bluuebunny/crossref_metadata_2025 huggingface dataset:
SAT482 A Case of Falsely Elevated Free T4 and Free T3 Levels Caused by Human Anti Mouse Antibodies.
Authors: Romao Isabela J , Shanik Michael Howard
Published: October 2023

Disclosure: I.J. Romao: None. M.H. Shanik: None.

Introduction: When there are clinical and biochemical discrepancies with thyroid function tests immunoassay interference should be considered (1). Human anti mouse antibodies (HAMA) are antibodies found in humans that react with immunoglobulins in mice and are used as diagnostic reagents for laboratory measurements. The presence of HAMA most commonly causes a false elevation of thyroid stimulating hormone but can also increase Free T4 and Free T3 levels. Case presentation: A 31 year old woman presented for evaluation of elevated Free T4 and Free T3 levels. For several weeks she complained of feeling neck soreness and palpitations. She had a recent infection and low-grade fever. She also felt pressure behind her eyes. She had a history of anxiety and took Xanax as needed, multivitamin and probiotic. Cousin had thyroid disease. On exam her blood pressure was 138/86, heart rate 80, respiratory rate 12, weight 149 lbs., height 5’5”. Her thyroid was firm and not tender. She had a thyroid ultrasound that showed a homogenous gland with no discrete nodules. TSH was 1.3 uIU/mL (0.27-4.2), Total T4 10.4 ug/dL (4.5 – 12), Free T4 4.6 ng/dL (0.9-1.7), Total T3 1.6 ng/mL (0.8-2.0), Free T3 10.1 pg/mL (2.0-4.4). C reactive protein, erythrocyte sedimentation and interleukin 6 levels were in the normal range. Thyroid peroxidase antibodies and thyroglobulin antibodies were elevated. The differential diagnosis included thyroiditis, pituitary tumor producing thyroid stimulating hormone and thyroid hormone resistance. She did not have a thyroid uptake and scan because she had small children at home. To rule out a pituitary adenoma she had a pituitary MRI that showed a normal small pituitary gland. The test for resistance to thyroid hormone mutation analysis was negative. Over a few months she had some clinical improvement, and her thyroid function tests remained the same which would not be consistent with thyroiditis. HAMA level was checked to evaluate for immunoassay interference with thyroid function tests. The HAMA level was elevated at greater than 600 ng/mL (0-188). Free T4 by equilibrium dialysis was normal at 1.6 ng/dL (1.1 – 2.4). Conclusion: HAMA can cause falsely elevated Free T4 and Free T3 levels. It is important to suspect immunoassay interference when there are inconsistencies in the clinical presentation and thyroid function tests. Identifying the presence of elevated HAMA can prevent misdiagnosis and inappropriate patient management. 1. Favresse J, Burlacu MC, Maiter D, Gruson D. Interferences with thyroid immunoassays: Clinical implications and detection algorithm. Endocrine Reviews. 2018. Pages 830-850.

Presentation Date: Saturday, June 17, 2023
SAT498 A Challenging Case of Hypothyroidism Requiring Frequent Primary Care Visits to Achieve Euthyroidism
Authors: Kaul Sabrina , Gupta Ankur
Published: October 2023

Disclosure: S. Kaul: None. A. Gupta: None.

Introduction: We report a patient with persistent primary hypothyroidism despite multiple adjustments in thyroid medication. Clinical Case: A 67-year-old white man with multinodular goiter underwent total thyroidectomy in 2016 for abnormal thyroid nodule biopsy. Surgical pathology revealed papillary thyroid cancer with lymph node metastasis. He subsequently received radioactive iodine ablation treatment. His plasma thyroid stimulating hormone (TSH) level was noted to be 0.275 uIU/mL (normal range 0.35-4.00 uIU/mL) in January 2017 on levothyroxine 224 micrograms daily. Subsequently, his plasma TSH level continued to remain elevated with variable levels despite multiple titrations of his levothyroxine dosage, counseling, and multiple follow-up visits. Plasma TSH level went up as high as 108.140 uIU/mL (normal range changed to 0.55-4.78 uIU/mL). In January 2022, plasma TSH level normalized to 3.125 uIU/mL with high plasma free thyroxine level of 2.45 ng/dL (normal range 0.89-1.76 ng/dL), but plasma TSH level increased again to 5.190 uIU/mL in April 2022. Home care nurse was involved in monitoring of the patient taking thyroid medication daily and correctly but was unsuccessful. The patient and his son reported taking thyroid medicine daily and correctly. There was no concern for malabsorption or interference with any of his medications. The patient was subsequently asked to come to primary care clinic every week for six weeks with all his medications. He was unable to come to endocrinology clinic due to travel time being more than one hour. His repeat plasma TSH normalized to 1.010 uIU/mL. The etiology of previously high plasma TSH level was suspected due to non-compliance with taking his thyroid medication. Non-compliance was discussed in detail with the patient and his son, including life-threatening consequences of hypothyroidism. The patient verbalized understanding and was willing to comply with the recommendations. The patient was then asked to stop coming weekly to primary care clinic. Repeat plasma TSH level in October 2022 was again noted to be high at 80.723 uIU/mL. He again claimed compliance, but weekly visits to primary care clinic were resumed. In December 2022, he was noted to have low plasma TSH level of 0.232 uIU/mL. Conclusion: Once weekly visits seem impractical but might be required in a certain group of patients with persistent abnormal thyroid hormone levels where no etiology can be found.

Presentation Date: Saturday, June 17, 2023
SAT503 Acute Psychosis and Paranoia as an Initial Manifestation of Myxedema Madness
Authors: Atam Sarin , Ahmad Mobeen , McGrath Glenn Alan
Published: October 2023

Disclosure: S. Atam: None. M. Ahmad: None. G.A. McGrath: None.

