Hyperfunctioning Thyroid Nodules Research Articles

Integrated Diagnostics of Thyroid Nodules.

Thyroid nodules are common findings, particularly in iodine-deficient regions. Our paper aims to revise different diagnostic tools available in clinical thyroidology and propose their rational integration. We will elaborate on the pros and cons of thyroid ultrasound (US) and its scoring systems, thyroid scintigraphy, fine-needle aspiration cytology (FNAC), molecular imaging, and artificial intelligence (AI). Ultrasonographic scoring systems can help differentiate between benign and malignant nodules. Depending on the constellation or number of suspicious ultrasound features, a FNAC is recommended. However, hyperfunctioning thyroid nodules are presumed to exclude malignancy with a very high negative predictive value (NPV). Particularly in regions where iodine supply is low, most hyperfunctioning thyroid nodules are seen in patients with normal thyroid-stimulating hormone (TSH) levels. Thyroid scintigraphy is essential for the detection of these nodules. Among non-toxic thyroid nodules, a careful application of US risk stratification systems is pivotal to exclude inappropriate FNAC and guide the procedure on suspicious ones. However, almost one-third of cytology examinations are rendered as indeterminate, requiring "diagnostic surgery" to provide a definitive diagnosis. 99mTc-methoxy-isobutyl-isonitrile ([99mTc]Tc-MIBI) and [18F]fluoro-deoxy-glucose ([18F]FDG) molecular imaging can spare those patients from unnecessary surgeries. The clinical value of AI in the evaluation of thyroid nodules needs to be determined.

FRI561 The Thyroid Trifecta

Abstract Disclosure: P. Kachhadia: None. S. Khan: None. A. Abu Limon: None. S. Aldasouqi: None. Introduction: Autoimmune Hashimoto’s Thyroiditis (HT) and Graves’ Disease (GD) may co-exist or may occur alternatingly, known in many case reports as Graves’s Alternans. Hyperfunctioning (Toxic, hot) thyroid nodules (TN) may also co-exist with GD, a rare condition called Marine-Lenhart syndrome. However, the co-existence of HT, GD and TN is perceivably rarer. Case Presentation: The patient is a 45 year old female with a prior history of HT for 20 years, who presented to the clinic with symptoms of minimal eye pain, tremors, fatigue, diarrhea and anxiety. She was not on thyroid replacement, with normal thyroid function tests (TFTs). Physical exam showed bilateral proptosis, a moderate goiter, hand tremors, mild anxiety and tachycardia. Labs showed high TPO (3995.0 IU/mL, n <18 IU/mL), Thyrotropin receptor antibody (5.25 IU/L, n<1.75 IU/L), and Thyroid-stimulating immunoglobulins (1.8 TSI index, n<1.3 TSI index) with low-normal TSH of 0.42 uIU/mL (0.35-4.01 uIU/mL) , mid-range free triiodothyronine (FT3) at 3.6 pg/mL (2.8-4.4 pg/mL) and normal free thyroxine (FT4) at 0.80 NG/dL (0.61-1.37 NG/dL). Thyroid US showed a 2.4 cm left lobe inferior nodule classified as TI-RADS 3. Fine needle aspiration of this nodule was benign. Radioactive Iodine-123 Uptake Scan showed a hot nodule in the left inferior lobe and with visible uptake in the rest of the gland (uptake was mid-normal). She was started on methimazole 5mg once daily and propranolol 10mg BID with improvement in her symptoms. Subsequent TFTs showed stable T4 and T3 and normalization of TSH to 1.78 uIU/mL (0.35-4.01 uIU/mL). Discussion: Marine-Lenhart syndrome was described in 1911 by surgeons David Marine and Carl Lenhart. Graves’ Alternans has been described in the literature, with variable time separation. Though thyroid nodules occur in up to 35% of those with GD, only 1-4.1% are deemed functional nodules. Nuclear medicine imaging via Tc-99m pertechnetate or I-123 iodine at diagnosis of GD generally shows such nodules as cold nodules lacking uptake, while the rest of the gland has diffuse uptake. However, with normalization of TSH through treatment, these cold nodules may alternate uptake and present as hot nodules. Conclusion: In conclusion, this case presents the co-existence of HT, GD and HN, a term we are calling “Thyroid Trifecta”. It is imperative that HNs should be identified if RAI treatment is planned in such patients. Literature review portrays cases in which if thyrotoxicosis persists post RAI treatment for GD, careful examination and repeat RAIU may show a hot nodule consistent with Marine-Lenhart Syndrome. These patients may benefit instead from thyroidectomy. In the case of our patient, definitive treatment options have been discussed and she has been referred for thyroidectomy due to the presence of the TN. RAI ablation will be avoided in view of mild but active thyroid eye disease. Presentation: Friday, June 16, 2023

