Hot Nodules Research Articles

Clinical characteristics associated with the finding of thyroid cancer originating from hot nodules in patients with hyperthyroidism: a case report and systematic review of the literature

Coexistence between thyroid cancer and hyperthyroidism is rare, and most of the nodular lesions from which a malignant tumor is documented in this group of patients correspond to cold nodules. Justified by the increasing number of reports in the literature about malignant tumors diagnosed from hot nodules, a systematic review was carried out to determine possible factors associated with the diagnosis of thyroid cancer from hot nodules in patients with hyperthyroidism. The results suggest that the clinical diagnosis of toxic nodular goiter, nodular lesions of diameter > 10 mm and a histological type compatible with a follicular carcinoma, are factors that on their own increase the risk of making the diagnosis of cancer from a hot nodule.

Abstract #1003850: Case of COVID-19 Related Thyroiditis

The severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) is a novel enveloped RNA beta-coronavirus responsible for the Coronavirus disease-19 (COVID-19) ranging from asymptomatic cases to severe respiratory involvement. The SARS-CoV-2 pandemic has spread rapidly worldwide. Few cases and case series have been published reporting COVID-19 related subacute thyroiditis. We report a case of COVID-19 related thyroiditis. 73-year-old female presented to the hospital with complaint of shortness of breath, fever and weakness. She was diagnosed with COVID-19 pneumonia and treated with dexamethasone and convalescent plasma. Patient was discharged home after 10 days. Two days after discharge, she presented with complaint of generalized weakness. She was noted to have thyrotoxicosis. Patient was not taking lithium or amiodarone and she did not receive iodinated contrast. She had no sign or symptoms of thyrotoxicosis. She denied neck pain or difficulty swallowing. On laboratory evaluation, SARS Coronavirus 2 RNA was positive. RSV, Influenza A and Influenza B by PCR were negative. TSH was low at 0.182 uIU/mL (0.450-5.330 uIU/mL), free T4 elevated at 3.00 ng/dL (0.58-1.64 ng/dL), free T3 elevated at 5.24 pg/mL (2.20-4.10 pg/mL). Her TSH 3 weeks ago was normal at 0.723 uIU/mL. Thyroid stimulating immunoglobulin negative < 0.10 (< =0.54 IU/L). Thyroid ultrasound showed normal sized gland, few sub centimeter nodules bilaterally. NM thyroid uptake and scan showed low uptake and no focal hot or cold nodule. Her workup was consistent with thyroiditis. Correlating with the diagnosis of COVID-19, this could be most likely COVID-19 related thyroiditis. Repeat labs in a week showed normal TSH 1.138 uIU/mL, normal free T4 1.28 ng/dL and low free T3 1.93 pg/mL. The patient likely had thyroiditis during early course of COVID-19 infection and was caught during the late phase and hence, improvement of thyroid function within a week of biochemical diagnosis. Subacute thyroiditis is a self-limited inflammatory disorder, characterized by neck pain, general symptoms and thyroid dysfunction. It has been linked to viral infection like mumps virus, coxsackievirus, adenovirus, Epstein-Barr virus, rubella and cytomegalovirus. In our patient, SARS-CoV-2 was the likely cause of thyroiditis. A single center retrospective study done in 287 patients hospitalized with COVID-19 in Milan, Italy reported 20% of patients with thyrotoxicosis, 5% with hypothyroidism and 74% with normal thyroid function test. We report this case to alert clinicians that thyroiditis and resultant thyrotoxicosis should always be considered as a differential diagnosis in patients with COVID-19.

A Rare Case of a Toxic Thyroid Nodule Found in a Hypothyroid Patient on Levothyroxine Therapy

