bluuebunny/crossref_metadata_2025 huggingface dataset:
PSAT250 Thyroid Carcinoma – the Diagnostic Value and Management: the Single-Centre Real-World Retrospective Study 2019–2021 (Part I)
Authors: Rasa Ingvars , Pokšāne Diāna , Fokins Vladimirs Vladimirs
Published: November 2022

Background

Ultrasound imaging and fine-needle aspiration (FNA) is the mainstay in evaluating thyroid nodules. There is a substantial lack of recent data from Latvia on thyroid carcinoma.

Aim

This study aimed to determine effectiveness in a particular service medical tool called Green Corridor. We collected the data on the prevalence of thyroid carcinoma by FNA and after surgical intervention and compared both data since the malignant result in the FNA is an indication for surgery.

Methods

We provided the single-centre real-world retrospective observational study (2019–2021). We analysed patients sent to physicians along the Green Corridor with code Z03.173 (ICD-10) in Riga East Clinical University Hospital. After surgical interventions, we collected FNA data, treatment types, thyroid cancer types, comorbidities, and thyroid antibodies. The data indicated the number of malignancies cytologically, starting from Bethesda III (atypia of undetermined significance or follicular lesion of uncertain significance) and histologically. We compared the two methods. We analysed the efficiency of the Green Corridor. The statistical analysis was conducted using IBM SPSS.

Results

We manually analysed the medical records of 563 patients for three years. Thyroid cancer was confirmed in 153 patients (27.2%); women were 123 patients (80.4%). The average age was 53.5 ± 14.3 SD years. 147 patients had surgical intervention (total thyroidectomy (91.5%) or hemithyroidectomy) and confirmed thyroid cancer histologically (mainly papillary carcinomas – 82 pts (59.4%)). Four patients (2.6%) had radiation therapy, two patients (1.3%) had palliative care due to an inoperable condition. FNA results of malignancy coincided with the histological analysis in 114 patients (77%). In 84 (73.7%) patients, FNA results of malignancy types coincided with the histological analysis.

Conclusion

The fine-needle aspiration biopsy is the gold standard for malignancy diagnostic in thyroid cancer and has proven its high diagnostic value in combination with cost-effectiveness and minimal invasiveness. According to the Green Corridor, the distribution of patients has proven its effectiveness, taking into account its percentage as far as the disease is histologically confirmed.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSAT325 Unmasking the Effect of IgG4 Disease Surge on Thyroid Gland: A Case of Bilateral Sialadenitis in Patient with Past History of Graves.
Authors: Baez Karla , Madera Arelis , Shaaban Noreen
Published: November 2022

Introduction

Immunoglobulin G4-related disease is a fibrous-inflammatory disease characterized by lymphoplasmacytic tissue infiltration of IgG4 positive plasmablasts and small lymphocytes, that may be related to storiform fibrosis, obliterative phlebitis and modestly increased tissue eosinophils. This condition was recently recognized in 2013. It has unknown pathophysiology. The common characteristics shared by the different entities that make up the IgG4-related disease are: raised serum IgG4 levels, alterations in the imaging tests with neoplastic-like swelling of the affected organs, specific histopathological characteristics, and in immunostaining, as well as a good response to treatment with glucocorticoids.

Clinical Case

A 75-year-old male with a history of Grave's disease with ophthalmopathy, osteopenia, gastroesophageal reflux disease, obstructive sleep apnea, and benign prostatic hypertrophy presented to the clinic after a neck ultrasound and CT neck were ordered for investigation of bilateral "neck lumps". Neck ultrasound was evident for the heterogeneous appearance of submandibular glands and a hypoechoic nodule in the left neck with internal vascularity below the left jaw. CT neck with IV contrast showed evidence of possibly sialadenitis and lobular soft tissue thickening in the inferior aspect of the left submandibular gland measuring approximately 3.5 cm. Surgical pathology report of the left submandibular gland demonstrated a significant increase with IgG and IgG4 plasma cells and CD38 confirmed a dense plasmacytic infiltrate. IN the laboratory, IgG4 was elevated, 462 mg/dL (2-96 mg/dl)

Conclusion

As with many autoimmune diseases, it is unknown what triggers the Immunoglobulin G4-related disease. Given that the latter has just recently been diagnosed and recognized it is imperative to continue to record and develop data regarding it to better understand it. Multiple endocrine organs could be involved in the pathology of IgG4 related disease. The health care providers need to be cognizant of this condition and the wide variety of manifestations it could have. This disease can be first encountered by any medical field due to the broad spectrum of clinical findings that it could encompass.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSAT351 Thyroiditis following COVID-19 vaccination
Authors: Choksi Palak , Esfandiari Nazanene
Published: November 2022

Background

COVID-19 vaccination has resulted in several unexplained side effects. However, thyroiditis has not been commonly reported.

Clinical Case

A 46- year-old woman without notable past medical history presented with new neck tenderness that began five days after the 1st Pfizer COVID vaccine. Symptoms progressed to nightsweats, heat intolerance, palpitations, mild tremors and fever of 101 F. Her neck tenderness was 4 out of 10 with muscle stiffness and 3 lb weight loss after receiving the vaccine. She took NSAIDS for fever every 12-24 hours. She denied any compressive symptoms, visual symptoms or sleep disturbances. She had no cough, sore throat or close contact with a COVID positive individual/sick contact. RT-PCR was done for COVID-19 and was negative. There was no personal history of radiation exposure or family history of Graves’ disease. There was no prior history of drug allergies.

