients; 2 in 332 (291 females, 41 males), 3 nodules in 26 (23 females, 3 males), and 4 nodules in 2 patients (1 female, 1 male). Subsequent information regarding the histological diagnosis was obtained in the cases that underwent surgical excision. RESULTS: The average age for patients with single or multiple nodules was the same (51 yr). The FNA specimens were diagnosed as benign (n = 1,663, 51%), neoplasm (n = 880, 27%), suspicious for neoplasm or papillary carcinoma (n = 234, 7%), malignant (n = 187, 6%), and non-diagnostic (n = 310, 9%). Surgical excision was performed in 1,135 patients: 993 patients with single nodules and 142 patients with multiple nodules. The surgical pathology diagnosis was benign in 656 nodules (52%) and malignant in 596 nodules (48%). In the malignant category 153 tumors were papillary microcarcinoma (<1 cm). Excluding these cases, the malignancy rate was 39% in patients with single nodules, 41% with two nodules, and 21% with three nodules. CONCLUSIONS: The cancer risk is similar for patients with one or two nodules over 1 cm and decreases with three or more thyroid nodules.

Biopsy, Fine-Needle↗

PubMed2005

Gray-scale three-dimensional sonography of thyroid nodules: feasibility of the method and preliminary studies.

The aim of the study was differential evaluation of new and classical sonographic features of benign thyroid nodules and thyroid cancer with three-dimensional gray-scale sonography and evaluation of the effectiveness of the thin-slice surface rendered images in comparison with multiplanar reformation (MPR) presentation. Fifty-four thyroid nodules were interactively evaluated with thin-slice smooth surface rendering: shape in the c-plane (parallel to the probe) and evaluation of echogenicity, margins and calcification/microcalcification-like echogenic foci in the a-plane (plane of the probe). Evaluation of the level of agreement in readers' interpretation and between sonographic techniques was performed using the kappa statistic. Surface rendering permitted visualization of the shape of the nodule in the c-plane in all cases, in contrast to only up to 48% of cases in MPR evaluation. Lobulated nodule shape in the c-plane was 82-100% sensitive and 47-53% specific in diagnosis of carcinoma. Surface rendered images showed more calcification/microcalcification-like echogenic foci than MPR ones. The level of agreement between the observers in the evaluation of features of thyroid nodules and the agreement between features of thyroid nodules on MPR and surface-rendered images showed at least moderate reproducibility (kappa>or=0.41). Three-dimensional thin-slice surface rendering sonography appears to be a feasible and effective method for thyroid nodule evaluation.

Adult↗

PubMed1999

Changes in thyroid nodule volume caused by fine-needle aspiration: a factor complicating the interpretation of the effect of thyrotropin suppression on nodule size.

The effectiveness of TSH suppression therapy for thyroid nodules remains controversial. Prior studies have assumed that the fine-needle aspiration biopsy (FNAB), used to confirm a benign condition before the establishment of control and treatment groups, has no effect on nodule volume. Seventeen untreated euthyroid patients with clinical solitary thyroid nodules that were solid (on high-resolution ultrasound) and a colloid goiter (on cytologic examination) had ultrasound measurements of nodule volume before a FNAB, immediately thereafter, and 1 month and 6 months later. Size differences and individual variability at each time period were analyzed. No significant difference in mean thyroid nodule volume was present at any point after the FNAB; however, the changes in nodule volume were quite marked and bidirectional among patients masking the cumulative effect. The variability of the change in individual nodule volume was statistically significant when comparisons were made across time (P = 0.0032). FNAB of thyroid nodules results in significant individual changes in volume after the procedure. Studies, such as the effect of TSH suppression on thyroid nodule volume, that incorporate the FNAB in both control and treatment arms of the experimental design, need to take these changes into account, less erroneous conclusions result.

Biopsy, Needle↗

PubMed1991

Evaluation of the thyroid nodule.

The evaluation and management of thyroid nodules remains an area of controversy. The past decade has witnessed two important advances. The increased availability and acceptance of fine-needle aspiration biopsy of thyroid nodules has dramatically altered the clinician's approach to this disease, and provides for the single most precise method for selecting appropriate patients for surgery. The introduction of high-resolution thyroid ultrasonography provides for anatomic definition that is clearly superior to thyroid scintigraphy. However, radionuclide imaging of the thyroid remains critical for determining the functional status of abnormal thyroid tissue. While aspiration, ultrasound, and scintigraphy all have appropriate indications, utility, and limitations, no single test or group of tests substitutes for careful clinical assessment and follow-up. This review attempts to provide a practical approach to the evaluation and management of the thyroid nodule.