Introduction: A hyperfunctional thyroid nodule can lead to symptoms of overt or subclinical hyperthyroidism but the association between a hyperfunctional thyroid nodule and hypothyroidism has not been well reported. We present a patient with a prior history of hypothyroidism previously controlled on Levothyroxine who later presented with an enlarging hot nodule. Case Presentation: A 62-year-old female with a history of factor V Leiden, hypothyroidism on levothyroxine therapy, and a meningioma presented to an outpatient clinic with complaints of fatigue, constipation, and 37-pound weight loss in one year. She was diagnosed with hypothyroidism 7 years ago after delivering her third child, but the underlying cause of her disease was unknown. She began taking levothyroxine 50mcg every morning after her diagnosis. She reported compliance and proper pill taking technique. Physical examination revealed a palpable thyroid nodule. The patient had a previous work up for thyroid nodules with a thyroid uptake and scan a few years prior, which showed a 1.42 x 0.96 x 1.87 cm hot nodule at the right middle lobe with a 24-hour uptake of 15.3%. The patient was asymptomatic at that time and thyroid function tests were within normal limits. She was instructed to continue taking levothyroxine. Repeat RAI Uptake scan at the time of her presentation to our office again showed the right middle lobe hot thyroid nodule with an increased 24-hour uptake of 27.5%. Ultrasound showed bilateral thyroid nodules and a hypervascular solid nodule measuring 2.28 x 1.27 x 1.9 cm that has increased in size. Lab work at this visit revealed a TSH of 0.329 uIu/mL, and free T4 of 1.25 ng/dL. Due to her low TSH and clinical presentation, the levothyroxine was discontinued. Anti-thyroid peroxidase antibodies were obtained to assess for Hashimoto’s Thyroiditis but were found to be normal. The patient was later referred to an endocrine surgeon for a total thyroidectomy. Conclusion: Although uncommon, hyperfunctional nodules in hypothyroid patients can create a confusing clinical picture with overlapping symptoms of underactive and overactive thyroid disease. It has been reported that patients with Hashimoto’s Thyroiditis can have hot nodules and coexisting hypothyroidism but the prevalence of hyperfunctional nodules in hypothyroid patients without Hashimoto’s Thyroiditis, as in this case, is not well-documented. Patients with hypothyroidism are treated with Levothyroxine but if coexisting hyperfunctional nodules are not detected, the patient may develop thyrotoxicosis. Clinicians should be aware of this rare but potentially life-threatening clinical condition.

A Grave Case of COVID-19: SARS-CoV-2 Induced Autoimmune Hyperthyroidism

Background: Autoimmune hyperthyroidism also known as Graves’ disease is the leading cause of hyperthyroidism. The pathogenesis of Graves’ disease is still an area of active research. We present a case of Graves’ disease, which developed following SARS-CoV2 infection. Clinical Case: A 43-year-old man with no prior history of thyroid disease, presented for evaluation due to fatigue palpitations, tremors, and hair loss in June 2020. Earlier that month, he was diagnosed with SARS-CoV2 infection and his thyroid function tests (TFTs) during a visit to the emergency department revealed thyroid stimulating hormone (TSH) level of <0.010 mIU/L (0.35-4.94) with a free T4 (FT4) 1.4 ng/dL (0.7-1.5); consistent with subclinical hyperthyroidism. He continued to report palpitations and tremors and further workup was done. A thyroid ultrasound showed two sub-centimeter nodules. A thyroid uptake scan followed, which showed heterogeneous activity in the thyroid gland, (12% and 32% uptake at 6 and 24 hours respectively) with focal increased uptake in the medial lobes, without cold nodules or hot nodules. Repeat TFTs one month later showed a suppressed TSH <0.010 mIU/L, and a normal FT4 1.3 ng/dL. Given suspicion for Graves’ disease, further labs were ordered. Thyroid stimulating immunoglobulin (TSI) were found to be elevated at 173 % baseline (<=140). Thyroid peroxidase (TPO) antibodies and thyroglobulin antibodies were also elevated at 362 IU/mL H* (<=9) and 2 IU/mL H* (<=1) respectively. The overall picture was consistent with evolving early Graves’ disease. Conclusion: Multiple factors are frequently cited in the pathogenesis of autoimmune hyperthyroidism including viral and bacterial infections1 and there have been several reported cases of autoimmune disease related to SARS-CoV2 infection2. This case is one of several emerging cases of autoimmune hyperthyroidism possibly linked to COVID-19.

