Thyroid Remnant Research Articles

8141 A Rare Case of Follicular Adenoma with Osseous Metaplasia and Mature Bone Formation- Is Surveillance Important?

Abstract Disclosure: K. Madani: None. Y. Al-Khazraji: None. D.H. Sacoto: None. G.K. Rai: None. R. Belokovskaya: None. A.A. Franco-Akel, MD: None. Osseous metaplasia and mature bone formation (MBF) are common in malignant thyroid and parathyroid tumors. It is very unusual to have MBF in a benign tumor-like follicular adenoma, as in the case we describe. We found only twelve such cases reported in the literature, and none addressed the cancer risk or need for surveillance for the development of potential malignancy. Thus, further studies are required to investigate the need for surveillance in patients not undergoing excision and in those with remnant thyroid tissue post-removal of the adenoma for recurrence. A 43-year-old female with history of hyperlipidemia and hypothyroidism had an incidental finding of midline neck mass during the evaluation of a left upper extremity lipoma. Ultrasound of the neck showed two nodules in the Left (L) thyroid lobe: a complex nodule measured 2.2 x 1.2 x 2.1 cm and a calcified nodule measuring 1.5 x 0.8 x 0.6 cm. MRI of the neck revealed a 1.9 cm heterogeneously enhancing nodule in the mid to lower pole of the L thyroid lobe. The patient had symptoms suggestive of compression, such as dysphagia, odynophagia, and hoarseness; thus, left hemothyroidectomy was performed. Tissue biopsy was notable for follicular adenoma with osseous metaplasia and mature bone formation. The patient remained clinically and biochemically euthyroid, with only mildly elevated thyrotropin level, and treatment with levothyroxine 25 mcg once daily was initiated. On post-surgical follow-up, there was a lack of data to support close monitoring modality and strategy for the remnant thyroid lobe and neck nodal compartments. We concluded with the patient to follow up in a clinical visit for a physical exam of the neck and to obtain a follow-up sonogram at an interval of six months, in addition to monitoring TSH levels to guide hypothyroidism therapy. Osseous metaplasia has not been established as a premalignant condition, but in certain tissues like the esophagus, metaplasia is a risk factor for malignant conversion, for instance, in Barrett’s esophagus leading to esophageal adenocarcinoma. Moreover, MBF in thyroid tissue has been attributed to the activity of basic fibroblast growth factor (bFGF) and bone morphogenetic protein-2 (BMP-2), which are linked with mitogenesis and tumorigenesis. Thus, the question arises if post-excision surveillance is required in patients with a history of osseous metaplasia in remnant thyroid tissue post-lobectomy or partial thyroidectomy. At this point, more epidemiological data on similar cases may help us understand the true risk of this clinical scenario, in order to develop a reasonable approach for surveillance. Presentation: 6/3/2024

Serum microRNA-146a-5p and microRNA-221-3p as potential clinical biomarkers for papillary thyroid carcinoma

Abstract Purpose Papillary thyroid carcinoma (PTC) is the most common malignant thyroid neoplasm, accounting for approximately 85% of all follicular cell-derived thyroid nodules. This study aimed to assess the diagnostic potential of circulating microRNA-146a-5p and microRNA-221-3p as biomarkers for PTC and their usefulness in monitoring disease progression during patient follow-up. Methods An observational study was conducted on two cohorts of PTC patients and healthy controls (HCs) using digital PCR. We collected patients’ clinical, biochemical, and imaging data during the post-surgery surveillance. We analyzed the levels of circulating miRNAs in serum samples of patients before surgery and during the follow-up, including those with indeterminate/biochemical incomplete response (IndR/BIR) and residual thyroid tissues (Thy Residue). Results Both miR-146a-5p and miR-221-3p were confirmed as effective biomarkers for PTC diagnosis. They enabled differentiation between pre-surgery PTC patients and HCs with an area under the curve (AUC) of 92% and 87.3%, respectively, using a threshold level of 768,545 copies/uL for miR-146a-5p and 389,331 copies/uL for miR-221-3p. It was found that miRNA fold change levels, rather than absolute levels, can be useful during patient follow-up. In particular, we found that a fold change of 2 for miR-146a-5p and 2.2 for miR-221-3p can identify a progressive disease, regardless of the presence of TgAbs or remnant thyroid. Conclusion MiRNA-146a-5p and miRNA-221-3p, particularly the former, could be valuable diagnostic biomarkers for PTCs. They also seem to be effective in monitoring disease progression during patient follow-up by evaluating their fold change, even when thyroglobulin is uninformative.