Biopsy, Needle↗

PubMed2000

Large-needle aspiration biopsy for the preoperative selection of palpable thyroid nodules diagnosed by fine-needle aspiration as a microfollicular nodule or suspected cancer.

The palpable thyroid nodules with a fine-needle aspiration (FNA) diagnosis of microfollicular nodule or suspected cancer usually are excised; however, most of them are proved benign by postoperative histologic examination. We reviewed the clinical and pathologic data for patients with thyroid nodules with an FNA diagnosis of microfollicular nodule or suspected cancer; nodules also were examined by large-needle aspiration biopsy (LNAB) to assess whether the distinction achieved by LNAB into pure microfollicular or mixed microfollicular-macrofollicular nodules could be used preoperatively to better predict malignancy. One hundred fourteen nodules of this type were excised. The prevalence of cancer was 22% (14/63) among the microfollicular and 4% (2/51) among the microfollicular-macrofollicular nodules at LNAB. These data indicate that histologic examination of the LNAB specimen can be used for preoperative selection of thyroid nodules diagnosed by FNA as a microfollicular nodule or suspected cancer.

Adenocarcinoma, Follicular↗

PubMedDate not supplied

[Thyroxine therapy in benign thyroid nodules].

Levothyroxine (LT4) treatment in benign thyroid nodules is a controversial management. The favorable response varies between 10-60%, being, in some studies, comparable between treated and untreated groups. The aim of this study was to evaluate the response of uninodular goiter at the LT4 treatment, in comparison with untreated patients. The study group (S) included 53 patients diagnosed with nodular goiter, treated with LT4 for 1 year. 26 patients with nodular goiter, age and sex-matched, untreated, constituted the control group (C). All patients were from a minor iodine deficient area. The including criteria were euthyroidism, single nodule, solid (ultrasonography), cold (Scintigraphy), and benign (FNAB). After 1 year mean nodular volume had a significant decrement in both groups, higher in group S (35%: from 7.8 to 5.2 mL, p = 0.0098) than in group C (25%: from 8.4 to 5.9 mL, p = 0.026). Linear regression showed a slight correlation between the nodular decrement and the initial volume (r = 0.23): the responders percentage was higher in nodules with a volume < 5 ml than in those with volume > 5 ml (51.5% vs o 19.6%, p < 0.0001). The evolution of treated nodules seamed to be better than of the untreated ones, but the differences were only slightly significant. We believe that the evolution of thyroid nodules under LT4 treatment can be influenced by the iodine supply, since in most of the studies from minor iodine deficiency regions (Europe, South America) the response is better than in regions with sufficient iodine supply (North America). Knowing the potential side effects of LT4 therapy, this kind of management of benign thyroid nodules should be reserved to selected cases.

Adult↗

PubMed1995

[Genesis of thyroid nodules. Physiological and pathological mechanisms, clinical implications].

Thyroid nodules are the most frequently encountered thyroid diseases since they are displayed by clinical examination and ultrasound thyroid study in 3-5% and 50% of any patients, respectively. Thyroid nodules are more frequent in females and their prevalence increases with age, iodine deficiency and exposure to radiation. Thyrocytes proliferation is under the control of two classic factor (TSH and iodine) and a dozen of newly identified growth factors/regulators. Indeed, the hyperplastic phase, its angiogenic counterpart, and the following expression of thyrocytes' differentiation are the result of a complex intercellular cooperativity. Moreover, the innate thyrocytes heterogeneity, regarding their tendency to proliferate and differentiate, determines a more complexified control. This complex mechanism which allows a fine tuning of the thyroid function is nevertheless responsible for the various targets that will be affected by manifold etiopathogenetic factors. Thyroid nodules genesis may thus be envisioned as an amplification, secondary to genetic or/and epigenetic mechanisms, of the thyroid gland heterogeneity. Experimental data and their conceptual outcomes should be kept in mind in the diagnostic, therapeutic or preventive care of thyroid nodular diseases.

Female↗

PubMed2004

SV40 in human thyroid nodules.

