bluuebunny/crossref_metadata_2025 huggingface dataset:
SAT154 Insulin Autoimmune Syndrome In The Setting Of Metastatic Colon Cancer: Case Report
Authors: Bernal Maria , Suarez Janine , Tuna Kubra M , Amer Farah , Lamas Marcos
Published: October 2023

Disclosure: M. Bernal: None. J. Suarez: None. K.M. Tuna: None. F. Amer: None. M. Lamas: None.

Insulin Autoinmune Syndrome is a rare cause of hypoglycemia. Its incidence is higher among Asians, Japanese patients. Also known as Hirata’s disease, it is characterized by the presence of a hyperinsulinemic state, hypoglycemia, elevated insulin antibodies titers without prior exposure to exogenous insulin, and no pathological abnormalities of the pancreatic islets cells. Some commonly used drugs and viruses have been identified as triggers. We present the case of 65-year-old male Caucasian patient who presented with recurrent episodes of hypoglycemia, that started after surgical resection of a metastatic liver lesion, in the context of metastatic colon cancer. During the workup, it was confirmed that patient had hyperinsulinemia, hypoglycemia, and positive auto-insulin antibodies without previous exposure to exogenous insulin and no imaging findings suggestive of a pancreatic abnormality. The relevance of this case is not only related to the rarity of this entity in the Western World, but also the possibility of being associated with a paraneoplastic syndrome in the setting of metastatic colon cancer, which to the best our knowledge, has not yet been described in the literature as a possible trigger of Insulin Autoimmune Syndrome.

Presentation: Saturday, June 17, 2023
FRI276 KNDy-Neuron Kisspeptin Is Dispensable For Feeding Behavior, But Critical For Energy Expenditure Leading To Metabolic Dysfunction In Female Mice
Authors: Nandankar Nimisha , Ganesh Harshini , Negron Ariel L , Al-Samerria Sarmed , Levine Jon E , Radovick Sally
Published: October 2023

Disclosure: N. Nandankar: None. H. Ganesh: None. A.L. Negron: None. S. Al-Samerria: None. J.E. Levine: None. S. Radovick: None.

Hypothalamic kisspeptin (Kiss1) is a critical master regulator of the hypothalamic-pituitary-gonadal axis responsible for reproductive development and function. Kiss1, originating from KNDy neurons in the arcuate nucleus (ARC) of the hypothalamus, is implicated in having a dual role in both reproductive and metabolic functions. Using KNDy neuron-specific Kiss1 KO mice (Pdyn-Cre/Kissfl/fl or KO), we explored the role of Kiss1 from KNDy neurons in peripheral metabolism without dietary intervention. Here, we report that KO females have significantly greater body weight, fat mass, and glucose intolerance vs. control females. Interestingly, these parameters did not differ between KO male mice and controls. To determine whether this phenotype was due to dysregulated feeding behavior (i.e., hyperphagia) in KO mice, we tracked daily food consumption in adult mice for 3 weeks. We found no significant differences in food intake between genotypes of either sex. We used the Comprehensive Laboratory Animal Monitoring System (CLAMS, Columbus Instruments) to analyze energy expenditure in our mouse model. Data from the CLAMS experiments revealed reduced energy expenditure in KO females vs. control females, whereas there was no difference in energy expenditure between KO males and control males. Specifically, the respiratory exchange ratio (RER) was not significantly different in KO females vs. control females, indicating that both groups utilize both carbohydrates and fats as their primary energy source. However, heat expenditure was significantly lower in KO females (20.27 ± 2.29 kcal/kg/hr vs. 14.02 ± 1.18 kcal/kg/hr, WT vs. KO, p < 0.0001, 2-way ANOVA, n = 6-7) during the active dark phase, suggesting a decreased energy expenditure. This data suggests that the obesity and impaired glucose tolerance in females lacking Kiss1 from KNDy neurons is likely due to lower energy expenditure (with the expended energy derived from both carbohydrates and fats), rather than hyperphagic behavior.

Presentation: Friday, June 16, 2023
FRI359 Postprandial Hypoglycemia With Elevated Pro-insulin As A Rare Presentation Of Insulinoma
Authors: Kalik Salina , Dehghani Shabnam , Zaidan Julie
Published: October 2023

Disclosure: S. Kalik: None. S. Dehghani: None. J. Zaidan: None.