Dosimetry of 131I in remnant ablation and metastasis of differentiated thyroid cancer treated with high radioactivities and rhTSH

Purpose: Ruling out that healthy organs receive doses higher than those allowed in treatments with Iodo-131 (131I) for ablation of thyroid remnant is crucial for the radiological protection of the patient who also received the recombinant human thyroid-stimulating hormone (rhTSH). So, the investigation aimed to determine the changes in energy imparted by 131I in multiple organs due to the rhTSH in thyroid remnants and metastases of patients treated with high 131I activities (≥ 5,550 MBq). Materials and methods: Nine patients were divided into three groups (three per group); Group I included thyroid hormone withdrawal (THW) patients, while patients in groups II and III were stimulated with rhTSH. The activity and absorbed dose in regions of interest (ROIs) was quantified using the conjugated views method using gamma camera images. Results and discussion: Dosimetric variations of 131I produced by using rhTSH in the remnant thyroid (groups II and III) were observed, absorbed doses were minor for groups treated with rhTSH. Conclusion: The application of the high activities > 5,500 MBq administered together with the application of rhTSH is safe in dosimetric terms, also for 9250 MBq do not exceed established limits of absorbed dose in the bone marrow. Furthermore, these high activities provide more than three times the radiation dose to remaining thyroid tissue and approximately 1.5 times to metastases.

Long-Term Effects of 0.1 mg Recombinant-Human-Thyrotropin-Stimulated Fixed-Dose Radioiodine Therapy in Patients with Recurrent Multinodular Goiter after Surgery.

(1) Background: After thyroid malignancy is ruled out, treatment options for multinodular goiter patients include surgery, levothyroxine suppressive therapy, and 131-I therapy. Surgery effectively reduces goiter size but carries risks of surgical and anesthetic complications. 131-I therapy is the only nonsurgical alternative, but its effectiveness diminishes with goiter size and depends on iodine sufficiency. This study aimed to assess the efficacy and safety of 0.1 mg rhTSH as an adjuvant to a fixed dose of 131-I therapy in patients with a recurrence of large multinodular goiter, several years after the initial thyroidectomy. (2) Methods: 14 patients (13 females and 1 male), aged 59.14 ± 15.44 (range, 35-78 years) received 11mciu of 131-I, 24 h after the administration of 0.1 mg rhTSH. The primary endpoint was the change in thyroid volume (by ultrasound measurements) as well as in the diameter of the predominant nodule during a follow-up period of 10 years. Secondary endpoints were the alterations in thyroid function and potential adverse effects. (3) Results: A significant decrease in the volume of initial thyroid remnants (32.16 ± 16.66 mL) was observed from the first reevaluation (at 4 months, 23.12 ± 11.59 mL) as well as at the end of the follow-up period (10 years, 12.62 ± 8.76 mL), p < 0.01. A significant reduction in the dominant nodule was also observed (from 31.71 ± 10.46 mm in the beginning to 26.67 ± 11.05 mm). (4) Conclusions: Further investigation is needed since this approach could be attractive in terms of minimizing the potential risks of reoperation in these patients.

Pre-Treatment and Post-Treatment I-131 Imaging in Differentiated Thyroid Carcinoma.

Radioiodine imaging in initial perioperative settings, after the total thyroidectomy, includes pre-treatment and post-treatment radioiodine imaging. While the benefit of post-treatment whole-body imaging (PT-WBI) is well established, the role of diagnostic whole-body imaging (dx WBI), prior to radioiodine (I-131) ablative or therapeutic doses, is controversial. Dx WBI has been abandoned in most nuclear medicine centers long ago. Planar low-dose dxWBI provides the volume of postoperative thyroid remnants, but it cannot detect occult metastatic foci in the neck. The modern integrated multimodality, i.e., SPECT/CT imaging, provides three dimensional images and accurate anatomic/metabolic data. This hybrid technology offers better spatial resolution but not better sensitivity. Dx WBI has low theranostic power because of the radioiodine indifference and low detection sensitivity for small-volume nodal disease in the neck. Since dx WBI cannot clarify the paratracheal cervical uptake, thyroid remnants may be easily misinterpreted as nodal disease, leading to a false N upstaging (from N0 stage to N1 stage) in DTC patients. Post-ablation I-131 imaging has a significant role in the initial staging of radioiodine-avid DTC and in the identification of non-radioiodine avid tumors. Additionally, SPECT/CT in the post-treatment setting provides more accurate initial TNM staging and better risk stratification of DTC patients. Post-treatment I-131 imaging is obligatory and must be performed in all DTC patients who receive radioiodine treatment.

Prognostic factors for postoperative papillary thyroid cancer with unexplained elevated Tg: A retrospective study

