bluuebunny/crossref_metadata_2025 huggingface dataset:
12441 Factors Affecting The Evaluation Of Adrenal Incidentalomas
Authors: Poloju A , Pabich S K , Syed S , Krueger A , Chiu A
Published: October 2024

Disclosure: A. Poloju: None. S.K. Pabich: None. S. Syed: None. A. Krueger: None. A. Chiu: None.

Introduction: Adrenal incidentalomas are increasingly being detected, owing to the increasing number of high-resolution radiologic studies performed. While most of the nodules are non-functional, 10-15% are hormonally active and hence merit workup. We assessed the rates of, and factors associated with appropriate workup of these nodules. Methods: A retrospective analysis of CT chest and abdominal scans between Jan 1, 2021, and June 1, 2022, in adults ≥18 years at a single tertiary care center was performed. Reports were screened with key phrases to identify adrenal nodules. A chart review was conducted to confirm the reported nodule, obtain demographic data, obtain data on co-morbid conditions, and evaluate for biochemical and radiologic workup. Exclusion criteria included: patients deceased at the time of our review, previously diagnosed nodules, sub-centimeter lesions, and adrenal hemorrhage. Patients were categorized as being from high or low disadvantaged neighborhoods based on their Area Deprivation Index (ADI) score. ADI above the 50th percentile was categorized as more disadvantaged. Charleston Comorbidity Index (CCI), a 10-year survival predictor based on the presence of common diseases was abstracted. Patients with any biochemical workup were compared to patients with no workup. Bivariate analysis was performed using chi-squared and Student’s t-test analysis. A multivariate logistic regression was performed to evaluate factors associated with biochemical workup. Results: A total of 533 records were reviewed. After applying the above exclusion criteria, a total of 245 patients were included in our analysis. Baseline characteristics included: 58.7% female and 41.2% male. 67.3% had hypertension diagnosis, 22% had sleep apnea diagnosis, and 30.6% had diabetes diagnosis. 86% were White, 5.7% Black, 3.2% Hispanic, 3.2% Asian, and 1.6% Other. 71% of the patients had no biochemical workup, 18% had partial workup, and 11% had full workup. Factors associated with having either partial or full workup compared to no workup included female sex (OR 2.33, CI 1.23-4.41), internal medicine/family medicine provider ordering the scan compared to Emergency Department providers (OR 3.84, CI 1.61-9.14), and ADI scores below the 50th percentile (OR 1.98, CI 1.04-3.78). There was no statistically significant difference based on age, race, ethnicity, and CCI. There was no significant difference in the workup for hypercortisolism based on the presence of co-morbid conditions like diabetes, sleep apnea, and overweight/obesity. Conclusions: In our study population, the rates of guideline-based biochemical workup of adrenal incidentalomas were very low at 11%. Factors associated with having at least partial biochemical workup included less socioeconomic disadvantage, female sex, and studies ordered by primary care providers.

Presentation: 6/3/2024
7639 A Rare Cause of Lung Adenocarcinoma with Metastasis to the Thyroid
Authors: Echevarria-Torres Edward , Yap Charmaine G , Izuora Kenneth E
Published: October 2024

Disclosure: E. Echevarria-Torres: None. C.G. Yap: None. K.E. Izuora: None.

A rare cause of lung adenocarcinoma with metastasis to the thyroid. Metastasis to the thyroid gland from non-thyroid malignancies is rare. When metastasis occurs, presenting symptoms are typically nonspecific, representing a diagnostic challenge. With the goal of raising awareness, we present a case of lung adenocarcinoma with metastasis to the thyroid. An 85-year-old man with a history of hypertension, hyperlipidemia and 60 years smoking history presented to the endocrine clinic for evaluation of subclinical hyperthyroidism. On the physical exam, there was fullness in the right thyroid area which on ultrasound showing a large right thyroid nodule occupying the entire lobe. There was also a solid 4.5 cm x 3.4 cm x 4.6 cm nodule in the mid-anterior left thyroid lobe. Fine needle aspiration cytology of right nodule revealed malignant cells and cell block material positive for TTF-1 (Thyroid Transcription Factor 1) concerning for malignancy. The left thyroid nodule cytology was consistent with benign follicular nodule. Chest CT ordered for surgical planning showed right upper lobe pleural-based lung opacity measuring 3.7 cm x 2.9 cm with supra clavicular lymphadenopathy. Biopsy of lung mass and supra clavicular lymph nodes revealed primary lung adenocarcinoma involving the lymph nodes consistent with stage Iva (cT3NxM1b). The patient was referred to oncology for further management. Discussion: Metastatic lesions to the thyroid gland account for less than 1 % of all malignant thyroid tumors with most cases found on autopsy. This is hypothesized to be due to the rich blood supply and high iodine content of the thyroid gland. Thyroid metastasis usually presents several years after initial diagnosis and treatment of non- thyroid malignancy. Patients can present with enlarging thyroid nodules, neck swelling, dysphagia and, in rare instances, upper airway obstruction. We present a rare case of lung cancer with metastasis into the thyroid. The thyroid nodule initially palpated upon physical exam led to eventual thyroid ultrasound and subsequently to his diagnosis of lung adenocarcinoma after findings of lung nodule which was biopsied and showed primary lung adenocarcinoma. TTF-1 was also positive which is typically expressed by lung adenocarcinomas. Treatment for thyroid metastasis is surgery, along with treatment of primary malignancy. The earlier the diagnosis and treatment the more favorable the prognosis. Radiotherapy and chemotherapy are other means to reduce the recurrence. Thyroid hormone replacement will be warranted post operatively for hypothyroidism. We present this uncommon case to raise awareness about the presentation of thyroid metastasis to enhance timely diagnosis and intervention.

