Abnormal Uptake Research Articles

Abstract 4136926: Premature Ventricular Complexes and Nonsustained Ventricular Tachycardia in Cardiac Sarcoidosis

Introduction: The prevalence and prognostic significance of PVC and NSVT in cardiac sarcoidosis (CS), especially in patients with normal or mildly decreased LV function, are not well known and were investigated in the current study. Methods: We included 192 patients with definite and probable CS with LVEF>35%, no prior history of VT/VF or sudden cardiac death, who underwent up to 48 hours of Holter monitoring. They were followed retrospectively for the composite endpoint of sustained VT/VF, advanced heart failure therapy, and all-cause mortality. We performed multivariable analysis for the association of PVC burden and NSVT with the composite endpoint. Covariates were considered if they were present in at least 95% of the study sample and were significantly associated with the composite endpoint in univariable analysis. Results: The median PVC burden in the overall population was 0.3% (IQR 0.02-2.5%) and 36 (18.8%) patients had a PVC burden ≥5%. Sixty-two (32.3%) patients had NSVT detected during monitoring. The PVC burden and prevalence of NSVT in patient subgroups are shown in Figures 1 and 2. A total of 33 (17.2%) patients experienced one of the composite endpoints at a median follow-up of 3 years. In the multivariable analysis (Figure 3), PVC burden ≥5% versus <5% (HR 3.96 [1.19, 5.97], p-value <0.01) and presence of NSVT (HR 4.55 [2.09, 9.94], p-value <0.01) were associated with the composite outcome. Conclusion: Our results suggest that a high PVC burden and the presence of NSVT carry isolated prognostic value in CS. In addition, ventricular ectopy does not appear to be an indicator of disease activity based on abnormal uptake on PET scan.

Abstract 4119267: Diagnosing An Uncommon Presentation of Cardiac Sarcoidosis with Isolated Bi-Atrial Involvement: A Case Report

Background: Sarcoidosis, a systemic granulomatous inflammatory disorder can involve various organs, including the heart but isolated bi-atrial cardiac involvement is rare. Advanced cardiac imaging especially in atypical presentations, can aid in early diagnosis. Case: A 59 year-old man with history of biopsy-proven pulmonary sarcoidosis presented with non exertional chest pain for 2 months. EKG, cardiac enzymes, and Initial echocardiogram(TTE) was unremarkable. Stress echocardiogram ruled out myocardial ischemia. CT scan noted mediastinal lymphadenopathy consistent with known sarcidosis. In absence of other explainable etiolgies for chest pain, Cardiac MRI was done and showed preserved biventricular function, subepicardial enhancement in the basal inferior, inferolateral, and anterolateral walls. The enhancement raised suspicion for CS. However, symptoms resolved spontaneously, cardiac workup paused and he was monitored conservatively with serial Echocardiogram(TTE) until onset of dyspnea 3 years later. Repeat TTE and EKG then noted newly enlarged left atrium and atrial tachycardia. Further testing with Cardiac positron emission tomographic imaging with F-18 fluorodeoxyglucose (FDG-PET CT) showed abnormal myocardial uptake in both atrial posterior walls but no ventricular involvement, indicative of isolated bi-atrial inflammation in CS. He was treated with prednisone and methotrexate. Successful symptom and inflammation resolution on FDG-PET CT occurred in 3 months Discussion: CS is rare and seen clinically in about 5% and diagnosed postmortem in 25% of sarcoidosis cases. Symptoms vary widely, with potential for severe heart complications. Left ventricle and interventricular septum are commonly involved, but isolated bi-atrial involvement is rare. Early diagnosis aided by Cardiac MRI and FDG-PET CT is crucial. Prednisone is mainstay of treatment, often combined with methotrexate. Cases of concurrent atrial CS involvement and bi-atrial fibrosis with Left ventricular hyperenhancement are documented, but this is the first known report of isolated bi-atrial hyperenhancement on FDG-PET CT for CS. This case highlights the need for symptom correlation with clinical and imaging follow-up, especially in atypical presentations.