Hot Thyroid Nodule Revealing a Papillary Microcarcinoma: A Case Report

Introduction: Autonomously hyperfunctioning thyroid nodules, also known as "hot nodules", are defined by increased uptake of radiotracers compared to the surrounding thyroid parenchyma on scintigraphy. It has been believed that hot nodules have a low rate of malignancy, while an increasing number of thyroid carcinoma cases are being diagnosed in patients with hyperthyroidism. Case Presentation: A. J, a 50-year-old patient. She presented with signs of hyperthyroidism. Laboratory tests showed peripheral hyperthyroidism with an inhibited TSH of 0.03 μIU/ml and T4L of 37 pmol/L. The scintigraphy revealed a focus of hyper fixation almost completely affecting the right lobe which corresponded to a hot nodule most likely pre-extincted in the remaining parenchyma. The patient was initiated on synthetic antithyroid medication and, after achieving euthyroidism, she was referred to surgery. Right loboishmectomy was performed. The histological study revealed a 0.5 cm intralobular non-encapsulated microcarcinoma papillary on a background of thyroid dystrophy. Discussion: The initial evaluation of a thyroid nodule begins is the measurement of serum TSH and the performance of a thyroid ultrasound, followed by a thyroid radionuclide scan if the TSH is subnormal. Malignant nodules are usually non-functioning. The prevalence of malignancy associated with a hot nodule range between 1-10.3%. In many cases, thyroid cancer is not known preoperatively but is found incidentally during the postoperative histological examination of the thyroid. Most of these malignancies were of papillary carcinoma and less often follicular or Hurthle histological types, and they are small in size, and the majority are microcarcinomas. Conclusion: Further evaluation and characterization of the association between a hot thyroid nodule and malignancy are needed. In the case of our patient, the discovery of papillary carcinoma was incidental and was made during the postoperative histological examination .......

Laser ablation for thyroid nodules has come to age—a review

: Benign thyroid nodules are traditionally treated with thyroidectomy when they become symptomatic. Surgery is expensive, results in scarring, and frequently requires subsequent thyroid hormone replacement. For these reasons, in 2000, a feasibility study proposed ultrasound (US)-guided laser ablation (LA) as a minimally invasive treatment for thyroid lesions. During the following 20 years, US-guided thermal ablation techniques performed with laser, radiofrequency, microwaves, and high-intensity focused US have become available for clinical practice. Clinical outcomes have demonstrated a nearly similar efficacy and safety of these techniques, but LA still appears as the less complicated and invasive procedure. LA results, in most cases, in a clinically significant volume decrease paralleled by improvement of local symptoms. Volume reduction is stable over the years, complications are rare, and cosmetic damage or thyroid function changes are nearly absent. LA may also be considered for small size hyperfunctioning thyroid nodules. In these cases, thyroid function normalization may be obtained with no irradiation or chance of hypothyroidism. Due to the efficacy and minimal cost of ethanol injection LA remains as a second-line treatment for cystic lesions which relapse after US-guided ethanol ablation. The use of LA and other minimally invasive techniques for non-surgical management of papillary thyroid microcarcinoma (PTMC) represents a rapidly evolving area. Currently, LA may be considered for patients with low-risk PTMC, mainly if they are surgically at risk, with short life expectation, and if they refuse surgery or active surveillance.