ObjectiveThis study aimed to investigate the underlying reasons for unexplained elevated thyroglobulin (Tg) in postoperative papillary thyroid cancer (PTC) patients according to follow-up results post RAT and to explore the long-term clinical outcomes and prognostic factors associated with these patients. MethodsFrom April 2016 to June 2019, a retrospective study was conducted on postoperative PTC patients who underwent RAT at our institution. Patients with preablative stimulated thyroglobulin (psTg) > 10 ng/mL but no structurally evident disease were enrolled. The causal categorization for elevated Tg was analyzed 6 months post RAT and the long-term therapeutic responses were assessed at the end of follow-up. To identify risk factors influencing recurrence-free survival (RFS), both univariate and multivariate Cox regression analysis were employed. Kaplan-Meier method was utilized for plotting survival curves. ResultsA cohort of 165 subjects was enrolled for the analyses. Based on the results of a six-month follow-up, the postoperative unexplained elevated Tg among 165 patients could be ultimately attributed to thyroid remnant in 13.94% (23/165), biochemical disease in 60.00% (99/165), and structural disease in 26.06% (43/165). With a median follow-up of 58 months, 51 (30.91%), 34 (20.60%), 21 (12.73%), and 59 (35.76%) of the 165 patients achieved ER, IDR, BIR and SIR, respectively. Univariate analysis showed that N stage, TNM stage and suppressed Tg 6 months post RAT may be prognostic factors affecting RFS. Multivariate analysis showed that N1b stage [HR:2.749, P = 0.003] and II/III stage [HR:2.910, P = 0.001] were independent risk factors for RFS. ConclusionThe proportion of 165 postoperative PTC patients with unexplained elevated Tg developing structural disease within nearly 5 years was over 30%. Patients with N1b stage and higher TNM stage were more likely to develop structural disease.

Correlation between remnant thyroid gland I-131 uptake and serum thyroglobulin levels: can we rely on I-131 whole body scans?

BackgroundI-131 treatment (RAI) decision relies heavily on serum thyroglobulin (Tg) levels, as higher Tg levels are assumed to be correlated with higher I-131 uptake. Tg elevation, negative iodine scintigraphy (TENIS) definition is becoming more clinically relevant as alternative treatment methods are available. This study examined the correlation between Tg levels with I-131 uptake in remnant thyroid gland to evaluate the reliability of serum Tg levels in predicting I-131 uptake.MethodsFrom March 2012 to July 2019, 281 papillary thyroid cancer patients treated with 150 mCi RAI were retrospectively enrolled. Early (2nd day) and Delayed (7th day) post-RAI whole-body scan (WBS) neck counts were correlated with clinical and pathologic findings. Patients with normal neck ultrasound and undetectable level of serum Tg (< 0.2 ng/mL) and thyroglobulin antibody (TgAb) (< 10 IU/mL) were defined as ablation success within 2 years after I-131 ablation.ResultsThyroid gland weight, tumor size and thyroiditis were independent factors of preoperative serum Tg levels. Serum off-Tg levels correlated with Early and Delayed WBS neck counts, and thyroiditis pathology contributed to lower neck counts in both Early and Delayed WBSs. In multivariable analysis, Delayed WBS neck count, serum off-Tg and off-TgAb were significant factors for predicting ablation success.ConclusionI-131 uptake and retention in remnant thyroid gland correlates with serum off-Tg levels, thyroiditis, and ablation success in thyroid cancer patients receiving high-dose I-131 therapy. Semi-quantitative I-131 analysis with Early and Delayed WBSs provides additional information in evaluating ablation success, with the potential application for metastasis treatment response evaluation.

P-71 Track recurrence of follicular thyroid carcinoma after transoral endoscopic thyroidectomy vestibular approach

Abstract Introduction While track recurrence of thyroid cancer following endoscopic and robotic transaxillary surgeries has been reported previously, no such cases have been reported for transoral endoscopic thyroidectomy vestibular approach (TOETVA). Clinical Case This case report describes the first documented case of recurrence of thyroid cancer along the surgical track after TOETVA. The patient underwent TOETVA to perform a right thyroidectomy for a 4 cm follicular thyroid carcinoma that was initially diagnosed as a benign follicular nodule on preoperative gun biopsy. Ultrasonography and computed tomography conducted 27 months after surgery revealed suspected track recurrence. A re-operation was done in two stages to perform a completion thyroidectomy, bilateral central lymph node dissection, and excision of recurrent nodules, which were pathologically confirmed as metastatic follicular thyroid carcinoma. The patient underwent two treatments of radioactive iodine therapy for remnant thyroid tissues, and post-therapeutic whole-body scintigraphy showed no iodine uptake after the second treatment. Follow-up computed tomography conducted one year after re-operation showed no recurrences. Careful monitoring after TOETVA is essential due to the rare but potential risk of track recurrence. Surgeons should be aware of this atypical complication and be prepared to recommend surgical and/or medical strategies to manage any local seeding of thyroid tissue that may occur.Figure 1.Track recurrence after TOETVA

The Impact of Dual and Triple Energy Window Scatter Correction on I-123 Postsurgical Thyroid SPECT/CT Imaging Using a Phantom with Small Sizes of Thyroid Remnants.

