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Open access

J L Reverter, L Ferrer-Estopiñan, F Vázquez, S Ballesta, S Batule, A Perez-Montes de Oca, C Puig-Jové, and M Puig-Domingo

Introduction

Computer-aided diagnostic (CAD) programs for malignancy risk stratification from ultrasound (US) imaging of thyroid nodules are being validated both experimentally and in real-world practice. However, they have not been tested for reliability in analyzing difficult or unclear images.

Methods

US images with indeterminate characteristics were evaluated by five observers with different experience in US examination and by a commercial CAD program. The nodules, on which the observers widely agreed, were considered concordant and, if there was little agreement, not concordant or difficult to assess. The diagnostic performance of the readers and the CAD program was calculated and compared in both groups of nodule images.

Results

In the group of concordant thyroid nodules (n = 37), the clinicians and the CAD system obtained similar levels of accuracy (77.0% vs 74.2%, respectively; P = 0.7) and no differences were found in sensitivity (SEN) (95.0% vs 87.5%, P = 0.2), specificity (SPE) (45.5 vs 49.4, respectively; P = 0.7), positive predictive value (PPV) (75.2% vs 77.7%, respectively; P = 0.8), nor negative predictive value (NPV) (85.6 vs 77.7, respectively; P = 0.3). When analyzing the non-concordant nodules (n = 43), the CAD system presented a decrease in accuracy of 4.2%, which was significantly lower than that observed by the experts (19.9%, P = 0.02).

Conclusions

Clinical observers are similar to the CAD system in the US assessment of the risk of thyroid nodules. However, the AI system for thyroid nodules AmCAD-UT® showed more reliability in the analysis of unclear or misleading images.

Open access

Laure Felix, Peggy Jacon, Maxime Lugosi, Justine Cristante, Julie Roux, and Olivier Chabre

Background and Objective

It has been reported recently in a cross sectional study that patients with amiodarone induced thyrotoxicosis (AIT) showed a ‘white’ thyroid on unenhanced computed tomography, due to intrathyroid iodine accumulation. However, the link between increase in thyroid radiologic density and amiodarone induced thyrotoxicosis remains unknown. We sought to analyze this link.

Methods

We present the case of a 34-year-old patient with severe sarcoidosis-related hypertrophic cardiomyopathy who was followed with successive unenhanced CT scans integrated with FDG PET scans. After the first CT scans the patient, who initially had a normal thyroid function, was exposed to amiodarone during 23 months and developed AIT, very likely by thyroiditis (AIT type 2). There were no thyroid antibodies, no evidence of thyroid sarcoidosis on FDG PET scan, while thyroid sonogram showed a homogenous 22 ml moderate goiter with normal echogenicity and no nodules.

Results

Analysis of the successive enhanced CT scans revealed that after initiation of amiodarone treatment, thyroid radiologic density steadily increased before detection of AIT, peaked after cessation of amiodarone and initiation of thyrotoxicosis treatment, before returning to normal as thyrotoxicosis receded. Thyroid volume also showed a moderate increase, peaking at the detection of thyrotoxicosis, before returning to normal.

Conclusion

This case suggests that AIT is preceded by a very high intrathyroid iodine accumulation before the ‘burst’ of thyroiditis occurs and that measurements of thyroid gland radiological density might predict the development and remission of AIT.

Open access

Eijun Nishihara, Yoshitaka Hobo, Akira Miyauchi, Yasuhiro Ito, Miyoko Higuchi, Mitsuyoshi Hirokawa, Mitsuru Ito, Shuji Fukata, Mitsushige Nishikawa, and Takashi Akamizu

Objective

This study aimed to elucidate disproportionately low serum thyroglobulin (Tg) values in Tg antibody (TgAb)-positive patients with structural recurrence of papillary thyroid carcinoma (PTC) using liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Design

A retrospective study was performed on 176 patients in whom Tg and TgAb levels were measured between 2016 and 2021. Several comprehensive analyses of Tg-LC-MS/MS with an electrochemiluminescence immunoassay for Tg (Tg-ECLIA) were conducted using serum samples.

Methods

TgAb-positive patients who underwent total thyroidectomy with multiple lung metastases due to PTC were evaluated using Tg-LC-MS/MS and Tg-ECLIA. Tg expression in lymph node metastases and metastatic lesions was evaluated by immunohistochemistry and Tg levels of aspiration washouts were also evaluated. Two in vitro assays were performed to elucidate TgAb interference.