Prevalence of differentiated thyroid carcinoma on hyperfunctioning or toxic thyroid nodules

Prevalence of differentiated thyroid carcinoma on hyperfunctioning or toxic thyroid nodules

Anti-thyroglobulin Antibodies as a Possible Risk Factor for Graves' Disease After Radioiodine Treatment for Toxic Nodular Goiter: Case Report

BackgroundThe manifestation of Graves' disease (GD) in patients treated with radioactive iodine (RAI) for hyperfunctioning thyroid nodules (RAI-induced GD or post-RAI GD) remains a long-standing challenge in radionuclide therapy. Known risk factors for post-RAI GD include preexisting subclinical hyperthyroidism, positive thyroid peroxidase autoantibodies (TPOAb), positive TSH receptor autoantibodies (TRAb) or otherwise undiagnosed GD. However, these risk factors are not present in all patients with post-RAI GD, and therefore it cannot always be predicted in a reliable manner if a given patient has a high risk for RAI-induced GD or not.Case PresentationWe describe the case of a 64 year-old woman known for hyperthyroidism due to toxic nodular goiter; she was treated initially with carbimazole, and then, due to recurrence, underwent RAI treatment. Three months later, symptomatic hyperthyroidism persisted. Diagnosis of new-onset GD was made based on typical ultrasound findings and newly-positive TRAb. Our patient had only positive thyroglobulin antibodies (TgAb) before RAI treatment, whereas TPOAb were negative.ConclusionsIn the literature, TgAb have never been reported as a possible risk factor for RAI-induced GD. The present case suggests that the assessment for pre-existing autoimmunity in patients considering RAI for hyperfunctioning thyroid nodules should probably also include TgAb.

Thyroid Tuberculosis Causing Fever of Unknown Origin in a Patient With Multinodular Goiter

Introduction: Tuberculosis (TB) involving the thyroid gland is rare and typically results in hypothyroidism. Here we report a case of thyroid TB that presented with hyperthyroidism. Clinical Case: A 54-year-old woman with a history of hyperthyroidism due to toxic multinodular goiter presented to the emergency department with fever of unknown origin associated with sore throat, non-productive cough, night sweats, diarrhea, and right anterior neck pain that worsened with coughing. Her fevers were intermittent, ranging from 38 to 39 degrees Celsius, and would subside with acetaminophen. She reported that her symptoms had started after getting a thyroid [Tc-99m] pertechnetate scan and 24 hour [I-131] sodium iodide uptake study a month prior. The scan at the time revealed hyperfunctioning thyroid nodules in the lower lobes bilaterally. The 24-hour uptake was 20.2% which is within the normal range of 7 to 30%. TSH on presentation was 0.01 mIU/L (Normal range 0.3-5.50 mIU/L), free T4 was 2.05 ng/dL (Normal range 0.76 -1.7 ng/dL), and free T3 was 5 pg/mL (Normal range 1.9-3.9 pg/mL). Exam revealed a multinodular goiter, which was firm with mild tenderness, and no cervical lymphadenopathy. Infectious workup was unremarkable other than a positive interferon-gamma release assay. As for TB risk factors, the patient immigrated to the United States from Albania about 13 years prior. The patient denied any known TB exposure, neither had she been treated for TB. Radiograph and computed tomography (CT) of the thorax were unremarkable other than re-demonstration of the multinodular goiter. Fluorodeoxyglucose-18 positron emission tomography (FDG-PET), which was performed to identify any focus of active TB, had revealed intense, infiltrative, heterogeneous FDG uptake of the nodular thyroid gland with reactive level 3 and 4 cervical lymph nodes. Also, the scan revealed hyper-metabolic hilar, pre-tracheal, and sub-carinal lymph nodes which could represent latent TB. Further workup for any other foci of active TB including broncho-alveolar lavage, sputum cultures, lumbar puncture, and bone marrow biopsy were unremarkable. Thyroid ultrasound revealed 2 right sided and 3 left sided thyroid nodules, mostly solid and hypoechoic. Fine needle aspiration of nodules revealed benign follicular nodules bilaterally, however the left aspirate contained loose aggregates of histiocytes consistent with non-necrotizing granulomas. Acid-fast bacilli stain of the aspirate was negative. The patient was started on therapy for active TB with isoniazid, rifampin, pyrazinamide, and ethambutol. Six weeks after treatment her fevers had resolved. Conclusion: Thyroid TB should be considered when the severity of symptoms cannot be explained by the degree of hyperthyroidism alone in patients with increased risk of TB. Additionally, TB in the thyroid can be challenging to identify in a patient with known underlying thyroid disease.