Introduction: Hypothyroidism is a common disease affecting approximately 1 in 300 Americans, with autoimmunity being the most common cause in the United States. Hypothyroidism is known to present with numerous psychiatric manifestations, including depression, cognitive deficits, and rarely psychosis. We present a case of profound hypothyroidism found in a patient who presented with visual hallucinations and paranoia. Case description: The patient was a 64-year-old man with past medical history of follicular Non-Hodgkin's Lymphoma, Type 2 diabetes, hypertension, and sinus bradycardia who presented to the emergency department with three-week history of increasing agitation, insomnia and cold intolerance. He had auditory and visual hallucinations with paranoid ideations, which started a few days prior. His initial vitals were temperature: 98.2°, heart rate: 81 beats per minute, respiratory rate: 20 breaths per minute, and blood pressure: 135/88 mmHg. The patient’s initial lab work was significant for: sodium: 143 mmol/L, potassium: 3.6 mmol/L, creatinine: 1.55 mg/dL (baseline of 1.2 mg/dL), AST: 240 IU/L, ALT: 252 IU/L, INR: 1.1, ammonia: 20 mcmol/L, TSH: 51.7 uIu/ml, free t4: <0.1 ng/dL, free t3: <0.4 ng/dL, and urine drug screen positive for cannabinoids. MRI imaging of the patient’s brain was negative for any acute intracranial process. Although the absence of hypothermia made myxedema coma unlikely, both the acuity and the severity of his psychiatric symptoms in the context of profound hypothyroidism, with no other identifiable cause, collectively suggested “myxedema madness”. The patient was started on intravenous levothyroxine therapy along with quetiapine and haloperidol for agitation. Further lab work demonstrated an anti-tpo antibody of 9.0 IU/mL (< 9) along with a benign lumbar puncture (glucose: 89 mg/dL, protein: 54 mg/dL, WBC: 9/uL, RBC: 1/uL). A review of his recent medical history revealed that last summer, as part of a chemotherapy regimen for relapsed lymphoma, he had been started on Lenalidomide, which is reported to cause primary hypothyroidism in 7% of patients. His overall neurologic function improved over a two-week course, and he was subsequently discharged. Discussion: Hypothyroidism can present with a spectrum of different psychiatric manifestations. However, cases of hypothyroidism-induced psychosis are infrequent. It is reported that only 5-15% of myxedematous patients develop some form of psychosis. Treatment of this altered mental state is centered on thyroid hormone supplementation along with the administration of antipsychotic medications. Improvement in psychotic symptoms is typically seen within weeks to months after initiation of treatment. Through this case, we hope to highlight this rare presentation of hypothyroidism and current proposed treatment strategies.

Presentation Date: Saturday, June 17, 2023
SAT512 Familial Thyroid Cancer With Negative Pre-operative Genetic Screening
Authors: Yuen Alexa , Owen Randall , Saul Shira R
Published: October 2023

Disclosure: A. Yuen: None. R. Owen: None. S.R. Saul: None.

Today it is estimated that the etiology of approximately 90% of thyroid cancer cases are understood, compared to only 25% in the 1990s. However, despite the encouraging progress with oncogenetic screening panels, thyroid cancer-specific testing are not always included. We present a family with 3 generations of thyroid cancer with negative genetic screening ultimately found to have BRAF mutation post-operatively. A 62-year-old woman of Brazilian descent with a medical history of papillary thyroid cancer (PTC) status-post total thyroidectomy presented to clinic. The patient’s PTC was diagnosed 10 years prior when she presented with dysphagia and vocal changes. A thyroid ultrasound revealed a right-sided 2.3 cm solid mass and a fine needle aspiration confirmed PTC. The patient underwent a total thyroidectomy with pathology verifying a PTC with lymphovascular invasion and minimal local extrathyroidal extension as well as a 0.4 cm microcarcinoma in the left lobe. Post-operatively, she received 100 millicurie of radioactive iodine and was started on levothyroxine. Interestingly, the patient reported as strong family history of varying cancers, notably colon, breast, uterine, and thyroid. Her mother was diagnosed at 55-years-old with thyroid cancer that metastasized to her lungs and her daughter was found to have PTC at age 31-years-old. Additionally, the daughter has two teenage sons, both with multiple thyroid nodules who are currently being followed by a pediatric endocrinologist. Given this history, the patient and her daughter both completed genetic testing which was negative for the 42 known mutations associated with an increased risk of cancer, though they both were heterozygous for a mutation of uncertain clinical significance in the MSH2 gene, specifically the c.959C>G (pT320S). Although the standard genetic panel was negative, due to concern for a hereditary mutation, the patient’s thyroidectomy specimen was sent for analysis and confirmed a BRAF mutation. Subsequently, the patient’s daughter also underwent completion thyroidectomy and was found to have the BRAF mutation. This family demonstrated likely hereditary BRAF-associated PTC across 3 generations with children in the fourth generation having known thyroid nodules, generally rare in youth. Although the patient and her daughter were both tested for genetic mutations linked to cancers, neither were positive and it was only after undergoing surgery that they were found to have the BRAF mutation. Although BRAF mutations account for 45% of PTC and are the most commonly associated mutation, they are not commonly included in pre-operative screening or the standard oncogenetic screening panel. Developing a thyroid cancer specific mutation panel to screen family members of patients with thyroid cancer will be an important step in determining these individuals’ best management.

Presentation Date: Saturday, June 17, 2023
SAT522 Validating Molecular Testing As An Adjunct To Fine Needle Aspiration In Pediatric Thyroid Malignancy
Authors: Aekka Apoorva , Arva Nicoleta , Raval Mehul , Rastatter Jeffrey , Finkelstein Sydney David , Levine Jonathan , Josefson Jami
Published: October 2023

Disclosure: A. Aekka: None. N. Arva: None. M. Raval: None. J. Rastatter: None. S.D. Finkelstein: Employee; Self; Interpace Biosciences. J. Levine: Employee; Self; Interpace Biosciences. J. Josefson: None.