I-123 is preferential over I-131 for diagnostic SPECT imaging after a thyroidectomy to determine the presence and size of residual thyroid tissue for radioiodine ablation. Scattering degrades the quality of I-123 SPECT images, primarily due to the penetration of high-energy photons into the main photopeak. The objective of this study was to quantitatively and qualitatively investigate the impact of two widely used window-based scatter correction techniques, the dual energy window (DEW) and triple energy window (TEW) techniques, in I-123 postsurgical SPECT/CT thyroid imaging using an anthropomorphic phantom with small sizes of remnants and anatomically correct surrounding structures. For this purpose, non-scatter-corrected, DEW and TEW scatter-corrected SPECT/CT acquisitions were performed for 0.5-10 mL remnants within a phantom, with 0.5-12.6 MBq administered activities within the remnants, and without and with background-to-remnant activity ratios of 5% and 10%. The decrease in photons, the noise and non-uniformity in the background region due to scatter correction were measured, as well as the signal-to-noise ratio (SNR) and the contrast-to-noise ratio (CNR) from small remnants. The images were also visually evaluated by two experienced nuclear medicine physicians. Scatter correction decreased photons to a higher extent in larger regions than smaller regions. Larger remnants yielded higher SNR and CNR values, particularly at lower background activities. It was found from the quantitative analysis and the qualitative evaluation that TEW scatter correction performed better than DEW scatter correction, particularly at higher background activities, while no significant differences were reported at lower background activities. Scatter correction should be applied in I-123 postsurgical SPECT/CT imaging to improve the image contrast and detectability of small remnants within the background.

The impact of intraoperative neural monitoring during papillary thyroid cancer surgery on completeness of thyroidectomy and thyroglobulin response: a propensity-score matched study

Background Intraoperative neural monitoring (IONM) has been utilized for a variety of thyroid pathologies, including papillary thyroid carcinoma (PTC). Remnant thyroid tissue following total thyroidectomy (TT) in patients with PTC is associated with increased recurrence. The aim of this study is to investigate whether the use of IONM in PTC surgery has an impact on the completeness of thyroidectomy. Methods Retrospectively, patients with preoperative diagnosis of PTC, who underwent TT in a tertiary center were reviewed. They were grouped based on the IONM usage, and 1:1 propensity-score match was performed. Primary outcome was the completeness of thyroidectomy, determined by measuring postoperative stimulated thyroglobulin levels (sTg). Results Among 274 clinically node-negative PTC patients who underwent TT and ipsilateral prophylactic central lymph-node dissection, a total of 170 patients (85:85) were matched. Postoperative sTg levels were significantly lower in the IONM group (1 ng/dL vs. 0.4 ng/dL; p < 0.01) with higher percentage of the patients with sTg levels <1 ng/ml (50.6% vs. 69.4%; p = 0.01). More patients in the no-IONM group received RAI ablation with significantly higher doses (mean mci: 120 vs. 102; p = 0.02). Conclusion The use of IONM during thyroidectomy provides improvement in the completeness of thyroidectomy and reduction in postoperative sTg levels which can be used as a guide by clinicians to avoid RAI ablation in selected PTC patients and to adjust low ablative doses in patients who are scheduled for remnant ablation.

Efficacy of prevention of recurrent laryngeal nerve injury in thyroid surgery

To evaluate the effectiveness of prevention of recurrent laryngeal nerve injury depending on thyroid gland lesion and extent of surgery. There were 2412 thyroid surgeries between 2000 and 2020. Patients were divided into the main group (1689 patients) and the control group (729 patients). Patients with nodular thyroid gland lesions prevailed in both groups (987 (58.4%) and 415 (56.9%), respectively). All ones underwent atraumatic extrafascial desection and thyroid resection (ultrasonic scalpel). He upper laryngeal nerve injury occurred in 35 cases (1.4%). The number of surgeries with thyroid remnant preservation was significantly lower in the main group. The number of procedures with subtotal thyroid resection and thyroidectomy increased by 2.4 times (from 414 to 1010 operations, p<0.05). Improvement of surgical treatment of thyroid gland lesions consisting in new operative technique of recurrent laryngeal nerve isolation using ultrasonic scalpel reduces the incidence of recurrent laryngeal nerve injury from 2.3% to 1%. At the same time, the number of extended procedures in the main group significantly exceeded that in the control group (by 2.5 times).

An Artificial Intelligence System for Optimizing Radioactive Iodine Therapy Dosimetry.

Thyroid cancer, specifically differentiated thyroid carcinoma (DTC), is one of the most prevalent endocrine malignancies worldwide. Radioactive iodine therapy (RAIT) using I-131 has been a standard-of-care approach for DTC due to its ability to ablate remnant thyroid disease following surgery, thus reducing the risk of recurrence. It is also used for the treatment of iodine-avid metastases. RAIT dosimetry can be employed to determine the optimal treatment dose of I-131 to effectively treat cancer cells while safeguarding against undesirable radiation effects such as bone marrow toxicity or radiation pneumonitis. Conventional dosimetry protocols for RAIT, however, are complex and time-consuming, involving multiple days of imaging and blood sampling. This study explores the use of Artificial Intelligence (AI) in simplifying and optimizing RAIT. A retrospective analysis was conducted on 83 adult patients with DTC who underwent RAIT dosimetry at our institution between 1996 and 2023. The conventional MIRD-based dosimetry protocol involved imaging and blood sampling at 4, 24, 48, 72, and 96 h post-administration of a tracer activity of I-131. An AI system based on a deep-learning neural network was developed to predict the maximum permissible activity (MPA) for RAIT using only the data obtained from the initial 4, 24, and 48 h time points. The AI system predicted the MPA values with high accuracy, showing no significant difference compared to the results obtained from conventional MIRD-based analysis utilizing a paired t-test (p = 0.351, 95% CI). The developed AI system offers the potential to streamline the dosimetry process, reducing the number of imaging and blood sampling sessions while also optimizing resource allocation. Additionally, the AI approach can uncover underlying relationships in data that were previously unknown. Our findings suggest that AI-based dosimetry may be a promising method for patient-specific treatment planning in differentiated thyroid carcinoma, representing a step towards applying precision medicine for thyroid cancer. Further validation and implementation studies are warranted to assess the clinical applicability of the AI system.