OA02 Blood, Sweat and Steroids

Abstract Introduction This 79 year old gentleman was referred to the Rheumatology department with arthralgia, myalgia, erythema nodosum, an ESR elevated at 106 mm/h and IgA 6.45 g/L. His GP commenced him on 30 mg Prednisolone once a day for one week. His symptoms and signs improved significantly with treatment, prior to his first Rheumatology review. Case description He initially presented to his GP with pain and a skin rash in his groin which was thought to be fungal and treated as such. He then developed erythematous tender lumps on his right proximal forearm and left hand which were in keeping with erythema nodosum. He had a background history of ischaemic heart disease, hypertension, hyperlipidaemia, squamous cell carcinoma and an elevated BMI. Once the initial course of prednisolone stopped he experienced recurrence of the skin rash, in addition to night sweats, dizziness and weight loss. Inflammatory markers rose. CT scan of chest, abdomen and pelvis, done to exclude malignancy, was normal. PET CT while off steroid showed uptake in the descending aorta, not in keeping with large vessel vasculitis, and generalised bone marrow uptake consistent with an inflammatory process. Prednisolone was re-commenced. Bloods including HIV, Hepatitis, B12, CMV, EBV, Syphilis, ANA, ANCA and Cryoglobulins were normal. Skin biopsy showed non-specific inflammatory change. Bone marrow biopsy showed myeloid hyperplasia and haemophagocytosis. He required two further inpatient admissions due to shortness of breath, anaemia and skin rash, which coincided with steroid reduction. He responded to an increased dose of steroid and antibiotics. Genetic testing then identified a gene for UBA1, a pathogenic variant causing VEXAS syndrome. Clinical features were in keeping – skin lesions, sweats, elevated inflammatory markers, macrocytic anaemia and steroid responsivity. He was commenced on Tocilizumab and responded well. Bloods normalised and prednisolone was weaned. Neutropenia resulted in stopping Tocilizumab and later Anakinra and Sarilumab. Half dose once monthly Tocilizumab and low dose steroid are now successfully treating his disease. Discussion This gentleman had symptoms and signs in keeping with an auto-inflammatory condition. However, it took a number of specialties to investigate him due to blood results and imaging not naturally leading to a diagnosis. Initial differentials included sarcoid and polyarteritis nodosa. The chest and joints were not involved, serum ACE, calcium and CT Angio were normal so these were excluded. PET CT was done to ensure this was not an atypical large vessel vasculitis and the abnormal bone marrow uptake led us to discuss with haematology. At that time he had a pancytopenia with poor reticulocyte response and so haematology carried out a bone marrow biopsy. The bone marrow biopsy result showed a myeloid shift felt to be reactive and there was a degree of haemophagocytosis but he did not meet diagnostic criteria for haemophagocytic lymphohistiocytosis. Still’s disease was queried but he was not pyrexic, there was no arthritis, no hepatomegaly or splenomegaly and there was neutropenia rather than a neutrophilia. Skin biopsy, while not diagnostic, did query a vasculitic process. Therefore it was decided, despite persisting diagnostic uncertainty that he should be treated with Tocilizumb, which did allow steroid reduction. Eventually genetic testing was sent looking for periodic fevers and that is when the UBA1 gene was identified and the diagnosis of VEXAS syndrome made. Subcutaneous Tocilizumab did cause leucopenia and he suffered from recurrent infections. He had also been trialled on Anakinra and Sarilumab but both of these caused neutropenia. We have been able to switch to intravenous Tocilizumab in order to titrate the dose, and he is now on a small dose of 2 mg/kg 4 weekly which has allowed inflammation to settle without causing a drop in white cell count. Key learning points • There is little guidance on treatment of VEXAS syndrome. This gentleman has been difficult to treat due to drug side effects, and so this case raises the issue of few treatment options in VEXAS. It seems little is known about the disease and so we quickly come to a treatment conundrum when side effects prohibit the use of standard therapies. More research is required in to this condition and its management. • This case also raises the importance of working closely with other specialties. Where there is multi-system involvement, multi-disciplinary working is invaluable. It brings other perspectives and breadth of knowledge to the case, increasing the likelihood of making the correct diagnosis. • This case also reminds us of the value of genetic testing. Where it seems there is an inflammatory syndrome but results don’t seem to add up, we should put our patients forward for testing. • At the BSR case based conference I would like to hear other cases of treating VEXAS and what difficulties and wisdom my colleagues have to share. I would also like to hear if there are other treatment strategies others are aware of.

Utility of Tau PET in the diagnostic work up of neurodegenerative dementia among Indian patients

Background and objectivesTau PET is being increasingly appraised as a novel diagnostic modality for dementia work up. Given limited data among South Asians, we assessed the frequency, patterns, phenotypic associations and incremental value of positive Tau PET scans in clinically diagnosed neurodegenerative dementia. MethodsThis cross-sectional study recruited consecutive patients of Alzheimer's disease (AD) and non-AD syndromes (September 2021 to October 2022, India). Participants underwent clinical interview, cognitive assessment, MRI brain and tau PET scan ([F-18]ML-104). Visual read in a priori regions of interest was used to identify patterns of tau deposition in the brain. ResultsWe recruited 54 participants (mean age: 63.2 ± 9.2 years, 70.4 % men, 77.8 % dementia, 70.4 % early onset cases, 37.8 % APOE4+). The analysis identified abnormal tau uptake in 40/54 (74.1 %) participants; with uptake in AD signature areas in 27/40 (67.5 %) cases [cortical subtype (74.1 %), limbic (14.8 %), combined cortical/limbic (11.1 %)], and patterns not conforming to AD in 13/40 (32.5 %) cases. Tau PET substantiated the diagnosis of AD among 17/19 (89.5 %) cases with clinically diagnosed AD dementia, 8/23 (34.8 %) cases with suspected non-AD cause, and 2/12 (16.7 %) cases with mild cognitive impairment. A trend for increasing proportion of early onset cases, and worsening cognition, behavior and functional ability was seen, from ‘limbic’ to ‘combined cortical/limbic’ to ‘cortical’ subgroups. ConclusionTau PET is a useful modality to differentiate AD dementia from other neurodegenerative causes in the Indian setting where amyloid biomarkers are not widely available. Biological subtypes of AD map well onto clinical phenotypes and need study in larger cohorts.