The standard diagnostic approach for thyroid malignancy includes evaluation of cytopathology derived from thyroid fine needle aspiration (FNA). Nearly 40% of pediatric cases have indeterminate FNA results, and there is no clear consensus regarding the management of these cases. Molecular analysis is beneficial in increasing diagnostic yield and informing treatment stratification in adults, although its use remains limited in pediatrics. This study sought to assess the validity of next-generation sequencing mutational analysis and microRNA (miRNA)-based risk classification of FNA cytopathology derived from a single-center cohort of pediatric patients. The study hypothesized that molecular analyses improve diagnostic performance of FNA for children with thyroid cancer. Interpace Diagnostics’ validated multiplatform tool comprised of ThyGeNEXT (mutational panel capturing 10 oncogene sequence variants and 38 fusions) and ThyraMIR (miRNA risk classifier including 11 miRNA markers) was utilized for this study. Multiplatform testing was performed on 27 archived FNA thyroid samples collected from patients ages 7-20 years (mean age 14.1 years, 78% female). Molecular results were compared with final surgical pathology or repeat FNA results to determine validity. Surgical pathology confirmed papillary thyroid carcinoma in 14 patients and benign pathology in 6 patients. Repeat FNA confirmed benign pathology in 2 patients. Surgical pathology or repeat FNA was unavailable for 5 cases, all of which had benign initial cytopathology. The most common mutational finding was BRAF_V600E (6/14) followed by RET-PTC fusions (3/14). MiRNA findings were as follows: 16 high-risk expression profiles, 3 low-risk expression profiles, and 8 negative profiles. The validation analysis included 22 samples that had corresponding surgical or repeat FNA results. All cases of malignancy demonstrated high-risk miRNA profiles and all benign cases demonstrated negative or low-risk miRNA profiles. Multiplatform molecular testing demonstrated 100% sensitivity, 87.5% specificity, 93.3% positive predictive value, and 100% negative predictive value in detecting malignant versus benign pathology in our population. Molecular analyses appear to be a valid adjunct to FNA in pediatric thyroid cancer evaluation. Incorporation of molecular diagnostics advances precision medicine in pediatric thyroid care and may better inform presurgical treatment stratification, mitigate risks associated with unnecessary procedures, and ultimately improve outcomes for children and adolescents with thyroid nodules.

Presentation Date: Saturday, June 17, 2023
SAT524 Relaxin: A Novel Marker for Pro-Tumoral Thyroid Cancer Microenvironment?
Authors: Kotwal Anupam , Bennett Robert G , Swanson Benjamin , Goldner Whitney , Yuil-Valdes Ana , Whiteman Nicholas , Shats Oleg
Published: October 2023

Disclosure: A. Kotwal: None. R.G. Bennett: None. B. Swanson: None. W. Goldner: None. A. Yuil-Valdes: None. N. Whiteman: None. O. Shats: None.

Background: Differentiated thyroid cancer (DTC) generally has a favorable prognosis, however, 30% have recurrence and progression hence there is a critical need to identify additional prognostic and potentially therapeutic markers. Relaxin inhibits the inflammatory macrophage type (M1) but promotes the anti-inflammatory macrophage type (M2) which is favorable for tumor growth, hence deserves to be investigated in the DTC tumor microenvironment (TME). Hypothesis: Relaxin is expressed in DTC and is associated with pro-tumoral macrophage infiltration. Methodology: A tissue microarray (TMA) with cores per specimen was created from surgical thyroid tissue from 55 adults with DTC localized to the neck. Fluorescent immunohistochemistry (FIHC) using antibodies against nucleus (DAPI), macrophage (CD68), M2 macrophage (CD163), and relaxin (RLN2) was performed on this TMA. Gene (qPCR) and protein (Western blot) expression of RLN2 and its receptor RXFP1 in thyroid cell lines were also identified. Results: The median age was 50 years (range 19-78), 73% were females, 65% were classic and 24% follicular variant of papillary thyroid cancer. 87% were AJCC stage I while the rest were stage II; 54% were ATA low risk, 31% intermediate risk and 15% high risk. Relaxin was strongly expressed in human DTC tissue and had a strong positive correlation with the abundance of CD163 (M2 macrophages) with an r2=0.55 (p<0.0001) but did not colocalize with macrophages. In vitro experiments demonstrated variable expression of relaxin and its receptor RXFP1 in human thyroid cell lines. Conclusions: Our pilot study concluded that relaxin expression and its positive correlation with pro-tumoral M2 macrophage infiltration in the TME make it a potential biomarker for the occurrence and prognosis of DTC in humans. Thyroid cell lines’ expression of relaxin and its receptor RXPF1 complement the TMA findings, hence may serve as a model for developing therapeutic options against advanced thyroid cancer.

Presentation Date: Saturday, June 17, 2023
SAT531 Thyroid Metastasis From Non-small Cell Lung Cancer: An Unusual Case Presentation
Authors: Ibrahim Eiman Y , Alvarez Ian Guillen , Hulinsky Ilja , Regelmann David , Janowiecki Christopher
Published: October 2023

Disclosure: E.Y. Ibrahim: None. I. Guillen Alvarez: None. I. Hulinsky: None. D. Regelmann: None. C. Janowiecki: None.