A Case of T3 Thyrotoxicosis With Concomitant Follicular Thyroid Carcinoma

Introduction: The coexistence of hyperthyroidism and thyroid cancer is considered a rare event. In these cases, the follicular thyroid carcinoma subtype is an even more rare finding. It is highly unlikely to find follicular carcinoma in a hyperactive thyroid nodule. Clinical Case: We report a case of an 85-year-old female with a past medical history of atrial fibrillation presenting to the clinic after she has noticed enlargement of her neck two weeks prior. The patient was seen by her primary care physician who ordered a CT neck that revealed a goiter and the patient was subsequently referred to our clinic. On further questioning, the patient denied palpitations, sweats, difficulty swallowing, heat or cold intolerance, weight changes, bowel changes, or any other complaints. The patient denied any prior history of thyroid disease or exposure to goitrogens. Her past medical history was not significant for any auto-immune related diseases. She denied any family history of thyroid disease or malignancy. On physical examination, the patient had a normal eye exam and mild goiter with a small palpated right thyroid nodule. Initial thyroid ultrasound revealed a heterogenous right lobe measuring 7.1 cm x 7.3 cm x 5.9 cm with one superior nodule measuring 1.3 cm x 0.7 cm x 0.8 cm and a heterogenous left lobe measuring 2.0 cm x 1.5 cm x 1.1 cm. Laboratory blood work up revealed total T4 of 10.5 μg/dL(normal: 5.0 to 12.0μg/dL), elevated total T3 at 322 ng/dl (normal: 80-220 ng/dL), suppressed TSH <0.01 uIU/mL (normal: 0.40-4.00 uIU/mL), markedly elevated thyroglobulin 2828 ng/mL(normal: 1-84 ng/mL), as well as elevated anti-TPO Ab 63.5 IU/mL (10.0-35.0 IU/mL). The patient underwent a thyroid uptake scan that revealed increased uptake in the right lobe. Three months after presentation, the patient underwent fine-needle aspiration (FNA) which was benign (Bethesda classification II). A decision was made to start the patient on Methimazole and the subsequent thyroid profile showed an improvement in her T3 and TSH, but thyroglobulin continued to uptrend despite treatment. The patient then underwent another thyroid ultrasound one year later that revealed increased right lobe size to 10.3 cm x 6.3 cm x 6.4 cm with enlargement of the superior nodule to 8.5 cm x 4.6 cm x 6.4 cm. The left lobe was also enlarged from the prior scan measuring 3.9 cm x 1.2 cm x 1.0 cm. The patient underwent a second FNA from that nodule which also revealed benign hyperplastic nodule (Bethesda classification II). Despite the benign FNA finding, a decision was made to perform genetic testing given the rapid progressive enlargement of the nodule. The genetic testing revealed TERT promoter gene mutation with a high risk for malignancy. The patient then underwent total thyroidectomy and the pathological analysis showed a 9 cm follicular thyroid carcinoma of the right nodule. The patient then underwent successful I-131 radioactive Iodine ablation. Subsequent thyroid ultrasounds were negative and TSH continued to downtrend while the patient continued to take thyroid hormone replacement. This patient’s presentation is unique in many aspects. The patient presented with a hyperactive hot nodule while follicular carcinoma of the thyroid gland is typically associated with clinical euthyroidism and a scan showing a cold nodule(1). In a study of 425 hyperthyroid patients, thyroid cancer was diagnosed in 7 (1.65%) hyperthyroid patients, and histological examination revealed the presence of papillary carcinoma in 5 cases and follicular carcinoma in only 2 cases (2). Our patient also had two negative FNAs despite the presence of follicular carcinoma. Hence, we are shedding the light on the importance of genetic testing in the setting of negative FNA for rapidly enlarging thyroid nodules. Conclusion: We urge physician’s awareness that on rare occasions, follicular thyroid carcinoma can be present in a hyperactive thyroid with a hot nodule. In the presence of negative FNA, hyperfunctioning rapidly growing thyroid nodules should be carefully evaluated by further genetic testing for the presence of concurrent malignancy.

Challenges in the functional diagnosis of thyroid nodules before surgery for TSH-producing pituitary adenoma.

SummaryA 50-year-old woman with thyroid-stimulating hormone (TSH)-producing pituitary adenoma (TSHoma) was diagnosed due to symptoms of thyrotoxicosis. Preoperatively, she showed thyrotoxicosis with the syndrome of inappropriate secretion of TSH (SITSH) and had a 5 cm nodule in her thyroid gland. Octreotide was administered preoperatively, which helped lower her serum TSH level but not her thyroid hormone level. These findings were atypical for a patient with TSHoma. The TSHoma was completely resected, and the TSH level dropped below the sensitivity limit shortly after surgery. Interestingly, however, thyroid hormone levels remained high. A clear clue to the aetiology was provided by consecutive thyroid scintigraphy. Although preoperative thyroid scintigraphy did not show a hot nodule and the mass was thought to be a non-functional thyroid nodule, the nodule was found to be hot in the postoperative phase of TSH suppression. By focusing on the atypical postoperative course of the TSHoma, we were able to conclude that this was a case of TSHoma combined with an autonomously functioning thyroid nodule (AFTN).Learning pointsThe diagnosis of autonomously functioning thyroid nodules (AFTNs) depends on suppressed serum TSH levels.If thyroid hormones are resistant to somatostatin analogue therapy or surgery for TSHoma, complications of AFTN as well as destructive thyroiditis need to be considered.It is important to revisit the basics when facing diagnostic difficulties and not to give up on understanding the pathology.

