Artificial intelligence-based CT-free quantitative thyroid SPECT for thyrotoxicosis: study protocol of a multicentre, prospective, non-inferiority study.

INTRODUCTION: Technetium thyroid uptake (TcTU) measured by single-photon emission CT/CT (SPECT/CT) is an important diagnostic tool for the differential diagnosis of Graves' disease and destructive thyroiditis. Artificial intelligence (AI) may reduce CT-induced radiation exposure by substituting the role of CT in attenuation correction (AC) and thyroid segmentation, thus realising CT-free SPECT. This study aims to compare the diagnostic accuracy for the differential diagnosis of thyrotoxicosis between CT-free SPECT and SPECT/CT. METHODS AND ANALYSIS: The AI-based CT-free SPECT is a single-blind, multicentre, prospective, non-inferiority, clinical trial with a paired design conducted in the Republic of Korea. Eligible participants are adult (≥19 years old) thyrotoxicosis patients without a previous history of hyperthyroidism or hypothyroidism. Approximately 160 subjects will be screened for quantitative thyroid SPECT/CT using Tc-99m pertechnetate. CT-free thyroid SPECT will be realised using only SPECT data by the trained convolutional neural networks. TcTU will be calculated by SPECT/CT and CT-free SPECT in each subject. The primary endpoint is the accuracy of diagnosing Graves' disease using TcTU. The trial will continue until 152 completed datasets have been enrolled to assess whether the 95% (two-sided) lower confidence limit of the accuracy difference (CT-free SPECT accuracy-SPECT/CT accuracy) for Graves' disease is greater than -0.1. The secondary endpoints include the accuracy of diagnosing destructive thyroiditis and predicting the need for antithyroid drug prescription within 1 month of the SPECT/CT. ETHICS AND DISSEMINATION: The study protocol has been approved by the institutional review board of Seoul National University Bundang Hospital (IRB No. B-2304-824-301), Konkuk University Medical Center (IRB No. 2023-05-022-006) and Chonnam National University Hospital (IRB No. CNUH-2023-108). Findings will be disseminated as reports, presentations and peer-reviewed journal articles. TRIAL REGISTRATION NUMBER: KCT0008387, Clinical Research Information Service of the Republic of Korea (CRIS).

Enhanced Differentiation of Amiodarone-Induced Thyrotoxicosis Types Using Semi-Quantitative 99mTc-MIBI Uptake Analysis: A Pilot Study.

BACKGROUND Technetium (99mTc)-labelled Methoxy-2-Isobutylisonitrile (MIBI) is a diagnostic lipophilic cationic radiotracer used to evaluate the cardiac, breast, thyroid, and parathyroid pathology. This study aimed to evaluate the role of MIBI combined with Tc-99m pertechnetate thyroid scintigraphy, thyroid ultrasonography, and measurement of thyrotropin, thyroid hormones, and autoantibodies to subtype amiodarone-induced thyrotoxicosis (AIT) and the contribution of semi-quantitative analysis of MIBI uptake. MATERIAL AND METHODS This cross-sectional study included 36 patients with AIT who underwent thyrotropin, thyroid hormone, and autoantibody analysis using chemiluminescent method, ultrasonography, pertechnetate, and MIBI thyroid scintigraphy with semi-quantitative uptake, including calculation of the target-to-background ratio (TBR) with 2 different background regions. The MIBI washout rate (WR) was analyzed in all groups. Statistical analysis was performed using descriptive statistics, correlations, and the receiver operating characteristic curve - area under the curve (ROC-AUC). The results were compared with the control group. RESULTS Based on visual and semi-quantitative analyses, patients were successfully categorized into AIT groups (AIT-1, AIT-2 and AIT-3) but the latter method enabled better differentiation of MIBI uptake between all groups. Additionally, ROC-AUC analysis determined cutoff values which enabled discerning between AIT-1 and AIT-2 groups, and AIT-1 and AIT-3 groups. WR showed no significant difference between all AIT groups and controls (P>0.05). CONCLUSIONS Visual MIBI analysis enabled differentiation between AIT-1 and 2 groups, but the method was substantially improved with semi-quantitative analysis, especially in defining AIT-3 group. However, multicenter collaboration with larger studies is needed to standardize the method and obtain more accurate and consistent results.