SAT538 Thyrotoxicosis in the Setting of Metastatic Poorly Differentiated Thyroid Carcinoma, a Marker of Disease Progression?

Abstract Disclosure: B.L. Chang: None. M.A. Fernandez: None. K.M. Shikuma Lee: None. Background: Thyrotoxicosis is a rare manifestation of thyroid cancer, and poorly differentiated thyroid carcinoma (PDTC) causing thyrotoxicosis has even more rarely been reported. Here, we report a case of PDTC with thyrotoxicosis developing in a previously euthyroid individual with longstanding untreated follicular neoplasm. Clinical Case: A 79-year-old veteran presented to routine endocrine follow up with new symptoms of thyrotoxicosis. Although previously euthyroid, the evaluation revealed new findings of low serum thyrotropin (TSH) (&amp;lt;0.01 uIU/mL, n=0.34 – 5.60 uIU/mL), elevated free thyroxine (FT4) (2.6 ng/dL, n=0.58 – 1.64 ng/dL), and high total T3 (TT3) levels (223 ng/dL, n=76 – 181 ng/dL). Thyroid stimulating immunoglobulin antibodies (TSI) were positive (214, n&amp;lt;140). Patient has a nine-year history of a fine needle aspiration (FNA) of a large right-sided thyroid nodule with cytology suspicious for follicular neoplasm but declined surgical removal. Thyroid uptake and scan showed heterogeneous uptake throughout the right lobe with a relative photopenic region centrally and spots of more increased activity in areas within the right lobe. The left thyroid lobe showed uniformly low uptake. PET-CT evaluation confirmed spotty FDG-avid areas within the right thyroid mass but did not show other areas of hyperactivity. Methimazole was started with clinical and biochemical improvement. Patient underwent total thyroidectomy, and histopathologic examination showed PDTC with extensive angioinvasion involving the majority of the right thyroid lobe with the left lobe containing a mix of benign thyroid tissue and PDTC fragments. Areas of hyperintensity on the uptake scan correlated to pathological PDTC locations within the right lobe. Within three weeks of thyroidectomy, patient developed recurrent hyperthyroidism. Laboratory studies showed low TSH (0.04 uIU/mL) and elevated FT4 (2 ng/dL). In contrast to pre-operative studies, repeat TSI was below the reference range. Levothyroxine (LT4) was held in anticipation of radioactive iodine therapy, but four weeks later the TSH remained suppressed. 131I was administered which showed accumulation within small thyroid remnants and a single left level three 131I-avid lymph node without other metastases. Following 131I treatment, patient returned to a euthyroid state on standard LT4. Conclusion: Hyperthyroidism has rarely been associated with PDTC, although previous reports have linked more aggressive, multifocal, and locally invasive thyroid cancers to concurrent Graves’ disease or productive bulky metastatic disease. Even without bulky metastatic disease, clinicians should be aware that hyperproductivity may indicate development of autoimmune thyrotoxicosis within PDTC. Presentation Date: Saturday, June 17, 2023

SAT549 False Alarm: Profoundly High Thyroglobulin Level Without Evidence Of Thyroid Malignancy