Malignancy risk of hyperfunctioning thyroid nodules compared with non-toxic nodules: systematic review and a meta-analysis

BackgroundHyperfunctioning or hot nodules are thought to be rarely malignant. As such, current guidelines recommend that hot nodules be excluded from further malignancy risk stratification. The objective of this systematic review and meta-analysis is to compare the malignancy risk in hot nodules and non-toxic nodules in observational studies.MethodsOvid MEDLINE Daily and Ovid MEDLINE, EMBASE, Scopus, and Web of Science databases were searched. Observational studies which met all of the following were included: (1) use thyroid scintigraphy for nodule assessment, (2) inclusion of both hyperfunctioning and non-functioning nodules based on scintigraphy, (3) available postoperative histopathologic nodule results, (4) published up to November 12, 2020 in either English or French. The following data was extracted: malignancy outcomes include malignancy rate, mapping of the carcinoma within the hot nodule, inclusion of microcarcinomas, and presence of gene mutations.ResultsAmong the seven included studies, overall incidence of malignancy in all hot thyroid nodules ranged from 5 to 100% in comparison with non-toxic nodules, 3.8–46%. Odds of malignancy were also compared between hot and non-toxic thyroid nodules, separated into solitary nodules, multiple nodules and combination of the two. Pooled odds ratio (OR) of solitary thyroid nodules revealed a single hot nodule OR of 0.38 (95% confidence interval (CI) 0.25, 0.59), toxic multinodular goiter OR of 0.51 (95% CI 0.34, 0.75), and a combined hot nodule OR of 0.45 (95% CI 0.31, 0.65). The odds of malignancy are reduced by 55% in hot nodules; however, the incidence was not zero.ConclusionsOdds of malignancy of hot nodules is reduced compared with non-toxic nodules; however, the incidence of malignancy reported in hot nodules was higher than expected. These findings highlight the need for further studies into the malignancy risk of hot nodules.

SUN-476 Risk of Thyroid Cancer in McCune-Albright Syndrome

Background: McCune-Albright syndrome (MAS) is a well described genetic syndrome characterized by café-au-lait spots, polyostotic fibrous dysplasia, and hyperfunctioning endocrinopathies. Hyperthyroidism is a common endocrine manifestation of MAS, but thyroid nodules are less frequently observed. Thyroid cancer is generally considered uncommon in patients affected by MAS. Clinical Case: A 15-year-old male was referred to endocrinology for evaluation of polyostotic fibrous dysplasia with onset at 6 years old. He had no café-au-lait spots and initial labwork revealed no endocrine abnormalities. Subsequent labwork revealed non-autoimmune hyperthyroidism, leading to a diagnosis of MAS. Repeat clinical assessment revealed a goiter. 123-I uptake and scan revealed diffusely increased uptake throughout the gland with increased intensity in two regions of the right lobe separated by a region of photopenia. Ultrasound demonstrated three right-sided thyroid nodules – two correlating with the areas of increased iodine uptake and one with the area of photopenia. The left lobe of the thyroid was normal. FNA biopsy was performed and cytopathology was consistent with Bethesda II and III for the hyperfunctioning nodules and Bethesda VI for the cold nodule.The patient received total thyroidectomy with right-sided central neck dissection, and he was found to have multiple foci of papillary thyroid carcinoma with central neck metastases. The largest hyperfunctioning thyroid nodule was benign. He received radioactive iodine ablation which demonstrated no distant metastases and has had no evidence of recurrent disease. Conclusions: Hyperthyroidism is a common manifestation of MAS, but thyroid nodules are much less frequently observed, and thyroid cancer is considered quite rare. This patient developed TSH-independent hyperthyroidism in normal thyroid cells as well as in two hyperfunctioning thyroid nodules. He developed two contemporaneous classical papillary thyroid cancers – one manifesting as a nonfunctioning thyroid nodule and one manifesting as a thyrotoxic nodule with lymphatic invasion.We conclude that individuals with MAS may be at an increased risk for thyroid nodules and thyroid cancer, although the data are not well established. Clinicians should have a low threshold for thyroid ultrasound in patients with MAS and goiter. Reference: (1) Collins, M. T., Sarlis, N. J., Merino, M. J., Monroe, J., Crawford, S. E., Krakoff, J. A., Guthrie, L. C., Bonat, S., Robey, P. G., & Shenker, A. (2003). Thyroid carcinoma in the McCune-Albright syndrome: contributory role of activating Gsα mutations. The Journal of Clinical Endocrinology & Metabolism, 88(9), 4413-4417.(2) Hannon, T. S., Noonan, K., Steinmetz, R., Eugster, E. A., Levine, M. A., & Pescovitz, O. H. (2003). Is McCune-Albright syndrome overlooked in subjects with fibrous dysplasia of bone?. The Journal of pediatrics, 142(5), 532-538.