Feature importance explanation of prosthetic valve endocarditis through machine learning via SHAP

Abstract Introduction Diagnosing prosthetic valve endocarditis poses a significant challenge in daily clinical practice. Accurately identifying these patients is vital due to its treatment implications. Clinical and imaging assessment of suspected cases yields a substantial number of interrelated variables, which can be analyzed through machine learning techniques in order to improve diagnostic accuracy. Feature ranking facilitates identification and interpretability of relevant clinical and imaging variables in this task. Purpose To utilize machine learning feature ranking and modeling in order to improve interpretable identification of patients with prosthetic valve endocarditis. Methods 89 cases defined by the endocarditis team and 173 controls were analyzed. We implemented the SHapley Additive exPlanations (SHAP) method to evaluate feature importance. 5-fold cross-validated Xgboost models were trained and independently tested with additive clinical, echocardiographic and 18F-FDG PET/CT data. Performance was evaluated through confusion matrices, F1-scores and AUCs. These were compared against conventional logistic regression of the Duke Criteria classification. Results Mean age was 59.6 ± 15.7, with 29.7% women. 14 clinical (demographic, laboratory and cultures), 2 echocardiographic, and 5 PET/CT features were included. The XGBoost model trained with all additive features demonstrated an AUC of 0.91±0.1 and outperformed simpler models as well as the Duke classification model (AUC=0.85). The clinical variables alone achieved an AUC of 0.85±0.11, while integration with echocardiography enhanced its performance to 0.90±0.04 (Fig. 1). Feature ranking demonstrated that antibiotic treatment duration, positive blood cultures, valve type, weight and CRP were the most relevant clinical variables, while the presence of vegetation or abscess, and abnormal uptake and uptake focality on PET/CT represented the most relevant imaging variables (Fig. 2). Conclusion Machine learning-based feature ranking and modeling may significantly enhance identification of patients with prosthetic valve endocarditis beyond standard clinical criteria. Feature selection offers interpretable performance in identifying these cases, model testing in clinical decision support may be warranted.Fig. 1:Comparative AUC Analysis.Fig. 2:SHAP feature importance.

Transpulmonary proteome gradients identify inflammatory pathways involved in the development of pulmonary vasculopathy in heart failure

Abstract Background Some, but not all, patients with heart failure (HF) develop pulmonary vascular disease (PVD), which contributes to poor prognosis. Mechanisms leading to PVD in HF are poorly understood. Unbiased analysis of transpulmonary gradients may identify not only markers but also mediators of PVD by identifying proteins that may be consumed or elaborated across the lungs. Purpose Examine hemodynamics and transpulmonary proteome gradients in HFrEF and controls. Methods 21 non-HF controls and 160 patients with advanced HFrEF underwent pulmonary artery (PA) catheterization with blood sampling from the PA catheter in the wedged position (02sat > 90%, indicating pulmonary venous blood) and the un-wedged position to obtain transpulmonary proteome gradients. Samples from controls and HF from the highest quartile (Q4, n=40) and lowest quartile (Q1, n=40) of pulmonary vascular resistance (PVR) were analyzed using proteomic PEA assay of 275 proteins (Olink Target 96, panels CVII, CVIII, Inflammation). Pulmonary artery concentrations ("markers") or transpulmonary fold-change gradients (i.e. putative "mediators") of normalized protein expression (NPX) were plotted against significance; Benjamini–Hochberg FDR<0.05 considered as significant. Results Patients displayed typical characteristics of HFrEF (age 56±8y, NYHA 3.0 ±0.6, 87% males, LVEF 24±9.6%), Controls had similar anthropometrics, gender and age. Comparing all HF to Con, 38 markers of HF were identified (NPX fold-change>2), including 33 up (top 5: NTproBNP, BNP, GDF15, FGF23, IL8) and 5 down. HF patients in Q1 had median PVR 1.5 (IQR: 0.3-1.7) WU and those in Q4 had PVR 5.4 (4.3-6.6) WU. Comparison of Q1 and Q4 identified 3 protein markers of high PVR in PA blood from HF: chemokine CCL3, TNFRSF13B and surfactant protein-D (PSP-D). Examination of protein gradients from HF lungs (Figure) showed significant uptake of 14 protein mediators, most of which were associated with inflammatory responses (top 5: OSM, MMP9, CCL19, BNP, TR), and release of 8 mediators (top 4: IL-6, IL33, CCL4, CXCL10). In contrast, protein gradients were negligible in controls. Patients in Q4 PVR group were characterized by the highest pulmonary uptake of OSM (Oncostatin-M), lymphatic chemokine CCL19, BNP, MMP9, and had more significant transpulmonary release of IL6 and IL33. Across all patients, OSM lung uptake was the strongest correlate of transpulmonary pressure gradient (r=-0.3, p<0.001). Conclusions Lungs of patients with HF, and particularly those with high PVR, display abnormal uptake and release of proinflammatory CC and CXC chemokines and cytokines from IL1 and IL6 family, along with increased pulmonary uptake of IL6-type cytokine Oncostatin-M, a known mediator of lung inflammation and fibrosis, that acts via gp130/JAK/STAT, suggesting a novel role in PVD due to HF.Transpulmonary proteome in HF patients

Comparison of sedation and general anesthesia protocols for 18F-FDG-PET/CT studies in dogs and cats: Musculoskeletal uptake and radiation dose to workers.

In veterinary medicine, PET/CT scans are generally performed with the patient under general anesthesia. The aim of this prospective crossover study was to compare the musculoskeletal uptake of 18F-FDG and radiation doses to workers during PET/CT studies of healthy dogs and cats between sedation and general anesthesia. Volume and maximal standard uptake values (SUVmax) values of abnormal 18F-FDG uptake in the skeletal musculature, presence of misregistration artifact, and radiation doses to workers for each PET/CT study were recorded. Sedation was associated with increased volume of 18F-FDG uptake in the musculature of the thoracic limbs (p=.01), cervical (p=.02), and thoracic (p=.03) spine. Increased volume and SUVmax of the musculature assessed altogether were associated with the lighter degree of sedation (p=.04 for both). A significant decrease in the odds of misregistration artifact was observed for anesthetized animals in comparison with sedated (OR: 0.0, 95% CI: 0.0-0.0, p=.01). Radiation doses to workers were significantly higher for sedation compared with general anesthesia (p=.01) and for the anesthesia technician compared with the nuclear medicine technologist (p=.01). Use of sedation for PET/CT studies in dogs and cats is feasible. However, it is associated with increased physiologic musculoskeletal uptake of 18F-FDG in the thoracic limbs, cervical, and thoracic spine, with increased frequency of misregistration artifact, and with increased radiation doses to workers. These limitations can be overcome by recognition of the uptake pattern and monitoring/rotation of the involved staff at institutions where a high caseload is expected.