On examination, she was afebrile. Right thyroid gland was visible and tender to touch without overlying redness. A right thyroid nodule was appreciated without discrete margins and was not fluctuant. Left lobe was palpable without any nodules. She was tachycardic and had fine tremors on her hands. The remaining of the exam was unremarkable.

Laboratory data showed TSH 0.01 mIU/L (0.3-5.50) with elevated FT4 of 3.05 ng/dL (0.76-1.70) and FT3 of 10.5 pg/mL (1.9-3.9). CBC showed a mild anemia with normal white blood cell count. ESR was elevated. TPO antibodies, thyroglobulin antibodies and Thyroid stimulating Immunoglobulins (TSI) were unremarkable but thyroglobulin level was significantly elevated at 1132 ng/mL (0-35). Thyroid scan demonstrated thyroiditis. Neck US showed diffusely heterogenous thyroid gland with asymmetric enlargement of the right lobe and isthmus and a new right exophytic thyroid nodule measuring 0.6×1.0×1.2 cm. Vascularity was not increased. Several non-enlarged lymph nodes were noted as well.

Beta blockers was started in addition to NSAIDs. Neck tenderness resolved within 2 weeks. She received her second dose of COVID-19 vaccine as scheduled. Within 2 months of the initial presentation, thyroid functions normalized. Four months from the initial presentation, symptoms of mild hypothyroidism were noted with a TSH of 5.88. Levothyroxine 50 mcg daily was initiated. Repeat thyroid labs were normal. Follow up thyroid US showed resolution of the right exophytic thyroid nodule, and atrophic thyroid gland. She has remained on levothyroxine replacement with biochemical and clinical euthyroidism.

Conclusion

Clinicians should be aware of thyroiditis as rare side effect of COVID-19 vaccine on thyroid gland.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSAT366 Liquid L-thyroxine (L-T4) Formulation Normalizes TSH in Hypothyroid Patients Treated with Tablets L-T4
Authors: Antonelli Alessandro , Ferrari Silvia Martina , Fallahi Poupak , Elia Giusy , Ragusa Francesca , Paparo Sabrina Rosaria , Balestri Eugenia , Botrini Chiara , Patrizio Armando , Mazzi Valeria
Published: November 2022

The absorption of L-thyroxine (L-T4) can be affected by different factors, such as the manner of L-T4 assumption (during breakfast, or with food), the age of the patient, the interference with other drugs, absorption kinetics, adherence to therapy, and others. L-T4 tablets malabsorption can occur due to the increased gastric pH in patients in treatment with proton pump inhibitors (PPI; omeprazole, pantoprazole, lansoprazole) for gastritis, gastric ulcer, etc.

We enrolled 25 patients in treatment with L-T4 in the tablet formulation, and with elevated serum thyroid-stimulating hormone (TSH) levels; they were switched to the same dose of an oral liquid L-T4 preparation.

A normalization, or reduction, of circulating TSH levels occurred after the switch from L-T4 in tablet formulation to the liquid one (at the same dose). Eleven of these subjects who, for different reasons, were switched back again to assume L-T4 in tablets (with the same dosage), had a worsening of TSH levels, reaching the hypothyroid range.

Our results show that the pH alteration issue due to PPI could be overcome by the assumption of the oral L-T4 liquid formulation. Other future studies are needed to investigate liquid L-T4 formulation also in other conditions of altered L-T4 absorption.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSAT371 Thyroid Ultrasound, Biopsy and Cancer in a US Veteran Population
Authors: Arif Azka , Gosmanov Niyaz , Gosmanova Albina , Scofield Robert Hal , Limon Ahmad Abu , Cantu-Clatza Antonio , Shakir Nabeela
Published: November 2022

Background

Thyroid cancer is a common malignancy and has an increasing incidence. The most common demographic is young adult women with papillary thyroid cancer, which constitutes about 75% of the disease. The decision to perform a fine needle aspiration biopsy of a thyroid nodule is based on the ultrasound appearance of the nodule. Both the American Thyroid Association and the American College of Radiology have systems by which to grade these nodules such that the risk of malignancy is predicted and biopsy is recommended.

Methods

We reviewed the medical records of all patient undergoing evaluation of a thyroid nodule at the Oklahoma City US Department of Veterans Affairs Medical Center. We recorded results of the biopsy as well as ultrasound findings and surgical pathology.

Results

Among 162 subjects undergoing evaluation of a thyroid nodule, 81% were men and average ago was >60 years. Only 7 of the 162 had a malignancy diagnosed. Neither age, sex, nor nodule size was associated with malignancy. All with malignancy had a TiRADS score or either 4 or 5 on ultrasonic study of the thyroid, but only a minority of TiRADS 4 (3.6%) or TiRADS 5 (5.5%) had thyroid cancer. Punctate calcium was found in 6 of the 7 with thyroid cancer and was the only finding statistically associated with malignancy. No patient with a Bethesda Classification of III or IV had malignancy

Conclusion

The presently available estimates of cancer using thyroid ultrasound are based on a general population are not applicable to this older, predominantly male population. Determination of the need for biopsy and surgery for thyroid nodules should take age and sex into account.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSAT386 Thyroglossal Duct Carcinomas: Systematic Review and Meta-analysis of 550 Cases Reported in the Literature
Authors: Paparodis Rodis , Zoupas Ioannis , Jaume Juan , Livadas Sarantis , Karvounis Evangelos , Bantouna Dimitra , Imam Shanawaz
Published: November 2022

Introduction

Thyroglossal duct (TGD) carcinoma is an uncommon entity, located in the TGD remnant, and is diagnosed in patients undergoing evaluation of the neck for midline swelling, or incidentally after removal of a TGD cyst. Despite the presence of multiple publications on the topic, no systematic characterization of these tumors has been performed to date. The present study aims to characterize the tumors found patients diagnosed with TGD remnant malignancies.