Prevalence of hyperfunctioning thyroid nodules among those in need of fine needle aspiration cytology according to ATA 2015, EU-TIRADS, and ACR-TIRADS

PurposeGiven the large number of patients with thyroid nodules, improvement of the specificity of current ultrasound-based thyroid nodule classification systems (ATA, EU-TIRADS, and ACR-TIRADS) is warranted to reduce the number of diagnostic thyroidectomies. Thyroid scintigraphy has been shown to demonstrate hyperfunctional nodules, associated with a low malignancy risk, in euthyroid patients. However, it is not known if thyroid scintigraphy could improve specificity of current classification systems. The aim of this study, therefore, was to determine the frequency of hyperfunctional nodules among those nodules in need of fine needle aspiration cytology (FNA) according to current classification systems and to test if nodule functional status is associated with sonographic features.MethodsFive hundred sixty-six euthyroid patients (TSH 0.55–4.20 μU/ml) presenting for thyroid nodule workup including thyroid sonography and scintigraphy at our department between 09/2013 and 02/2018 were included in this retrospective study. All nodules > 10 mm were classified according to ATA, EU-TIRADS, and ACR-TIRADS and correlated to their functional status as assessed by 99mTc-pertechnetate scintigraphy.ResultsUltrasound detected 1029 thyroid nodules ≥ 10 mm, including 545 nodules ≥ 15 mm. Prevalence of hyperfunctional nodules among those with recommendation for FNA according to ATA 2015, EU-TIRADS, and ACR-TIRADS was 6.4%, 6.9%, and 6.5% for nodules ≥ 10 mm and 7.2%, 7.6%, and 7.5% only considering nodules ≥ 15 mm. No sonographic feature was correlated to hyperfunctionality of nodules.ConclusionIn euthyroid patients, thyroid scintigraphy demonstrates hyperfunctionality, which cannot be predicted by ultrasound, in up to 6.9% of nodules in need of FNA according to ultrasound-based classifications. Given the known low risk of malignancy in hyperfunctional nodules, thyroid scintigraphy can lower the frequency of fine needle aspirations and—potentially—the frequency of diagnostic hemithyroidectomies in euthyroid patients.