Presentation: 6/1/2024
8176 An Unusual Case of Thyroid Eye Disease (TED) Occurring in Autoimmune Hypothyroidism
Authors: Prasongdee K , Tessier C M
Published: October 2024

Disclosure: K. Prasongdee: None. C.M. Tessier: None.

Background: It is unusual for TED to present in patients with autoimmune thyroid disease who are euthyroid or hypothyroid. Clinician recognition of this rare presentation is important in ensuring proper treatment and improving patient outcomes. Clinical Case:Our patient is a 57-year-old female with a past medical history of COPD, hypothyroidism presenting with several months of blurry vision. She reports double vision when looking down, and eye pain at rest and with eye movement. She was diagnosed with hypothyroidism one year prior to presentation, and her TSH subsequently normalized after titration to levothyroxine of 112 mcg daily. She reported no history of head or neck radiation. No family history of thyroid disease. She smoked for 30 pack years but stopped 2 years prior. Physical exam showed eye lid swelling and redness, pain and diplopia on end-lateral gaze, no chemosis, no conjunctival injection, or inflammation of the caruncle, lids closed completely, proptosis with Hertel ophthalmometer measured 23 mm on the right eye and 22 mm in the left eye (normal range < 18 to 20 mm for Caucasians), thyroid not enlarged with no palpable nodules, no thyroid bruits. The initial Clinical Activity Score (CAS) was 4, which indicated active TED. A thyroid ultrasound showed Inhomogeneous echogenicity with increased vascularity consistent with autoimmune thyroiditis. An MRI of the orbits revealed diffuse extraocular muscle enhancement and enlargement with tendinous insertion sparing, increased T2 hyperintensity findings which favored thyroid eye disease. Further laboratory testing confirmed the presence of multiple thyroid autoantibodies: Thyrotropin binding inhibitory immunoglobulin 2.76 IU/L (normal range < 1.75 IU/L), Thyroid peroxidase antibody 1135 IU/mL (normal range <9 IU/mL), Thyroglobulin antibodies 157 IU/mL (normal range < 116 IU/mL), thyroid-stimulating immunoglobulin 447% (normal range <140 % Baseline). She was referred to ophthalmology for management of TED and was started on teprotumumab. Her CAS improved to 0 and her diplopia resolved. Her proptosis remained stable. This case illustrates an unusual clinical course in a patient who initially presented with autoimmune hypothyroidism, later developed Thyroid Eye Disease. A study by Kahaly GJ et al showed that in Hashimoto’s thyroiditis (HT), thyroid-stimulating autoantibodies are highly correlated with thyroid eye disease (TED) with positive thyroid-stimulating autoantibodies detected in 5.5% of the patients with HT and 68.2% in the patients with HT and TED. Even though it is less common, up to 6% of patients with HT may be affected by TED. Rare presentations such as this case emphasizes the need to be vigilant when evaluating eye symptoms in patients with autoimmune thyroid disease. Teprotumumab that showed improvement in patients with Grave’s and thyroid eye disease, was also successful in treating our patient symptoms.

Presentation: 6/3/2024
8183 An Unusual Cause of Fluctuating Thyroid Hormone Levels
Authors: Taqi V , Akhter W , Gilden J L
Published: October 2024

Disclosure: V. Taqi: None. W. Akhter: None. J.L. Gilden: None.

Background: Thyroid disease, especially congenital hypothyroidism is a common endocrine problem with an estimated global prevalence of 4.25%. Since every organ system is affected by thyroid hormones, untreated hypothyroidism can lead to profound adverse outcomes. Many drugs, hormones, and dietary supplements have been noted to affect the efficacy of thyroid hormones, yet there was always concern about the effect of the excessive growth of intestinal flora in the small intestine on thyroid supplement absorption. Drugs, malabsorption, celiac disease and increased excretion are common causes of fluctuating thyroid hormones. In this case, we present a young male patient with congenital hypothyroidism, who required fluctuating doses of levothyroxine due to abnormal thyroid hormone levels, despite compliance with proper administration, and dramatic improvement of thyroid hormone levels after starting probiotic therapy. Case : An 18-year-old Caucasian male with congenital hypothyroidism had been treated with varying doses of thyroid hormone replacement by a Pediatric Endocrine Center. Due to his recall that TSH=4.13 mIU/L and he was “tired of taking medication”, he stopped taking 125 mcg of levothyroxine. Four months later, TSH was > 200 mIU/L (nl=0.48-4.17). Levothyroxine 137 mcg was then started. However, 11 months later, TSH=14.2 mIU/L, Free T4=1.6 ng/dL (nl=1.03-1.64). He was then referred to our Endocrine Clinic. He denied symptoms of hypo or hyperthyroidism or other medical issues. His grandfather was known to have hypothyroidism and diabetes mellitus (details unknown). On exam: Wt. was 149 Ib, Ht= 67 Inch. VS: BP 98/46, P 69, R:16,temp: 97.9F, Physical exam showed normal findings without thyromegaly, but there was a delay in tendon reflexes. Laboratory-unremarkable CBC, CMP panels with normal thyroid antibodies, and Celiac titers. TSH initially improved from 14.2 to 8.4 mIU/L after increasing the thyroxine dosage from 137 to 150 mcg for 2 weeks, then to 175 mcg after 4 weeks, but TSH increased to 12.1 mIu/L, despite being compliant with medication and ensuring proper way of administration. He continued to deny symptoms of hypo or hyperthyroidism, or any other medical issues, including lactose intolerance or malabsorption. However, probiotics were then added to his regimen, and continuation of the current dose resulted in a suppressed TSH=0.15 mIU/L. The levothyroxine was then decreased to 150 mcg with continuation of probiotics. One month later, TSH was 1.31 mIU/L with Free T4 of 1.5 ng/dL. Conclusion : Common causes for fluctuating thyroid hormone levels include intestinal malabsorption, celiac disease, nephrotic syndrome, drugs, and food interaction. This case demonstrates that despite proper administration, fluctuating thyroid hormone levels can result from some uncommon causes, such as lactose intolerance, which can be unmasked by co-administration of probiotics.