Incident of Thyroid Carcinomas and Other Pathologies with Age Correlation in Patients Presented with Palpable Thyroid Masses Undergoing Thyroidectomies

Background: Thyroid cancer is the leading cause of death both in developing and developed countries. Patients present with enlarged thyroid. Radiology shows hot and cold nodules. Thyroidectomy or lobectomy is done to rule out malignancy. Objective: To determine the incidence of thyroid carcinomas and other pathologies in thyroidectomy specimen of different age group patients presenting with clinically enlarged thyroid. Study Design: Cross-sectional study. Settings: Department of Histopathology, Foundation University Medical College (FUMC), Islamabad and Department of surgery, Fauji Foundation Hospital (FFH), Rawalpindi Pakistan. Duration: from Jan 2012 to March 2019. Methodology: All the thyroidectomies specimens send from Surgery department of FFH to Histopathology Department of FUMC during study period and fulfilling the pre-set criteria were included in the study. All the data and results were analyzed using SPSS version 17.0. Results: Out of 500 total patients, 89% (n=445) were diagnosed as having multinodular goiter, 2.6% (n=13) thyroiditis, 2.2% (n=11) follicular adenoma, 0.8% (n=4) Hurthle cell adenoma, 0.2%(n=1) hyalinizing trabacular adenoma and thyroid carcinomas. The carcinomas comprised 2.6%(n=13) papillary carcinoma, 0.8%(n=4) poorly differentiated carcinoma,0.8%(n=4) anaplastic carcinoma,0.6%(n=3) medullary carcinoma and 0.4%(n=2) follicular carcinoma. In 445 patients of multinodular goiter 158 patients were in the age range of 41-50 years, in 13 cases of thyroiditis 7 were in the age range of 31-40 years, in 11 cases of follicular adenoma 4 patients were in the age range of 31-40 years, in 4 cases of hurthle cell adenoma 3 patients were in the age range of 41-50 years, in 13 cases of papillary thyroid carcinoma 5 patients were in the age range of 31-40 years, in 4 cases of poorly differentiated carcinoma 2 patients were in the age range of 41-50 years and in 4 cases of anaplastic carcinoma 2 patients were in the age range of 61-70 years. Conclusion: The study concluded that thyroid carcinomas collectively constituted 5.20% of the study cases. Papillary carcinoma was the most frequent malignant neoplasm constituting 2.6 % and occurring mostly in the age range of 31-40 years, while anaplastic carcinoma comprised of 0.8% of malignant lesions occurring in the age range of 61-70 years. The most frequent cause of thyroid enlargement was multinodular goiter (89%) with majority of the patients in the age range of 41-50 years.

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.

Simultaneous hot and cold thyroid nodules: Which is malignant?

Physicians should be aware of the risk of malignancy in patients with toxic multinodular goiter. Radionuclide scan cannot be used to predict the malignant potential of thyroid nodules. A comprehensive evaluation of imaging studies is needed.

Thyroid scintigraphy in the era of fine-needle aspiration cytology.

To evaluate whether thyroid scintigraphy would alter the clinical management of patients referred for fine-needle aspiration cytology (FNA). We reviewed the medical and imaging records of patients referred to our Department between 2016 and 2019. All the patients had to take a serum thyrotropin test administered in our hospital at least two months before the FNA; where the TSH level was ≤1.5mIU/L, the patients were subjected to a scan and subsequently to FNA, where indicated. We selected only healthy patients with no previous history of thyroid disease, who were not taking any drugs and who had a TSH level of ≤1.5mIU/L. We excluded patients with multinodular goitre. A total of 176 patients were analysed. A total of 67/176 patients (38%) showed a serum of TSH≤0.27mIU/L. Scintigraphy identified a hot nodule in 142 lesions (80.7%), a warm nodule in 8 lesions (4.5%) and a cold nodule in 26 lesions (14.8%). The ROC curve analysis indicated that a TSH value of ≤0.42mIU/L identified patients with hyperfunctioning nodules with a sensitivity of 65% and a specificity of 77%. All patients with cold and warm nodules were submitted to FNA: 22/26 (85%) and 5/8 (63%) lesions showed suspected malignancy or were compatible with malignancy, respectively. Speculating on our data, if we had subjected our patients to FNA as indicated by the 2015 ATA guidelines, we would have subjected 117 patients to cytology, from whom 83 had undetected hot nodules. Conversely, by adopting scintigraphy for all patients with TSH≤1.5mIU/L, 109 patients have avoided FNA. However, our study was performed in a region with a history of mild iodine deficiency. Therefore, we cannot claim that our observation is valid for patients born and living in areas with sufficient iodine uptake. We recommend thyroid scintigraphy for treating single thyroid nodules in euthyroid patients born and living in regions with an iodine deficiency, when TSH levels are below 1.5mIU/L before FNA.