SUN-562 Hurthle Cell Carcinoma Presenting as Hyperfunctioning Nodule

Background: Hurthle cell carcinoma (HCC) is a rare type of aggressive follicular carcinoma comprising a small percentage of all thyroid cancers. It is associated with high metastasis and mortality rates with 20-30% of this type of cancer having metastatic extension at the time of treatment. HCC may be asymptomatic until a lump is noticed on the anterior neck. The inability to establish a preoperative diagnosis of HCC creates a dilemma with hyperfunctioning thyroid nodules which are commonly managed as benign. Clinical Case: This is a case of a 48-year old female, who presented with a multinodular thyroid gland on initial imaging associated with palpitations and chest discomfort. Further workup revealed subclinical hyperthyroidism and a thyroid scan showing hyperfunctioning nodules on both lobes. She underwent fine needle aspiration (FNA) biopsy which revealed benign colloid nodule on the right thyroid and cellular findings consistent with follicular neoplasm with oncocytic features on the left thyroid nodule prompting surgery. Surgical specimen histopathology eventually revealed Hurthle cell carcinoma with lymphovascular invasion of the left thyroid nodule. Conclusion: Hurthle cell carcinoma is a relatively uncommon thyroid neoplasm. Though toxic nodules are rarely malignant, HCC is more commonly seen in hyperfunctioning nodules compared with general thyroid nodules. This case supports further evaluation of toxic nodules for possible risk of thyroid cancer. Reference: (1) Mirfakhraee, Sasan & Mathews, Dana & Peng, Lan & Woodruff, Stacey & M Zigman, Jeffrey. (2013). A solitary hyperfunctioning thyroid nodule harboring thyroid carcinoma: Review of the literature. Thyroid research. 6. 7. 10.1186/1756-6614-6-7.

Ultrasonographic Characteristics of the Hyperfunctioning Thyroid Nodule and Predictive Factors for Thyroid Stimulating Hormone Suppression

Background and Objectives: Thyroid scan is a good tool for diagnosis of hyperfunctioning thyroid nodules (HNs), however it has been limited in use in a primary clinical practice, because of its inconvenience and low accessibility. This study aimed to analyze ultrasonographic (US) characteristics of HNs and to predict HNs by US. Materials and Methods: We included 114 patients who exhibited results of ‘hot’ nodule in the thyroid scan from 2008 to 2017. Analysis for US characteristics included 73 patients without unclear US images and other inevitable reasons. We compared US characteristics of HNs with cold nodules that showed “cold” in the thyroid scan. Additionally, we compared US characteristics of HNs between suppressed thyroid-stimulating hormone (TSH) (＜0.25 uIU/mL) or normal TSH, and analysis receiver operating characteristics (ROC) curve for prediction of suppressed TSH among HNs. Results: The HNs showed more partially cystic nodule, isoechoic echogenicity, hypervascularity and presence of halo in the US finding than the cold nodule. In subgroup analysis of nodules with TSH suppression among HNs, the TSH suppression nodules was lager in max size and volume than the normal TSH nodules. In ROC analyses for prediction of the TSH suppression among HNs, area under receiver operating characteristics curves was 0.736 in max size, 0.761 in volume. Conclusion: HNs showed more frequently partially cystic contents, isoechoic echogenicity, hypervascularity, and peripheral halo sign in US finding. Thyroid nodule size and volume were associated with suppressed TSH level of HNs, and optimal cutoff levels for prediction of TSH suppression among HNs were 2.6 cm and 1.13 ㎤, respectively.

The Pathology of Hyperthyroidism.

This article reviews those pathologic lesions which are associated with clinical and/or biochemical hyperthyroidism. Beginning with the descriptive pathology of classical Graves' disease and the less common toxic nodular goiter and hyper-functioning thyroid nodules, this paper describes the effects of non-thyroidal hormones, glandular function (including pituitary and hypothalamic lesions), ectopic production of thyroid stimulating proteins by non-thyroidal neoplasms, exogenous drug reactions causing hyper-function and finally conditions associated with a mechanic- destructive cause of hyperthyroidism.

Risk Stratification of Thyroid Nodules Using the Thyroid Imaging Reporting and Data System (TIRADS): The Omission of Thyroid Scintigraphy Increases the Rate of Falsely Suspected Lesions.