Presentation: 6/2/2024
8171 Analysis of Inflammatory Bowel Disease and Hashimoto's Disease: A Nationwide Study
Authors: Yang Charles , Joo Lucy , Blair Brian
Published: October 2024

Disclosure: C. Yang: None. L. Joo: None. B. Blair: None.

Analysis of Inflammatory Bowel Disease and Hashimoto’s Disease: A Nationwide Study Introduction: The U.S. population is aging rapidly. There is limited data specifically for patients with Hashimoto’s disease who are older than or equal to 80 years old. We sought to examine the national inpatient sample database to describe in-hospital outcomes among these older patients. Methods: Data were extracted from the National Inpatient Sample (NIS) Database for the years 2019 and 2020. The NIS was searched for hospitalizations of adult patients with Hashimoto's disease using international classification of diseases 10th revision codes. We then examined the outcomes in patients who were older than or equal to 80 years old (YO) vs. younger than 80 years old. Linear regression and multivariate logistic was used accordingly to adjust for confounders. The primary outcome was inpatient mortality. Secondary outcomes were hospital length of stay (LOS), and total hospital charges (TOTHCG). SPSS software was used for statistical analysis. Results: This study included 48,649 patients with Hashimoto’s disease, of which 3,038(6.2%) patients were over or equal to the age of 80. Admissions with Hashimoto’s and old age had higher prevalence of hypertension (12.3% Vs 11.3 %, p<0.001), diabetes mellitus (14.8% VS 11.4% p <0.001), and obesity (6.9% Vs 3.1%, p<0.001). In-hospital mortality was higher among the older cohort (2.6% Vs 0.87, p< 0.001). On linear regression analysis, increased age was associated with increased in-hospital mortality (p<0.001). On multivariable regression, age >80 years was associated with higher odds of inpatient mortality (OR1.229, CI 1.174-1.286, p<0.001)). It was also shown that older Hashimoto’s patients pay significantly more total hospital charges ($82,361vs $70,231) with higher length of stay (7.4 days vs 5.6 days, p<0.001). On secondary analysis, it has shown that Hashimoto’s patients aged more than or equal to 80 years old had higher odds of having Crohn’s Disease (OR 1.032, CI 1.014-1.049, p<0.001) and Ulcerative Colitis (OR 1.025, CI 0.991-1.061, p<0.001). Conclusion: In this nationally representative population-based retrospective cohort study, aging was associated with higher mortality and worse outcomes among patients with Hashimoto’s disease. These results were distinguished in patients with inflammatory bowel disease.

Presentation: 6/2/2024
9209 Functional Evaluation Of Novel CYP21A2 Variants: Expanding The Genetic Basis Of Non-classic CAH
Authors: Matveeva Anna , Xu Yingtong , Tardy-Guidollet Véronique , Pandey Amit V
Published: October 2024

Disclosure: A. Matveeva: None. Y. Xu: None. V. Tardy-Guidollet: None. A.V. Pandey: None.

Introduction: Congenital adrenal hyperplasia (CAH) comprises a group of autosomal recessive genetic disorders affecting the production of glucocorticoids, mineralocorticoids, and gonadocorticoids. In approximately 95% of cases, CAH results from a deficiency in CYP21A2. A Non-Classic form of CAH (NC-CAH) arises when CYP21A2 activity decreases to 20-50% of the normal level, occurring at an estimated frequency of 1 in 200 - 1000 individuals. The clinical picture is characterized by the accumulation of androgen precursors, causing hirsutism, acne, metabolic syndrome, menstrual irregularities, infertility in females, and androgenic alopecia, oligospermia in males. Methods: We selected mutations from CYP21A2 sequence data of patients with NC-CAH symptoms admitted to CHU Lyon, France (L49V, A81T, R125G, I161T, L199F, L289H, L289F, V306D, L462P). Additional variants were selected from the SNP databases (dbSNP, gnomAD, ClinVar) based on a high frequency in humans (H393Q, P387L, T201A, S203G S274Y, S494N, R76K, Leu10del). All variants underwent in silico assessment considering evolutionary, structural, and functional aspects (ConSurf, Predict SNP2, CADD, DANN, FATHMM, FunSeq2, GWAVA, PANTHER, SNPs&GO, PhD-SNP, SIFT, SNAP, Meta-SNP, Polyphen2, HDIV, DUET). The CYP21A2 proteins carrying the mutations were overexpressed in HEK 293T cells. We evaluated CYP21A2 enzyme activities by measuring the conversion of 14C-Progesterone into 11-deoxycortisol by thin layer chromatography and autoradiography. Samples were tested in duplicates, using the activity of WT CYP21A2 as a control. Results: Computational analysis revealed that A81T, R125G, I161T, and L289H substitutions significantly impair protein structure, while other variants showed moderate effects. Except for L199F, all patient-derived variants exhibited reduced 21-hydroxylase (CYP21A2) activity associated with NC-CAH phenotypes. Variants from databases did not demonstrate a significant loss of function related to CAH. Conclusion: In this study we investigate the pathogenicity of uncharacterized CYP21A2 variants in relation to non-classic congenital adrenal hyperplasia (NC-CAH), contributing to a better understanding of associated phenotypes. The findings, particularly the identification of novel mutations and the assessment of their impact on CYP21A2 activity, hold promise for improving diagnosis and treatment strategies aimed at mitigating severe outcomes of NC-CAH, such as miscarriages or irreversible alopecia. It also raises awareness among heterozygous carriers, assisting in family planning and medical decisions.