Abstract Disclosure: F.L. Thelmo: None. J. Watari: None. J.L. Miller: None. Thyroglobulin (TG) remains a clinical mainstay for monitoring of disease burden and recurrence in patients with differentiated thyroid cancer. TG levels are expected to be low to undetectable in patients who undergo total thyroidectomy and less than 30 ng/mL in patients who undergo thyroid lobectomy. We describe a case of a 52-year-old patient who underwent thyroid lobectomy for a 16 mm minimally invasive follicular thyroid carcinoma (single vessel angioinvasion) who was later found to have a TG level in excess of 2,000 despite no signs of metastatic disease. A 52-year-old male with past medical history of prediabetes and minimally invasive follicular thyroid cancer presented for follow-up after right lobectomy five years prior. The patient was lost to follow-up after his lobectomy. During work-up of paresthesias, a cervical spine MRI incidentally noted a 41 mm enhancing mass in the left thyroid lobe. The patient had a TSH of 1.1 mIU/L. A dedicated thyroid ultrasound was performed which found a left 2.9 cm TI-RADS 3 nodule which was biopsied and found to be benign (Bethesda II). TG level was obtained and found to be significantly elevated at 2,479.9 ng/mL with negative thyroglobulin antibodies. This was repeated twice with subsequent levels being 1,857.5 ng/mL and 2,555.1 ng/mL. TG antibodies remained undetectable throughout the clinical course. The patient had a CT chest, abdomen, and pelvis exam for which no signs of metastatic disease were detected. A skeletal survey was performed which showed no evidence of metastatic disease. The patient elected for a completion thyroidectomy to ensure there was no undetected malignancy. The patient underwent successful completion thyroidectomy. Surgical pathology showed benign nodular hyperplasia. The patient was started on replacement levothyroxine and one month later the TG level became undetectable. We would like to draw attention to this patient’s profoundly high TG levels which are normally associated with recurrence of thyroid malignancy or large goiter. After comprehensive evaluation this patient was found to have no underlying disease recurrence. A completion thyroidectomy showed no malignancy within remnant thyroid tissue or adjacent lymph nodes and repeat TG level was undetectable after completion showing that native thyroid tissue had significantly high TG production without underlying disease. We believe his remaining relatively normal thyroid lobe was a super producer of thyroglobulin. Despite TG being a sensitive marker for residual thyroid tissue and disease, the standard cut-off for lobectomy must be used with caution and may not apply to every patient. Presentation Date: Saturday, June 17, 2023

Assessment of three different radioiodine doses for ablation therapy of thyroid remnants: Efficiency, complications and patient comfort.

I-131 radioiodine (RAI) ablation removes postoperative residual tissue and facilitates follow-up in low- and intermediate-risk differentiated thyroid cancer (DTC). Although low doses have been reported to be as effective as higher doses for ablation, the doses administered still vary depending on the patient and the practitioner. We aimed to evaluate the ablation efficiency, complications, and length of stay (LOS) of patients with DTC treated with 3 different doses for ablation. Patients with DTC who received RAI therapy were retrospectively reviewed. One hundred thirty patients with low-intermediate-risk, according to American Thyroid Association classification, without known lymph nodes or distant metastases were included. Patients were divided into 3 groups as 30 to 50 mCi, 75 mCi, and 100 mCi. Residue thyroid and salivary glands were evaluated from 9 to 12 months post-RAI I-131 scans. No significant difference was found between groups regarding ablation success (P = .795). In multivariable analyses, pretreatment thyroglobulin (hazard ratio = 0.8, 95% confidence interval 0.601-0.952, P = .017) and anti- thyroglobulin antibody (hazard ratio = 1.0, 95% confidence interval 0.967-0.998, P = .024) were 2 independent predictors of ablation success. The mean LOS was 2.1 ± 0.3, 2.6 ± 0.6, and 2.9 ± 0.4 days, respectively, (P = .001). LOS rates of ≥ 3 days were 13.2%, 54.3%, and 84.8%, respectively. Mild decreases in hemoglobin, white blood cell (WBC), and platelet counts were observed in all groups after 6 weeks without any clinically significant findings. A lower rate of change in WBC counts was observed in the 30 to 50 mCi group compared to others. There was no dose-dependent difference regarding the early complaints questioned. Ablation with 30 to 50 mCi provides benefits such as shorter LOS, better patient comfort, less salivary gland dysfunction, and less WBC suppression, thus reducing costs without decreasing efficacy.

Development of a predictive score for post-hemithyroidectomy hypothyroidism using skeletal muscle index, remnant thyroid index, and thyroid-stimulating hormone levels: a retrospective cohort study.

Hypothyroidism is a major complication of hemithyroidectomy. Low remnant thyroid volume and high serum thyroid-stimulating hormone (TSH) levels are suggested as risk factors for post-hemithyroidectomy hypothyroidism. Reduced skeletal muscle mass is associated with a variety of postoperative complications. However, its impact on post-hemithyroidectomy hypothyroidism has not yet been studied. This study aimed to evaluate the association between skeletal muscle mass and the onset of post-hemithyroidectomy hypothyroidism and develop a predictive score using skeletal muscle mass in combination with previously reported risk factors. This study retrospectively analyzed 226 consecutive patients who underwent hemithyroidectomy at Shinshu University Hospital between January 2011 and December 2020. The skeletal muscle area at the fourth thoracic vertebral level and maximal remnant thyroid area were quantified using preoperative computed tomography and standardized by dividing them by the square of the patient's height, designated as the skeletal muscle index (SMI) and remnant thyroid volume index (RTI). Subclinical hypothyroidism was defined as a postoperative elevated serum TSH level (>5 µU/mL) with a normal free thyroxine (FT4) level (≥0.9 ng/dL), overt hypothyroidism as a postoperative increase in serum TSH level (>5 µU/mL) and a decrease in serum FT4 level (<0.9 ng/dL), and symptomatic hypothyroidism as an elevated serum TSH level (>5 µU/mL) with hypothyroidism-related symptoms. Logistic regression analysis was used to determine the factors associated with the onset of hypothyroidism. Patients with euthyroid status had significantly higher SMI and RTI than those who developed post-hemithyroidectomy hypothyroidism (SMI, euthyroid: 12.0±2.4 vs. subclinical hypothyroid: 10.2±1.7, P<0.001, euthyroid vs. overt or symptomatic hypothyroid: 10.1±1.7, P<0.001, RTI, euthyroid: 1.19±0.41 vs. subclinical hypothyroid: 0.92±0.35, P<0.001, euthyroid vs. overt or symptomatic hypothyroid: 0.84±0.30, P<0.001). Multivariable analysis demonstrated that low SMI, low RTI [hazard ratio (HR): 3.35, P<0.001], and preoperative high serum TSH levels (HR: 2.54, P=0.003) were independent predictive factors for hypothyroidism. Patients who had low SMI, low RTI, and preoperative high serum TSH levels were more likely to develop hypothyroidism (68.8%) than those with either one (25.3%), two (47.8%), or none (15.2%) of these three factors. Preoperative evaluation of the SMI, RTI, and serum TSH levels may be useful in predicting the development of post-hemithyroidectomy hypothyroidism.