Deep Learning Analysis With Gray Scale and Doppler Ultrasonography Images to Differentiate Graves' Disease.

CONTEXT: Thyrotoxicosis requires accurate and expeditious differentiation between Graves' disease (GD) and thyroiditis to ensure effective treatment decisions. OBJECTIVE: This study aimed to develop a machine learning algorithm using ultrasonography and Doppler images to differentiate thyrotoxicosis subtypes, with a focus on GD. METHODS: This study included patients who initially presented with thyrotoxicosis and underwent thyroid ultrasonography at a single tertiary hospital. A total of 7719 ultrasonography images from 351 patients with GD and 2980 images from 136 patients with thyroiditis were used. Data augmentation techniques were applied to enhance the algorithm's performance. Two deep learning models, Xception and EfficientNetB0_2, were employed. Performance metrics such as accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and F1 score were calculated for both models. Image preprocessing, neural network model generation, and neural network training results verification were performed using DEEP:PHI® platform. RESULTS: The Xception model achieved 84.94% accuracy, 89.26% sensitivity, 73.17% specificity, 90.06% PPV, 71.43% NPV, and an F1 score of 89.66 for the diagnosis of GD. The EfficientNetB0_2 model exhibited 85.31% accuracy, 90.28% sensitivity, 71.78% specificity, 89.71% PPV, 73.05% NPV, and an F1 score of 89.99. CONCLUSION: Machine learning models based on ultrasound and Doppler images showed promising results with high accuracy and sensitivity in differentiating GD from thyroiditis.

Using Bedside Spectral Doppler Ultrasound for the Assessment of Patients With Thyrotoxicosis.

OBJECTIVE: To assess the bedside utility of Spectral Doppler Ultrasound (SDUS) in the initial evaluation of patients presenting with thyrotoxicosis. METHODS: This is a retrospective cross-sectional study of patients diagnosed with thyrotoxicosis at an academic outpatient endocrinology clinic from August 2019 to November 2022. The thyroid arteries' peak systolic velocities (PSV) were measured bilaterally using SDUS. PSV ≥40 cm/s in at least a single thyroid artery was considered a reasonable cut-off for Graves' disease and PSV of perinodular artery ≥ 25 cm/s for toxic adenoma. RESULTS: We identified 73 patients. Mean age ± standard deviation 45.2 ± 16.4 years, 54 (74.0%) were female, 49 (67.1%) were Caucasian, 23 (31.5%) were African American, and 1 (1.4%) was Asian. The confirmed diagnoses were 48 (65.8%) Graves' disease, 13 (17.8%) thyroiditis, four (5.5%) toxic adenoma, four (5.5%) amiodarone-induced thyroiditis type 2, 1 (1.4%) toxic multinodular goiter, 1 (1.4%) had an unremarkable repeat thyroid function testing, and two (2.7%) were unconfirmed. Diagnosis based on the SDUS initial assessment was accurate in 65 (89.0%) of the patients, and it was conclusive and confirmatory during the initial encounter in 55 (75.3%) of the patients before additional testing. A thyroid scan was obtained in nine (12.3%) patients. Incorrectly diagnosed patients were observed in two patients of each of the following categories: Graves' disease, thyroiditis, toxic adenoma, and unconfirmed diagnoses. CONCLUSIONS: SDUS can be a valuable, efficient, and cost-effective bedside tool in the initial assessment of patients presenting with thyrotoxicosis.

99m Tc-Sestamibi Thyroid Scintigraphy in Amiodarone-Induced Thyrotoxicosis : Functional Imaging-Histopathologic Correlation.

ABSTRACT: 99m Tc-sestamibi thyroid scintigraphy (STS) can aid in differentiating between types 1 and 2 amiodarone-induced thyrotoxicosis (AIT). We present a consecutive case series of 4 men (aged 56-75 years) in whom both 99m Tc-STS and thyroid histology were consistent with a diagnosis of type 2 AIT, representing the first reported histopathologic correlation for this diagnostic test. Median amiodarone treatment duration was 26 months (range, 10-39 months), and amiodarone was discontinued a median of 3 months preoperatively (range, 2-4 months) in all 4 cases. 99m Tc-STS is a promising functional imaging modality, which has the potential to aid clinicians in the diagnostic workup and treatment of AIT.