Presentation: 6/1/2024
7637 Characteristics of Thyroid Nodules Among Adolescents and Adults in Medina, Saudi Arabia
Authors: Alradadi R , Sindi M , Alrehaili O , Alanazi S , Alahmadi S , Mansuri F , Zain A
Published: October 2024

Disclosure: R. Alradadi: None. M. Sindi: None. O. Alrehaili: None. S. Alanazi: None. S. Alahmadi: None. F. Mansuri: None. A. Zain: None.

Background: Thyroid Nodules are common clinical finding, with a prevalence of about 20% in young adults and around 70% in the elderly population. A significant increase in the incidence rate of Thyroid Cancer in our population has been noted, over the past 30 years. The aim of the study is to define the characteristics of Thyroid Nodules in adolescents and adults in our region compared to what published worldwide. Method: A retrospective chart review, conducted at our Health Institution. The study included adolescents and adult who had Thyroid Nodules and was seen in the outpatient endocrine clinic in the period between 2018 and 2022, using non-probability consecutive sampling. Patient medical records provided demographic, medical, and laboratory data, and the analysis employed SPSS for statistical assessment​​. Data collection conducted from October through December of 2023 Result: Out of the total sample of 552 patients, there were 84.8% females. More than half of the patients (55.9%) were between 36-55 years of age. 57.4% of patients were overweight or obese. 56.4% presented with goiter. FT3, FT4 and TSH levels were normal among 88.4%, 78% and 83.3% respectively. Anti TPO antibodies were reported in 14.2% as compared to thyroglobulin antibodies in 2.2%.Follicular neoplasm/suspected neoplasm was detected among 8.15% of the sample. Papillary thyroid carcinoma [27/41] was the most frequent finding with positive FNA. Multiple nodules were more prevalent 38.8% as compared to solitary nodules in 34.1%. The right sided nodules were mostly solid 49.2% while hypervascularity was noted in 9.1% and51.4% were of more than 1.5cm. In contrast, left lobe nodule 37% were found to be solid and 6.2% showed hypervascularity and size was more than 1.5cm in 45% of the left nodules Conclusion: The vast majority of adults and adolescents with thyroid nodule were female as expected based on what reported from previous studies. Preexisting Thyroid Diseases present in only small number of patients 15.4 %. Anti-TPO antibody was more predominant than Thyroglobulin Antibody. Follicular neoplasm/suspected neoplasm was detected among 8.15% of the sample. Papillary thyroid carcinoma was the most frequent finding among the positive FNA results.

Presentation: 6/3/2024
8091 Clinical Features Associated with ICU Admission and Mortality in Thyroid Storm and Impending Thyroid Storm
Authors: Zhang Emily Danica , Hussain Iram
Published: October 2024

Disclosure: E.D. Zhang: None. I. Hussain: None.

Introduction: Thyroid storm is a rare, life-threatening manifestation of thyrotoxicosis characterized by a clinical syndrome of acute multi-organ failure, which can result in significant morbidity and mortality. Impending thyroid storm is a stage of thyrotoxicosis that may progress to thyroid storm if untreated. The aim of this study was to evaluate the demographics and outcomes of patients with thyroid storm at our institution and determine the clinical features associated with severe complications and mortality. We also evaluated the differences in clinical features and outcomes in patients diagnosed with impending thyroid storm versus thyroid storm. Methods: This was a retrospective single-center cohort study evaluating patients aged 18 years or older who were clinically diagnosed with thyroid storm or impending storm at two affiliated tertiary academic centers from 2008-2021. A search of the electronic medical record system using ICD-10 codes for thyroid storm identified patient charts which were reviewed for eligibility. Results: This study included 121 admissions, with 75 (62.0%) patients with thyroid storm and 46 (38.0%) patients with impending thyroid storm. Our study cohort was notably more racially and ethnically diverse than prior U.S. studies with 5.0% non-Hispanic White, 52.9% Black, 33.9% Hispanic, and 8.3% Asian patients. The mortality rate was 4.7%, with all patient deaths occurring in the thyroid storm group. Multivariable logistic regression analysis showed atrial fibrillation (OR 4.09, 95% CI 1.21, 13.85, p=0.02) and acute respiratory failure (OR 22.18, 95% CI 2.29, 215.19, p=0.008) to be significantly associated with a composite outcome of intensive care unit (ICU) admission or death. Comparison of impending storm and thyroid storm groups showed fever (p=0.02), acute respiratory failure (p=0.03), and ICU admission (p=0.02) to be significantly different between groups. Conclusions: This study describes the largest published single-center cohort of patients treated for thyroid storm in the United States. Furthermore, our study contributes importantly to the data for racial/ethnic minorities who are under-represented in prior studies. The mortality rate in this study is lower than most recent studies. The presence of atrial fibrillation and acute respiratory failure were noted to be significantly associated with a composite outcome of ICU admission or death, and the five fatal cases had high rates of cardiac arrest and shock. These findings suggest that complications involving cardiopulmonary compromise are clinically important in predicting severe disease and poor outcomes. Acute respiratory failure was also noted to be significantly different between impending storm and thyroid storm groups indicating that while not currently included in existing diagnostic systems, it is an important complication of thyroid storm that may have prognostic value.