Results

Tg concentrations of negative TgAb in both assays were similar (R2= 0.99; n  = 52). Patients with structural recurrence showed higher Tg values with Tg-LC-MS/MS than with Tg-ECLIA. The undetectable proportion was significantly lower with Tg-LC-MS/MS (31.6%, 6/19) than with Tg-ECLIA (68.4%, 13/19; P  = 0.023). The spike-recovery rate and Tg concentrations determined by the serum mixture text (n  = 29) were significantly reduced to 75.0% (118.3–88.7%) and 81.3% (107.0–87.0%), respectively, with TgAb using Tg-ECLIA (both P  < 0.001) confirming assay interference but not using Tg-LC-MS/MS (91.8–92.3%, P  = 0.77 and 98.4–100.8%, P  = 0.18, respectively).

Conclusions

TgAb had no effect on the Tg-LC-MS/MS assay but yielded 19–25% lower values in Tg-ECLIA. Tg-LC-MS/MS is preferable for monitoring serum Tg levels in TgAb-positive patients, although those with structural recurrence often had disproportionally low Tg values.

Open access

Markus Eszlinger, Paul Stewardson, John B McIntyre, Adrian Box, Moosa Khalil, Martin Hyrcza, Konstantin Koro, Dean Ruether, Jiahui Wu, and Ralf Paschke

Objective

The aim of the study was to identify patients with NTRK fusion-positive or RET fusion/mutation-positive thyroid cancers, who could benefit from neurotrophic tyrosine kinase receptor (NTRK) or receptor tyrosine kinase (RET) inhibitors.

Methods

Patients were identified in the Calgary prospective thyroid cancer database (N= 482). Patients were ‘pre-screened’ with clinically available MassARRAY® BRAF test, Colon Panel, Melanoma Panel, or ThyroSPEC™. Mutation-negative tumors were ‘screened’ for NTRK fusions and RET fusions/mutations with the Oncomine™ Comprehensive Assay v3 (OCAv3).

Results

A total of 86 patients were included in 1 of 2 separate analyses. Analysis A included 42 patients with radioactive iodine (RAI)-resistant distant metastases. After pre-screening, 20 BRAF and RAS mutation-negative patients underwent OCAv3 screening, resulting in the detection of 4 patients with NTRKfusions and 4 patients with RET fusions (8/20, 40% of analyzed patients). Analysis B included 44 patients, 42 with American Thyroid Association (ATA) high and intermediate risk of recurrence and 2 with medullary thyroid carcinoma. During pre-screening, 1 patient with an NTRK fusion, 1 patient with a RET fusion, and 30 patients with BRAF mutations were identified. The remaining 9 patients received OCAv3 screening, resulting in detection of 1 patient with an NTRKfusion and 1 with a RET fusion (4/11, 36% of analyzed patients).

Conclusions

Our findings indicate a higher rate of NTRK fusions and RETfusions in patients with thyroid cancer with RAI-resistant distant metastases and ATA high or intermediate risk of recurrence. This highlights the importance of early screening to enable intervention with a NTRK or RET inhibitor.

Open access

Bruno Bouça, Ana Cláudia Martins, Paula Bogalho, Lídia Sousa, Tiago Bilhim, Filipe Veloso Gomes, Élia Coimbra, Ana Agapito, and José Silva-Nunes

Introduction

Amiodarone-induced thyrotoxicosis (AIT) can sometimes lead to life-threatening complications, especially in patients with congenital heart disease (CHD). We report the case of a patient with refractory AIT that was successfully treated with thyroid arterial embolization (TAE).

Case report

A 34-year-old man with complex cyanotic CHD complicated with heart failure (HF), pulmonary hypertension, and supraventricular tachyarrhythmias, was treated with amiodarone since 2013. In March 2019, he presented worsening of his cardiac condition and symptoms of thyrotoxicosis that were confirmed by laboratory assessment. Thiamazole 30 mg/day and prednisolone 40 mg/day were prescribed, but the patient experienced worsening of his cardiac condition with several hospital admissions in the next 5 months, albeit increasing dosages of thionamide and glucocorticoid and introduction of cholestyramine and lithium. Thyroidectomy was excluded due to the severity of thyrotoxicosis, and plasmapheresis was contraindicated due to the cardiac condition. TAE of the four thyroid arteries was then performed with no immediate complications. Progressive clinical and analytical improvement ensued with gradual reduction and suspension of medication with the patient returning to euthyroid state and his usual cardiac condition previous to the AIT.