Background: Cases of thyroid tumors metastasizing from the lungs are rare, and their diagnosis is often challenging and can be mistaken for primary thyroid tumors or subacute thyroiditis. Thyroid function tests are typically normal and not helpful in establishing the diagnosis. Ultrasonography commonly shows focal or diffuse hypoechoic lesions. Correspondingly, heterogeneous hypodense areas with mild contrast enhancement are seen on CT scans. Clinical Case: Our patient is a 61-year-old male with a history of diabetes mellitus and 40 years tobacco use, who presented with a 1-week history of right-sided weakness and 3-weeks of dry cough. The weakness of his leg progressed to the point he could not ambulate. Initially, he was evaluated for a stroke and underwent CT imaging showing extensive lesions of the bilateral frontal, temporal, and parietal lobes. These findings were suspicious, and confirmed by MRI, to reflect multifocal metastatic lesions with vasogenic edema. Initial physical examination revealed a palpable thyroid nodule in the right lobe with bilateral cervical lymphadenopathy. CT of the neck demonstrated lymphadenopathy as well as multiple bilateral hypoechoic thyroid nodules, the largest of which measured 0.8 cm in the right thyroid lobe. TSH was 0.34 (0.48-4.17mU/L) with Free T4 at 1.39 (0.8-1.90ng/dL). The patient had denied symptoms of heat intolerance, tremor, or palpitations. A CT chest with contrast found a 3.5 cm cavitary lesion in the right upper lobe concerning for a primary lung neoplasm, as well as multiple bilateral lung nodules, mediastinal and hilar lymphadenopathy, and bilateral adrenal masses. Subsequent ultrasound-guided biopsy of the thyroid tumor revealed histologic features of a poorly differentiated non-small cell carcinoma, with features of a primary lung origin. These features were also present on a concurrent fine needle biopsy of an enlarged cervical lymph node. Immunohistochemistry staining showed the tumor was highly expressive for PDL1, focally positive for p40, pancytokeratin AE1/AE3, and negative for TTF-1 and thyroglobulinDue to the vasogenic cerebral edema, he was given dexamethasone with good response, and his weakness improved to the point that patient was able to ambulate. Treatment also included radiation therapy with subsequent pembrolizumab upon completion of radiotherapy. Conclusion: Several thyroid lesions representing metastases may go unnoticed because the physician’s attention toward lesions at other, more common sites, and detailed thyroid examination can be commonly overlooked. Patients with newly diagnosed malignancies should also be screened for thyroid involvement, including detailed physical, radiographic, and histologic examination of pathologic findings.

Presentation Date: Saturday, June 17, 2023
SAT532 A Rare Case of Thyroid Carcinoma Noted in a Patient with Thyroid Nodule Showing Prior Benign Biopsy and Prior Negative Molecular Testing
Authors: Hillhouse Melodie Mariah , Madhavan Parvathy , Woron Felicia M
Published: October 2023

Disclosure: M.M. Hillhouse: None. P. Madhavan: None. F.M. Woron: None.

Background: Molecular studies have a high sensitivity for ruling out malignancy (1). This patient was diagnosed with the follicular variant of papillary thyroid carcinoma despite negative molecular testing and benign cytology in multiple prior biopsies. Clinical Case: 31 y.o. female with a past medical history of Hashimoto's disease on levothyroxine presented for follow up of thyroid nodules. She does not have a family history of thyroid cancer or personal history of neck radiation. The patient was noted to have a right thyroid nodule around 14 years of age and this was monitored during her childhood. The nodule measured 2.3 x 0.6 cm on ultrasound in 2015. The nodule measured 2.0 x 1.6 x 1.5 cm in 2017. FNA in 2017 revealed benign cytology (Bethesda II). On ultrasound in 03/2019, the nodule measured 2.2 x 1.5 x 1.8 cm. The nodule demonstrated a greater than 20% increase in all dimensions on ultrasound images in 12/2020 to 2.9 x 2.0 x 2.6 cm. A repeat ultrasound in 04/2021 demonstrated no significant change in size. Repeat FNA performed in 07/2021 demonstrated clusters of follicular cells in flat and microfollicular groups and was interpreted as atypia of undetermined significance (Bethesda III). AFIRMA testing was benign (∼4% of malignancy. The nodule increased in size to 3.5 x 2.6 x 3.1 cm on ultrasound in 07/2022. It appeared solid and hyperechoic and was classified as TI-RADS 3. A new 0.8 cm nodule on the left lobe was also identified. Repeat FNA of the right nodule in 09/2022 demonstrated macrophages, colloid and groups of follicular cells and was classified as non-diagnostic (Bethesda I). She reported difficulty breathing in the supine position and she underwent a right hemithyroidectomy and isthmusectomy in 11/2022. Pathology results were remarkable for invasive encapsulated follicular variant of papillary thyroid carcinoma with focal angioinvasion and tumor capsular invasion. The margins were negative for tumor. The parenchyma was consistent with lymphocytic thyroiditis. Ultrasound after interval right hemithyroidectomy in 12/2022 in an outside facility demonstrated an unchanged subcentimeter left thyroid nodule and multiple bilateral anterior cervical/level 6 lymph nodes suspicious for metastatic disease given the absence of hilum. Patient is currently undergoing repeat imaging and work up for the lymphadenopathy. Conclusion: This case study highlights the importance of maintaining high clinical suspicion for thyroid malignancy in cases of increasing thyroid nodule size and compressive symptoms despite negative cytological and molecular testing. References: (1) Kloos, R. Molecular Profiling of Thyroid Nodules: Current Role for the Afirma Gene Expression Classifier on Clinical Decision Making, Mol Imaging Radionucl Ther. 2017 Feb; 26(Suppl 1): 36-49.