Background: Insulinoma, a neuroendocrine neoplasm, typically presents with fasting hypoglycemia with abnormally elevated insulin levels but can infrequently present with post-prandial hypoglycemia with elevated pro-insulin levels. Clinical Case: A 49-year-old non-diabetic male, presented with a 3-year history of episodes of blurry vision, sweating, and palpitations associated with low finger stick glucose (45-70mg/dL). Episodes primarily occurred 2-3 hours post-meals particularly after eating a high carbohydrate meal. Symptoms improved after taking glucose tabs consistent with Whipple’s triad. He denied fasting hypoglycemia symptoms. Patient had symptoms at the office 2 hours after eating breakfast and Lab work done at that time showed glucose <35 of mg/dL (70-99 mg/dL), inappropriately high-normal c-peptide level of 3.57 ng/mL (0.81-3.85 ng/mL), elevated pro-insulin level of 12.8 pmol/L (<8.0 pmol/L), and a high insulin level of 29.8 uIU/mL (3-25.0 uIU/mL). Insulin antibodies and Sulfonylurea screen were negative. Review of old imaging revealed unremarkable pancreas on Ct scan done three years ago and a month prior to presentation. Given persistent symptoms and lab results Patient underwent an endoscopic ultrasonography with advanced gastroenterology which showed a 14.2 x 11mm hypoechoic, well circumscribed, regularly shaped and homogenous mass at the pancreatic head that was sampled using fine needle biopsy. Pathology confirmed pancreatic neuroendocrine neoplasm, low grade, consistent with insulinoma. Patient went for MRI of abdomen and pelvis which confirmed a 1.4 x 1.2cm slightly T2 hyperintense, hyper-enhancing lesion in the uncinate process suspicious for islet cell tumor. In addition, a 0.6cm liver lesion was identified although not clearly characterized but small metastatic lesion could not be excluded. PET/CT scan did not reveal any metastatic lesions except the focal uptake at the pancreatic uncinate process. Patient was evaluated by surgery and underwent a successful Whipple procedure for resection of the insulinoma. Discussion: 20% of all insulinomas are misdiagnosed with a seizure disorder or psychiatric disorder before an insulinoma is recognized. This case highlights the fact that insulinoma can be present as post prandial hypoglycemia and the superior imaging modality of EUS and MRI for localizing and identifying smaller functional insulinomas. Conclusion: Insulinoma can present as postprandial hypoglycemia with elevated pro-insulin levels. If high clinical and biochemical suspicion for insulinoma, patient should be evaluated with EUS or MRI even in the setting of a negative CT due to higher diagnostic specificity for insulinoma.

Presentation: Friday, June 16, 2023
THU167 Trends Of Recombinant Human Growth Hormone Treatment In Korea: Data From The Health Insurance Review And Assessment Service 2015-2020
Authors: Kim Jaehyun , Rhie Young-Jun , Kim Yoo-Mi , Lee Hae Sang , Lee Young Ah , Chae Hyun Wook , Choi Jin-Ho , Chung Sochung , Kim Hyoungseok , Son Yunjeong , Han Seungju , Hwang Il-Tae
Published: October 2023

Disclosure: J. Kim: None. Y. Rhie: None. Y. Kim: None. H. Lee: None. Y. Lee: None. H. Chae: None. J. Choi: None. S. Chung: None. H. Kim: None. Y. Son: None. S. Han: None. I. Hwang: None.