Methods

We performed a systematic search for the term "Thyroglossal duct" in Pubmed, Embase and Cochrane databases on December 1, 2021 and retrieved 1229 records. We included all manuscripts containing cohorts, case reports or case series, when the manuscript or its abstract was available in English, Italian, French or Spanish language. We reviewed the demographics, the histological report of the thyroglossal duct and the thyroidectomy specimen (when this was performed) and the features of tumor aggressiveness, when these were available.

Results

We incorporated data from 366 manuscripts, comprising 1202 patients operated for TGD disease. Out of these, n=550 cancers were identified, consisting of n=475 (86.4%) Papillary thyroid carcinomas (PTC), n=8 Follicular thyroid carcinomas (FTC) (1.5%), n=5 Hürthle cell carcinomas (HCC) (0.9%), n=27 Squamous cell carcinomas (SCC) (4.9%), n=2 poorly differentiated/anaplastic thyroid carcinomas (ATC) (0.4%), n=1 Adeno-SCC (0.18%), n=1 Adenocarcinoma (0.18%), n=12 synchronous PTC/FTC (2.2%), n=1 synchronous PTC/SCC (0.18%) and n=18 of unclear histological diagnosis (4.75%). N=173/446 (38.8%) patients were males and n=273/446 (61.2%) were females; gender was not available in n=104 cases. Mean cancer size was 1.4±1.4cm (range 0.01-7.0cm); n=88/173 (50.9%) were microcarcinomas (<1cm). Distant metastasis was present in n=7 patients (1.3%). Lymph node involvement was reported in n=76/286 cases (26.6%); extrathyroidal extension was present in n=75/234 cases (32.1%); capsular invasion was present in 72/142 cases (50.7%). Adjuvant therapy with I-131 was used in n=131/550 cases (23.8%).

Conclusions

TGD remnant cancers include various tumors, with histology and features of aggressive behavior similar to what we see in thyroid cancer cases. More research is needed to enhance our understanding of the mechanisms involved in the pathogenesis and malignant behavior of these infrequently identified tumors.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
LBSUN345 Diagnostic Dilemma In A Case of Vipoma
Authors: Priyadarshini Shista
Published: November 2022

Introduction

Vasoactive intestinal polypeptide secreting tumors (VIPoma) are rare neuroendocrine tumors that have nonspecific features of watery diarrhea, hypokalemia and achlorhydria. With an incidence of 1 in a million per year, it is diagnosed based on serum VIP levels (>75pg/ml) followed by imaging studies to localize the tumor and look for metastases. We present a challenging case of VIPoma that was successfully managed with surgical exploration despite classic yet nonspecific clinical features and poor evidence on imaging.

Case Discussion

A 78-year-old Caucasian woman presented with persistent secretory diarrhea for 2 months. Past medical history was significant for intractable peptic ulcer disease and Billroth II reconstruction. Laboratory investigations showed severe hypokalemia (2.1 mmol/l), serum bicarbonate 13 and chloride 117. Blood glucose and calcium levels were within normal range. Stool studies confirmed secretory diarrhea with stool osmotic gap of 10 mOsm/kg but no growth. Serum gastrin, parathyroid hormone, chromogranin and urine 24-hour 5-hydroxy indoleacetic acid (5-HIAA) levels were within normal limits. Plasma VIP levels were elevated at 79 pg/mL. Computed tomography of the abdomen and pelvis did not show any evidence of pancreatic tumor or biliary ductal dilatation. Endoscopic ultrasound could not fully evaluate the head of pancreas but showed unremarkable liver, pancreatic body and tail. Capsule endoscopy was unremarkable as well. An octreotide scan, however, demonstrated increased activity near the head of the pancreas and abdominal aorta. As clinical picture and octreotide scan findings were consistent with VIPoma, operative exploration for possible pancreaticoduodenectomy was pursued. No evidence of palpable or occult metastatic disease was found; but intraoperative color doppler ultrasound localized two lesions less than 1 cm in size at the level of the uncinate process and ampulla. An open pancreaticoduodenectomy was performed and the existing Billroth II anatomy was modified to accommodate pancreatojejunostomy, gastrojejunostomy and choledochojejunstomy. A jejunostomy tube was placed for enteral access. At 2-month post-operative follow-up, the patient had significant improvement of his diarrhea. Radiographic resolution was noted on repeat octreotide scan 4 months following resection.

Conclusion

VIPomas are usually diagnosed by elevated VIP levels and imaging studies are used to localize the tumor for further treatment. However, this case highlights that in secretory diarrhea with elevated VIP level and no alternate diagnosis, despite negative imaging studies further exploration with octreotide scan is warranted. Surgical exploration may show the site of lesion and appropriate surgical intervention may lead to resolution of VIPoma.

Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
ODP541 Burr Under the Saddle: A Case of Sellar Plasmacytoma
Authors: Alkaissi Hussam , Kubbar Alaa , Gliwa Agnieszka
Published: November 2022

Background

Sellar and parasellar plasmacytoma is a rare tumor that often poses a diagnostic challenge as it can often be misdiagnosed as a nonfunctioning pituitary adenoma. Here we present a case of sellar plasmacytoma and point to clues helping establish the diagnosis.