Functional and molecular thyroid imaging.

Nuclear medicine methods were introduced in the 1940s for thyroid disease diagnosis and therapy. They is still a crucial part of thyroid nodules work-up. Thyroid imaging with iodine or iodine-analog isotopes is widely employed in patients with thyrotoxicosis and remains the only examination able to prove the presence of autonomously functioning thyroid tissue, which excludes malignancy with a high probability. In addition, technetium-99m-methoxyisobutylisonitrile ([99mTc]Tc-MIBI) scintigraphy and positron emission tomography/computed tomography (PET/CT) with 18F-fluoro-2-deoxy-d-glucose ([18F]FDG) are able to avoid unnecessary surgical procedures for cytologically inconclusive thyroid nodules, as confirmed by meta-analysis and cost-effectiveness studies. All considered thyroid molecular imaging allows functional characterization of different thyroid diseases, even before clinical symptoms become manifest, and remains integral to the management of such conditions. This paper summarizes main concepts of thyroid scintigraphy and its clinical use. In addition, it elaborates development of thyroid scintigraphy, as well as thyroid molecular imaging in patients with thyroid nodules and thyrotoxicosis.

Evaluation of the role of thyroid scintigraphy in the differential diagnosis of thyrotoxicosis.

OBJECTIVE: A differential diagnosis of thyrotoxicosis is crucial as the treatment of the main causes of this condition can vary significantly. Recently published diagnostic guidelines on thyrotoxicosis embrace the presence of thyrotropin receptor (TSH-R) antibodies (TRAb) as the primary and most important diagnostic step. The application of diagnostic algorithms to aid in the treatment of hyperthyroidism supports using thyroid radionuclide scintigraphy (TRSt) in baffling clinical scenarios, when TRAb are absent or when third-generation TRAb are not available. First-generation TRAb measurement may have limitations. Consequently, patients with thyrotoxicosis and first-generation TRAb results may be misdiagnosed and consequently improperly treated. Our purpose was to compare first-generation TRAb values to TRSt in the differential diagnosis of hyperthyroidism. METHODS: We conducted a retrospective study of 201 untreated outpatients with overt or subclinical hyperthyroidism on whom first-generation TRAb and TRSt had been performed at the time of diagnosis. Histological specimens were analysed in patients who had previously undergone thyroid surgery at our centre. SPSS 20.0 was used in statistical analysis. RESULTS: Seventy-three out of 201 (36.3%) patients had positive TRAb. A diffuse uptake was present in 83.5% (61/73), whereas 13.7% (10/73) had a heterogeneous uptake and 2.7% (2/73) had an absent uptake. Thirty out of 91 (33%) patients with diffuse uptake were negative for positive TRAb and were diagnosed with Graves' disease. Analysis of 37 histological specimens indicated that TRSt had greater accuracy (81% vs 75.7%) and specificity (79.2% vs 57.1%) when compared to TRAb in the differential diagnosis of thyrotoxicosis. However, TRSt sensitivity was inferior to TRAb (84.6% vs 92.3%). CONCLUSIONS: Our study endorses that initial differential diagnosis of thyrotoxicosis should not be based solely on first-generation TRAb as this approach may leave nearly 20% of the patients misdiagnosed and, consequently, improperly treated. Our results underscore that thyroid scintigraphy should also be performed when only first-generation TRAb assays are available during the initial differential diagnosis of thyrotoxicosis.

Acute spontaneous suppurative thyroiditis caused by Eikenella corrodens presented with thyrotoxicosis.