BACKGROUND: Simian virus 40 (SV40) has been a model experimental system for the study of cell transformation and tumorigenesis for many years. The study of SV40 in humans has aroused interest in the related BK virus (BKV) and JC virus (JCV) and their role in human disease. OBJECTIVES: SV40 has been found in a variety of human samples, both malignant and normal. Many independent studies have suggested that SV40 plays a role for some cancers. However, in most cases the role of SV40 remains unclear. STUDY DESIGN: The subject of this study consisted of 99 patients with thyroid nodules. Both thyroid nodule and normal thyroid tissue were taken from each patient to test whether they contained SV40 sequences. RESULTS: We detected SV40 sequences by polymerase chain reaction (PCR) in four of 99 thyroid nodules. Two of them were papillary thyroid carcinomas and the others were benign thyroid nodules. No SV40 was detected in 99 of normal thyroid tissues of the same patients. DNA sequence analysis, performed in four positive samples, confirmed that PCR products belong to the SV40 T antigen (Tag) region. CONCLUSION: The possible role of SV40 in the development of thyroid nodules and the spread of SV40 by horizontal infection in the human population are discussed.

Adolescent↗

PubMed1993

Morphological and functional polymorphism within clonal thyroid nodules.

Thirty-nine thyroid nodules, removed because of recent growth, were analyzed morphologically by serial histological sections for the classical histomorphological hallmarks of follicular cell replication and for immunohistochemically demonstrable overexpression of the growth-associated ras-gene product p21ras. Clonal analysis was performed using the highly informative probe M27 beta that detects polymorphisms on the locus DXS255 of the X-chromosome. Twenty-four nodules were of clonal and 15 nodules were of poly-clonal origin. Only 3 out of the 24 clonal nodules were histomorphologically uniform. In all others, the structural hallmarks of active growth and the P21ras growth-marker expression were remarkably heterogeneous throughout the tumors. There were no histomorphological characteristics distinguishing these clonal tumors from polyclonal nodules. Even if a clonal thyroid tumor may be originally homogeneous in respect to the parameters studied here, mechanisms must exist that create wide heterogeneity of growth and of morphogenetic potential among the individual follicular cells during further expansion of the nodule. Thus, clonal nodules are much more common in nodular goiters than hitherto assumed on grounds of the classical morphological criteria. The diagnosis of a true monoclonal nodule can no longer rely on morphological and functional criteria alone but requires molecular or cytogenetic analysis of clonality.

Adult↗

PubMed2005

[Significance of galectin-3 and CD44v6 expression in differential diagnosis of thyroid nodules].

OBJECTIVE: To investigate the difference of galectin-3 and CD44v6 expression between benign and malignant thyroid nodules, and to evaluate their clinical value in distinguishing thyroid cancer from benign thyroid nodules. METHODS: The expression of galectin-3 and CD44v6 was immunohistochemically detected by the ABC method in 143 benign and malignant thyroid nodule samples. RESULTS: Expression of these two markers in benign thyroid nodules: galectin-3 was negative in 10 cases of para-cancer normal tissue and 14 cases of benign nodules found in the other benign thyroid disease. It was weakly positive in 4 of 52 nodular goiter (7.7%). Also it was weakly positive in 2 of 22 follicular adenomas (9.1%). But all three eosinophilic follicular adenomas were diffusely or focally positive for galectin-3. CD44v6 was negative in 10 cases of para-cancer normal tissue, but positive in 4 of 14 nodular lesions found in benign thyroid diseases (28.6%). It was also positive in 16 of 52 nodular goiters (30.8%), and weakly positive in 7 of 22 follicular adenomas (31.8%). The two markers in malignant lesions: galectin-3 was positive in 50 of 52 thyroid adenocarcinoma (96.2%), CD44v6 was positive in 42 of 52 thyroid adenocarcinoma (80.8%). The positive rate of galectin-3 and CD44v6 expression in thyroid cancer was significantly higher than that in benign thyroid nodule and normal tissue (P < 0.001). The sensitivity, specificity and accuracy of galectin-3 combined with CD44v6 in differentiating benign from malignant thyroid nodule were 80.8%, 93.4%, 88.8%; they were 96.2%, 90.1%, 92.3% for Galectin-3 alone. CONCLUSION: The immunohistochemical expression of galectin-3 and CD44v6 by the ABC method is significantly higher in thyroid cancers than in benign thyroid nodules, especially galectin-3 in thyrocyte being helpful in differentiating benign thyroid nodule from thyroid cancer.

Adenocarcinoma, Papillary↗

PubMed2006

Thyroid nodule: a potentially malignant lesion; optimal management from a surgical perspective.