Significance of nuclear cathepsin V in normal thyroid epithelial and carcinoma cells

Altered expression and/or localization of cysteine cathepsins is believed to involve in thyroid diseases including cancer. Here, we examined the localization of cathepsins B and V in human thyroid tissue sections of different pathological conditions by immunolabeling and morphometry. Cathepsin B was mostly found within endo-lysosomes as expected. In contrast, cathepsin V was detected within nuclei, predominantly in cells of cold nodules, follicular and papillary thyroid carcinoma tissue, while it was less often detected in this unusual localization in hot nodules and goiter tissue. To understand the significance of nuclear cathepsin V in thyroid cells, this study aimed to establish a cellular model of stable nuclear cathepsin V expression. As representative of a specific form lacking the signal peptide and part of the propeptide, N-terminally truncated cathepsin V fused to eGFP recapitulated the nuclear localization of endogenous cathepsin V throughout the cell cycle in Nthy-ori 3-1 cells. Interestingly, the N-terminally truncated cathepsin V-eGFP was more abundant in the nuclei during S phase. These findings suggested a possible contribution of nuclear cathepsin V forms to cell cycle progression. Indeed, we found that N-terminally truncated cathepsin V-eGFP expressing cells were more proliferative than those expressing full-length cathepsin V-eGFP or wild type controls. We conclude that a specific molecular form of cathepsin V localizes to the nucleus of thyroid epithelial and carcinoma cells, where it might involve in deregulated pathways leading to hyperproliferation. These findings highlight the necessity to better understand cathepsin trafficking in health and disease. In particular, cell type specificity of mislocalization of cysteine cathepsins, which otherwise act in a functionally redundant manner, seems to be important to understand their non-canonical roles in cell cycle progression.

Sensitive Sequencing Analysis Suggests Thyrotropin Receptor and Guanine Nucleotide-Binding Protein G Subunit Alpha as Sole Driver Mutations in Hot Thyroid Nodules.

Background: Constitutively activating mutations in the thyrotropin receptor (TSHR) and the guanine nucleotide-binding protein G subunit alpha (GNAS) are the primary cause of hot thyroid nodules (HTNs). The reported prevalence of TSHR and GNAS mutations in HTNs varies. Previous studies show TSHR mutations in 8-82% of HTNs and GNAS mutations in 8-75% of HTNs. With sensitive and comprehensive targeted next-generation sequencing (tNGS), we re-evaluated the prevalence of TSHR and GNAS mutations in HTNs. Methods: Samples from three previous studies found to be TSHR and GNAS mutation negative were selected and re-evaluated using high-resolution melting (HRM) PCR. Remaining mutation negative samples were further reanalyzed by tNGS with a sequencing depth between 3000 × and 10,000 × . Our tNGS panel covered the entire TSHR coding sequence along with mutation hot spots in GNAS. Sequencing reads were aligned to reference and variants were called using Torrent Suite software v5.8. Results: In total, 154 of 182 previously mutation negative HTNs were positive for TSHR or GNAS mutations, resulting in an 85% prevalence of TSHR and GNAS mutations in HTNs, 79% and 6%, respectively. In a subset of 25 HTNs with multiple samples per nodule, and analyzed by tNGS at high sequencing depth, TSHR mutations were detected in 23 (92%) HTNs and 1 GNAS mutation was detected in 1 (4%) HTN, 96% mutation positive HTNs in this subset. Conclusions: Owing to the higher sensitivity of tNGS as compared with denaturing gradient gel electrophoresis and HRM-PCR, TSHR or GNAS mutations could be detected in 85% of HTNs. The detection of TSHR and GNAS mutations occurred in 96% of HTNs in a sample set with multiple samples per nodule analyzed by tNGS. Taken together with the fact that no other driver mutations could be identified by whole exome sequencing, our study strongly supports the hypothesis that TSHR and GNAS mutations are the main somatic mutations leading to HTNs.