Presentation: 6/2/2024
7744 Diagnosis of Papillary Thyroid Cancer After Radiofrequency Ablation
Authors: Barton Isaye S E , Tylee Tracy Susan , Zern Nicole , Roth Mara Yvonne
Published: October 2024

Disclosure: I.S. Barton: None. T.S. Tylee: None. N. Zern: None. M.Y. Roth: None.

Background: Radiofrequency ablation (RFA) is a procedure used to decrease the size and compressive symptoms due to a large nodule. Current recommendations are for two fine needle aspirations (FNA) prior to RFA to rule out malignancy. The risk of malignancy after two benign FNAs has been shown to be less than 3%[1]. Here we present a case of nodule regrowth 6 months following RFA, with high-grade thyroid cancer found on subsequent surgical pathology despite 2 benign FNAs prior to RFA. Clinical Case: A 31-year-old female first presented with a thyroid nodule in 2019. Initial thyroid ultrasound demonstrated a 5.0 x 4.0 x 5.5 cm TI-RADS 3 nodule in the right isthmus. TSH was 1.5. She had no family history of thyroid disease, thyroid cancer, or history of radiation exposure. She underwent FNA twice separated by 5 months which both showed benign cytology. Due to compressive symptoms, she underwent RFA of the nodule. Her symptoms improved for approximately 6 months, but she then developed recurrent compressive symptoms. Ultrasound completed 13 months post-RFA demonstrated enlargement of the nodule to 6.0 x 5.8 x 4.0 cm with extension into the right lobe. The nodule remained TI-RADS 3 based on ultrasound characteristics. Due to her compressive symptoms, she underwent right hemithyroidectomy and isthmusectomy. Pathology showed a unifocal 6.5cm differentiated high-grade thyroid carcinoma with extensive angioinvasion, tumor necrosis, focal abutting of surgical margin, and 4 negative lymph nodes (pT3aN0a). She underwent completion thyroidectomy which identified a 5mm infiltrative papillary thyroid cancer in the contralateral lobe. She was treated with radioactive iodine for remnant ablation and adjuvant therapy. Conclusion: This case demonstrates the rare outcome of a high-grade thyroid malignancy diagnosed post-RFA, despite two prior benign FNAs. This may be due to sampling error in large thyroid nodules. Given that most nodules that undergo RFA are larger, it is possible two benign FNAs may not rule out malignancy. This is supported by other studies that have found malignancy in up to 19% of nodules that demonstrate regrowth following RFA2. Thus, ongoing ultrasound follow-up after RFA is important to monitor for nodule regrowth and to recognize potential malignancy. References: (1) Orlandi A, et al. Thyroid. 2005. (2) Kim MK, et al. Korean J Radiol. 2023.

Presentation: 6/2/2024
8332 Genotype/Phenotype Profile Of Pheochromocytoma/Paraganglioma Patients In A Single Tertiary Referral Center Of South Texas
Authors: Desai Viraj , Armaiz Pena Gustavo , Escobar Vasco Maria A , Estrada-Zuniga Cynthia , Landry Bethany , Gonzalez-Cantu Hector , Pruthi Deepak , Tozzi Federico , Ferrell Jay , Kitano Mio , Solis-Herrera Carolina , Bruder Jan M , Raghunathan Sapna , Dahia Patricia L
Published: October 2024

Disclosure: V. Desai: None. M.A. Escobar Vasco: None. C. Estrada-Zuniga: None. B. Landry: None. H. Gonzalez-Cantu: None. D. Pruthi: None. F. Tozzi: None. J. Ferrell: None. M. Kitano: None. C. Solis-Herrera: None. J.M. Bruder: None. S. Raghunathan: None. P.L. Dahia: None.

Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors. Nearly 40% of patients with PPGLs have a heritable germline mutation and around 30% carry somatic mutations in one of >20 known susceptibility genes. 15-20% of cases can progress to metastatic disease. Recently, ethnic differences have been suggested in PPGLs and support further evaluation of ethnically diverse cohorts which can offer guidance for surveillance and patient care. Goal: The objective of this study is to identify genetic and clinical features of patients with a diagnosis of PPGL in predominant ethnic groups located in a single tertiary referral center of South Texas that is a designated Pheo-Para Alliance Clinical and Research Center of Excellence. Methods: Medical records were utilized to obtain demographic and clinical data, including age at diagnosis, gender, ethnicity, family history, tumor location, metastasis, clinical disease vs. carrier status, and genotype from patients enrolled in an IRB-approved repository. Results: 62 index patients who were diagnosed with PPGL or had a pathogenic germline mutation with no clinical disease were enrolled between 2006 to 2023. Patients were predominantly Caucasian (n=30/59, 50.8%) and Hispanic (n=24/59, 40.6%). In the Hispanic group, twenty-one were diagnosed with PPGL and three were asymptomatic carriers. This group had an average age of 38.3 years (range, 13-77), 85.7% had pheochromocytomas (11.1% were bilateral), 14.3% were metastatic, 16.7% had a positive family history, and 65% had an identifiable germline mutation. The most commonly mutated genes in Hispanics were VHL (n=5), SDHx (n=5), and EPAS1 (n=3). In the Caucasian group, thirty patients were diagnosed with PPGL and three were asymptomatic carriers. The average age for Caucasians was 46.4 years (range, 19-80). 23% had a positive family history, 66.7% had pheochromocytoma, 22.2% had metastatic disease, and 77.3% had a germline mutation. The most common genotype in Caucasians was SDHx (n=12) followed by NF1 (n=4). Conclusion: In this PPGL cohort, Hispanic patients tended to be younger at diagnosis, have lower proportion of SDH germline mutations and higher frequency of somatic mutations compared to Caucasians. This preliminary observation should inform further investigation into PPGL genotype-phenotype associations across ethnic groups toward improving surveillance and patient care.