Objectives: Recombinant human growth hormone (rhGH) has been used for treating diseases associated with short stature for several decades worldwide and in Korea. The trends in prescribing rhGH in children and adolescents in Korea were evaluated using the nationwide claim data. Methods: Data from the Health Insurance Review and Assessment Service (HIRA) between 2015 and 2020 were used. The nationwide claim data on the prescription of rhGH for approved indications were extracted from the HIRA database and analyzed. Off-label use of rhGH was not investigated. Results: The number of all patients treated with rhGH increased from 5,812 in 2015 to 16,248 in 2020. The number of newly treated patients with rhGH was from 1,763 in 2015 to 5,177 in 2020. Among children and adolescents with short stature, those who were prescribed rhGH increased from 1.9% in 2016 to 5.7% in 2020. The overall proportion of the indications for rhGH treatment was 55% for growth hormone deficiency (GHD), 27% for idiopathic short stature (ISS), 13% for small for gestational age (SGA), and 5% for Turner syndrome. From 2015 to 2020, the increment in newly treated patients was highest in GHD, followed by ISS and SGA. In all indications, male to female ratio decreased during the period: 1.52 in 2016 and 1.30 in 2020 for GHD; 1.18 in 2016 and 0.91 in 2020 for ISS; and 1.13 in 2016 and 1.03 in 2020 for SGA. Expenditure for claims to rhGH also increased from 25.9 billion KRW in 2015 to 62.5 billion KRW in 2020. The mean age at the start of rhGH and the mean discontinuation age was 7.8 years (boys 8.0 years and girls 7.7 years) and 12.0 years (boys 12.2 years and girls 11.8 years), respectively. The mean treatment duration was 3.2 years. Conclusion: In Korea, the prescription of rhGH in the pediatric population showed a 2.8-fold increase in number and a 2.4-fold increase in expenditure over 6 years according to nationwide HIRA data. Boys were treated more with rhGH than girls, whereas the discrepancy decreased. Long-term follow-up for prescription patterns, effectiveness and safety in rhGH treatment is required.

Presentation: Thursday, June 15, 2023
FRI598 Evolving Growth Hormone Deficiency: A Proof Of Concept
Authors: Chimatapu Sri Nikhita , Sethuram Swathi , Samuels Julie , Savage Martin , Rapaport Robert
Published: October 2023

Disclosure: S. Chimatapu: None. S. Sethuram: None. J. Samuels: None. M. Savage: None. R. Rapaport: None.

Introduction: Most cases of growth hormone deficiency (GHD) in pediatric patients are idiopathic, isolated and acquired. All acquired conditions commence with a period during which the diagnosis maybe unapparent. We document here evidence for evolution of GHD in a group of adolescent males who tested sufficient on initial GH stimulation test (GST) but tested deficient upon reevaluation. The rationale for repeat GST was ongoing growth failure. Hypothesis: We hypothesize that GHD in some individuals evolves with time and can be diagnosed by repeat testing (EGHD). We also postulate that their response to GH therapy is similar to other patients with GHD. Methods: We performed an IRB-approved retrospective chart review of children who presented for short stature (height less < 2SD for mean or < 2SD for mid-parental height) to pediatric endocrinology at Kravis Children’s Hospital at Mount Sinai, New York and who had 2 GST. GST were performed using two different stimuli (arginine and glucagon) and highly sensitive assay serum GH measurements were processed by the same laboratory, Esoterix. No patient had obesity, chronic illnesses, or any genetic conditions affecting growth. Data were collected from electronic medical records and analyzed using SPSS v28.0 once at least half the population studied reached adult height. We defined adult height as bone age ≥ 16 years and growth velocity ≤ 2 cm/year. Results: Of 42 charts analyzed, all male, 25 had EGHD. Their average GH peak on initial GST was 15.48 ± 4.92 ng/ml, mean age 10.07 ± 2.65 years, mean height -1.68 ± 0.56 SD , IGF-1 -1.00 ± 0.88 SD. After 2.23 ± 1.22 years, at 12.04 ± 2.41years, height decreased to -1.82 ± 0.63 SD and IGF-1 was -1.08 ± 0.84 SD. At repeat GST, GH peak was 7.59 ± 2.12 ng/mL and 28% were in puberty. All patients had MRI before starting GH therapy; 40% had small anterior pituitary glands. 12 males who reached adult height had a height of -1.88 ± 0.64 SD, IGF-1 of -1.15 ± 0.81 SD, with 42% pubertal and peak GH of 7.33 ± 2.47 ng/mL at repeat GST. They had a mean height gain of 1.83 ± 0.56 SD(p<0.005), with an adult height of 0.09 ± 0.70 SD after 4.64 ± 1.4years of treatment. They were 2.10 ± 4.20 cm taller than their mid-parental target heights. Discussion/Conclusions: We provide proof of concept for the diagnosis of EGHD. The diagnosis could be established by repeat GST in children with ongoing growth deceleration despite pubertal progression and a non-diagnostic initial GST. Our patients who reached adult height had a height gain consistent with that reported by KIGS for patients with growth hormone deficiency (1.7SD; Cutfield,1999) and indeed better than patients with ISS (0.7SD; Maghnie,2022).