Clinical case

60-year-old male presented with two weeks of worsening morning headache followed by eyelid drooping. A physical exam was notable for left-sided ptosis, mydriasis, poor pupillary light reflex, and otherwise normal eye movement in cardinal positions . Head CT revealed 33×32×30 mm sellar mass; thus endocrinology team was consulted for evaluation. Further workup revealed normal TSH, free T4, ACTH and morning cortisol, FSH, LH, and IGF-1. He had a minimal elevation of prolactin levels at 33 ng/ml after serial dilutions (reference range: 2-17.7 ng/ml). We noticed the patient had an elevated serum protein concentration of 10.6 g/dl (reference range: 6.4-8.3 g/dl) with an albumin level of 4 gm/dl with an elevated gamma gap at 6.6 g/dl, suggestive of elevated gamma globulins. Serum protein electrophoresis showed an M-spike of 3.8 g/dl, and urine was positive for Bence Jones protein. Brain MRI with and without contrast showed homogeneously enhancing mass mainly within the sphenoid sinus extending down to the clivus, isointense on T1, hyperintense on T2 with no diffusion restriction, encasing the left internal carotid artery with intact pituitary and optic chiasm. Transsphenoidal biopsy showed sheets of plasma cells. Immunohistochemistry showed lambda light chain only and negative for kappa light chain. Flow cytometry was positive for CD38, CD138, CD200, and CD56, confirming a diagnosis of plasmacytoma. Fluorescent in situ hybridization was positive for FGFR3-IGH t(4;14) translocation, indicating a higher risk. Otherwise, beta-2-microglobulin, lactate dehydrogenase, and albumin were within normal. Initial management included pulsed dexamethasone of 40 mg for four days, followed by a taper with skull base radiotherapy, a total of 3500 cGy. Ptosis and eye movement gradually improved. The patient was discharged to start bortezomib-based treatment by the oncology team.

Clinical lesson: Based on large case series, sellar plasmacytoma often presents as headache (70%), visual changes (77%), and hyperprolactinemia (38%). Imaging shows clinal invasion (74%), cavernous sinus invasion (49%), encasement of the internal carotid artery (17%) [1]. The differential diagnosis for such findings on imaging includes nonfunctioning pituitary adenoma, chordoma, and meningioma. Special attention to gamma gap, urinary, and serum protein electrophoresis can urge to perform a biopsy to prove the diagnosis of plasmacytoma and avoid delay in therapy. Reference: 1. Lee J, Kulubya E, Pressman BD, et al. Sellar, and clival plasmacytomas: case series of 5 patients with systematic review of 65 published cases. Pituitary. 2017;20(3): 381-392. doi: 10.1007/s11102-017-0799-5

Presentation: No date and time listed
OR16-2 Steroid Receptor Co-Activator Complexes Regulate Metabolic PFKFB Enzymes to Drive Therapy Resistant ER+ Breast Cancer
Authors: Benner Elizabeth , Dos Santos Camila , Hagen Kyla , Lange Carol , Ostrander Julie , Temiz Nuri , Trousdell Marygrace , Truong Thu
Published: November 2022

Recurrence of metastatic breast cancer stemming from acquired endocrine and chemotherapy resistance remains a health burden for women with luminal (ER+) breast cancer. ER+ tumor cells can remain viable but quiescent for years to decades. Contributing factors to metastatic spread include the survival and expansion of breast cancer stem cells (CSCs). Breast CSCs are poorly proliferative and frequently exist as a minority population in recurrent tumors. Our objective is to define novel signaling pathways that govern therapy resistance in ER+ breast cancer. We previously showed that cytoplasmic complexes composed of steroid receptor (SR) co-activators, PELP1 and SRC-3, modulate breast CSC expansion through upregulation of the HIF-activated metabolic target genes PFKFB3 and PFKFB4. PELP1 interacts with PFKFB proteins, and inhibition of PFKFB3 and PFKFB4 kinase activity blocks PELP1-induced tumorspheres and protein-protein interactions with SRC-3. PFKFB inhibitors in combination with ER targeted therapies blocked proliferation and tumorsphere formation in multiple models of advanced breast cancer, including paclitaxel (TaxR) and tamoxifen (TamR) resistant models and ER+ patient-derived organoids (PDxO). Chemotherapy and endocrine therapy resistant models contained increased levels of cytoplasmic PELP1, PELP1/SRC-3 complexes, and phenocopied PELP1/SRC-3/PFKFB biology and CSC behavior. To better understand CSC-mediated pathways in the context of therapy resistance, we performed RNA-seq on 3D-cultured TaxR tumorspheres to enrich for CSCs. Pathway analysis revealed that TaxR tumorspheres upregulate stem (Sox2-Oct4-Nanog), HIF, and progesterone mediated pathways. Progesterone receptor (PR) is a known contributor to CSC populations, and we observed increased PR mRNA and protein expression in TaxR cells grown as tumorspheres. Additionally, in vivo emergence of circulating tumor cell (CTC) populations was observed in ER+ TaxR mammary intraductal (MIND) xenografts. Together, our data suggest that PELP1, SRC-3, and PFKFBs cooperate to drive ER+ tumor cells that include CSCs and CTCs. Our findings are applicable to therapy resistant models, indicating that SR co-activator complexes are a key mediator of resistance in ER+ breast cancer and may cooperate with PR to promote therapy resistant CSCs. Identifying non-ER pharmacological targets offers a useful approach to blocking metastatic escape from standard of care ER/estrogen (E2)-targeted strategies to overcome endocrine and chemotherapy resistance in ER+ breast cancer.