Presentation: 6/2/2024
7507 Early Detection of Hyperglycemia Using CGM Despite Reduced Dosing of Teprotumumab
Authors: Needleman Leor , Kim Sun H , Kossler Andrea L , Dosiou Chrysoula
Published: October 2024

Disclosure: L. Needleman: None. S.H. Kim: None. A.L. Kossler: None. C. Dosiou: None.

Background: In a previous longitudinal observation study, we showed that patients with prediabetes increased HbA1c by a mean of 0.7% and 30% progressed to type 2 diabetes after treatment with teprotumumab for 3 months, or after 4 infusions [1]. However, temporal effects of hyperglycemia and the impact of lower doses of teprotumumab on hyperglycemia are unknown. Clinical case: An 86-year-old woman was diagnosed with Graves’ disease after evaluation for palpitations showed undetectable TSH, free T4 2.31 ng/dL (ref. 0.8-1.8 ng/dL), total T3 252 ng/dL (ref. 76-181 ng/dL), and elevated TSI (5.0, ref. <1.3). Thyroxine levels normalized four weeks after starting methimazole. Nine weeks after the initial presentation she developed diplopia and bilateral proptosis. She was diagnosed with active moderate-to-severe thyroid eye disease (CAS 4/7) and was started on teprotumumab 10 mg/kg intravenously every three weeks. The dose was not increased to 20 mg/kg due to concern for adverse effects given the patient’s age and underlying hearing impairment. At baseline, she had prediabetes based on a HbA1c of 6.0%. Additional risk factors for type 2 diabetes included older age and Asian race [1]. Continuous glucose monitoring (CGM, Dexcom G7) before starting teprotumumab showed 71% time in tight range (TITR, 70-140 mg/dL) with average fasting glucose of 115 mg/dL. Prior to starting teprotumumab, she received counseling for lifestyle modification including carbohydrate moderation. Ten days following her first teprotumumab dose, her TITR reduced to 66%. After three doses of teprotumumab, her proptosis improved by 2 mm, CAS decreased to 1/7, and diplopia resolved. However, the TITR was 59% and average fasting glucose increased to 128 mg/dL. HbA1c also increased to 7.4% and the patient was started on metformin. Conclusion: In this case, teprotumumab increased glucose as early as after the first infusion. Glucose tolerance continued to worsen with subsequent doses, with development of type 2 diabetes, even with reduced dosage of teprotumumab. This case demonstrates that monitoring for teprotumumab-related hyperglycemia can be optimized with use of CGM and that lower doses of teprotumumab do not eliminate the risk of worsening glucose tolerance. Whether hyperglycemia would have been more severe with full dose teprotumumab remains uncertain. Reference: [1] Amarikwa L, Mohamed A, Kim SH, Kossler AL, Dosiou C. Teprotumumab-Related Hyperglycemia. J Clin Endocrinol Metab. 2023 Mar 10;108(4):858-864.

Presentation: 6/3/2024
12217 Exploring Thyroid-stimulating Hormone As A Potential Cardiovascular Disease Risk Marker In Euthyroid Individuals
Authors: Neto Alfredo Pinheiro , Lucchesi Henrique , Silva Janovsky Carolina Castro Porto , Bensenor Isabela , Ward Laura Sterian , Cunha Lucas Leite
Published: October 2024

Disclosure: A.P. Neto: None. H. Lucchesi: None. C.C. Silva Janovsky: None. I. Bensenor: None. L.S. Ward: None. L.L. Cunha: None.

Previous studies have suggested that TSH levels may predict longevity primarily in elderly individuals. Aging is associated with a high prevalence of cardiovascular and metabolic diseases that reduce survival. However, the relationship between serum TSH levels and these conditions, especially traditional cardiovascular risk markers, remains poorly explored. We employed data from the longitudinal multicenter cohort study ELSA-Brasil, which includes workers from five Brazilian Universities, to evaluate thyroid function in 8,452 participants aged between 34 and 75 years, classified as euthyroid and followed for 8.9 ± 0.6 years. The participants were evaluated for the presence of diabetes, hypertension, angina, peripheral arterial disease, and cardiovascular mortality. Additionally, we measured cardiovascular markers, including global cardiovascular risk score, HbA1c, microalbuminuria (mg/dl), LDL levels, and triglyceride levels. Statistical analysis was used to compare TSH levels with clinically relevant outcomes and classical cardiovascular risk markers. We observed that higher TSH levels correlated negatively with global cardiovascular risk (Spearman rank -0.023, p-value=0.038), microalbuminuria (Spearman rank -0.055, p<0.000), and HbA1c (Spearman rank -0.041, p<0.000). However, TSH levels were positively correlated with hypertriglyceridemia (Spearman rank +0.125, p<0.000) but had no relationship with LDL (p >0.05). The appraisal of cardio-metabolic diseases showed that individuals without diabetes had higher TSH levels (1.79 mIU/L, IQR 1.07) than individuals with diabetes (1.71 mIU/L, IQR 1.07). Patients with arteriosclerosis diseases, such as coronary and peripheral arterial disease, had lower TSH levels (1.66, IQR 0.98 and 1.67, IQR 0.94, respectively) than those who did not have these comorbidities (1.79, IQR 1.07, and 1.79, IQR 1.07). Furthermore, TSH levels did not correlate with the incidence of hypertension (p >0.05). Finally, we divided the population into two groups: higher and lower TSH levels based on the median TSH levels (1.78 mIU/L, IQR 1.06). The Kaplan-Meier curve did not show a difference between these groups (p=0.758) in survival after cardiovascular events (08 events in total) during follow-up. In conclusion, our results suggest that higher serum TSH levels in euthyroid individuals are associated with a lower prevalence of metabolic and cardiovascular disease. However, the relatively short observation duration and low frequency of cardiovascular events in our cohort made it difficult to statistically analyze several endpoints, such as survival. Further investigation is necessary to completely understand whether TSH is a cardiovascular risk indicator.