Cadherin-16 (CDH16) immunohistochemistry: a useful diagnostic tool for renal cell carcinoma and papillary carcinomas of the thyroid

Cadherin-16 (CDH16) plays a role in the embryonal development in kidney and thyroid. Downregulation of CDH16 RNA was found in papillary carcinomas of the thyroid. To determine the expression of CDH16 in tumors and to assess the diagnostic utility a tissue microarray containing 15,584 samples from 152 different tumor types as well as 608 samples of 76 different normal tissue types was analyzed. A membranous CDH16 immunostaining was predominantly seen in thyroid, kidney, cauda epididymis, and mesonephric remnants. In the thyroid, CDH16 staining was seen in 100% of normal samples, 86% of follicular adenomas, 60% of follicular carcinomas, but only 7% of papillary carcinomas (p < 0.0001). CDH16 positivity was frequent in nephrogenic adenomas (100%), oncocytomas (98%), chromophobe (97%), clear cell (85%), and papillary (76%) renal cell carcinomas (RCCs), various subtypes of carcinoma of the ovary (16–56%), various subtyped of carcinomas of the uterus (18–40%), as well as in various subtypes of neuroendocrine neoplasms (4–26%). Nineteen further tumor entities showed a weak to moderate CDH16 staining in up to 8% of cases. Our data suggest CDH16 as a potential diagnostic marker—as a part of a panel—for the identification of papillary carcinomas of the thyroid, nephrogenic adenomas, and the distinction of renal cell tumors from other neoplasms.

Efficiance of radioiodine remnant ablation in cases of locally differentiated thyroid cancer

On the territory of Russia has increased the of thyroid cancer after Chernobyl NPP incidence at 1986, and currently accounts for up to 14,000 newly identified cases. Postoperative radioiodine (RAI) remnant ablation is the second stage of combine treatment of differentiated thyroid cancer, except for the prevalence of pT1N0M0, with minimal level of TG and AT-TG, according to international guidelines. In the past 20 years a significant number of published practice guidelines for the treatment of this disease. However, the discussion is the amount of medication for administration activity (GBq) 131I, is required for successful ablation of thyroid remnants. The study analyzed 353 clinical cases after radical surgical treatment for DTC. In our study, the effectiveness of radioiodablation was compared with certain indicators of specific therapeutic activity 131I (MBq/kg), in groups of patients with different levels of TSH stimulation (less than 30 mME/ml, and more than 30 mME/ml). We evaluated the absorbed dose in the thyroid remnant in patients with residual thyroid tissue volume determined by US when administering 131I empirical therapeutic activity. The control of the WBS with 131I was carried out in 6 months. The average eղciency RAI was 85.5 %, there were no significant differences in the TSH stimulation groups of more than 30 mME/ml and 4-30 mME/ml (p &gt; 0.05). If the thyroid remnant is not detected by US, the effective range of 131I specific therapeutic activity is 30-40 MBq/ kg against a background of TTG stimulation greater than 4 ՏME/ml and strict adherence to a 14-day low iodine diet. Direct radiometry followed by neck scintigraphy (1200 kBq 131I) and calculation of therapeutic activity is recommended when determining thyroid remnant by US to plan for TAD = 300 Gy and reduce the risk of radiation sialoadenitis. At the time of RAI, 3.9 % of patients had previously undetectable X-rays lung metastases with stimulated TG levels greater than 124 ng/mL after surgical treatment with SPECT/CT.