SUN-478 Poorly Differentiated Thyroid Cancer Arising from a Hyperfunctioning Nodule Treated with I-131

Thyroid nodules are a common clinical problem with an incidence of up to 1% in men and 7–15% of cases representing thyroid cancer. Current American Thyroid Association guidelines do not recommend cytologic evaluation of hyperfunctioning nodules as they rarely harbor malignancy. We present a case of a hyperfunctioning nodule which years after ablation was diagnosed as a poorly differentiated thyroid cancer.A 38 year old male had a 4cm thyroid nodule discovered in 1994. Nuclear Medicine (NM) imaging revealed a warm nodule though patient was euthyroid. Biopsy was benign with good sample. Nodule was followed with serial ultrasound (US) and TSH. In 2008 he became hyperthyroid. Scan showed hot nodule and he was given 27.3 mCi I-131 with normalization of the TSH. In 2013 patient again developed hyperthyroidism. NM imaging showed a hot nodule. After 29.5 mCi I-131 he became hypothyroid requiring levothyroxine. Intermittent US showed stability. In early 2019 nodule was 3.7cm, solid and hypoechoic but more heterogeneous. Despite TIRADS recommendation that nodule no longer be followed by US, FNA was performed and revealed Bathesda IV cytology. Gene classification with Thyroseq revealed a TERT mutation. On total thyroidectomy pathology demonstrated a 4.5cm poorly differentiated carcinoma thought to be of follicular origin. Tumor was partially encapsulated with multiple areas of vascular invasion and extensive tumor necrosis. Tumor was present at inked margin but no extrathyroidal extension was noted. There was a <1mm metastasis noted in 1 peri-isthmus lymph node. One month post operatively thyroglobulin was 123.5 ng/mL. I-123 whole body scan demonstrated bilateral uptake in the region of the thyroid suggesting adenopathy; there were similar findings on FDG-PET scan but no adenopathy was identified on US or the CT portion of the PET. Patient was treated with 129mCI of I-131 with focally intense activity in the lower neck on post treatment scan but nothing elsewhere. Follow up lab testing is pending.Though thyroid nodules are a common clinical problem, there are only isolated case reports of hyperfunctioning nodules being later found to have thyroid cancer. One retrospective series of over 6000 patients found a thyroid cancer prevalence of 0.15% in hyperthyroid patients treated with I-131.i Poorly differentiated thyroid cancer is thought to occur as a mutation from a differentiated cancer. Here, we present a novel case of the 25 year course of a benign, hyperfunctioning nodule later mutating into an aggressive poorly differentiated cancer. We hypothesize that this nodule mutated late in the course as it was clearly benign on initial biopsy and had a benign course until recent events. This case supports periodic screening of hyperfunctioning nodules after ablation, especially if the nodule does not shrink significantly after I-131.Endnotes i Angusti T et al. The Journal of Nuclear Medicine 41(6):1006–1009.

Multinodular Goiter Hot Nodules with Amazing Shape of Thyroid

A 45-year-old female presented with symptoms of hyperthyroidism and hot nodules in the right lobe, which was diagnosed as nodular goiter by fine-needle aspiration. An anomalous thyroidectomy and difficult dissection with multiple rotations were performed around the trachea. As a remark, the pathology confirmed the presence of goiter with modular nodules (Figure 1). A macroscopic photograph showing the thyroid.

TEKNIK PEMERIKSAAN KEDOKTERAN NUKLIR SIDIK TIROID DI INSTALASI RADIOLOGI RSUP DR. KARIADI SEMARANG

Background: Examination of thyroid scintigraphy or thyroid gland scintigraphy is a nuclear medicine examination using radioactive substances or radiopharmaceuticals that are inserted into the body through intravenous injections which aim to obtain functional morphological imaging of the thyroid and to assess the ability of the thyroid gland to capture radioactive substances or radiopharma-ceuticals.Methods: This imaging prosedure using Tc-99m (Technisium-99m) radiopharmaceuticals as much as 2-5 mCi. To get maximum results, patients are asked to stop taking drugs that can interfere with iodine accumulation in the thyroid gland.Results: Imaging was carried out 10-15 minutes after injection of the radiopharmaceutical. Marked with the thyroid cartigalo, jugulum and surgical sutures. The scanning process lasts for 5-10 minutes.Conclusions: The imaging results of hot nodules are generally identical to autonomic thyroid nodules, about 10-30% of cold nodules are found in the thyroid malignancy process while the rest are thyroid cysts.