Thyroid nodules are very common lesions, frequently detected by modern imaging methods (mainly ultrasonography). Despite that most thyroid nodules represent benign lesions, a small but significant percentage of them are malignant. Surgery is indicated when there is underlying malignancy (or suspicion for), pressure symptoms, or for cosmetic reasons. Total/near total thyroidectomy is the most radical procedure, which achieves cure, avoids the possibility of reoperation in the future (completion thyroidectomy), and facilitates postoperative management of the patient with underlying malignancy. Simple observation and thyroid hormone suppressive therapy are acceptable management options for patients with presumably benign thyroid nodules. Radioiodine therapy may be used for the management of patients with hyperfunctioning ("hot") thyroid nodules. Ablation of thyroid nodules (sclerosing therapy [alcohol injection] and laser photocoagulation) have been used for the in situ destruction of thyroid nodules; ablation therapy is currently viewed as experimental therapeutic method. Careful evaluation is required in order to avoid both overtreatment (mainly unnecessary surgery) as well as undertreatment of these potentially malignant, but highly curable lesions.

Algorithms↗

PubMed1993

Importance of repeat fine-needle biopsy in the management of thyroid nodules.

Fine-needle aspiration (FNA) biopsy of a thyroid nodule was performed in 797 patients. Ninety-six patients had resection of the thyroid nodule performed subsequent to a one-time FNA biopsy. The surgical pathology of these 96 cases demonstrated a 5.8% false-negative rate and a 9.9% false-positive rate. As a consequence, we prospectively evaluated the routine practice of repeat FNA of cytologically benign thyroid nodules. Repeat FNA confirmed the original benign cytology in 183 (93%) of 196 patients. Seventeen of these 183 patients with benign FNA on both biopsies had resection of the nodule performed because of the development of suspicious clinical signs or in response to the patient's choice; 1 recurrent cyst was found to be carcinomatous. Of the 13 patients demonstrating a change in cytology on repeat FNA biopsy, 9 had a nodule that was classified as possibly malignant (suspicious); 6 of these patients underwent resection, and 1 patient was found to have a carcinomatous nodule. Four patients had nodules that were classified as probably malignant on repeat FNA biopsy; all of their nodules were resected, and three of them were found to be carcinomatous. This study demonstrates that, although one-time FNA biopsy of thyroid nodules is highly accurate, with a relatively low false-negative rate, repeat fine-needle biopsy improves on this diagnostic accuracy, thereby decreasing the risk of misdiagnosing a thyroid nodule that is malignant.

Adult↗

PubMed2006

Pathogenesis, diagnosis and management of thyroid nodules in children.

According to the literature thyroid nodules are quite rare in the first two decades of life. However, there are some exceptions, relating to areas with an iodine deficiency or affected by radioactive fallout, where the risk of nodules and carcinomas is increased. Therefore, it is a great challenge for the physician to distinguish between benign and malignant lesions preoperatively, and not only in these areas of greater risk. A careful work-up, comprising the patient's history, clinical examination, laboratory tests, thyroid ultrasound, scintigraphy, fine-needle aspiration biopsy (FNAB) and molecular studies, is mandatory to improve the preoperative diagnosis. The differential diagnosis should also include benign thyroid conditions such as: (i) congenital hypothyroidism due to dyshormonogenesis or ectopy, (ii) thyroid hemiagenesis, (iii) thyroglossal duct cyst, (iv) simple goiter, (v) cystic lesion, (vi) nodular hyperplasia, (vii) follicular adenoma, (viii) Graves' disease and (ix) Hashimoto thyroiditis, all of which can predispose to the development of thyroid nodules. The majority of thyroid carcinomas derive from the follicular cell (papillary, follicular, insular and undifferentiated (or anaplastic) thyroid carcinoma), whereas medullary thyroid carcinoma derives from calcitonin-producing cells. Inherited forms of thyroid cancer may occur, especially in relation to medullary thyroid carcinoma. FNAB is a critical factor in establishing the preoperative diagnosis. However, we should keep in mind the fact that a conventional cytological evaluation can miss the neoplastic nature of a lesion and the employment of immunocytochemical and molecular studies of aspirates from FNAB can give us a more precise diagnosis of neoplasia in thyroid nodules once they are detected.

Biopsy, Fine-Needle↗

PubMed2002

Effectiveness of thyroid hormone suppressive therapy in benign solitary thyroid nodules: a meta-analysis.