Conclusion

For patients with medication refractoriness and whose condition precludes thyroidectomy, embolization of thyroid arteries may be an effective and safe option.

Established facts

  • Amiodarone-induced thyrotoxicosis (AIT) can be refractory to a combination therapy of thionamides and glucocorticoids.

  • Restoration of euthyroidism is of paramount importance in heart failure (HF) patients.

  • Emergency thyroidectomy for AIT unresponsive to medical therapy is recommended in patients with severe underlying cardiac disease or deteriorating cardiac function.

Novel insights

  • Thyroid arterial embolization (TAE) appeared as a salvage therapy in this patient.

  • To the best of our knowledge, few case reports in the literature have described the embolization of the four thyroid arteries in AIT context.

  • Endovascular embolization techniques are a valuable therapeutic option and can be considered in cases where standard forms of treatment are ineffective or involve unacceptable risks.

Open access

David Shaki, Marina Eskin-Schwartz, Noam Hadar, Emily Bosin, Lior Carmon, Samuel Refetoff, Eli Hershkovitz, Ohad S Birk, and Alon Haim

Objective

Bi-allelic loss-of-function mutations in TSHB, encoding the beta subunit of thyroid-stimulating hormone (TSH), cause congenital hypothyroidism. Homozygosity for the TSHB p.R75G variant, previously described in South Asian individuals, does not alter TSH function but abrogates its detection by some immune detection-based platforms, leading to erroneous diagnosis of hyperthyroidism. We set out to identify and determine the carrier rate of the p.R75G variant among clinically euthyroid Bene Israel Indian Jews, to examine the possible founder origin of this variant worldwide, and to determine the phenotypic effects of its heterozygosity.

Design

Molecular genetic studies of Bene Israel Jews and comparative studies with South Asian cohort.

Methods

TSHB p.R75G variant tested by Sanger sequencing and restriction fragment length polymorphism (RFLP). Haplotype analysis in the vicinity of the TSHB gene performed using SNP arrays.

Results

Clinically euthyroid individuals with low or undetectable TSH levels from three apparently unrelated Israeli Jewish families of Bene Israel ethnicity, originating from the Mumbai region of India, were found heterozygous or homozygous for the p.R75G TSHB variant. Extremely high carrier rate of p.R75G TSHB in Bene Israel Indian Jews (~4%) was observed. A haplotype block of 239.7 kB in the vicinity of TSHB shared by Bene Israel and individuals of South Asian origin was detected.

Conclusions

Our findings highlight the high prevalence of the R75G TSHB variant in euthyroid Bene Israel Indian Jews, demonstrate that heterozygosity of this variant can cause erroneous detection of subnormal TSH levels, and show that R75G TSHB is an ancient founder variant, delineating shared ancestry of its carriers.

Open access

Zhen Gao, Hongtao Zhang, Lijuan Zhang, Huimin Yu, Xuemin Di, Zeyang Wang, Zezhou Liu, Aixia Sui, Juan Wang, and Gaofeng Shi

Background: Papillary thyroid carcinoma (PTC) is typically treated with surgical resection, even in recurrent cases. However, some cases of recurrent PTC are refractory to the conventionally used locoregional radiotherapy and resection methods. <sup>125</sup>I seed permanent brachytherapy has emerged as a promising alternative for such PTCs, but no effective brachytherapy protocol has been reported for tumors with a huge volume, liquefaction, necrosis, and skin invasion. Case Presentation: A 47-year-old man presented with recurrence 8 years after 2 thyroidectomy procedures for PTC and recurrent PTC. The tumor measured 6 × 7 × 8 cm<sup>3</sup> and exhibited liquefaction, necrosis, and skin invasion. The patient was treated at our hospital from December 2017 to November 2018. He received one round of <sup>125</sup>I seed temporary brachytherapy and 4 rounds of <sup>125</sup>I seed permanent implantation. The activity of the seeds was 0.3–3.0 mCi, and the total dose delivered to the tumor was 145 Gy. The recurrent tumor was successfully removed by <sup>125</sup>I seed brachytherapy guided with a 3D-printed template and ultrasound and CT scanning. The refractory tumor healed uneventfully after <sup>125</sup>I seed brachytherapy without recurrence over the 25-month follow-up. Conclusions: To the best of our knowledge, this is the first reported case of a large thyroid carcinoma that was effectively treated by 3D-printed template-guided <sup>125</sup>I seed brachytherapy.