Thyroid nodules are a common finding, especially in iodine-deficient regions. Ultrasonographic scoring systems such as the Thyroid Imaging Reporting and Data System (TIRADS) are helpful in differentiating between benign and malignant thyroid nodules by offering a risk stratification model. Depending on the constellation or number of suspicious ultrasound features, a fine-needle biopsy is recommended. However, none of the previous TIRADS publications considered the functional status of the nodules. Hyperfunctioning thyroid nodules (HTNs) were presumed to exclude malignancy with a very high negative predictive value. Particularly in regions where the iodine supply is low, most HTNs are seen in patients with normal thyroid-stimulating hormone levels. Therefore, thyroid scintigraphy is essential for the detection of HTNs. We investigated whether TIRADS identifies HTNs as nonsuspicious. Methods: We evaluated 615 HTNs (23.2 ± 10.0 mm in maximum diameter in 582 patients ([442 women, 57.7 ± 13.2 y old, and 140 men, 60.1 ± 12.7 y old) detected by 99mTc-pertechnetate or 123I scintigraphy. Before evaluating the scintigraphic appearance, all nodules were analyzed prospectively with sonography, using the TIRADS model referenced in Kwak et al., wherein fine-needle biopsy is recommended for TIRADS 4A or higher. We also investigated 2 subgroups, 42 nodules with available histology and 117 patients with subclinical or overt hyperthyroidism. Results: Whereas 15.9% of the nodules were classified as TIRADS 3 or lower and less than 0.1% as TIRADS 5, most of the nodules were classified as TIRADS 4A (29.3%), 4B (29.3%), or 4C (24.9%). Altogether, more than 80% of the autonomous thyroid nodules were classified as TIRADS 4A or higher, a grade that would result in a recommendation of fine-needle biopsy. Focusing on those 117 HTNs that were already associated with hyperthyroid laboratory values, the rates were similar: 81.2% were categorized as TIRADS 4A or higher (4A, 33.3%; 4B, 29.9%; 4C,17.1%; 5, 0.9%). In the subgroup of patients who underwent thyroid surgery, all nodules were benign, confirming the known negative predictive value of HTNs with regard to malignancy exclusion. Conclusion: Integration of thyroid scintigraphy into the TIRADS model is essential to prevent unnecessary fine-needle biopsy and thyroid surgery.

A case of papillary thyroid carcinoma in toxic adenoma: are hyperfunctioning nodules truly innocent all the times?

Thyroid nodule is seen commonly in clinical practice. Thyroid scintigraphy should be performed for the evaluation of thyroid nodules in case of suppressed TSH. We would like to present a case of toxic adenoma with the diagnosis of papillary thyroid carcinoma. Forty-four-year-old female patient had applied to the hospital with the diagnosis of thyroid nodule. Thyroid fine needle aspiration biopsy (FNAB) was performed for the evaluation of thyroid nodule measured as 47x12 mm. This nodule was in mixed solid form bearing cystic components. FNAB revealed that the thyroid nodule was benign. Our ultrasonographic evaluation was consistent with a thyroid nodule located at right lobe with a diameter of 43x18x28 mm. The patient underwent right thyroid lobectomy. Pathology report revealed macrofollicular variant of papillary thyroid carcinoma. The tumor was 3.5 cm in diameter with regular margin and 0.2 cm away from the surgical border. The tumor didn’t spread out of the thyroid capsule. Second thyroid surgery was performed due to remaining thyroid tissue. After that ablative radioactive iodine therapy was applied. Guidelines in Endocrine literature report that hyperfunctioning nodules are almost always benign. However, the risk of malignancy was reported as a weighted rate of 3.1%. As follicular lesions are seen in high percentage in hot nodules, surgery should be recommended in case of the cytological results of a follicular neoplasm of a hyperfunctioning nodule. So, hyperfunctioning thyroid nodules warrants careful evaluation and appropriate therapy. We wanted to draw attention of the clinicians for this rare issue.

The efficacy of radioiodine therapy in patients with hyperfunctioning thyroid nodules

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Free thyroxine in needle washout after fine needle aspiration biopsy of toxic thyroid nodules.

The main diagnostic tool for toxic adenomas (TA) is radionuclide imaging indicated in patients with evidence of thyroid nodules in combination with thyrotoxic syndrome. Thyroid ultrasound and fine-needle aspiration biopsy (FNAB) are widely used for the valuation of thyroid masses. There is no literature data concerning the utility of FNAB and related tests for the diagnosis of hyperfunctioning thyroid nodules. The purpose of this study is to determine the levels of free thyroxine (FT4) in the needle washout after FNAB of hot thyroid nodules. The results of our study show that the FT4 levels in needle washout from TA were significantly higher than the surrounding parenchyma and correlated with the hormonal changes in patients with thyroid hyperfunctioning nodules. Further studies on a large number of patients are needed to refine the diagnostic value of this method and evaluate its importance in quantitative risk assessment of thyroid autonomy.

