New-Onset Thyroid Eye Disease After COVID-19 Infection in Patient with Graves' Disease Post-Radioactive Iodine Treatment

Introduction: Coronavirus disease 2019 (COVID-19) has been associated with dysregulation of the immune system and abnormal thyroid function. The aim of this novel case report is to inform physicians of the possibility that COVID-19 infection may precipitate thyroid eye disease (TED) in patients with Graves' Disease (GD) even after treatment with radioactive iodine (RAI). Case Description: In this report, we describe a patient with GD treated with RAI who developed TED after COVID-19 infection. The patient was initially diagnosed with GD in 2018. A thyroid uptake scan (I-123) was consistent with GD with moderately elevated uptake. She was initially managed with methimazole and atenolol and was eventually treated with RAI (16.32 millicurie I-131) in February 2021. She had post-ablative hypothyroidism managed with levothyroxine. The patient contracted COVID-19 in January 2022. In February 2022, the patient started experiencing eye irritation, dryness, protrusion of eyes, eyelid swelling, and visual disturbances. Thyroid stimulating hormone (TSH) receptor auto-antibodies (7.33 IU/L, normal < /=1.00 IU/L) and thyroid stimulating immunoglobulin (4.30 IU/L, normal < /=1.00 IU/L) were elevated. TSH was normal (2.180 mIU/L, normal 0.270 - 4.200 mIU/L) on levothyroxine 125 mcg daily. She was later diagnosed with TED. Discussion(s): GD is an autoimmune thyroid disorder related to the presence of TSH receptor-stimulating antibodies and is often associated with ocular symptoms. Activation of an autoimmune response during COVID-19 infection, may induce onset or relapse of GD. A study using the national health insurance service database in South Korea noted an increase in the incidence of subacute thyroiditis in 2020 in association with the COVID-19 pandemic. TED is usually seen in patients with GD. Radioactive iodine is widely used in the treatment of GD and has been associated with development or worsening of TED. There are published cases of TED occurring in patients with GD after receiving COVID-19 vaccine. It is thought that the inflammatory syndrome induced by the adjuvants could induce molecular mimicry, which could trigger TED. In most cases this adverse effect was transient, lasting a few months after treatment. There have been case reports of TED occurring after 3 to 21 days of COVID-19 vaccination in patients with controlled GD. Symptoms improved in 4-8 months. Development of TED in patients with GD who have been treated with RAI typically occurs soon after RAI therapy. For TED to occur in a GD patient 11 months after receiving RAI therapy is unusual. COVID-19 infection appears to have been the trigger for this patient's eye disease. This is highly unusual and has not been published to our knowledge.Copyright © 2023

Last year challenge of Nuclear Medicine: medical radioisotopes supply

Aim/Introduction: 99mTc is used in about 80% of the convencional diagnostic nuclear imaging procedures and represent yearly approximately 30 million examinations/year worldwide a year in diagnostic tests in hospitals, among others by oncology, cardiology and neurology.The production of radiopharmaceuticals for use in Nuclear Medicine has a complex system. It involves carefully calculated production schedules that take into account supply, demand and many logistical operations.The aim of this study is to show how our nuclear medicine department manage the impact of the shortly 99Mo supply chain and consequently, in the 99mTc availability and other radiopharmaceuticals produced in nuclear reactora. Material(s) and Method(s): European nuclear medicine organizations had just pay attention to how the COVID-19 pandemic might affect different parts of the 99Mo supply chain when had to dealt again faced with a new problem;the shortness 99Mo production. There are only five nuclear reactors involved in the production of 99Mo on industrial scale. These aging reactors are subject to unscheduled shutdowns and longer maintenance periods making the 99Mo supply chain vulnerable. In the last few months at our nuclear medicine department we had to reinvent ourselves so as not to completely stop carrying out the previously scheduled exams and therapies. Result(s): The use of technetium generators in Europe represents about 17% - 25% of the worldwide consumption of 99Mo, representing 30,000 exams per day and about 1.1 million doses per month. The main consequences at the IPO-Porto was;Delays in diagnosis/staging, rescheduling exams, change of surgery dates (Sentinel Ganglion and Myocardial Perfusion Cardiacs), weeks of overbooking, delay in follow-up of Glomerular Filtration Rate in pre- or post-transplant patients, postponement of 131I Therapies, Scintigraphy and Whole Body Scintigraphy in patients who were already in hypothyroidism. we had to reinvent the use of 99mTc generators, change exams appointments times, reagroup exams types by defined days and other radiopharmaceutical management tools that were not commonly used. Conclusion(s): Approximately 2/3 of scheduled exams were postponed and we had to deal with weekly and daily stock updates. Our department suggest some measures and procedures that could help with future 99Mo shortages, in order to be ready in future situations and to avoid shortness of production: the creation of a centralized European radiopharmacy system, European policies to encourage long-term investment, homogenization of marketing specifications in the Member States, solid databases of radiopharmaceuticals used/ available in Europe and encouraging cooperation between other countries outside the European Union.