Analysis of options for prescribing hormone replacement therapy after thyroid organ-sparing surgery

Background. Performing thyroid organ-sparing surgery primarily aims to preserve the quality of life. Organ-sparing surgery should be understood as hemithyroidectomy with mandatory removal of the isthmus and pyramidal lobe of the thyroid (if present). The choice of one or another concept of prescribing hormone replacement therapy remains debatable. The purpose of the study is to determine the proportion of patients who do not need replacement therapy with levothyroxine after organ-sparing surgery on the thyroid gland, among those who were prescribed replacement therapy immediately and one month after discharge from the hospital, as well as to analyze the factors causing hypothyroidism in people with hemithyroidectomy. Materials and methods. The first group included 82 patients with hemithyroidectomy who were prescribed replacement therapy immediately after discharge from the hospital. The second group included 61 patients with hemithyroidectomy. The administration of replacement therapy was postponed for one month. A month after the operation, clinical examinations and monitoring of thyroid-stimulating hormone and free thyroxine indicators were performed. Results. After one month of observation, 72 (87.8%) of 82 patients in the first group continued to take levothyroxine, and 8 (13.1%) of 61 persons in the second group began to take it. In the first group, there was a moderate direct correlation between thyroid-stimulating hormone level before surgery and levothyroxine dose one month after (Spearman’s correlation coefficient 0.304, p=0.009). It was found that the chances of continuing taking levothyroxine after one month in the first group were 47 times higher than the chances of prescribing levothyroxine after one month in the second group. The proportion of patients in the first group who continued to take levothyroxine after one month was significantly higher than the proportion of patients in the second group who started taking levothyroxine after one month (87.8±3.6% vs. 13.1±3.5%, p&lt;0.0001, Fisher’s exact test). Conclusions. Among patients who were prescribed hormone replacement therapy immediately after hemithyroidectomy, 12.2% did not need to continue taking levothyroxine after one month. Among persons in whom the administration of hormone replacement therapy was postponed for one month after hemithyroidectomy, 86.9% of patients did not require the use of levothyroxine in the future. The volume of the thyroid remnant ≤ 3.67 cm3 can be considered a predictor for hypothyroidism occurrence in the future, with a high risk of prescribing hormone replacement therapy. The study of such a factor as the ratio of the remnant thyroid volume to the body weight did not provide statistically reliable data for its use as a predictor of hypothyroidism occurrence in the postoperative period.

Thyroglobulin measurement in the needle washout for diagnosis of lymph node metastases of differentiated thyroid cancer

Introduction. Measurement of thyroglobulin (Tg) in a washout after fine-needle aspiration (FNA) is recommended for the diagnosis of metastases of differentiated thyroid cancer (DTC), but the method is not standardized and there is no recommended threshold value of Tg washout, which makes it difficult to interpret the results.Aim. To analyze Tg in the washout after FNA of lesions of different origin on the neck and to determine its optimal cutoff for the diagnosis of DTC metastases.Materials and methods. Ultrasound-guided FNA was performed in 1258 neck masses from 591 patients, 566 of them with confirmed DTC. In 1023 lesions, FNA was performed after thyroidectomy, 22 – after lobectomy, 213 – with preserved thyroid gland. The needle after FNA was washed in 1 ml of saline, in which the concentration of Tg was then examined. The level of Tg in the washout was compared with the histological (n = 522) or cytological diagnosis if no surgery was performed. The cut-off for Tg washout was determined by ROC analysis.Results. DTC lymph node metastases detected in 577 specimens. Nine specimens were obtained from metastases of thyroid cancer (TC) that does not express Tg (anaplastic TC, poorly differentiated TC, columnar-cell variant DTC), 22 – from neck metastases of other malignancy (lung cancer, mucinous soft tissues tumor, ovarian cancer, esophageal cancer, melanoma, neuroendocrine tumor), 6 – from other tumors of the neck (lymphoma, parathyroid adenoma, neurinoma). In 26 cases, the specimen was regarded as normal thyroid tissue left after thyroidectomy, 37 – postoperative seroma or granuloma, 1 – cyst of the neck, 578 – lymph node hyperplasia, 2 – sarcoidosis. The level of Tg washout from DTC metastasis and thyroid remnant significantly differed from that of non-thyroidal origin (p &lt;0.0001). At the cut-off of 7.8 ng/ml, the sensitivity and specificity of Tg washout in the diagnosis of DTC metastases is 94 and 95 %, and at the cut-off of 20 ng/ml, 90 and 98 %, respectively. False-negative results were obtained from DTC with squamous metaplasia or sparse tumor cells in a specimen. False-positive results were obtained more often from lesions of level VI and IV compared with other localizations (8 % versus 4 %; p = 0.04). There were no differences in false positive rate in patients before and after thyroidectomy (p = 0.17), but in patients after thyroidectomy with a serum Tg &gt;200 ng/ml, the false positive rate of Tg washout was significantly higher than that with a lower level of serum Tg (28 % versus 3 %; p = 0.0004). When comparing diagnostic performance of cytology and Tg washout, the advantage of the latter is in the diagnosis of cystic metastases, and the former is in the diagnosis of micrometastases and tumors that do not express Tg. Thyroglobulin in the washout increased the sensitivity of the cytology by 8 %. The combined use of these methods detected DTC metastases in 100 % of patients.Conclusion. Measurement of Tg in the washout is a useful addition to the cytology, increasing the diagnostic performance of the latter, mainly due to better detection of cystic metastases of DTC. The optimal suggested cut-off for Tg washout is 20 ng/mL, at which there are fewer false positives.