Large Multinodular Toxic Goiter: Is Surgery Always Necessary?

Patients suffering from multinodular toxic goiter (MNTG) are candidates to thyroidectomy or radioiodine 131I (131I) therapy. Thyroidectomy may be preferable especially when the volume of hyperfunctioning tissue is so large that a single administration of 131I is unlikely to cure the patient in terms of nodule's volume reduction and thyroid function. We describe the case of a 71-year-old man suffering from thyrotoxic state for the presence of two large hyperfunctioning thyroid nodules. As the patient refused surgery, at first we administered 600 MBq dose of 131I, which was unable to solve hyperthyroidism and local compressive symptoms. Then, before administering another 131I dose, the patient underwent a laser ablation treatment (LAT) in both nodules. After a significant shrinkage due to LAT, the patient received 400 MBq 131I. This procedure was able to definitely cure hyperthyroidism, to induce a significant reduction of nodules' volume, and to render the patient asymptomatic for compressive symptoms. This case demonstrates that 131I preceded by LAT represents a valid alternative strategy to surgery, even in the presence of two large coexistent hot nodules.

Trefoil factor 3 is required for differentiation of thyroid follicular cells and acts as acontext-dependent tumor suppressor.

Trefoil factor 3 (TFF3) is overexpressed in avariety of solid epithelial cancers, where it has been shown to promote migration, invasion, proliferation, survival and angiogenesis. On the contrary, in the majority of thyroid tumors, it is downregulated, yet its role in the development of thyroid cancer remains unknown. Here we show that TFF3 exhibits strong cytoplasmic staining of normal thyroid follicular cells and colloid and the staining is increased in hyperfunctioning thyroid nodules, while it is decreased in all thyroid cancers of follicular cell origin. By meta-analysis of gene expression datasets, we found that in the thyroid cancer, conversely to the breast cancer, the expression of TFF3 mRNA was downregulated by estrogen signaling and confirmed this by treating thyroid cancer cells with estradiol. Forced expression of TFF3 in anaplastic thyroid cancer cells resulted in decreased cell proliferation, clonal spheroid formation and entry into the Sphase. Furthermore, it induced acquisition of epithelial-like cell morphology and expression of the differentiation markers of thyroid follicular cells and transcription factors implicated in the thyroid morphogenesis and function. Taken together, this study provides the first evidence that TFF3 may act as atumor suppressor or an oncogene depending on the cellular context.

Septin 7 immunoexpression in papillary thyroid carcinoma: A preliminary study

Papillary thyroid carcinoma (PTC) is the most common type among thyroid cancers. The diagnosis of PTC may be challenging when follicular variant (FVPTC) of this disease is present due to the resemblance of nuclear properties of the classical type (CVPTC). However, making use of ancillary molecular markers in the diagnosis of PTC may help. In our study, we aimed to evaluate the SEPT7 protein expression in PTC. A total of 55 paraffin block tissue samples comprising encapsulated FVPTC (FVPTC(e), n=25), and CVPTC (n=15), and benign hyperfunctioning thyroid nodules (HypN, n=15) were used in this study. Nuclear, cytoplasmic, and overall (total) SEPT7 protein expression levels were determined by using immunohistochemistry. Nuclear, cytoplasmic, and overall SEPT7 expressions (p=0.02, p=0.001, p=0.002, respectively) were significantly lower in FVPTC(e) tissues when compared to HypN. In CVPTC group, nuclear expression was significantly lower (p=0.004) while overall and cytoplasmic expressions were not changed (p>0.05). In HypN group, highest nuclear (mean=2.73), cytoplasmic (mean=2.86), and overall (mean=2.86) expression scores were detected. Significantly lower SEPT7 expression in all expressional categories in FVPTC(e) group may be a sign of different molecular signature in this type of tissue.