Safety, Biodistribution, and Dosimetry Study of Meplazumab, a Potential COVID-19 Therapeutic Drug, with 131I-Labeling and SPECT Imaging.

Coronavirus disease 2019 (COVID-19) is a serious threat to public health and is in urgent need of specific drugs. Meplazumab, a humanized monoclonal antibody targeting CD147, was confirmed to competitively block the binding between the spike of syndrome coronavirus 2 (SARS-CoV-2) and CD147, making meplazumab a promising candidate drug for COVID-19. In this study, biodistribution and dosimetry of 131I-labeled meplazumab were performed to further evaluate its potential as a therapeutic drug for COVID-19. 131I-meplazumab was both safe and tolerant in mice and healthy volunteers. A biodistribution study was performed in normal mice, and blood samples were used for pharmacokinetic analysis. Three healthy volunteers were included and subjected to single-photon-emission computed tomography (SPECT) imaging of 131I-meplazumab within 2 weeks. The distribution in mice and humans was consistent with the in vivo distribution of CD147. Biodistribution and SPECT imaging results exhibited that the liver was the organ with the highest uptake for both mice and humans. Deiodination of 131I-meplazumab can be observed in vivo, and taking Lugol's solution can protect the thyroid gland effectively. The pharmacokinetic characteristics of 131I-meplazumab in mice and humans best fit the two-compartment model. The clearance half-life (T1/2ß) in mice and humans was 117.4 and 223.5 h, respectively. The results indicated that its pharmacokinetic properties in vivo were ideal. The effective dose calculated from healthy volunteers was 0.811 ± 0.260 mSv·MBq-1, which was twice the value calculated from mice. It was safe and feasible to perform human clinical imaging experiments using a diagnostic dose of 131I-meplazumab after thyroid closure by Lugol's solution. This study will provide more experimental basis for advancing the clinical translation of meplazumab and will be valuable in evaluating therapeutic interventions for patients with COVID-19, as well as providing a reference for clinical translation studies of other antibody drugs.

False positive finding on whole-body iodine-131 scan secondary to contaminated face mask: an uncommon peril in current COVID pandemic.

Covid-19 has changed the practice of present-day medicine. Social-distancing, hand-sanitation and use of face-mask are important measures taken against its spread. Post-thyroidectomy whole-body diagnostic I-131 scan is an important preliminary investigation for risk stratification and further management in thyroid cancer. False positive findings on diagnostic scan are not uncommon and must be evaluated to avoid unnecessary work-up and treatment. Clinical and biochemical correlation with adjunct SPCET/CT imaging may differentiate true from false-positive lesions. We report a case of unusual false positive linear neck tracer on whole-body diagnostic I-131 scan due to the use of an I-131 contaminated face mask.

Ipax-1: Phase 1/2 Study of 131i-Iodophenylalanine (131iipa) Combined with External Radiation Therapy as Treatment for Patients with Relapsed Glioblastoma