Heterogeneous Uptake of Al 18 F-NOTA-FAPI and 18 F-FDG in Apical Aneurysm in Apical Hypertrophic Cardiomyopathy.

Apical aneurysm in apical hypertrophic cardiomyopathy (HCM) is a very rare condition in clinical practice. Some studies have reported abnormal uptake of 18 F-FDG and 18 F-FAPI in HCM, respectively. We presented a case of FAPI and FDG imaging in a patient with apical aneurysm in apical HCM, and further analyzed the discrepancy of spatial distribution pattern of these 2 radiotracers.

8477 Medullary Thyroid Carcinoma Masquerading as a Cold Nodule in a Patient With Graves' Disease

Abstract Disclosure: T. Umashree: None. K.J. Farooqui: None. A. Mithal: None. Background: Only a handful of cases of MTC have been reported in the setting of Graves’ disease. Clinical Case: A 38 year old lady presented with symptoms of significant weight loss and palpitations for past six months. Thyromegaly was present, with non tender left lobe enlargement of about 3x3 cm. On further probing it was found that her father had been operated for thyroid cancer 22 years ago, the type of which patient was not aware of. TFTs reflected a thyroxtoxic state (TSH -<0.01mIU/mL [0.34-5.6] FT4 - 3.38 ng/dL [0.58-1.64] FT3 - 8.46 pg/mL [2.6-4.2]) and TRAb was positive (8.74 IU/L [<1.22]). USG neck revealed a hypoechoic lesion of 18x18x13 mm in left lobe thyroid with internal calcifications, with multiple bilateral non-significant lymph nodes. Technetium99 (Tc99) scan showed an enlarged left lobe, with diffuse thyroid uptake at 20 minutes of 4%, and a well-defined photopenic area in left lobe, corresponding to the nodule seen on USG. FNAC of the nodule was suggestive of Hürthle cell neoplasm and patient underwent left hemithyroidectomy. Surprisingly, HPE was consistent with medullary thyroid cancer. Serum calcitonin was raised at 148 pg/mL (N<4.8 for females) and plasma free metanephrines and normetanephrine were normal. F-18 DOPA PET CT showed uptake in residual right lobe of thyroid only, no other abnormal uptake was seen. She underwent completion thyroidectomy with central compartment clearance and is now under regular follow up. Genetic analysis showed RET gene mutation of Cys634Ser, which is heterozygous for MTC. Cold nodules in Graves’ disease should be viewed with suspicion, and while PTC and FTC have been reported more commonly, MTC is extremely rare in this setting. A calcitonin washout of the FNAC may have prevented this patient from undergoing two surgeries. Moreover, Hürthle cell change can also occur in C-cells of the thyroid, not just the follicular cells. Lastly, given the history of thyroid cancer in her father, index of suspicion of MTC should have been higher in this patient. Conclusion: Cold nodules in Graves’ Disease may be malignant, and should always be examined by FNAC. Though MTC is rare, it is not unknown in Grave’s disease. Presentation: 6/3/2024

8812 Incidence And Clinical Experience Of Immune Checkpoint Inhibitors-Induced Endocrine Side Effects Among Filipino Cancer Patients: A Single-Center Retrospective Study

Abstract Disclosure: N.B. Luna: None. E. Mendoza: None. S.A. Kho: None. Incidence And Clinical Experience Of Immune Checkpoint Inhibitors-Induced Endocrine Side Effects Among Filipino Cancer Patients: A Single-Center, Retrospective Study Immune checkpoint inhibitors (ICIs) serve as immunomodulatory antibodies, which enhance the immune system and substantially improve the prognosis for patients with advanced malignancies [1]. Referral to endocrinology have been increasing because ICIs were associated with endocrine-related adverse effects including hypothyroidism, hyperthyroidism, diabetes, hypophysitis and adrenalitis. Hence, the study aimed to retrospectively determine the local prevalence and profile of Filipino patients who developed endocrinopathies during ICI therapy at the University of Santo Tomas Hospital (USTH), Manila, Philippines from 2013-2019. A single-center retrospective study of ICI-treated cancer patients with serial biochemical and/or radiologic monitoring of endocrine adverse effects was done upon approval by the Research Ethics Committee. A total of 27 subjects were included with a median age of 60 years and male predominance. Pembrolizumab consisted 93% of the ICIs given. The incidence of thyroid dysfunction was 36% (18% overt hypothyroidism, 9% subclinical hypothyroidism, and 9% subclinical hyperthyroidism). The median time at risk for development of overt hypothyroidism is 4 weeks with median TSH level of 9.05 uIU/mL from baseline level of 3.77 uIU/mL. All patients who had baseline hypothyroidism worsened with increase from baseline levothyroxine dose by 50 to 230% in order to achieve euthyroidism (p 0.037). Serial monitoring was done every 2 weeks until euthyroidism. ICIs were temporarily put on hold in 75%. Diabetes (p 0.05), renal carcinoma (p 0.001) and dose of 200mg (p 0.42) were associated to developing overt hypothyroidism. Checking of glycemic levels was not routine among non-diabetic patients. Fifteen percent of diabetic patients had worsening of control (median HbA1c 8.5% [8-9] and 23% were newly diagnosed pre-diabetes (median fasting glucose 114mg/dL [104-120]). With the available imaging results, there were no abnormal adrenal metabolic uptake on PET scan and no evidence of hypophysitis in pituitary MRI. In conclusion, overt hypothyroidism is a common occurrence during ICI therapy (18%). Worsening occurred among all patients with hypothyroidism at baseline. New-onset pre-diabetes and worsening of glycemic control were seen in 15 and 23%, respectively. Serial clinical and biochemical monitoring is important and referral to endocrinology should be made if deemed necessary. [1] L Agrawal, A Bacal, S Jain, V Singh, N Emanuele, Ma Emanuele & F Meah (2020) Immune checkpoint inhibitors and endocrine side effects, a narrative review, Postgraduate Medicine, 132:2, 206-214, DOI: 10.1080/00325481. 2019. 1709344 Presentation: 6/1/2024