Presentation Date: Saturday, June 17, 2023
OR32-05 Proteogenomics-based Development For Thyroid Cancer Molecular Classifier
Authors: Kim Yoo Hyung , Wang Injae , Jung Jin Woo , Cheon Seongmin , Cho Sun Wook , Han Dohyun , Park Young Joo
Published: October 2023

Disclosure: Y. Kim: None. I. Wang: None. J. Jung: None. S. Cheon: None. S. Cho: None. D. Han: None. Y. Park: None.

BackgroundCurrent leading-edgemolecular tests of thyroid nodule/cancer were based on DNA mutation/fusionprofile, and/or the expression profiles of mRNA and miRNA. They discriminated normalthyroid nodule from thyroid cancer with high performances. However, they could notsuggest any protein markers for the discrimination, and evaluate the risk ofcancer progression. Here, we deployed proteogenomics to discriminate normalthyroid from thyroid cancer, as well as capture the risk of cancer progression. MethodmRNAsequencing data of 86 normal thyroid (NT), 125 papillary thyroid cancer (PTC), 64follicular thyroid cancer (FTC) were obtained from our previous studies. Ofthese, 62 PTC samples harbored BRAFV600E, and 24 FTC samplesharbored H/N/K RAS mutations, referred to as PTC-B and FTC-R, respectively. Freshfrozen tissues from 4 NT, 3 PTC-B, and 5 FTC-R were preparedfor tandem mass tag labeling, and followed by LC-MS/MS analysis. Differentiallyexpressed genes and differentially expressed proteins were determined betweenNT and PTC-B, as well as between NT and FTC-R, which were 86 genes and referredto as NPF (NT-PTC-FTC) genes. NPF genes were tested for their discriminativepower in our development cohort, and validated in TCGA-THPA, and new globalproteomics data including 72 FTC, and 76 PTC. Protein markerswith high discriminative performances validated with tissuemicroarray, which included formalin-fixed paraffin-embedded samples of 22 NT, 196PTC, and 76 FTC. NPF scores were calculated, and analyzed for the progressionof thyroid cancer in our development cohort and TCGA-THPA. ResultK-meansclustering using NPF genes identified 4 clusters; BRAF-like, RAS-like, Immune-rich,and NT-like subtypes. Samples with lymphoid thyroiditis were mainly involved inimmune-rich subtypes. We developed thyroid molecular classifier with NPF usingdecision tree model. The accuracy of this model to predict thyroid cancersubtypes was 0.92 in our development cohort. We validated our model with TCGA-THPAwhich predicted 97% of tumors with BRAFV600E and 84% of tumors with H/K/N RASmutation, and new global proteomics data which predicted 77.8% of FTC and 64.4%of PTC. MarkerA, MarkerB, and MarkerCshowed best discriminative performances in our classifier. In thevalidation by immunohistochemistry, MarkerAhigh- MarkerBlow-MarkerChigh indicated 70.6% of NT, MarkerAlow- MarkerBhigh-MarkerClow indicated 97.2% of PTC, and MarkerBlow-MarkerClow indicated 58.2% of FTC. Both in PTCand FTC, high NPF score was associated with intermediate to high risk based on ATArisk stratification in our development cohort and TCGA-THPA, and poorprogression-free survival in TCGA-THPA. ConclusionWedeveloped thyroid cancer molecular classifier which reflected molecularsubtypes of thyroid cancer, and their risk of progression using proteogenomics.

Presentation: Sunday, June 18, 2023
SAT402 A Multimodal Curriculum To Improve Medical Student Gender-affirming Communication Skills
Authors: Jones Robert Benson , Maskart Cori , Radway Janice M , Amaro Anastassia , Cardillo Serena
Published: October 2023

Disclosure: R.B. Jones: None. C. Maskart: None. J.M. Radway: None. A. Amaro: None. S. Cardillo: None.

Introduction: Transgender and gender-diverse (TGD) people, whose gender identities and/or expression(s) exist outside the gender binary, are marginalized in healthcare. They often meet medical providers who do not have the skills or experience to address issues relevant to TGD persons. This can lead to suboptimal care and in some situations, micro- or macroaggressions. Physicians can help create a welcoming environment for gender-diverse people by addressing them in a respectful and affirming way. Physicians and trainees, however, rarely receive formal instruction or simulated training to practice providing gender-affirming care.

Objective: The goal of the session was to give medical students an opportunity to observe, practice, and debrief medical encounters with gender-diverse patients. We collaborated with TGD standardized patients (SPs) and the standardized patient program to design a multimodal communication skills session:

- 20-minute didactic lecture reviewing health care disparities affecting gender-diverse individuals and examples of gender-affirming language

- 15-minute video encounter showing a provider misgendering a TGD SP then recovering, followed by a provider not misgendering the patient

- 45-minute small group session where students take a history for a patient beginning hormone treatment to facilitate gender transition.

Students receive feedback from the SP and preceptor. Notable design characteristics include TGD SPs involved in the curriculum and case scenario creation, piloting of the session, and recruitment of only faculty preceptors with clinical experience in gender-affirming hormone treatment (GAHT) to facilitate sessions.

Results/Conclusions: 124 students completed the curriculum. Prior to and one week after the curriculum, students completed a 5-point self-assessment survey measuring six items: pronoun use, recovery from misgendering, communication skills with TGD knowledge, ability to take a targeted history, mental health effects of GAHT, and how to assess for treatment goals, skills, and attitudes with respect to gender-diverse healthcare. 85 students completed the pre-survey and 32 students completed the post-survey. When results were dichotomized to low (1-3 on scale) and high (4-5) comfort or ability, over 50% of students who completed the post-survey changed from low to high in their self-rated ability to take a targeted history, knowledge of the mental health effects of GAHT and how to assess for treatment goals. Qualitatively, SPs thought preceptors were particularly knowledgeable and affirming in the topic. Student feedback suggested the need for smaller group sizes which will be adapted for future iterations.