A threshold-based method to predict thyroid nodules on scintigraphy scans

Nuclear Medicine imaging is an important modality to follow up abnormalities of thyroid function tests and to uncover and characterize thyroid nodules either de novo or as previously seen on other imaging modalities, namely ultrasound. In general, the hypofunctioning ‘cold’ nodules pose a higher malignancy potential than hyperfunctioning ‘hot’ nodules, for which the risk is <1%. Hot nodules are detected by the radiologist as a region of focal increased radiotracer uptake, which appears as a density of pixels that is higher than surrounding normal thyroid parenchyma. Similarly, cold nodules show decreased density of pixels, corresponding to their decreased uptake of radiotracer, and are photopenic. Partly because Nuclear Medicine images have poor resolution, these density variations can sometimes be subtle, and a second reader computer-aided detection (CAD) scheme that can highlight hot/cold nodules has the potential to reduce false negatives by bringing the radiologists’ attention to the occasional overlooked nodules. Our approach subdivides thyroid images into small regions and employs a set of pixel density cutoffs, marking regions that fulfill density criteria. Thresholding is a fundamental tool in image processing. In nuclear medicine, scroll bars to adjust standardized uptake value cutoffs are already in wide commercial use in PET/CT display systems. A similar system could be used for planar thyroid images, whereby the user varies threshold and highlights suspect regions after an initial reader survey of the images. We hypothesized that a thresholding approach would accurately detect both hot and cold thyroid nodules relative to expert readers. Analyzing 22 nodules, half of them hot and the other half cold, we found good agreement between highlighted candidate nodules and the consensus selections of two expert readers, with nonzero overlap between expert and CAD selections in all cases.

False-positive staining of thyroglobulin distinguished from mixed medullary and follicular thyroid carcinoma by duplex in situ hybridization.

Medullary thyroid carcinoma (MTC) may mimic mixed medullary and follicular thyroid carcinoma (MMFTC). MTC originates from para-follicular cells, while MMFTC is an uncommon tumor characterized by coexistence of follicular and para-follicular cell-derived tumor populations. A 35-year-old woman was diagnosed with MTC but showed a hot nodule in thyroid scintigraphy. The tumor included diffusely-spread follicular lesions within it, which were immunostained with thyroglobulin and calcitonin. Immunofluorescence showed the presence of several tumor cells that were double-stained with thyroglobulin and calcitonin. To clarify whether or not the tumor was MMFTC, we used duplex in situ hybridization (ISH). Thyroglobulin and calcitonin-related polypeptide alpha mRNA were not expressed together in a single cell, so we suspected false-positive staining of tumor cells with thyroglobulin. To make comparisons with other follicular lesions in MTC, we searched our hospital database. Five cases within a ten-year period had been pathologically diagnosed as MTC. All had follicular lesions in the tumor, but unlike the other case, they were peripherally localized. Dual differentiation into follicular or para-follicular tumor cells was not indicated by either immunofluorescence or duplex ISH. Compared with the case suspected to be MMFTC, there was only mild invasion of tumor cells into the follicular epithelium. The extent of follicular lesions and invasiveness of tumor cells may be associated with pseudo-staining of thyroglobulin in MTC. Duplex ISH can distinguish MTC that are stained with thyroglobulin from MMFTC.

Study of Pathological Variations of Solitary Thyroid Nodule

Objective: To find out the incidence of malignancy in patient with solitary thyroid nodule. Methods: This cross-sectional study was carried out with 100 solitary thyroid nodular patients who admitted in Otolaryngology &amp; Head-Neck Surgery Department of Sir Salimullah Medical College Mitford Hospital (SSMCMH) &amp; Bangabondhu Sheikh Mujib Medical Univercity (BSMMU), Dhaka, from July 2012 to December 2013, where all patients were admitted throughout patient department. All patients were selected as per described criteria from the Department of Otolaryngology &amp; Head-NeckSurgery,SSMCMH &amp; BSMMU.Diagnosed the cases by detail history,clinical examination,investigations,analysed data presented by various tables,figures. Results: In this study mean age of the patients of solitary thyroid nodule was 35.613.54 years and the highest frequency (38%) was within 21-30 years of age with female predominance(78%).Thyroid swelling was the common presentation in all9100%) cases, some patients also presented with other symptoms like cervical lymphadenopathy 13(13%) cases, dysphagia 1(1%), dyspnoea 1(1%), hoarseness of voice 1(1%) case &amp; no bone metastetic found.In this series of solitary thyroid nodules constituted 73% firm, 6% hard and 11% cystic. Malignancy was found more in firm nodule 13(72.22%).Isotopes scanning of the thyroid gland were done to see the functional status of the nodule. We found most 96(96%) of the nodules were cold &amp; 4(4%) were warm nodule &amp; no hot nodule found. In our study out of 96 cold nodular goiters we found 18(18.75 %) malignant &amp; no malignant case found from rest of 4 warm cases. In our study, out of 89 solid nodule 72(80.89%) were benign &amp; 17(19.10%) nodule were malignant and out of 11 cystic nodule 10(90.9%) were benign &amp; 1 (9.1%) was malignant. In this study, most of the benign &amp; malignant nodules were predominantly solid. Study showed the malignancy is significantly (p&lt;0.001) more in solid than cystic solitary thyroid nodule. Final diagnosis in this study was on the basis of histopathological reports record. Out of 100 cases, 54 cases (54%) were proven as nodular goitre &amp; 2 % were thyroiditis in non-neoplastic lesion &amp; in neoplastic lesion we found 26(26%) Bangladesh J of Otorhinolaryngology; October 2018; 24(2): 105-114