6537 Recurrent Graves Thyrotoxicosis After Prolonged Radioiodine-Induced Hypothyroidism

Abstract Disclosure: H.K. Deveaux: None. A. Gundeti: None. K. Mitrollari: None. A.P. Calimag: None. T. Yasmeen: None. Radioactive iodine (I-131) ablation (RAI) is one of the effective therapies for Graves’ disease (GD). Successful treatment is indicated by sustained, irreversible hypothyroidism requiring lifelong replacement for which recurrence of disease rarely develops. Recurrent hyperthyroidism is a rare development without apparent predisposition. Here, we describe a case of recurrent thyrotoxicosis after 36 years of RAI.70-year-old female PMH atrial fibrillation (AFib) on apixaban s/p cardioversion, HTN, HFpEF, Pulmonary HTN, and Graves’ Disease s/p RAI ablation 36 years ago with RAI-induced hypothyroidism. The patient was initially on levothyroxine for post-ablative hypothyroidism and stopped taking levothyroxine around 2019. NM scintigraphy done in 2019 showed an abnormal I-123 thyroid uptake and scan with the five-hour radioiodine thyroid uptake showed mildly hyperthyroid. On the thyroid scan, there is a note of a prominent pyramidal lobe with some thyroid gland asymmetry. In 2022, the patient was admitted for new-onset AFib and was noted to have subclinical hyperthyroidism with TSH 0.157, fT4 1.4, TrAb>40, and TSI 34.8. The patient was started on methimazole, which she stopped one month later. During this admission, the patient presented secondary to a mechanical fall and was found to be in AFib with a rapid ventricular rate. Her labs were significant for TSH<0.008 fT4 4.2, TrAb >40. Methimazole was restarted with maximal doses of diltiazem and metoprolol for rate control. Thyroid ultrasound demonstrated an enlarged, heterogeneous thyroid gland with increased vascularity and multiple bilateral TR3 thyroid nodules.Hyperthyroidism affects approximately 1.2% of the population. GD involves autoantibodies activating the thyrotropin receptor, increasing synthesis and release of thyroid hormone and is for 50-60% of cases with a 5-to-10-fold preference for females. RAI ablation is preferred, being inexpensive, with a cure rate approaching 100%. The incidence of transient hypothyroidism post-RAI varies from 9-17%. Retrospective studies have observed hyperthyroidism within the first 12 months post-RAI; however, some cases have seen a resurgence as late as 22 years later. Recurrent hyperthyroidism is an uncommon occurrence with various postulated aetiologies, such as inadequate dosing/incomplete ablation with residual cells remaining viable and regenerating in the setting of increased TSIiv, Marine-Lenhart syndrome (MLS), or an unclear mechanism associated with autoimmunity in the presence of TSI. Hyperthyroidism rarely recurs in GD after successful post-ablative treatment with RAI. Our case, while an uncommon presentation and underlying aetiology yet to be determined, illustrates the importance of continued surveillance, even after successful treatment.‌ Presentation: 6/3/2024