BACKGROUND: A novel therapeutic approach using molecularly targeted radiation is currently in development for patients with recurrent GBM. Many tumor types, including GBM, overexpress the L-type amino transporter 1 (LAT-1)4, which is able to internalize the small-molecule amino acid derivative, 4-L-[131I] iodo-phenylalanine (131I-IPA). In preclinical research, combining 131I-IPA with external radiation therapy (XRT) yielded addi- tive cytotoxic effects. Tumoral accumulation of 131I-IPA was confirmed in a proof-of-principle study using single doses of 2-7 GBq 131I-IPA as a monotherapy or in combination with XRT in patients with recurrent GBM. The objective of the IPAX-1 study was to evaluate the safety, tolerability, dosing schedule, and preliminary efficacy of 131I-IPA in combination with secondline radiotherapy in patients with recurrent GBM. METHOD(S): IPAX-1 is a multi-center, open-label, single-arm, dose-finding phase 1/2 study. Key inclusion criteria: 1. Confirmed histological diagnosis of GBM with evidence of first recurrence 2. History of GBM standard therapy 3. >= 6 months since end of first-line XRT 4. Pathologically increased amino acid tumor uptake shown by molecular imaging 5. Current indication for repeat radiation 6. Gross tumour volume of up to 4.8 cm diameter. Treatment: In phase 1 of the study patients received intravenous 131I-IPA at a dose level of 2 GBq administered in one of three different dosing regimens: single dose group with 2 GBq before radiation, 3 (f)-fractionated-parallel group: 3 x 0.67 GBq during XRT and 3 (f)-fractionated-sequential group: 0.67 GBq x 1 -> XRT -> 0.67 GBq x 2. XRT is delivered in 18 fractions of 2 Gy each. RESULT(S): 10 patients were randomized;one patient with Covid related death was withdrawn from analysis. Survival from start of TLX101 therapy showed mPFS2 of 4.33 M (95% -CI 4.18 - 4.48), PFS-6: 18 % and mOS2 of 15.97 M (95% -CI 2.9 - 29.1) at data lock 09/2021. Updated results will be presented at the meeting. CONCLUSION(S): There were no clinically relevant laboratory changes over time. Urinalysis, vital signs, and ECG did not show any clinically relevant changes from baseline. There were no notable differences in safety and tolerability between groups. Injections of single or fractionated doses of 131I-IPA containing a total activity of 2 GBq in combination with XRT in patients with recurrent GBM were safe and well tolerated. Survival data look promising;extension cohort will be treated in a phase II study in Linz;phase 1/2 study in first line setting is planned.

Unilateral Massive Pleural Effusion as Manifestation of Severe Hyperthyroidism

Introduction: Non-cardiogenic pleural involvement in hyperthyroidism is rare, with unilateral involvement being rarer still. We present the case of a patient with Graves’ disease (GD) with thyroid storm criteria who presented right pleural effusion compatible with exudate. Case Description: A 40-year-old female patient, with a history of hyperthyroidism for 3 years without treatment for severe rash to thiamazole on two occasions. She was admitted to the emergency room of a private clinic due to dyspnea that progressed to respiratory failure, a massive right pleural effusion was found for which they performed evacuatory thoracentesis, prescribed lugol, bisoprolol and dexamethasone, and she was transferred to our hospital with a total of 45 points on the Burch-Wartofsky’s scale, had respiratory failure and jaundice. The analysis showed: Hemogram: Leukocytes 9700, Hemoglobin: 10.8 g/dl;CRP: 0.43 mg/dl;Glucose 157 mg/dl;Creatinine: 0.29 mg/dl, TSH: < 0.004 uIU/ml, Free T4: > 7.77 ng/ml;Free T3: > 16 pg/ml, Anti-thyroperoxidase: > 1000 IU/ml;Total bilirubins: 5.52 mg/dL;Direct bilirubin: 3.79 mg/dL. COVID infection was ruled out, the analysis of the pleural fluid was compatible with exudate, an echocardiogram showed LVEF: 60% and mild pulmonary hypertension. Thyroid ultrasound revealed diffuse hypervascularized goiter;thyroid scintigraphy showed diffuse hyper-uptake goiter. Dexamethasone with lithium carbonate was indicated with gradual improvement in thyroid function tests and cholestatic pattern. Once compensated she received 20mCi of 131I. She was discharged with an improvement in her symptoms. Her X-ray and her control chest ultrasound did not show the presence of pleural effusion. Discussion: GD is a pathology that presents with a variety of symptoms and signs due to its multisystemic involvement, which can become life-threatening, such as a thyroid storm, if it is not treated properly and in a timely manner. The fact of presenting unilateral massive pleural effusion is a rare presentation of hyperthyroidism reported in other cases.