Presentation: Sunday, June 12, 2022 11:15 a.m. - 11:30 a.m.
OR30-3 Direct and VGLL1-Mediated Gene Regulation by GRHL2 During Mesenchymal to Epithelial Transition in Breast Cancer
Authors: Audemard Eric , Boucher Jonathan , Lemieux Sebastien , Mader Sylvie , Roux Philippe , Haidar Salwa
Published: November 2022

The transcription factor (TF) GRHL2 controls normal epithelial differentiation in different tissues. It is expressed in all breast cancer subtypes except those with a mesenchymal phenotype (claudin-low subtype), where its ectopic expression leads to induction of a mesenchymal-epithelial transition (MET) (1). Here we explored the mechanisms by which GRHL2 induces MET in claudin-low breast cancer cell lines using a combination of ChIP-seq and RNAseq analyses upon modulation of GRHL2 expression in mesenchymal and epithelial cell lines. Direct DNA binding by GRHL2 was enriched in proximity of genes positively regulated in mesenchymal cell lines, which include several epithelial TFs as well as an array of epithelial genes. Biotinylation and mass spectrometry analysis of membrane proteins confirmed surfaceome remodeling via induction of membrane proteins with roles in cell-cell contacts and adhesion. Repression of mesenchymal genes was mediated in part by direct induction of miRNAs targeting mesenchymal transcription factors. In addition, GRHL2 strongly induced expression of the cofactor VGLL1, whose expression is high in the triple-negative (TNBC) basal-like subtype. VGLL1 overexpression in mesenchymal cell lines and suppression in basal-like TNBC cells confirmed its role in mediating part of GRHL2 signaling, in particular via interaction with and modulation of TEAD transcription factors. In addition, GRHL2 also interacted with VGLL1 upon its induction in mesenchymal cells, recruiting it to some of its binding motifs, suggesting a multilayered cross-talk between GRHL2 and TEAD factors. Together, our results indicate that GRHL2 acts as a master regulator in the induction of TNBC epithelial differentiation via direct upregulation of epithelial transcription factors, miRNAs and TEAD cofactor VGLL1, resulting in both upregulation of epithelial genes and suppression of mesenchymal genes.(1) Cieply B. et al., Cancer Res. 2013 Oct. 1;73 (20): 6299-309

Presentation: Tuesday, June 14, 2022 10:15 a.m. - 10:30 a.m.
PSAT275 A Rare Case of Thyroid-Stimulating Immunoglobulin-Induced Thyrotoxicosis in Poorly Differentiated Metastatic Thyroid Cancer
Authors: Berardo Jeronimo , Fogelfeld Leon A , Mihailescu Dan V , Padilla Sorto Maria E , Trepashko Donald W
Published: November 2022

We report case of a rare of hyperthyroidism secondary to functional metastatic thyroid carcinoma, which is an infrequent phenomenon that can be challenging to diagnose and treat, as low thyroid-stimulating hormone (TSH) levels can suppress the development and growth of differentiated thyroid carcinoma cells. Previous studies have reported that hyperfunctioning thyroid carcinoma may present as autonomous functioning thyroid nodules (AFTN) within the thyroid gland, or as functioning lesions in metastatic foci, which is our case. Functional thyroid carcinomas are capable of absorbing iodine, as well as synthesizing and releasing thyroxine, are often associated with follicular thyroid carcinomas. Potential mechanisms for the thyrotoxicosis include a large aggregate tumor mass, as well as the presence of thyroid-stimulating immunoglobulins (TSIs) that are able to stimulate the thyroid-stimulating hormone (TSH) receptors of the thyroid carcinoma. In this clinical case, patient presented with high titers of TSIs, and metastatic thyroid carcinoma, with persistent hyperthyroidism after thyroidectomy and with a remarkable radioactive iodine treatment response.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSAT279 Thyroid Oncocytic tissue: Presenting as metastatic thyroid carcinoma
Authors: Gannamani Gowtham , Gibbs Otto , Milazzo Eliana , Harper Jennifer , Kaczmar John , Richardson Mary , Fernandes Jyotika
Published: November 2022

Case

A 76-year-old male with status post thyroidectomy in 2017 for compressive multi-nodular goiter. Pathology reported as benign thyroid tissue with follicular hyperplasia.

In 2020, he presented with incidental finding of left neck mass on MRI. Ultrasound neck confirmed two extra-thyroidal masses left neck largest dimension of 2.9 cm. FNA reported as benign follicular cells favoring benign thyroid tissue. Surgical resection of the neck masses revealed benign thyroid tissue with focal oncocytic features and two benign lymph nodes.

In 2021, he presented with left chest mass. Biopsy reported benign thyroid tissue, no evidence of papillary cancer. PET CT confirmed hypermetabolic chest mass, multiple lytic bone lesions and pulmonary nodules. Referred to Endocrinology for further evaluation, Thyroglobulin level elevated at >4500 ng/mL (Tg Ab <1.0 IU/mL). Molecular testing of chest wall mass was positive for TERT and HRAS mutations, loss of 22q and gain of 17q on microarray consistent with changes found in thyroid cancer.

Surgical resection of the chest wall mass not feasible due to size and location. External beam radiation for cytoreduction of the sternal mass planned and radioactive iodine therapy if tumor RAI (radioactive iodine) avid. He is currently not a candidate for tyrosine kinase inhibitor (TKI) as he recently had acute coronary event. Zoledronic acid infusions initiated for bone involvement.