Acute suppurative thyroiditis is a very rare and life-threatening endocrine emergency. Thyrotoxicosis is a rare condition accompanying acute suppurative thyroiditis. While the majority of the cases in the literature are caused by different reasons, spontaneous development is very rare. We present a patient with acute suppurative thyroiditis who presented to our clinic with thyrotoxic findings, and we compared the case to the literature. A 31-year-old male patient was admitted to our clinic with a complaint of progressive neck pain, swelling and redness on midline neck, fever, and palpitations. On physical examination, swelling, redness and tenderness were detected on the neck region that was consistent with the thyroid location. He presented with tremor on the hands, tachycardia and agitation. Thyroid function tests were compatible with thyrotoxicosis, but there were findings supporting the presence of infection in biochemistry tests. On his radiological evaluations, a heterogeneous lesion divided with small septs was observed, with consolidation areas in the left thyroid lobe. In fine needle aspiration biopsy, 2mL of purulent fluid could be aspirated due to the presence of small, separated consolidation areas. He initiated on antibiotic therapy, propranolol, steroid and symptomatic treatment. Eikenella corrodens was detected on the culture antibiogram. Antibiotic therapy was continued for 14 days due to less symptoms and better biochemical values. After treatment, the patient had normal thyroid function, had relief of fever and redness of the neck, and was followed-up. It should be kept in mind that acute suppurative thyroiditis may develop spontaneously with the findings of thyrotoxicosis, with no risk factors.

The Influence of Thyroid Hormones on Brain Structure and Function in Humans.

The pleiotropic function of thyroid hormones (TH) is mediated by an organ specific expression of thyroid hormone transporters, deiodinases and TH receptors. In a series of studies we used the model of an experimentally induced hyper- or hypothyroidism in human volunteers to delineate TH action on the brain. A battery of neuropsychological testing paradigms was employed and complemented by structural and functional multimodal neuroimaging. Experimentally induced mild thyrotoxicosis for 6 weeks was associated with changes in brain structure (determined with voxel-based morphometry), resting state functional connectivity, and task-related functional activation in a working memory paradigm. Partial withdrawal of TH replacement in patients without thyroid (subclinical hypothyroidism) likewise lead to changes on multiple functional and structural brain measures. Importantly, the series of studies reviewed here identified the cerebellum as one crucial site of action.

Acute spontaneous suppurative thyroiditis caused by Eikenella corrodens presented with thyrotoxicosis / Tireoidite supurativa espontânea aguda causada por Eikenella corrodens acompanhada de tireotoxicose

ABSTRACT Acute suppurative thyroiditis is a very rare and life-threatening endocrine emergency. Thyrotoxicosis is a rare condition accompanying acute suppurative thyroiditis. While the majority of the cases in the literature are caused by different reasons, spontaneous development is very rare. We present a patient with acute suppurative thyroiditis who presented to our clinic with thyrotoxic findings, and we compared the case to the literature. A 31-year-old male patient was admitted to our clinic with a complaint of progressive neck pain, swelling and redness on midline neck, fever, and palpitations. On physical examination, swelling, redness and tenderness were detected on the neck region that was consistent with the thyroid location. He presented with tremor on the hands, tachycardia and agitation. Thyroid function tests were compatible with thyrotoxicosis, but there were findings supporting the presence of infection in biochemistry tests. On his radiological evaluations, a heterogeneous lesion divided with small septs was observed, with consolidation areas in the left thyroid lobe. In fine needle aspiration biopsy, 2mL of purulent fluid could be aspirated due to the presence of small, separated consolidation areas. He initiated on antibiotic therapy, propranolol, steroid and symptomatic treatment. Eikenella corrodens was detected on the culture antibiogram. Antibiotic therapy was continued for 14 days due to less symptoms and better biochemical values. After treatment, the patient had normal thyroid function, had relief of fever and redness of the neck, and was followed-up. It should be kept in mind that acute suppurative thyroiditis may develop spontaneously with the findings of thyrotoxicosis, with no risk factors.