Presentation: Saturday, June 17, 2023
SAT404 Achieving Both Target Testosterone And Target Estradiol Levels May Not Be Practical In All Trans Feminine Users Of Estradiol - Which To Prioritize?
Authors: Slack Daniel , Krishnamurthy Nithya , Contreras-Castro Felix , Safer Joshua David
Published: October 2023

Disclosure: D. Slack: None. N. Krishnamurthy: None. F. Contreras-Castro: None. J.D. Safer: None.

For feminizing gender affirming hormone therapy (GAHT), the Endocrine Society and WPATH SOC 8 suggest targeting testosterone (T) levels below 50 ng/dL and estradiol (E2) levels in the range of 100-200 pg/mL. However, studies have shown variability in correlation between E2 and T levels. We sought to determine how often medically treated trans feminine individuals on estradiol needed to achieve the E2 goal in order to achieve the T goal. We conducted a chart review of patients actively engaged in GAHT in the Mount Sinai Health System. Included in our analysis were all individuals who had active prescriptions for feminizing GAHT with both T and E2 levels recorded (n = 1,195). We divided the patients between those with T levels at goal < 50 ng/dL (n = 737) and those with T >= 50 ng/dL (n = 458). The mean E2 level was higher in the T < 50 ng/dL group compared to the T >= 50 ng/dL group (292 vs 101 pg/mL; p <.001). We then compared the proportions of individuals with E2 above target > 200 pg/mL (n = 279), at target 100 - 200 pg/mL (n = 296), and below target < 100 pg/mL (n = 620) in the two groups. The T < 50 ng/dL group contained a higher proportion of individuals with E2 > 200 pg/mL (33.5% vs 7%; p < .001) and E2 100 - 200 pg/mL (30% vs 16.4%; p < .001), along with a lower proportion of individuals with E2 < 100 pg/mL (36.5% vs 76.6%; p <.001). Our results indicate that those with E2 > 100 pg/mL were more likely to have a T < 50 ng/dL, but approximately one-third of the T < 50 ng/dL group was made up of individuals with E2 < 100 pg/mL. That is, nearly half (43%) of all individuals with E2 < 100 pg/mL had T levels at goal < 50 ng/dL. Would more exogenous estradiol add benefit for these people or would it simply increase VTE risk for no reason? Also, while the majority of individuals with E2 100 - 200 pg/mL (74.7%) and E2 > 200 pg/mL (88.5%) had a T < 50 ng/dL, there were still many who did not. Our findings suggest that not all trans feminine individuals on feminizing hormone therapy will achieve target levels of both T < 50 ng/dL and E2 100-200 pg/mL. It may be reasonable to expand the target T and E2 ranges to allow for more flexibility or it may be practical to focus on one goal, rather than both. Further stratification by spironolactone (or other adjunct agent) use, estradiol route of administration, and other testing (e.g. LH and FSH levels) may inform the strategy.

Presentation: Saturday, June 17, 2023
SAT407 Hematospermia In Transgender Woman Revealing Occult Endometriosis
Authors: Coleman-Belin Janet C , Reisman Tamar
Published: October 2023

Disclosure: J.C. Coleman-Belin: None. T. Reisman: None.

Background: While hematospermia (visible blood in ejaculate) is most frequently benign, etiology includes idiopathic, infection, prostate disease, iatrogenic, obstruction, systemic disorders, and (rarely) malignancy. The incidence and prevalence of hematospermia in transgender women is unknown.

Clinical Course: A 35-year-old transgender woman treated with estradiol valerate and leuprolide presents with persistent hematospermia and two years of intermittent hematuria. She does not report dysuria, urgency, frequency, or gastrointestinal symptoms and is a lifetime nonsmoker. Chlamydia, gonorrhea, and HIV tests are negative. CT scan 4/2021, cytoscopy 5/2021, and MRI prostrate 7/2022 (with and without IV contrast) were unremarkable.

Transrectal ultrasound 9/2022 reveals 17cc prostate and posterior cyst with hemorrhagic products. Two ultrasound-guided transperineal biopsy samples obtained from the cystic structure 11/2022 reveal benign prostatic tissue with a small focus of endometrial-type epithelium (positive immunostains for PAX 8 and ER in epithelium and CD10 in stroma). These findings may indicate endometriosis or a Müllerian cyst.

Discussion: The prevalence of endometrial tissue in transgender woman has not been described. Risk factors for endometriosis in AMAB* individuals are hypothesized to include prolonged estrogen exposure, cirrhosis, or chronic post-procedural inflammation1. Because transgender women are routinely treated with extended estrogen-containing regimens, it is of interest to determine if the presence of endometrial tissue is more common than previously thought. Guidelines for management of benign endometrial-type epithelium in transgender women are lacking, including whether ectopic endometrial tissue should be excised due to concern for malignant transformation2.

Conclusion: Hematospermia in transgender women on GAHT** may indicate occult Müllerian epithelial tissue growth.

*AMAB: Assigned Male at Birth **GAHT: Gender-Affirming Hormone Therapy

References: 1. Rei C, Williams T, Feloney M. Endometriosis in a Man as a Rare Source of Abdominal Pain: A Case Report and Review of the Literature. Case Rep Obstet Gynecol. 2018 Jan 31;2018:2083121. doi: 10.1155/2018/2083121. PMID: 29670782; PMCID: PMC5833878.

2. Robinson, K.A., Menias, C.O., Chen, L. et al. Understanding malignant transformation of endometriosis: imaging features with pathologic correlation. Abdom Radiol 45, 1762–1775 (2020). https://doi.org/10.1007/s00261-019-01914-7

Presentation: Saturday, June 17, 2023
FRI213 Multiple Endocrine Neoplasia Syndromes: A Rare Case With Variable Presentation
Authors: Gomez D' Aza Danelly J , Kasap Melih , Zahedi Tooraj , Zhang Fan
Published: October 2023

Disclosure: D.J. Gomez D' Aza: None. M. Kasap: None. T. Zahedi: None. F. Zhang: None.