Discussion

Thyroid carcinomas that exhibit vascular invasion, or anaplastic dedifferentiation are readily and consistently diagnosed. However, the morphology of primary oncocytic thyroid tumors is similar to their non-oncocytic counterparts posing a huge challenge for the pathologist. This controversial and often confusing area of thyroid pathology requires careful evaluation for accurate diagnosis and management for patients with oncocytic thyroid lesions. Molecular and microarray testing should be considered when in doubt.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSAT374 Prognostic Utility of BRAF V600E Mutation as a Risk Factor for Tumor Recurrence among Filipino Patients with Papillary Thyroid Cancer
Authors: Chiu Harold Henrison , Corpuz Dianne Grace , Tonga Angelo Dela , Galarion Ma Jowina , Hernandez-Diwa Michele , Macalalad-Josue Anna Angelica , Maningat Patricia , Paragas Sahra May , Pintor Oliver
Published: November 2022

Background

Epidemiological studies have shown that Filipinos have a higher prevalence of well-differentiated thyroid cancer and a higher rate of recurrence amongst the different ethnicities. The BRAF V600E mutation has long been proposed as a potential prognostic marker in aggressive papillary thyroid cancers. In this study, we determined whether BRAF V600E mutation can be a novel risk factor for tumor recurrence in papillary thyroid cancer.

Methodology

We conducted an age and sex-matched case-control study of 14 patients for each arm using the histopathologic diagnosis of papillary thyroid cancer and with an available paraffin block as sample source. Pertinent demographic, clinical and histopathologic data were collected. The BRAF V600E mutation was detected using polymerase chain reaction following DNA extraction from the paraffin-embedded tissue blocks. Multivariate logistic regression was performed to determine the association between presence of BRAF V600E mutation with tumor recurrence at 95% confidence interval.

Results

The BRAF V600E mutation prevalence was at 32.14% (95% CI: 15.88-52.35%) for all cases; 21.43% (95% CI: 4.66-50.80%) among those with recurrence and 42.86% (95% CI: 17.66-71.14%) among those without recurrence. There was insufficient evidence to prove a significant association between BRAF V600E mutation and recurrence, OR 0.50 (95% CI: 0.08-2.34, p = 0.327).

Conclusion

Our study showed that there was a trend towards no association between BRAF V600E mutation and recurrence. However, due to the small sample size, we cannot accurately establish an association between the presence of the BRAF V600E mutation and increased recurrence rates among Filipinos diagnosed with papillary thyroid cancer. Despite the dismal results, we still opted to present the results of our study as there were many challenges encountered in the molecular diagnosis of thyroid cancer in developing countries like the Philippines. This opens the many possibilities for future studies and collaborations amongst different institutions to firmly establish the role of BRAF V600E in Filipinos with papillary thyroid cancer tumor recurrence.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSUN375 What Blindness and Paraganglioma Have in Common? A Rare Case of Paraganglioma Syndrome
Authors: Esaki Yumiko , Harbuz-Miller Inga
Published: November 2022

Background

Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors with an annual incidence in the U.S. of 500-1600 cases per year. Approximately 30-35% of PPGLs harbor germline mutations, while 35-40% are due to somatic mutations. Recent studies have identified the association between somatic mutations of the hypoxia-inducible factor 2 alpha (HIF2A) gene and a new syndrome of PPGLs associated with congenital polycythemia. Patients present with recurrent PPGLs, congenital malformation of intracranial veins, malformation of macula and retina, and type I Chiari malformations.

Case

A 44-year-old man with history of in-utero stroke, congenital blindness, polycythemia and spinal stenosis had an incidental para-aortic lesion found during workup of back pain. He experienced episodic palpitations associated with diaphoresis, headache and uncontrolled hypertension for the past eight year. There was no family history of neuroendocrine tumors. Dedicated abdominal computer tomography with contrast showed a right adrenal enhancing lesion measuring 1.4×1.2 cm and a conglomerate of heterogenous enhancing periaortic lesions measuring up to 5 cm in the mid-abdomen. Biochemical work up revealed plasma free normetanephrine of 27.5 nmol/L (0.00-0.89) and plasma free metanephrines of 0.49 nmol/L (0.00-0.49). Gallium 68 DOTATATE scan showed multiple avid retroperitoneal lesions measuring up to 4.4 cm and an avid right adrenal nodule. He underwent right adrenalectomy and para-aortic lesion resection with perio-operative alpha blockade. Pathology confirmed synchronous pheochromocytoma (1.5 cm, Ki-67< 1%, with capsular and periadrenal fat invasion) and paraganglioma (9.3 cm, Ki-67 < 1%, with lymphovascular invasion and one out of nine lymph nodes positive for metastatic disease). Post-operatively, his metanephrines normalized and a six-months positron emission tomography scan showed no evidence of disease. Genetic testing has been delayed.

Discussion

This case illustrates a rare syndrome of PPGLs, congenital blindness, and polycythemia, likely due to somatic mutations of HIF2a. HIF is an alpha/beta heterodimer. HIF2a becomes a transcription factor after dimerization with HIF2b. Any mutations that stabilize HIF protein leads to transcription of hypoxia inducible genes resulting in angiogenesis, polycythemia, and tumorigenesis. In our patient, we suspect the stroke in-utero may have been related to abnormal intracranial angiogenesis and/or polycythemia. Recognition of this syndrome and lifelong surveillance is imperative due to risk of recurrence of PPGL. Targeted therapies such as a HIF2a inhibitor have been proposed and trials are ongoing. Our patient remains disease free on radiographic and biochemical surveillance.

Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
RF03 | PMON290 Transcriptional regulation of immune-pathways by chromatin reader ZMYND8 in triple-negative breast cancer
Authors: Ramos Enrique , Swagata Adhikari , Choudhari Ramesh , Das Chandrima , Gadad Shrikanth
Published: November 2022

Zinc Finger transcription factors are crucial in modulating various cellular processes, including inflammation and immune response. Zinc Finger MYND (Myeloid, Nervy, and DEAF-1) type containing 8 (ZMYND8), a putative chromatin reader. We have observed this chromatin reader's unique role in regulating immune genes expression in triple-negative breast cancer (TNBC). TNBC is a very aggressive subtype of breast cancer. It is characterized as a heterogeneous group of tumors defined by the absence of estrogen receptor, progesterone receptor, and overexpression of the human epidermal growth factor receptor 2 gene. Ectopic expression and genetic deletion of ZMYND8 in triple-negative breast cancer cells modulated the expression of several genes implicated in immune response and cancer. Mechanistically, ZMYND8 regulates transcription by epigenetically modulating key promoters of target genes. Collectively our results elucidate a novel role for ZMYND8 in triple-negative cancer biology.

This work was supported by grants from the Cancer Prevention and Research Institute of Texas (RR170020) and the Lizanell and Colbert Coldwell Foundation to S.S.G.

Presentation: Saturday, June 11, 2022 1:54 p.m. - 1:59 p.m., Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
RF07 | PSUN384 Hepatocyte Deletion of IGF2 Prevents DNA Damage and Tumor Formation in Hepatocellular Carcinoma
Authors: Das Manasi , Ellies Lesley , Jih Lily , Kumar Deepak , Oberg Alexis , Sahoo Debashis , Sauceda Consuelo , Webster Prof Nicholas , Wu Panyisha
Published: November 2022

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide with a 18% 5-year survival rate. Mice lacking the splicing factor SRSF3 in hepatocytes (SKO mice) overexpress IGF2 and are predisposed to developing HCC with age. Loss of Igf2 in the SKO background prevented hepatic fibrosis and inflammation, and completely prevented tumor formation. This was associated with decreased proliferation, apoptosis and DNA damage, and restored DNA repair enzyme expression. Mechanistically, IGF2 treatment of HepG2 cells in vitro caused DNA damage and decreased DNA repair enzyme expression, and tumors from the SKO mice show mutational signatures consistent with double strand break and defective mismatch repair. Looking at human data, HCC patients with high IGF2 mRNA expression had worse survival compared to patients with normal IGF2 expression. The patients also showed a switch in IGF2 promoter usage that correlated with increased expression. HCC patients having high SRSF3 mRNA expression also showed poor survival as did patients with alterations in known SRSF3-dependent splicing events. The level of SRSF3 protein was decreased 6-fold in human HCC tissues compared with normal liver tissues. The results indicate that IGF2 overexpression in conjunction with reduced SRSF3 splicing activity could be a major cause of DNA damage and driver of liver cancer.

Presentation: Saturday, June 11, 2022 1:18 p.m. - 1:23 p.m., Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
PSAT024 A Case of Mild Autonomous Cortisol Secretion Managed with Active Surveillance
Authors: Thakkar Aditi , Greb Alexandra , Reikes Andrew
Published: November 2022

Mild autonomous cortisol secretion is characterized by the failure to suppress cortisol sufficiently after dexamethasone administration but without the stigmata of overt Cushing's syndrome. This condition, diagnosed in up to 50% of adrenal incidentalomas, has low overall rates of progression and mild cases can present a treatment dilemma. Here we describe one such case of cortisol excess well managed with a surveillance strategy rather than surgical intervention.

A 49-year-old female with a past medical history of hypothyroidism was evaluated in the endocrine clinic for an incidental adrenal mass. CT imaging revealed a 2.7 cm left adrenal nodule, stable in size compared to prior imaging, with features typical of benign adrenocortical adenoma. Initial 1 mg DST with 8 am cortisol of 11.7µg/dl. Late night salivary cortisol (LNSC)level was found to be elevated at 130 ng/dl (nl<100 ng/dL). At that time, 24-hour urine free cortisol (UFC) was found to be borderline at 23.98 µg/day (nl<24 µg/day). Further testing at 6 months and 1 year from initial assessment showed persistently elevated LNSC level (110 ng/dL) and stable 24-hour UFC at 24 µg/day. Morning ACTH level was 19 pg/mL. One year after initial assessment, LNSC continued to be elevated at 0.106 µg/dL (nl <0.010–0.090 µg/dL) and repeat overnight 1 mg DST with 8am cortisol was unsuppressed at 10 mcg/dL representing at least two years of autonomous, mildly elevated cortisol levels. DHEA-S was low at 13.6 µg/dl (41.2 - 243.7 µg/dL). She had no history of diabetes, hypertension, obesity, hyperlipidemia or clinical osteoporosis. Her social history was negative for tobacco or alcohol abuse. Repeated physical exams were within normal limits, and she did not have any signs of central adiposity, abdominal striae, thinning of skin or hirsutism. She continued to deny any subjective symptoms of lethargy or muscle weakness.