7958 Organ Of Zuckerkandl Paragangliomas

Abstract Disclosure: L. McVicker: None. S. Egan: None. K.C. Conlon: None. J. Gibney: None. J. Feeney: None. M. Whelan: None. A. Garrahy: None. Background: The Organ of Zuckerkandl (OoZ) was first described in 1901 by an Austrian anatomist Emile Zuckerkandl as a para-aortic paraganglia located laterally to the abdominal aorta at the level of the inferior mesenteric artery. It represents the largest accumulation of extra-adrenal chromaffin cells in mammals. Paragangliomas (PGL) of the OoZ are rare entities with prior retrospective study of 371 patients with phaeochromocytoma or sympathetic PGL revealing only 21 cases of OoZ PGLs of which 14 of which (66%) had metastases at diagnosis (1). 70% of cases are in association with SDHB or less commonly, SDHD mutations (2). Clinical Case: A 48-year-old female presented with a year long history of palpitations and headache. Plasma normetanephrine level was 6340 pmol/L (lab reference 0-1180), plasma metanephrine 412 pmol/L (lab reference 0-510) and plasma 3-methoxytyramine <100 pmol/L (lab reference 0-180). CT adrenals showed normal adrenal glands. A 4.5 cm x 2.1 cm hyper-vascular retroperitoneal mass was visualised. A 68Ga-DOTATOC PET/CT showed no abnormal uptake in the area of the mass. [1]23I-MIBG scan showed increased uptake within the mass compatible with a PGL of the OoZ. Following surgery, histology confirmed PGL of the OoZ and plasma metanephrines normalised following. Genetic testing for predisposing mutation was negative. A 38-year-old male presented with sweating episodes, palpitations, and hypertension. Plasma normetanephrine level was 2,230 pmol/L (lab reference 0-1180) and plasma metanephrines 223 pmol/L (lab reference 0-520). CT adrenals showed normal adrenal glands with no other abnormalities noted. [1]23I-MIBG showed increased uptake in the region of the origin of the inferior mesenteric artery from the aorta consistent with PGL of the OoZ. The patient underwent laparoscopic resection with resultant normalisation of metanephrine levels. Histology showed a 21 mm encapsulated tumour in keeping with PGL with a PASS Score of 7. As with the first case, genetic testing for predisposing mutations returned negative. Conclusion: OoZ PGLs represent rare presentations of phaeochromocytoma-paraganglioma disease. This small case series is notable as neither case was associated with a predisposing genetic mutation, which has previously been shown to be more common in OoZ PGLs. There was also no evidence of metastasis in either case which is more commonly associated with this OoZ disease. The first case is also remarkable in terms of the tumour’s imaging characteristics. Previous studies have shown greater sensitivity using 68Ga-DOTA-Somatostatin Analogue PET/CT in comparison to [1]23I-MIBG in the detection of PGLs (3). In the first case, the tumour did not show any significant avidity on 68Ga-DOTATOC PET/CT but was avid on [1]23I-MIBG. Reference: 1. Ayala-Ramirez et al. J Clin Endocrinol Metab. 2011 2. Lodish et al. Endocr Relat Cancer. 2010 3. Carrasquillo et al. J Nuclear Medicine. 2021 Presentation: 6/2/2024

Diffuse Uptake of 68Ga-Pentixafor in the Breasts During the Ovulatory Phase in a Patient With SAPHO Syndrome.

We report a case of a woman with SAPHO syndrome who exhibited increased tracer uptake in the sternal angle on a 99mTc-MDP bone scan. This patient was enrolled in a 68Ga-pentixafor PET/CT trial for inflammatory diseases. The PET/CT showed no abnormal tracer uptake in the sternal angle. Unexpectedly, diffuse uptake of 68Ga-pentixafor was observed in both breasts, which might be due to hormonal stimulation because the woman underwent the 68Ga-pentixafor PET/CT scan during the ovulatory phase.

Histopathological Correlation of Robotic-Assisted Radical Prostatectomy Specimen with Simultaneous 68GA-PSMA PET/MRI Findings in Cases of Adenocarcinoma Prostate

Background and Aims: 68Ga-PSMA PET represents a reasonable biomarker for presence of cancer of prostate (CaP). 68Ga-PSMA PET combined with simultaneous ‘multiparametric MRI’ (mpMRI) has the potential to be used for the detection and localisation of primary prostate cancer. It is therefore essential to correlate the histopathological findings of robotic-assisted radical prostatectomy (RARP) specimens with pre-operative PSMA PET/MRI. In addition, imaging with PSMA could be useful in estimating the aggressiveness of CaP. The current study aims at the correlation of histopathologic findings of RARP specimens with pre-operative combined 68Ga-PSMA PET/MRI imaging. Materials and Methods: Specimens retrieved after RARP in 38 patients of localised CaP were synchronised with pre-operative images obtained with simultaneous 68Ga-PSMA PET/MRI. Maximum scores of individual parameters such as PI-RADS, Gleason’s score and PSMA uptake (in SUV) were taken for each sector and used for statistical analysis. Results: The positive predictive value (PPV) and negative predictive value (NPV) of simultaneous 68Ga-PSMA PET and MRI in detecting malignancy were found to be 84.23% (95% CI: 80.74%–87.18%) and 63.92% (95% CI: 57.77%–69.65%), respectively. Combining 68Ga-PSMA PET and mpMRI improves the sensitivity to 81.48% (95% CI: 76.70%–85.67%), but the specificity was found to be 68.24% (95% CI: 60.09%–75.64%). It was found that SUV max correlated with the severity of GS ( P value < .001). Conclusion: Prediction and localisation of histological malignancy in the prostate could be improved pre-operatively by adding 68Ga-PSMA PET to mpMRI imaging. The SUV of abnormal uptake of 68Ga-PSMA radiotracer is predictive of aggressiveness of tumour as reflected in the Gleason score.

Excellent RAI therapeutic response on a patient presenting skull metastasis of follicular thyroid cancer after 15 years.

Bone is the second most common site of metastasis for differentiated thyroid carcinoma (DTC). Bone metastasis (BMs) occur in about 10% of patients with DTC and is observed more often in follicular thyroid carcinoma (FTC) (7-28%) than papillary thyroid carcinoma (PTC) (1-7%). Bone metastasis is associated with unfavorable clinical outcomes mainly including skeletal-related events (SREs), such as pathologic fractures, bone pain, spinal cord compressions, and hypercalcemia, which negatively impact the quality of life of patients and reduce their life expectancy. Patients with BMs from DTC require comprehensive and multimodal treatment approaches, including radioiodine (RAI) therapy, palliative care, surgery, external beam radiotherapy, and targeted drug therapy. RAI therapy is the first-line treatment, despite being rather ineffective, especially in large BMs. The response to RAI therapy, either alone or in combination with BM focal treatment depends on iodine avidity. This study reports a rare case of metachronous skull bone metastasis from FTC in a 72-year-old female patient 15 years after initial treatment. The patient had an excellent response to RAI therapy, which resulted in the abnormal uptake disappearing. Following treatment, the patient has been disease-free for six years. This case confirms that a complete response to RAI treatment for BM depends on the degree of dedifferentiation of cancer cells, which highlights the need for long-term follow-up, especially for FTC patients.

