bluuebunny/crossref_metadata_2025_split huggingface dataset:
8183 An Unusual Cause of Fluctuating Thyroid Hormone Levels
Authors: Taqi V , Akhter W , Gilden J L 
Published: October 2024

Abstract
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 &gt; 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

Abstract
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&lt;0.001), diabetes mellitus (14.8% VS 11.4% p &lt;0.001), and obesity (6.9% Vs 3.1%, p&lt;0.001). In-hospital mortality was higher among the older cohort (2.6% Vs 0.87, p&lt; 0.001). On linear regression analysis, increased age was associated with increased in-hospital mortality (p&lt;0.001). On multivariable regression, age &gt;80 years was associated with higher odds of inpatient mortality (OR1.229, CI 1.174-1.286, p&lt;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&lt;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&lt;0.001) and Ulcerative Colitis (OR 1.025, CI 0.991-1.061, p&lt;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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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 &gt;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

Abstract
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. &lt;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