Given low normal range ACTH values, mildly increased midnight salivary cortisol, failure to suppress after 1 mg overnight DST with no clinical evidence of overt hypercortisolism, patient was diagnosed with mild autonomous cortisol secretion. She did not show any signs of hypertension, hyperglycemia or physical changes that would warrant concern for hypercortisolemic end organ effects. As the patient was largely asymptomatic, with stable CT imaging of left adrenal adenoma, left adrenalectomy was discussed but not recommended as patient preferred an observation surveillance strategy with laboratory evaluation every 6 months to monitor for hypercortisolemia. This case demonstrates that a surveillance strategy, rather than surgery, may be appropriate in selected cases of mild autonomous cortisol secretion from an incidentally discovered adrenocortical adenoma, especially when end organ effects of cortisol excess are clinically absent.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
OR20-1 Impact of Intra-Procedural Sedation on Outcomes of Adrenal Vein Sampling
Authors: Chee Nicholas , Chong Winston , Doery James , Fuller Peter , Lau Kenneth , Libianto Renata , Shen Jimmy , Wan Ken , Yang Jun
Published: November 2022

Background

The subtyping of primary aldosteronism (PA) requires interpretation of aldosterone and cortisol concentrations measured during adrenal vein sampling (AVS). The use of intravenous sedation during AVS is not standardized but may affect AVS outcomes.

Purpose

To characterize the impact of sedation on the outcomes of AVS, including cortisol and aldosterone concentrations, cannulation success and rates of lateralisation.

Materials and Methods

This is a retrospective cohort study based at a tertiary health centre. Consecutive patients who underwent AVS both before and after ACTH stimulation between June 2018 and July 2020 were included. AVS was performed without IV sedation in patient cohort 1 (n = 70), with sedation (midazolam and fentanyl) in cohort 2 (n = 34) and both before and after sedation in cohort 3 (n = 14). Comparisons were performed using the nonparametric (Mann Whitney U) test for continuous variables and the Chi square test for categorical variables.

Results

Overall, 118 patients (median age, 53 years; 67 men) were evaluated with no significant demographic differences between the three cohorts. Compared to cohort 1, patients in cohort 2 displayed significantly lower cortisol concentrations in the peripheral vein (median of 141 nmol/L vs 218 nmol/L), left adrenal vein (522 nmol/L vs 1284 nmol/L) and right adrenal vein (577 nmol/L vs 1578 nmol/L) in unstimulated AVS. Fewer patients were assessed to have successful right sided cannulation in cohort 2 (79% vs 93% in cohort 1, p = 0.047). In cohort 3, cortisol concentrations were markedly lower after sedation, with the decrease being more marked in the adrenal veins compared to peripheral veins, hence leading to lower selectivity indices. There were no clinically significant changes in aldosterone concentration or rates of lateralisation after sedation.

Conclusions

IV sedation reduces cortisol concentrations during unstimulated-AVS, leading to lower selectivity indices and fewer cannulations judged as successful. Importantly, radiologists are turning to point-of-care rapid cortisol tests to determine if the catheter is 'in' the adrenal vein in real-time. Adrenal vein samples collected after sedation are more likely to be considered "unsuccessful" using these semi-quantitative assays. The need for IV sedation during AVS should be carefully assessed.

Presentation: Monday, June 13, 2022 11:00 a.m. - 11:15 a.m.
OR20-6 Histopathology and Genetic Causes of Primary Aldosteronism in Young Patients
Authors: Baker Jessica , Bancos Irina , Bick Nolan , Cohen Debbie , Else Tobias , Giordano Thomas , Liu Chia-Jen , Lyden Melanie , Nanba Kazutaka , Rainey William , Reincke Martin , Udager Aaron , Wachtel Heather , Williams Tracy , Young William , Blinder Amy
Published: November 2022

Background

Primary aldosteronism (PA) is the most common cause of endocrine-related hypertension. However, due to its rare incidence in younger patients, the molecular features of young-onset PA have not been well defined. Recent advances in targeted mutation analysis have identified aldosterone-driver somatic mutations in aldosterone-producing lesions including aldosterone-producing adenomas (APAs) and aldosterone-producing nodules (APNs).

Objective

To determine the histologic and somatic mutation profile in young-onset PA.

Methods

Formalin-fixed paraffin-embedded adrenals from 73 patients with unilateral PA (53 women, 19 men, and one with unknown sex) under 35 years old were analyzed. Aldosterone synthase (CYP11B2) immunohistochemistry was used to define the histopathologic classification of the aldosterone-producing lesions based on the HISTALDO consensus as well as guide DNA capture. Somatic mutations were identified by direct Sanger sequencing or Ion Torrent-based targeted next-generation sequencing.

Results

We identified 48 APAs, 20 APNs, 2 multiple aldosterone-producing nodules (MAPNs), and 3 non-functioning adenomas (NFAs). Of the 45 APAs and 18 APNs with successful sequencing, 43 APAs (96%) and 17 (94%) APNs harbored somatic mutations. The most frequent alterations in APAs were KCNJ5 mutations (35/45, 78%), while CACNA1D mutations were the most common in APNs (8/18, 44%). The mutation prevalence for KCNJ5 mutations did not vary between men and women. In both MAPNs, multiple CYP11B2-expressing lesions shared an identical somatic KCNJ5 mutation (c.451G>A, p.G151R). No somatic mutations were detected in the 3 NFAs.

Conclusion

APAs are the most common histologic feature of unilateral young-onset PA. Somatic KCNJ5 mutations are more commonly seen in APAs in both men and women, while somatic CACNA1D mutations are frequently seen in APNs in these younger patients.

Presentation: Monday, June 13, 2022 12:15 p.m. - 12:30 p.m.