Performance and value of 18F‑FDG PET/CT in patients with fever of unknown origin.

Fever of unknown origin (FUO) is a common clinical and diagnostic challenge. The main aim of the present study was to evaluate the diagnostic accuracy of 18F-fluorodeoxyglucose (18FDG) positron emission tomography (PET)/CT in patients who present with FUO. Overall, 105 consecutive patients (61 men and 44 women) with a mean age of 51±35 years with FUO underwent 18FDG PET/CT scans. The performance of 18FDG PET/CT in determining the etiology of FUO was assessed. According to the PET/CT results, patients were classified into four groups: Group 1, patients with true-positive results (n=51; 49%), in whom abnormal 18FDG uptake identified the final diagnosis; group 2, patients with false-positive results (n=24; 23%), in whom 18FDG uptake was not consistent with the final diagnosis; group 3, patients with true-negative results (n=10; 9.5%), in whom the 18FDG uptake was normal and no final disease was established; and group 4, patients with false-negative results (n=20; 19%), in whom 18FDG uptake was normal and disease was finally established. Of the 51 patients with true-positive PET/CT results, 51% had infections, 35% had malignancies and 14% had inflammatory processes. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 72, 29, 68, 33 and 58%, respectively. In conclusion, the present results demonstrated that 18FDG PET/CT established the final diagnosis of FUO in the majority of patients (72%). These results support the use of 18FDG PET/CT in the initial evaluation and management of patients with FUO.

The [99mTc]Tc-HMPAO-labelled white blood cell SPECT/CT as a novel criterion for infective endocarditis diagnosis

Aims: Infective endocarditis (IE) poses a significant clinical challenge, necessitating nuanced diagnostic tools for early and accurate detection. The diagnostic role of the hybrid technique of single-photon emission tomography-computed tomography with technetium-99 m-hexamethylpropyleneamine oxime–labelled leukocytes ([99mTc]Tc-HMPAO-SPECT/CT) has evolved in recent years. This single-center study assessed whether the recent inclusion in the 2023 European Society of Cardiology modified diagnostic criteria of IE (2023 ESC) of infectious lesions detected with [99mTc]Tc-HMPAO-SPECT/CT affects their diagnostic performance.Methods and results: Between 2015 and 2019, we enrolled 205 consecutive adults with suspected IE. All participants underwent [99mTc]Tc-HMPAO-SPECT/CT scans (370–740 MBq). Scans were deemed positive in the presence of intracardiac abnormal tracer uptake and/or within the cardiac implantable electronic device. Patients were prospectively followed-up for 12 ± 10 months. Local device infection (LDI) or IE was diagnosed in 75 (36.6 %) patients, while 72 (35.1 %) [99mTc]Tc-HMPAO-SPECT/CT results returned positive. Moreover, extracardiac infectious foci were detected in 25 % of [99mTc]Tc-HMPAO-SPECT/CT scans. The inclusion of both intracardiac and extracardiac lesions detected with [99mTc]Tc-HMPAO-SPECT/CT yields significantly higher sensitivity (p = 0.003) and negative predictive value (NPV) (p = 0.009).Conclusion: The inclusion of [99mTc]Tc-HMPAO-SPECT/CT into the IE diagnostic work-up improves the appropriate classification of patients. For patients with IE, the extended inclusion of lesions detected with [99mTc]Tc-HMPAO-SPECT/CT in the ESC 2023 diagnostic criteria significantly improves sensitivity and NPV while reducing potential IE misdiagnoses. This pioneering imaging modality is poised to become an integral component of clinical practice, promising to advance IE diagnosis and management.

The Diagnostic Value of Endobronchial Ultrasound-Guided Fine Needle Aspiration (EBUS-FNA) in Diagnosing FDG-PET-Avid Lymph Nodes in Extrapulmonary Malignancies.

Background and objective The accurate diagnosis of extrapulmonary malignancies with mediastinal lymphadenopathy is crucial for effective patient management. Endobronchial ultrasound-guided fine-needle aspiration(EBUS-FNA)has emerged as a valuable tool in assessingfluorodeoxyglucose (FDG)-positron emission tomography(PET)-avid lymph nodes (LNs).In this study, we aimed to evaluate the diagnostic value of EBUS-FNA in patients with mediastinal lymphadenopathy in extrapulmonary malignancies and compare its efficacy with PET-CT. Methodology Thisretrospective, cross-sectional study was conducted at Shaukat Khanum Memorial Cancer Hospital and Research Center, Lahore, from February 2018 to February 2023. It included patients with extrapulmonary malignancies with mediastinal lymphadenopathy displaying abnormal PET-CT uptake, with LN diameters ≥5 mm, excluding lung cancer cases. Data on demographics, malignancy type, LN involvement, PET-CT findings, and EBUS-FNA histopathology were collected. EBUS-FNA procedures involved a 22-gauge needle, and samples were analyzed cytologically and histologically. SPSS Statistics version 20 (IBM Corp., Armonk, NY) was used to perform the statistical analysis. Results The study analyzed a total of 216 patients. Males comprised 56.3% of the cohort, and females 43.7%. The most common malignancy was lymphoma (33.0%), followed by breast cancer (12.6%). EBUS-FNA exhibited a sensitivity of 90.9% compared to PET-CT's sensitivity of 72.7%. Lymph node morphology on EBUS showed low echogenicity and irregular borders in malignant cases. Subcarinaland right hilar were the most frequently sampled lymph nodes. The study found significant differences in lymph node characteristics between non-malignant and malignant groups, with EBUS-FNA effectively identifying malignancies. Conclusions EBUS-FNA demonstrates high sensitivity and diagnostic utility in identifying malignant lymph nodes in patients with extrapulmonary malignancies. Its effectiveness in detecting true positive cases highlights its importance as a complementary diagnostic tool to PET-CT in oncological diagnostics.