Open access

Camille Buffet, Sophie Leboulleux, Françoise Kraeber-Bodéré, Caroline Bodet-Milin, Laure Cabanes, Anthony Dohan, Pascal Leprince, Martin Schlumberger, Olivier Huillard, and Lionel Groussin

Background: Cardiac metastases from thyroid cancers are uncommon with a poor prognosis. There is a lack of long-term follow-up studies. Cases: We report 2 cases of cardiac metastasis from medullary thyroid cancer (MTC). Both patients presented limited metastatic disease apart from a cardiac metastasis. The initial diagnosis was challenging and was facilitated by functional imaging with an immuno-PET-CT using an anti-CEA bispecific antibody and a <sup>68</sup>Ga-labeled peptide. Both patients were treated with the multitarget kinase inhibitor vandetanib with prolonged stability. The first patient was alive at the last follow-up, 14 years after the diagnosis of cardiac metastasis. The second patient required surgical excision of the cardiac mass because of disease progression under vandetanib. Conclusion: These cases illustrate long-term survival and effectiveness of clinical management of 2 patients who developed cardiac metastases from MTC, in the current era of personalized medicine with targeted therapy.

Free access

Natsuko Watanabe, Jaeduk Yoshimura Noh, Naomi Hattori, Kenji Iwaku, Nami Suzuki, Ai Yoshihara, Hidemi Ohye, Miho Suzuki, Masako Matsumoto, Kei Endo, Yo Kunii, Gen Takagi, Kiminori Sugino, and Koichi Ito

Introduction: High-sensitive cardiac troponin reflects micro-myocardial injury in the absence of overt myocardial infarction. Objective: This study aimed to clarify how thyrotoxicosis affects cardiac troponin. Methods: This was a prospective observational study in Japan. Untreated patients with thyrotoxicosis who visited Ito Hospital were enrolled, and medical treatment was initiated for hyperthyroidism. Thyroid function, high-sensitive troponin I (hsTnI), and brain natriuretic peptide (BNP) were measured at baseline and then every 3 months for 1 year. Results: Data from a total of 143 patients (median age, 42 years; 32 men and 111 women) were investigated. At baseline, median hsTnI was 1.9 pg/mL and ranged from 0 to 69.6 pg/mL. Five patients (3.5%) had a high hsTnI value that exceeded 26.2 pg/mL, which is used as the cutoff for diagnosis of myocardial infarction, and 22 patients (15.4%) had an intermediate value between 5.0 and 26.2 pg/mL. Multivariable regression analysis showed that significant predictors of the hsTnI value were age (β = 0.20, p = 0.01) and BNP (β = 0.43, p < 0.0001) (R<sup>2</sup> = 0.27, F = 26.0, p < 0.0001), and significant predictors of the BNP value were age (β = 0.23, p = 0.001), hemoglobin (β = −0.43, p < 0.0001), free T<sub>4</sub> (FT<sub>4</sub>) (β = 0.23, p = 0.001), and hsTnI (β = 0.27, p < 0.0001) (R<sup>2</sup> = 0.49, F = 33.8, p < 0.0001). Correlations were found between a decrease in hsTnI and BNP in the first 3 months (ρ = 0.49, p < 0.0001). A decrease in FT<sub>4</sub> in the first 3 months was weakly correlated with decreases in hsTnI (ρ = 0.32, p = 0.0004) and BNP (ρ = 0.32; p = 0.0003). Of the 27 patients with elevated hsTnI (≥5.0 pg/mL), the hsTnI level was normalized in 20 patients within a year. Conclusions: In thyrotoxicosis, the myocardial biomarker hsTnI is elevated in about 20% of patients; hsTnI levels decrease as thyroid function improves and BNP decreases.

Free access

Daniela Rodrigues Cavaco, Ana Alves Rafael, Rafael Cabrera, Helena Vilar, and Valeriano Leite

Diffuse thyroid lipomatosis is a rare histopathological condition of unknown etiology, characterized by diffuse fatty infiltration of the thyroid stroma, which can result in diffuse goiter with compressive symptoms. We report a case of a 46-year-old man with 1-year history of progressive goiter enlargement with compressive symptoms. Imaging studies revealed multiple coalescent nodules. The patient underwent surgery, and the microscopic appearance revealed a diffuse infiltration of thyroid stroma by mature adipose tissue with associated amyloid deposition. A final diagnosis of diffuse lipomatosis of the thyroid gland was established. This patient represents one of the few reported cases of diffuse lipomatosis with coexisting deposition of amyloid protein of the thyroid gland and contributes to the better understanding of this extremely rare condition.