Introduction: Multiple endocrine neoplasia (MEN) syndromes are rare autosomal dominant inherited groups of disorders characterized by the presence of two or more primary endocrine glands tumors. MEN type 1 is usually associated with neoplastic lesions of the pituitary gland, the parathyroid gland, and the pancreas. MEN type 2 typically presents with overgrowth of parathyroid, adrenal glands (pheochromocytoma), and parathyroid hyperplasia (MEN 2A), Marfanoid body habitus, or mucosal neuromas (MEN 2B). It can also manifest with non-endocrine tumors including carcinoid tumors, adrenocortical tumors, meningiomas, facial angiofibromas, collagenomas, lipomas, and germline mutations (MEN type 4). It is extremely rare for MEN type 1 syndrome to have concomitant pheochromocytoma. Case Report: We present a case of a 69 yo female with multiple comorbidities who was hospitalized for heart failure exacerbation. CT scan showed incidental findings of a 4.1 cm right adrenal nodule, a 2.1 cm left anterior mediastinum nodule, and a 1.1 cm oval pituitary mass. She had multiple episodes of hypertension urgency during the last two years. After patient recovered to her base line, workup labs revealed elevated serum Catecholamine with Metanephrine 431.1 pg/mL, Normetanephrine 466.5 pg/mL, Norepinephrine 137 pg/mL, and high PTH 258 pg/mL. Further study was normal for pituitary function tests, aldosterone, renin, cortisol, thyroid, and renal function. PET scan showed mild hypermetabolic activity in bilateral adrenal glands without any abnormal hypermetabolic activity in the chest. Thyroid Ultrasound identified a 1 cm thyroid nodule. Phenoxybenzamine was started due to concern for pheochromocytoma. Patient was monitored closely since she declined surgical intervention. Discussion: MEN syndromes have variable clinical presentation with multiple hormone excess. This patient has imaging and laboratory findings highly suggestive of MEN syndrome with pituitary adenoma, pheochromocytoma, and hyperparathyroidism. Further work up and genetic testing would be helpful to identify the mutation of MEN type 1 or type 2. Clinicians should be aware of the variable presentation of MEN syndrome, and prompt treatment is warranted to prevent life-threatening conditions.

Presentation: Friday, June 16, 2023
OR31-02 Persistence Of Gender Identity And Hormone Therapy Use In Transgender Adolescents: A Retrospective Cohort Study
Authors: Gupta Pranav , Patterson Briana Cary , Gold Sarah , Chu Lena , Yeung Howa , Goodman Michael , Tangpricha Vin
Published: October 2023

Disclosure: P. Gupta: None. B.C. Patterson: None. S. Gold: None. L. Chu: None. H. Yeung: None. M. Goodman: None. V. Tangpricha: None.

Introduction: Adolescents with gender dysphoria often seek feminizing or masculinizing hormone therapy to affirm their gender identity. While receipt of gender-affirming hormone therapy (GAHT) has been associated with improved quality of life and well-being, the incidence of discontinuation of GAHT and the reasons for discontinuation are not known. The purpose of this study was to 1) assess the discontinuation rate of GAHT, and 2) explore the reasons for GAHT discontinuation.

Methods: This was a retrospective cohort study approved by Emory University’s and Children’s Healthcare of Atlanta’s Institutional Review Board. Medical charts of transgender adolescents seen at Children’s Healthcare of Atlanta were reviewed. Patients met the inclusion criteria if they were prescribed GAHT (estradiol or testosterone) between 01/01/2016 to 01/01/2019. We defined continuation of GAHT if the participant was still taking estradiol or testosterone as of 01/01/2019. If the participant stopped taking hormonal therapy prior to 01/01/19, they were deemed to have discontinued hormonal therapy and the reason for discontinuation was collected from the chart if documented. If the reason was not documented or if the status of hormone discontinuation was not known, the participant was contacted via telephone to ascertain whether still taking GAHT or not and to ascertain the GAHT discontinuation reason if not taking GAHT as a part of phase II of the study.

Results: This study included 82 participants; 36 (43.9%) transgender girls, 45 (54.9%) transgender boys, and 1 (1.2%) non-binary adolescent. The mean age of participants was 16.7 (SD= 1.7) years and the majority were white (N= 71; 86.6 %) and non-Hispanic or Latino (N=76; 92.7%). The majority (N= 59, 72.0 %) of the participants were privately insured. The mean duration of hormonal therapy was 21.5 (SD= 15.4) months spanning over a maximum of 66 months. Only 3 participants had discontinued GAHT therapy: one participant stopped hormonal therapy due to insurance issues, one participant stopped GAHT temporarily to conceive a baby and one stopped testosterone to transition to a non-binary gender. No participant re-transitioned to the gender congruent with the sex assigned at birth.

Conclusion: Discontinuation of GAHT in this group of transgender adolescents was infrequent. No participant re-transitioned to the gender congruent with the sex assigned at birth while 3 participants discontinued GAHT due to external factors. Pediatric providers should prescribe GAHT in accordance with the Endocrine Society guidelines if the adolescent needing GAHT meets the diagnosis of gender dysphoria, has parental consent, and is pubertal.

Presentation: Sunday, June 18, 2023
FRI216 A Rare Case Of Cushing Syndrome Secondary To Adenocarcinoma Of The Lung
Authors: Masauding Alheraki Samee Zane , Horani Mohamad Hosam , Alharraki Faizah Z
Published: October 2023

Disclosure: S.M. Alheraki: None. M.H. Horani: None. F.Z. Alharraki: None.