Presentation: Friday, June 16, 2023
FRI388 Follicle-Stimulating Hormone And Salt-inducible Kinases Crosstalk On The Regulation Of Genome-wide Gene Expression In Human Granulosa Cumulus Cells
Authors: Hayes Emily , Filzen Rachael , Esquivel Miriam Rodriguez , Winston Nichola , Fierro Michelle , Sana Salih , Stocco Carlos Oscar
Published: October 2023

Disclosure: E. Hayes: None. R. Filzen: None. M. Rodriguez Esquivel: None. N. Winston: None. M. Fierro: None. S. Sana: None. C.O. Stocco: Grant Recipient; Self; NIH R01HD097202.

Infertility affects approximately 15% of couples, 40% are due to ovulatory defects. Successful ovulation requires the timely and tight regulation of folliculogenesis by gonadotropins, more crucially, follicle-stimulating hormone (FSH), which is needed to form preovulatory follicles. However, the mechanisms governing folliculogenesis are incompletely understood. We previously showed that salt inducible kinases (SIKs) are critical regulators of female fertility. Specifically, knockout of SIK2 enhances ovulation, whereas deletion of SIK3 results in anovulation and premature ovarian failure. At the molecular level, SIK2, but not SIK3, attenuates the expression of FSH-induced steroidogenic genes. This report aimed to outline the genome-wide effect of SIK inhibition on gene expression in the presence or absence of FSH. Here, we treated human cumulus cells with a SIK inhibitor, HG-9-91-01 (HG), FSH, or their combination. We then performed RNA sequencing and identified 3,472 differentially expressed genes (DEGs) across treatment groups. Interestingly, 498/646 (77%) of DEGs in FSH-treated cells were also identified as DEGs in HG-treated cells. Further, HG + FSH resulted in 865 DEGs not differentially regulated by FSH or HG alone. Analysis of DEGs by Gene Set Enrichment Analysis (GSEA) revealed top enriched gene ontology terms including processes related to the extracellular matrix, steroid hormone biosynthesis, PI3K-Akt signaling, and cAMP signaling. The data suggest that SIK activity profoundly affects gene expression in human granulosa cells, likely via regulation of FSH signaling and other mechanisms. These findings provide new insights and directions for investigating the mechanisms by which SIKs regulate ovarian function and fertility.

Presentation: Friday, June 16, 2023
FRI398 A Case Of Secondary Amenorrhea: Is It Only PCOS To Blame?
Authors: Panjawatanan Panadeekarn , Riahi Shayan , Chaidarun Sushela S
Published: October 2023

Disclosure: P. Panjawatanan: None. S. Riahi: None. S.S. Chaidarun: None.

Background: One of the most common causes of secondary amenorrhea is PCOS (polycystic ovary syndrome) which accounts for 30% of the cases. Though not as common, hyperprolactinemia similarly contributes to the condition. Here we describe a patient who presented with secondary amenorrhea from medication-induced hyperprolactinemia with underlying PCOS.

Clinical Case: A 31-year-old female with a past medical history of bipolar disorder, hypothyroidism, and PCOS, presented with secondary amenorrhea. The patient started menarche at 11 years old and was diagnosed with PCOS a year later due to irregular menses and hirsutism. The estrogen-containing pill was prescribed, but she developed a blood clot due to Factor V Leiden thrombophilia. She was taking atomoxetine, lithium, mirtazapine, and olanzapine for her psychiatric issues and recently started on paliperidone last year. She reported no period in the past two years after stopping oral contraception. Pregnancy was ruled out. She tried progesterone challenge test but did not have any flow. Transvaginal ultrasound showed thin endometrium. She had IUD placed for contraception. Laboratory testing four months and one year after starting paliperidone showed prolactin of 79.2 ng/mL and 110 ng/mL consecutively. The patient reported headaches but denied galactorrhea or visual loss. There are no signs or symptoms of Cushing’s disease, acromegaly, or hypothyroidism. Further workup showed TSH 1.52 mcIU/mL, estradiol 16 pg/mL, FSH 5.6 mIU/mL, 17-OH progesterone <40 ng/dL, total testosterone 14 ng/dL, ACTH 11 pg/mL, IGF-1 z-score -0.67 SD. MRI brain was ordered, which ruled out pituitary adenoma. Repeat prolactin level remained elevated at 87.7 ng/mL without treatment. We concluded that the patient has secondary amenorrhea from PCOS and antipsychotic-induced hyperprolactinemia. Patient was referred to a psychiatrist for antipsychotic medication changes.