Presentation: 6/2/2024
8080 Factors Affecting Survival of Lymph Node Positive Medullary Thyroid Cancer: A Population-Based Study From Surveillance, Epidemiology, and End Results (SEER) Program
Authors: Mortagy Mohamed , Abdelhameed Aya , Hegazy Mohamed Tharwat
Published: October 2024

Disclosure: M. Mortagy: None. A. Abdelhameed: None. M. Hegazy: None.

Introduction: 50-70% of patients with MTC have positive lymph nodes. The Aim is to identify factors affecting survival of the lymph node positive MTC sub-population. Understanding these factors is important in treating these patients. Methods 1359 patients with lymph node positive MTC who were diagnosed with positive histology or cytology from 1975 to 2020 were extracted from SEER after removing duplicates. Survival analysis was performed, and Kaplan-Meier graph was produced. Univariate and multivariable Cox regression were performed, and respective hazard ratios (HR) were generated. Results: The cohort were 54% males with a median age of 55 years. Median survival: for the cohort was 163 months with survival of 91%, 80% and 74% at 1, 3, and 5 years respectively. Univariate Cox regression was statistically significant for age (HR 1.04), female sex (HR 0.64), T4 stage (HR 2.48), M1 stage (HR 5.43), bone metastasis (HR 4.74), brain metastasis (HR 17.1), liver metastasis (HR 5.41), lung metastasis (HR 5.97), distant lymph node metastasis (HR 6.00), number of positive lymph nodes (HR 1.008), lymph node ratio (HR 4.50), tumor size (HR 1.02), multifocal tumor (HR 0.69), total number of malignant tumors (HR 1.21), not performing total thyroidectomy (HR 6.35), chemotherapy (HR 3.85), radiotherapy after surgery (HR 1.67), beam radiotherapy (HR 2.20), systemic therapy after surgery (HR 0.67). Univariate Cox regression was not statistically significant for grade, treatment delay, total number of benign tumors, race/ethnicity, income, and living in rural areas. Multivariable cox regression was done after inclusion of all significant variables from univariate Cox regression. It was only significant for number of positive lymph nodes (HR 1.03), bone metastasis (HR 0.18), liver metastasis (HR 14.57), multifocal tumor (HR 3.49), total number of malignant tumors (HR 2.66), T4 stage (HR 3.57), M1 stage (HR 3.65), not performing total thyroidectomy (HR 352.43), tumor size (HR 1.03). Conclusion: Number of positive lymph nodes, T4 stage, M1 stage, presence of liver metastasis, presence of multifocal tumor, not performing total thyroidectomy and large tumor size lead to worse prognosis. Age, gender, chemotherapy, and lymph node ratio don’t affect survival. Future research is required to study this group of patients.

Presentation: 6/2/2024
8061 Factors Affecting Survival of Metastatic Medullary Thyroid Cancer: A Population-Based Study From Surveillance, Epidemiology, and End Results (SEER) Program
Authors: Abdelhameed Aya , Ibrahim Hesham , Mortagy Mohamed
Published: October 2024

Disclosure: A. Abdelhameed: None. H. Ibrahim: None. M. Mortagy: None.

Introduction: Medullary thyroid cancer (MTC) arises from parafollicular cells of the thyroid. 43% of patients with MTC have metastasis. It was shown that the overall 5-year survival of patients with MTC is 40.4%. The clinical course of MTC is highly variable. The Aim is to identify factors affecting survival of the metastatic MTC sub-population. Understanding these factors is important in treating these patients. Methods 340 patients: with metastatic MTC who were diagnosed from 1975 to 2020 were extracted from SEER after removing duplicates and those not diagnosed by positive histology or cytology. Survival analysis was conducted, and Kaplan-Meier graph was generated. Univariate Cox regression was performed for all variables and respective hazard ratios (HR) were produced. Multivariable cox regression was performed for statistically significant variables. Results: The cohort were 59% males with a median age of 60 years. Median survival for the cohort was 20 months with survival of 63%, 41% and 31% at 1, 3, and 5 years respectively. Univariate Cox regression was statistically significant for age (HR 1.02), brain metastasis (HR 2.70), liver metastasis (1.65), lung metastasis (1.42), not performing total thyroidectomy (HR 2.77), lymph node ratio (HR 2.45), and systemic therapy after surgery (HR 0.34). Univariate Cox regression was not statistically significant for sex, grade, radiotherapy, chemotherapy, treatment delay, bone metastasis, distant lymph node metastasis, multifocal cancer, total number of benign and malignant tumors, race/ethnicity, income, tumor size and living in rural areas. Multivariable cox regression was done after inclusion of all significant variables from univariate Cox regression. It was only significant for age (HR 1.04), presence of lung metastasis (HR 1.91), and systemic therapy before surgery (HR 14.41). Conclusion: Increasing age, presence of lung metastasis and systemic therapy before surgery lead to worse prognosis in metastatic MTC. Gender, grade, radiotherapy, chemotherapy, treatment delay, bone or brain or liver metastasis, presence of multifocal cancer, race, tumor size and surgery don't affect survival according to multivariable cox regression. Future research is needed to study this group of patients.