RESUMO A tireoidite supurativa aguda é uma emergência endócrina muito rara e com risco de vida. A tireotoxicose é uma doença rara, que acompanha a tireoidite supurativa aguda. A maioria dos casos descritos na literatura tem diferentes causas, mas o desenvolvimento espontâneo é muito raro. Relatamos o caso de um paciente com tireoidite supurativa aguda, que veio a nossa clínica apresentando achados tireotóxicos, e o comparamos com a literatura. Trata-se de paciente do sexo masculino, 31 anos, que foi internado em nossa clínica com queixa de dor progressiva, edema e vermelhidão na linha média do pescoço, febre e palpitações. Ao exame físico, foram observados edema, vermelhidão e sensibilidade à dor na região do pescoço, consistente com a localização da tireoide. Apresentava tremor de mãos, taquicardia e agitação. Embora os exames de função tireoidiana fossem compatíveis com tireotoxicose, houve achados que sustentavam a presença de infecção nos exames bioquímicos. Nas avaliações radiológicas, observou-se lesão heterogênea dividida por pequenos septos, com áreas de consolidação no lobo tireoidiano esquerdo. Na biópsia por aspiração por agulha fina, foi possível aspirar apenas 2mL de líquido purulento, devido à presença de pequenas áreas de consolidação separadas umas das outras. Iniciaram-se antibioticoterapia, administração de propranolol e esteroides, além de tratamento sintomático. Eikenella corrodens cresceu na cultura do antibiograma. A antibioticoterapia foi estendida por 14 dias devido à melhora nos sintomas e dos valores bioquímicos. Após o tratamento, o paciente se apresentava eutireoideo, com melhora na febre e na vermelhidão no pescoço, sendo então acompanhado. Deve-se ter em mente que a tireoidite supurativa aguda pode se desenvolver espontaneamente com achados de tireotoxicose, sem nenhum fator de risco.

A Case of Marine-Lenhart Syndrome with Predominance of Plummer Disease.

A 74-year-old woman with a left neck mass and thyrotoxicosis was referred to our hospital, and was later diagnosed with Marine-Lenhart syndrome based on positivity for thyroid autoantibodies, ultrasonographically evident left lobe thyroid nodule with increased blood flow, and scintigraphically identified not only increased tumor-like accumulation but also diffused uptake. Disease control was difficult despite administration of antithyroid drugs, so subtotal thyroidectomy was performed. No hyperplastic changes or histopathological findings characteristic of Graves disease were evident on histopathology, so Plummer disease was considered to be dominant. In case of hot in low type which showed higher uptake in the nodule and lower uptake in the extranodular part on scintigraphy, there is a possibility of relapse in drug treatment.

Mean peak systolic velocity of superior thyroid artery for the differential diagnosis of thyrotoxicosis: a diagnostic meta-analysis.

BACKGROUND: Thyrotoxicosis is often caused by destructive thyroiditis (DT) or Graves' disease (GD), and a prompt and accurate differential diagnosis for thyrotoxicosis is needed as management strategy differs. A meta-analysis of published literature was performed to evaluate the diagnostic accuracy for differentiating GD from DT patients by the measurement of mean peak systolic velocity of superior thyroid artery (STA-PSV) using ultrasonography. METHODS: The databases of Embase, Pubmed, Cochrane, Web of Science, Wanfang, and CNKI were retrieved without time limit to identify eligible studies. The statistical information and scientific quality were assessed and classified. The data were analyzed using Stata12.0 software. RESULTS: A total of 11 studies with 1052 cases only from Asia were included. Meta-analysis results showed the pooled sensitivity and pooled specificity of STA-PSV by ultrasonography were 0.86 (95% CI, 0.80-0.90) and 0.93 (95% CI, 0.86-0.97) in distinguishing GD from DT, respectively, with the AUC of 0.94 (95% CI, 0.92-0.96) . CONCLUSION: STA-PSV by ultrasonography is a useful diagnostic method in differentiating GD from DT. More studies from other countries are needed to further evaluate the accuracy of STA-PSV for the differential diagnosis of thyrotoxicosis.

Acute Right Ventricular Heart Failure: An Uncommon Case of Thyrotoxicosis.

Right ventricular failure can be secondary to right ventricular ischemia, pulmonary or tricuspid valvular disease, myocardial shunts, cardiomyopathy, acute and chronic pulmonary hypertension, myocarditis and pericardial disease and it generally carries a poor prognosis. Thyrotoxicosis is a clinical state resulting from high thyroid hormone action in tissues generally due to high thyroid hormone levels. The association between severe hyperthyroidism and high-output heart failure is well-known. Less widespread is the concept that hyperthyroid patients, irrespective of coexisting diseases and through mechanisms not fully elucidated, are at higher risk for pulmonary hypertension and right heart failure, both reversible with the achievement of euthyroidism and associated with a good prognosis. We describe the case of a 44-year-old woman with right ventricular failure and moderate pulmonary hypertension in the setting of thyrotoxicosis, which resolved rapidly after antithyroid treatment. The potential mechanisms underlying this condition will also be discussed.