Conclusion: Antipsychotics, typically first-generation, are known to cause hyperprolactinemia due to their dopamine-antagonist effect. Prolactin level ranging from 25-100 ng/mL is seen in medication-induced hyperprolactinemia, while particular medication like risperidone and phenothiazines can raise the level to more than 200 ng/mL. Newer agent paliperidone has been reported to induce hyperprolactinemia similarly to risperidone which explains significant prolactin elevation in this patient. Hyperprolactinemia poses a risk for hypogonadism due to suppressed pituitary-gonadal axis, resulting in anovulation and bone loss. Estrogen therapy is considered an adjunct to help with hypogonadism. However, it is contraindicated in patients with thrombophilia. The guideline recommends switching to a low-risk antipsychotic agent if feasible. Despite having an established diagnosis of PCOS, it is important to consider other secondary causes of amenorrhea which may occur concomitantly.

Presentation: Friday, June 16, 2023
SAT422 Gender Affirming Hormone Therapy in a Non-Binary Individual with Swyer Syndrome
Authors: Yohannan Jiby M , Reisman Tamar
Published: October 2023

Disclosure: J.M. Yohannan: None. T. Reisman: None.

Background: Swyer syndrome is a rare genetic disorder of sexual development. Patients with Swyer syndrome require physiologic hormone replacement congruent with their gender identity in order to prevent bone loss. It is also important to screen for complications of this condition including osteopenia and dysgerminomas. Clinical Case: A 25 year old individual with a history of Swyer syndrome (46 XY gonadal dysgenesis) presents to clinic to discuss initiation of gender affirming hormone therapy. The patient identifies as non-binary and is interested in starting testosterone for masculinization.

The patient was initially diagnosed with Swyer syndrome at age 23 during an evaluation for primary amenorrhea. At that time the patient had a laparoscopic gonadectomy and was found to have a dysgerminoma. Upon diagnosis the patient was started on hormone replacement therapy with norethindrone acetate-ethinyl estradiol 1 - 0.01 mg for bone loss prevention. They had a bone mineral density scan two years prior to presentation that was reportedly normal. To avoid the deleterious effects of hypogonadism they were started on estradiol-norethindrone 0.05 - 0.25 mg patch to provide bone protection. They were also provided testosterone gel for masculinization as part of their gender affirming care. Swyer syndrome is a disorder of sex development in which individuals with XY chromosomes develop phenotypically female Mullerian structures (uterus, fallopian tubes, and vaginal canal). Individuals with Swyer syndrome typically have non-functional “streak gonads” and are diagnosed during evaluation for primary amenorrhea. While some cases may be from a novel mutation, there are case reports showing that the condition can have an autosomal dominant, autosomal recessive, or even X-linked pattern of inheritance depending on the mutated gene. Patients with Swyer syndrome require physiologic doses of hormone replacement for maturation of secondary sex characteristics and bone health. For this patient in particular it is also important to provide appropriate hormone replacement congruent with their gender identity. Additionally, approximately 30% of patients with this condition may develop a gonadal tumor, including dysgerminomas. Because of this, patients frequently have their gonads removed upon diagnosis. Conclusion: Patient’s with Swyer syndrome should be on appropriate hormone replacement as they do not make endogenous sex steroids. Additional consideration of masculinizing hormone replacement should be made for patients that have a gender identity other than cisgender female. It is also important to screen patients for gonadal tumors as there is an increased incidence in this population.

References: King, Thomas F.J.; Conway, Gerard S. Swyer syndrome. Current Opinion in Endocrinology & Diabetes and Obesity: December 2014 - Volume 21 - Issue 6 - p 504-510, doi: 10.1097/MED.0000000000000113

Presentation Date: Saturday, June 17, 2023
SAT009 Investigating The Role Of Hepatic Small Heterodimer Partner In Regulating Gallstone Formation
Authors: Dang Nathanlown Mun , Anakk Sayeepriyadarshini
Published: October 2023

Disclosure: N.M. Dang: None. S. Anakk: None.