Application of 18F-fluorodeoxyglucose positron emission tomography/computed tomography imaging in recurrent anastomotic tumors after surgery in digestive tract tumors.

This study was to investigate the application value of whole-body dynamic 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) imaging in recurrent anastomotic tumors of digestive tract after gastric and esophageal cancer surgery. Postoperative patients with gastric and esophageal cancer have a high risk of tumor recurrence, and traditional imaging methods have certain limitations in early detection of recurrent tumors. Whole-body dynamic 18F-FDG PET/CT imaging, due to its high sensitivity and specificity, can provide comprehensive information on tumor metabolic activity, which is expected to improve the early diagnosis rate of postoperative recurrent tumors, and provide an important reference for clinical treatment decision-making. To investigate the clinical value of whole-body dynamic 18F-FDG PET/CT imaging in differentiating anastomotic recurrence and inflammation after the operation of upper digestive tract tumors. A retrospective analysis was performed on 53 patients with upper digestive tract tumors after operation and systemic dynamic 18F-FDG PET/CT imaging indicating abnormal FDG uptake by anastomosis, including 29 cases of gastric cancer and 24 cases of esophageal cancer. According to the follow-up results of gastroscopy and other imaging examinations before and after PET/CT examination, the patients were divided into an anastomotic recurrence group and anastomotic inflammation group. Patlak multi-parameter analysis software was used to obtain the metabolic rate (MRFDG), volume of distribution maximum (DVmax) of anastomotic lesions, and MRmean and DVmean of normal liver tissue. The lesion/background ratio (LBR) was calculated by dividing the MRFDG and DVmax of the anastomotic lesion by the MRmean and DVmean of the normal liver tissue, respectively, to obtain LBR-MRFDG and LBR-DVmax. An independent sample t test was used for statistical analysis, and a receiver operating characteristic curve was used to analyze the differential diagnostic efficacy of each parameter for anastomotic recurrence and inflammation. The dynamic 18F-FDG PET/CT imaging parameters MRFDG, DVmax, LBR-MRFDG, and LBR-DVmax of postoperative anastomotic lesions in gastric cancer and esophageal cancer showed statistically significant differences between the recurrence group and the inflammatory group (P < 0.05). The parameter LBR-MRFDG showed good diagnostic efficacy in differentiating anastomotic inflammation from recurrent lesions. In the gastric cancer group, the area under the curve (AUC) value was 0.935 (0.778, 0.993) when the threshold was 1.83, and in the esophageal cancer group, the AUC value was 1. When 86 is the threshold, the AUC value is 0.927 (0.743, 0.993). Whole-body dynamic 18F-FDG PET/CT imaging can accurately differentiate the diagnosis of postoperative anastomotic recurrence and inflammation of gastric cancer and esophageal cancer and has the potential to be an effective monitoring method for patients with upper digestive tract tumors after surgical treatment.

Challenges in the approach to a patient with aortic stenosis and cardiac amyloidosis with ATTR mutation associated with negative scintigraphy - A case report

IntroductionCardiac amyloidosis (CA) poses significant diagnostic and therapeutic challenges. In this case report, we detail a patient with CA due to a rare transthyretin (CA-TTR) mutation, manifesting with negative myocardial scintigraphy and requiring genetic testing for diagnosis. The patient also had severe aortic stenosis (AS), necessitating discussion with a heart team to determine the optimal treatment strategy. Case reportA 70-year-old male with a family history of sudden death was previously diagnosed with third-degree atrioventricular block and treated with a pacemaker. He presented with worsening exertional dyspnoea, and examination revealed a third heart sound, a systolic murmur indicative of AS and bilateral muscular atrophy in the thenar region. Transthoracic echocardiography indicated severe AS and moderate left ventricular dysfunction, with images suggesting infiltrative disease. Pyrophosphate scintigraphy revealed no abnormal cardiac tracer uptake. Cardiac magnetic resonance imaging (MRI) revealed extensive, heterogeneous, subendocardial late gadolinium enhancement in both the atria and ventricles, which was consistent with CA. Genetic testing identified the Phe84Leu mutation in the TTR gene. Following heart team discussions, the patient underwent successful transcatheter aortic valve implantation (TAVI) and remained asymptomatic in follow-up, being monitored at an outpatient clinic specializing in CA and using tafamidis. DiscussionCA-TTR can be an autosomal dominant disease with variable penetrance involving abnormal amyloid protein deposition in tissues and can often be diagnosed noninvasively via myocardial scintigraphy. However, some TTR mutations do not affect scintigraphy results, necessitating genetic testing when clinical suspicion is high, potentially avoiding endomyocardial biopsy. Moreover, AS occurs in up to 16 % of TTR amyloidosis patients, with the conditions mutually exacerbating each other. Recent consensus suggests that TAVI reduces mortality in patients with severe AS and amyloidosis. ConclusionsVarious diagnostic algorithms emphasize the use of myocardial scintigraphy for suspected CA-TTR. Genetic testing is crucial when scintigraphy results are negative, but clinical suspicion remains high, potentially circumventing invasive procedures. Compared with medical management alone, TAVI has been shown to improve quality of life and survival in patients with concurrent severe AS and CA.