Amiodarone-Induced Thyrotoxicosis: Differential Diagnosis Using 99mTc-SestaMIBI and Target-to-Background Ratio (TBR).

PURPOSE OF THE REPORT: Distinguishing between amiodarone-induced thyrotoxicosis (AIT) caused by excessive hormone synthesis (AIT-1) or by a destructive process (AIT-2) has important therapeutic implications, but is still difficult and debated. Tc-sestaMIBI thyroid scintigraphy (99m-STS) has been proposed as a tool for classifying the two forms. MATERIAL AND METHODS: 30 AIT patients (11 females and 19 males) who underwent 99m-STS were retrospectively assessed for the present study. For each patient, a target-to-background ratio (TBR) was obtained on planar images. The TBR was then correlated with the qualitative assessment of the scans and the final clinical diagnosis. RESULTS: Considering clinical response to treatment as the gold standard for differential diagnosis, 14 cases of AIT-1, 12 of AIT-2, and 4 mixed forms were identified. 99m-STS was able to qualitatively identify all the mixed forms, while 1/14 AIT-1 and 6/12 AIT-2 cases were misdiagnosed as mixed forms. When the quantitative index (the TBR) was compared with the final clinical diagnosis, ROC curve analysis enabled us to identify an IBR of 0.482 during 99m-STS as a cut-off capable of discriminating between AIT-1 and AIT-2, with 100% specificity and 91.7% sensitivity (P < 0.0001, area under the curve: 0.982). CONCLUSIONS: Taking the TBR into consideration, 99m-STS proved a very useful tool for distinguishing AIT-1 from AIT-2, and thus offering patients appropriate treatment as of their diagnosis. This approach can avoid pointless and potentially dangerous combined overtreatments, and may speed up the return to normal thyroid function, which is crucial in AIT patients suffering from heart disease.

The Role of Radiopharmaceuticals in Amiodarone-Induced Thyroid Pathology.

BACKGROUND AND OBJECTIVE: The use of amiodarone for the treatment of ventricular and supraventricular dysrhythmias brings in organism an increased amount of iodine, interfering with thyroid function. If the treatment needs to be interrupted, iodine remains at abnormal levels for months or even years. The aim of the study was to review the literature regarding the optimal tests for early diagnostic and to analyze the role of nuclear medicine tests in the differential and correct assessment of the amiodarone-induced thyroid pathology. METHODS: We made a review of available publications in PUBMED referring the amiodaroneinduced thyroid pathology, focusing on the differential diagnosis, made by nuclear medicine tests, of hypothyroidism (AIH) and hyperthyroidism expressed as: type I amiodarone induced thyrotoxicosis (AIT I), type II amiodarone induced thyrotoxicosis (AIT II), and less frequently as a mixt form, type III amiodarone induced thyrotoxicosis (AIT III). We presented cases from the database of a tertiary center in Cluj-Napoca, Romania. RESULTS: Despite the frequent complication of thyroid function, this pathology is underestimated and diagnosed. There is a limited number of studies and clear protocols, especially in the mixed forms cases. This increase in iodine uptake interferes seriously with thyroid hormone production and release. The nuclear medicine tests are essential in the correct assessment and differential diagnosis of different forms of induced thyroid dysfunction. The destruction of the follicular cells can result in the release of excessive thyroid hormone into the circulation, with potential development of atrial fibrillation, worsening the cardiac disease, so any benefic therapeutic procedure should be known; the use of radioiodine as therapy alternative, despite the known limitations induced by blockade was clear benefic in the case presented. A special attention needs to be addressed to those patients with differentiated thyroid cancer, which will be submitted to radioiodine therapy and are under chronic therapy with amiodarone. CONCLUSION: The nuclear medicine procedures are essential in the correct assessment and differential diagnosis of different forms of induced thyroid dysfunction. The radioiodine is not recommended in AIT, due to stunning effect induced by iodine excess, but in some special, lifethreatening condition, radioiodine I-131 might be a treatment option.