Presentation: 6/2/2024
6998 Giant Pheochromocytoma: A Retrospective Single-Center Study
Authors: Bahrani Fard Bahar , Nikravangolsefid Nasrin , Maroun Justin W , Cross Ashton E , Foster Trenton R , McKenzie Travis J , Young William F , Dy Benzon M , Lyden Melanie , Bancos Irina
Published: October 2024

Disclosure: B. Bahrani Fard: None. N. Nikravangolsefid: None. J. Maroun: None. A. Cross: None. T. Foster: None. T. McKenzie: None. W. Young Jr: None. B.M. Dy: None. M. Lyden: None. I. Bancos: None.

Background: Giant pheochromocytomas (PHEO), defined based on size > 10 cm, are rare. Data on clinical presentation, management, and prognosis of giant PHEOs are scarce. Objectives: to determine prevalence of giant PHEO and compare presentation, management, and outcomes of patients with giant vs non-giant PHEOs. Methods: We conducted a single-center retrospective cohort study of consecutive patients with giant PHEO and randomly chosen patients with non-giant PHEO (referents) at 6:1 ratio, evaluated between 2000-2023. All variables were extracted from the electronic medical record. Results: Of 828 patients with PHEO evaluated between 2000 and 2023, 31 (3.7%) had giant PHEO (median size 12 cm, IQR 10.0-13.5). In comparison to referents (n=186, median size 4 cm, IQR, 2.9-5.0), patients with giant PHEO were similar in age (median age 53 vs 55 years, P=.55), more frequently discovered based on symptoms (52% vs 32%, P=.04), and less likely to be bilateral (3% vs 12%, P=.31). Genetic testing was performed in 103 (48%) of patients, without group differences, however, patients with giant PHEO were less likely to have an associated germline mutation detected (7% vs 47%, P=.004). Patients with giant PHEO had more symptoms of catecholamine excess (median of 2 vs 1, P=.04) and presented with a higher prevalence of severe metanephrine excess >10 times above upper normal range (76% vs 30%, P<.0001). Adrenalectomy was performed in 94% of patients with giant PHEOs and in 100% referents, with higher rates of open adrenalectomy in giant PHEO (86% vs 14%, P<.0001). In addition to preoperative alpha-adrenergic blockade (89%), metyrosine was used in 14 (7%) patients, mostly in patients with giant PHEO (26% vs 3%, P<.0001). Patients with giant PHEO had a longer hospital length of stay (laparoscopic: median 5 vs 2 days, P<.0001; open: median 6 vs 5 days, P=.24), and a higher complication rate (31% vs 10%, P=.006).Median follow up was 3 years (IQR 1-8) years, similar in patients and referents. Metastases developed at a much higher rate in patients with giant PHEOs (45% vs 4% in referents, P<.0001). Disease specific mortality was 7% in patients with giant PHEOs and 0% in referents. Conclusion: Patients with giant PHEO were more symptomatic, had a higher degree of catecholamine excess, and a higher rate of perioperative complications. Almost half of patients with giant PHEO developed metastases, warranting a close follow-up.

Presentation: 6/2/2024
8291 Graves’ Disease and Moyamoya Syndrome: A Complex Case of Thyroid Dysfunction and Neurovascular Abnormalities
Authors: Jamil Abid , Luong Quyen Vi , Bonilla Aidaliz Llorens , Siddiqui Ayesha
Published: October 2024

Disclosure: A. Jamil: None. Q.V. Luong: None. A. Llorens Bonilla: None. A. Siddiqui: None.

Background: Moyamoya disease is a cerebrovascular disease characterized by progressive stenosis and occlusion of cerebral arteries, particularly the internal carotid arteries, proximal anterior and middle cerebral arteries associated with a net-like collateral vessel formation. Moyamoya disease in association with certain systemic conditions (e.g. Graves’ disease, sickle cell anemia, neurofibromatosis type 1, and Down Syndrome) has been referred to as moyamoya syndrome. Graves’ disease is an autoimmune disease in which the development of thyroid-stimulating hormone (TSH) receptor autoantibodies leads to overproduction of thyroid hormones. Although the pathophysiology is unclear, Graves’ disease can adversely impact the clinical course of moyamoya syndrome.Clinical Case: A 26-year-old woman diagnosed with Graves’ disease at the age of 20 years who was in remission presented to the ED with right upper extremity weakness and headache. A stroke work-up was performed, and an initial CT head without contrast showed an acute infarct in the left temporal area. Extensive workup for hypercoagulability and cardiac causes were negative. MRI brain showed multiple infarcts of the left cerebral hemisphere with ivy sign, which are prominent linear or punctate high intensity areas in the subarachnoid space reflecting the development of collaterals that occurs in moyamoya disease. TSH at the time was noted to be <0.01 uIU/mL (range: 0.30-4.20 uIU/mL), indicating a thyrotoxic state. She was discharged on methimazole and antiplatelet therapies. However, the patient continued to have hypertension and headaches which did not resolve with the return to euthyroidism. At age 29, she again developed acute right upper and lower extremity weakness, and consequently presented to the ED. Imaging studies showed multiple punctate infarcts in her bilateral frontal lobes and bilateral ICA stenosis consistent with moyamoya disease. However, her biochemical studies showed euthyroidism. Ultimately, she underwent right frontotemporal craniotomy and direct parietal superficial temporal artery to middle cerebral artery bypass by neurosurgery to decrease her future stroke risk for her moyamoya syndrome, and her Graves’ disease remains in remission.Conclusions: The coexistence of Graves’ disease in moyamoya syndrome may suggest a pathophysiologic connection. It has been suggested that hemodynamic changes in cerebrovascular flow due to thyrotoxicosis might contribute to ischemic neurologic deficits. Surgical intervention for revascularization procedures should be attempted after optimal control of thyrotoxicosis, as this may help to prevent further ischemic events in the future and improve patient outcomes.

Presentation: 6/1/2024