Cushing syndrome is one of the endocrine diseases that is mainly due to the high levels of cortisol. An overproduction of adrenocorticotropic hormone (ACTH) by a pituitary adenoma or an ectopic, paraneoplastic foci (small cell lung cancer) is the primary cause of secondary hypercortisolism. While small cell lung cancer and carcinoids cause the majority of ectopic ACTH syndromes, in this article, we describe a case of Cushing syndrome secondary to lung adenocarcinoma. It is highly likely that patients with malignancies are suffering from ectopic ACTH syndrome if they exhibit clinical signs such as weakness, hypertension, or lab values indicating hyperglycemia, hypokalemia, or metabolic alkalosis.

Presentation: Friday, June 16, 2023
THU492 Functional Characterization Of Nuclear-enriched Non-coding Genes In Triple-negative Breast Cancer
Authors: Reid Victoria A , Choudhari Ramesh , Yang Barbara , Ramos Enrique Ivan , Dhandayuthapani Subramanian , Gadad Shrikanth
Published: October 2023

Disclosure: V.A. Reid: None. R. Choudhari: None. B. Yang: None. E.I. Ramos: None. S. Dhandayuthapani: None. S. Gadad: None.

Breast cancer, the top diagnosed cancer in women worldwide, is the second leading cause of cancer-related deaths in women. There are several molecular subtypes of breast cancer, which can be classified into two main groups, estrogen receptor-positive (ER+) and estrogen receptor-negative (ER-) subtypes. An ER+ diagnosis typically results in a better overall prognosis than ER- cases, as these tumors often have more available treatment options. Of the ER- subtypes, triple-negative breast cancer (TNBC) cases are the most aggressive and present the worst overall survival than any other molecular subtype. Recent studies have shown that long non-coding RNAs (lncRNAs) exhibit oncogenic or tumor-suppressive roles across different cancer types, in addition to traditionally being known to have multiple functions in regulating gene expression. Our previous studies demonstrated that lncRNA161 is regulated by estrogen, localized to chromatin, and regulates the estrogen-dependent growth of ER+ breast cancer cells and tumor growth. However, our current study revealed its opposite role in TNBC. We are investigating the role of lncRNA161 in TNBC cells utilizing multi-omics approaches, along with in vivo studies, to analyze multiple ER- cell lines, including the more aggressive TNBC subtype. Intriguingly, we found that doxycycline-induced expression of lncRNA161 in various TNBC cell lines attenuated the expression of several epithelial-to-mesenchymal transition (EMT) markers. In vivo, we observed that TNBC tumor growth was significantly decreased in mice after injection with MDA-MB-231 cells overexpressing lncRNA161. Together, our data indicate that lncRNA161 acts as a tumor suppressor in TNBCs, which could potentially lead to establishing it as a prognostic biomarker and therapeutic target for treating TNBCs in the future. S.S.G. is supported by grants from a) The Cancer Prevention and Research Institute of Texas (CPRIT; RR170020); b) Lizanell and Colbert Coldwell foundation; c) The Edward N. and Margaret G. Marsh Foundation; and d) The American Cancer Society

Presentation: Thursday, June 15, 2023
THU496 A Positive Relationship Exists Between CARF And AR In Prostate Cancer
Authors: Hasan Kamrul M , Khambati Hussain , Huerta Roxana Ramirez , Vadgama Jaydutt , Sinha-Hikim Amiya P , Friedman Theodore C
Published: October 2023

Disclosure: K.M. Hasan: None. H. Khambati: None. R.R. Huerta: None. J. Vadgama: None. A.P. Sinha-Hikim: None. T.C. Friedman: None.

Prostate cancer (PCa) is the second most prevalent cancer among men worldwide. Since PCa onset is androgen dependent, androgen deprivation therapy (ADT) is the first treatment choice for a primary tumor or metastatic PCa. However, ADT eventually leads to the development of castration resistant PCa (CRPC), which is the leading cause of higher mortality in PCa. Thus, there is a need to identify the underlying mechanisms of CRPC to manage this aggressive disease. Increased androgen receptor (AR) expression is one of the most important factors contributing to the development of CRPC. It has been shown that tumor suppressor p53 negatively regulates the expression of AR. So, loss of p53 functions has been associated with increased expression of AR in advanced PCa. However, the mechanism of p53-mediated inhibition of AR is not well understood. In this study, we demonstrated that CARF (CDKN2AIP), a p53 pathway regulatory protein, is highly expressed in PCa, but its significance in PCa development is unknown. Since, like AR, CARF is negatively regulated by p53, we hypothesize that a reciprocal relationship between CARF and p53 could regulate AR expression in PCa cells. Indeed, we found that activation of p53 by DNA damage stress inhibited both CARF and AR in LnCap and 22RV1, AR-positive, and wtp53 cell lines. Our result indicated that CARF and AR were decreased dose-dependent manner, and presumably, that could trigger cell death. Consistent with this speculation, we found that silencing CARF by ShRNA in LnCap triggered apoptosis and inhibition of cell proliferation. With great interest, we further demonstrated that silencing of CARF downregulated the AR level in LnCap and 22RV1 cells suggesting that CARF regulates the expression of AR in PCa. RT-PCR results showed that AR transcripts remained unchanged in CARF-depleted LnCap cells. This result indicated that CARF could regulate the AR stability but not the transcription. Intriguingly, we found that the expression of NEDD4, one of the AR-targeting E3 ligases, was increased in CARF-depleted cells. Therefore, by enhancing the stability, CARF could positively regulate the expression of AR in PCa cells. Further studies are in progress to know more details about the CARF-mediated AR regulation and its impact on androgen-independent PCa development and progression.

Presentation: Thursday, June 15, 2023