The Mitochondrial DNA Control Region Might Have Useful Diagnostic and Prognostic Biomarkers for Thyroid Tumors

The literature suggests that mitochondrial DNA (mtDNA) defects are associated with a large number of diseases including cancers. The role of mtDNA variations in thyroid cancer is a highly controversial topic. Therefore, we investigated the role of mt-DNA control region (CR) variations in thyroid tumor progression and the influence of mtDNA haplogroups on susceptibility to thyroid tumors. For this purpose, in total, 108 hot thyroid nodules (HTNs), 95 cold thyroid nodules (CTNs), 48 papillary thyroid carcinoma (PTC) samples with their surrounding tissues and 104 healthy control subjects' blood samples were screened for all mtDNA CR variations using Sanger sequencing. We found that MtDNA haplogroup U was significantly associated with susceptibility to benign thyroid entities. In addition, eight single nucleotide polymorphisms (SNPs) (T146C, G185A, C194T, C295T, G16129A, T16304C, A16343G and T16362C) in the mtDNA CR were associated with the occurrence of benign and malign thyroid nodules in the Turkish population. As compared with samples taken from a healthy Turkish population and HTNs, the frequency of C7 repeats in D310 polycytosine sequence was found to be higher in CTNs and the PTC samples. In addition, the frequency of somatic mutations in mtMSI regions including T16189C and D514 CA dinucleotide repeats were found to be higher in PTC samples than benign thyroid nodules. Conversely, the frequency of somatic mutations in D310 was found to be higher in HTNs than CTNs and PTCs. In conclusion, mtDNA D310 instability does not play a role in the tumorigenesis of PTC but the results indicate that it might be used as a diagnostic clonal expansion biomarker for premalignant thyroid tumor cells. In addition, D514 CA instability might be considered as a prognostic biomarker for benign to malign transformation in thyroid tumors.

CAD system based on B-mode and color Doppler sonographic features may predict if a thyroid nodule is hot or cold.

The aim of this study was to evaluate if the analysis of sonographic parameters could predict if a thyroid nodule was hot or cold. Overall, 102 thyroid nodules, including 51 hyperfunctioning (hot) and 51 hypofunctioning (cold) nodules, were evaluated in this study. Twelve sonographic features (i.e., seven B-mode and five Doppler features) were extracted for each nodule type. The isthmus thickness, nodule volume, echogenicity, margin, internal component, microcalcification, and halo sign features were obtained in the B-mode, while the vascularity pattern, resistive index (RI), peak systolic velocity, end diastolic velocity, and peak systolic/end diastolic velocity ratio (SDR) were determined, based on Doppler ultrasounds. All significant features were incorporated in the computer-aided diagnosis (CAD) system to classify hot and cold nodules. Among all sonographic features, only isthmus thickness, nodule volume, echogenicity, RI, and SDR were significantly different between hot and cold nodules. Based on these features in the training dataset, the CAD system could classify hot and cold nodules with an area under the curve (AUC) of 0.898. Also, in the test dataset, hot and cold nodules were classified with an AUC of 0.833. 2D sonographic features could differentiate hot and cold thyroid nodules. The CAD system showed a great potential to achieve it automatically. • Cold nodules represent higher volume (p = 0.005), isthmus thickness (p = 0.035), RI (p = 0.020), and SDR (p = 0.044) and appear hypoechogenic (p = 0.010) in US. • Nodule volume with an AUC of 0.685 and resistive index with an AUC of 0.628 showed the highest classification potential among all B-mode and Doppler features respectively. • The proposed CAD system could distinguish hot nodules from cold ones with an AUC of 0.833 (sensitivity 90.00%, specificity 70.00%, accuracy 80.00%, PPV 87.50%, and NPV 75.00%).