The effectiveness of thyroid hormone suppressive therapy in reducing the volume of benign thyroid nodules is controversial. It is important to clarify this therapeutic effect of thyroid hormone, because its prolonged use needs to be carefully weighed against its potential deleterious effects in the skeletal and cardiovascular systems. To evaluate the best available evidence, we conducted a systematic review and meta-analysis of the randomized controlled trials that fulfill the following inclusion criteria: single thyroid nodules proven benign by fine needle aspiration, treatment, and follow-up of at least 6 months; documented suppression of TSH; measurement of thyroid nodule volume by ultrasound; and response to therapy defined as more than 50% volume reduction from baseline. Six randomized clinical trials published between 1987 and 1999, with 346 patients, were included in the meta-analysis. Ninety percent of the participants were female. Using a random effects model, the overall effect size showed a relative risk of 1.9 (95% confidence interval, 0.95-3.81) favoring a treatment effect. A sensitivity analysis showed significant changes in the results. Suppressive thyroid hormone therapy for longer than 6 months is associated with a trend toward a reduction of more than 50% in volume of benign thyroid nodules, without achieving statistical significance. The results are highly sensitive to changes in the statistical analysis, especially if the method used ignores heterogeneity among the effect sizes. More studies are needed before this therapy can be widely recommended.

Humans↗

PubMedDate not supplied

Management of the thyroid nodule.

The approach to the patient with a palpable solitary thyroid nodule remains controversial. In the rare patient with signs and symptoms suggestive of malignancy, the course of action is reasonably established. However, the patient with an asymptomatic solitary thyroid nodule presents a dilemma. The therapeutic alternatives range from suppressive medical therapy with serial examinations to surgical excision; therefore, to obviate unnecessary surgery, several diagnostic techniques and approaches have evolved which attempt to predict the presence of malignancy. A multitude of articles reflects the widespread disagreement among physicians regarding these diagnostic approaches. Thus, many questions still remain as to the proper management of patients with solitary nodules. The issue is further confounded by problems in assimilating and practically applying the results of the various studies, which often differ in their results. In this report, data regarding the prevalence of the solitary thyroid nodule are reviewed, and the clinical significance of the solitary thyroid nodule is discussed. The problem of management is examined in terms of the various diagnostic approaches to the solitary thyroid nodule: history and physical examination, laboratory tests, ultrasonography, thyroid suppressive therapy, scanning techniques, and fine-needle aspiration. The efficacy of each technique is critically evaluated with an emphasis upon the ability to distinguish benign from malignant disease. The overall aim of this report is to establish a reasonable diagnostic approach to the asymptomatic patient with the solitary palpable thyroid nodule, based upon a critical review of the literature.

Age Factors↗

PubMed1999

Coincidence of hot thyroid nodules and primary hyperparathyroidism.

Hyperthyroidism is frequently associated with hypercalcemia, which usually subsides after successful treatment of hyperthyroidism. Moreover, thyroid nodules are frequently detected by preoperative thyroid ultrasound in patients with primary hyperparathyroidism. Sensitised by the observation of a patient with coexisting hyperthyroidism and hyperparathyroidism we prospectively evaluated thyroid nodules in euthyroid patients with hyperparathyroidism by thyroid scintigraphy. Whereas the first patient with hyperparathyroidism was hyperthyroid the subsequent four patients with hyperparathyroidism and thyroid nodules had normal fT3 and fT4. Two patients had hypercalcemia and nephroureterolithiasis. Three patients suffered from hypercalcemia and bone pain due to osteoporosis. In the hyperthyroid patient hypercalcemia persisted after euthyroidism was achieved intact parathyroid hormone was found to be elevated. Subsequently, thyroid nodules, detected by preoperative ultrasound in four euthyroid patients with primary hyperparathyroidism, were identified as compensated hot nodules by thyroid scintigraphy. All patients underwent combined subtotal thyroidectomy and parathyroid resection. Histology showed hyperplastic parathyroid glands in one patient and a single parathyroid adenoma in four cases. Postoperatively calcium and PTH levels returned to normal and TSH levels increased in all patients. Persistence of hypercalcemia after successful treatment of hyperthyroidism should be reason for the determination of parathyroid hormone. Thyroid nodules detected by preoperative ultrasound in patients with hyperparathyroidism living in areas of iodine deficiency should be further evaluated by scintigraphy even if TSH is normal. In the case of hot thyroid nodules both parathyroid and partial thyroid resection should be performed.

Aged↗