Nuclear receptor, Small Heterodimer partner (Shp) regulates bile acid homeostasis by inhibiting transcription of Cholesterol 7 alpha-hydroxylase (Cyp7a1), the rate-limiting enzyme involved in converting cholesterol to bile acids, within the liver. Bile acid regulation prevents the formation of gallstones as cholesterol is excreted into bile along with bile acids and phospholipids. How hepatic Shp affects the development of gallstones and the mechanisms underlying these effects remain unclear. Here we used a liver-specific knockout mouse model and a lithogenic diet model to uncover potential liver-to-gallbladder crosstalk that contributes to gallstone development. Previously, we had shown that the knockout of Shp alters bile acid composition, resulting in higher percentages of secondary bile acid, deoxycholic acid. This increased the hydrophobic index of hepatic bile acids and also implicated a trend for a subsequent increase in the hydrophobicity of biliary bile. Higher hydrophobicity is sufficient to increase susceptibility to developing gallstones by promoting cholesterol nucleation. Of note, the expression of transporter genes Abcg5 and Aqp1 were altered in the gallbladder of hepatic Shp knockout mice, indicating a potential change in their bile composition. The enterokine, Fgf15 is known to stimulate gallbladder filling through its interaction with its receptor, Fgfr4. Recently, the Fgf15-Fgfr4 axis was shown to prevent degradation of the SHP protein such that impeding this axis led to higher Cyp7a1 transcript, increased bile acid levels, and altered gallbladder filling. Taken together, these findings suggest that hepatic Shp acts as a central node that regulates bile acid transport, homeostasis, and composition within the gall bladder and thus can prevent gallstone development. Elucidating Shp-mediated liver-to-gallbladder crosstalk is important for understanding the contribution of liver dysfunction towards gallbladder diseases and gallstones.

Presentation: Saturday, June 17, 2023
FRI497 Thyroid Storm And Recurrent Myopericarditis
Authors: Gomez D' Aza Danelly J , Zahedi Tooraj , Zhang Fan
Published: October 2023

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

Introduction: Thyroid storm is an acute life-threatening complication of hyperthyroidism with high mortality rate. Plasmapheresis is often used in patients who are unresponsiveness to conventional treatment for thyroid storm. About 5% of thyroid storm patients present with heart failure while other cardiovascular dysfunctions include tachycardia, arrhythmias, hypertension, and pericardial disease. Myopericarditis is characterized by pericarditis associated with myocardial inflammation evident by elevated cardiac biomarkers. Thyrotoxicosis associated with pericarditis and myocarditis is rare. Here, we report a case of recurrent myopericarditis and thyroid storm in Grave’s disease treated with plasmapheresis. Case Report: A 47 years male with a history of Schizophrenia and Hyperthyroidism due to Grave’s disease was presented with poor oral intake, generalized weakness, and tachycardia with HR 180 bpm. Labs showed elevated troponin 0.505 ng/mL, Free T4 > 6.99 mg/dL, T3 > 651 ng/dL, and low TSH < 0.015 mg/dL. Burch-Warsofsky scale was 50 points which suggested thyroid storm. EKG revealed atrial fibrillation. Patient was managed with propranolol, propylthiouracil (PTU), iodine solution, hydrocortisone, and Diltiazem. However, his mental status deteriorated requiring intubation and patient developed cardiac shock with BP 77/53 mmHg. Troponin I trended up to 23.60 ng/mL and EKG showed ST-segment elevation in the anterior and inferior leads. Echocardiogram revealed severely reduced ejection fraction of 15 % and diffuse hypokinesis. Cardiac catheterization was unremarkable. PTU was discontinued due to liver dysfunction with AST and ALT levels above 1500 U/L and 2500 U/L. A session of plasmapheresis was initiated and the post labs showed an improvement of thyroid and liver function to Free T4 2.46 mg/dL, TSH 0.022 mg/dL, and ALT/AST 641/682 U/L. Patient was hemodynamically stable with normal sinus rhythm. Cardiac magnetic resonance images revealed left ventricular dilation with high T2 signal, late gadolinium enhancement in the pericardial region of basal inferolateral, inferior, and mid segments, consistent with pericarditis. Previous record showed patient had a similar admission 4 months ago with a diagnosis of myopericarditis. Discussion: The association of recurrent myopericarditis and hyperthyroidism may be related with the autoimmune dysfunction and underlying viral infection that precipitated inflammation of the thyroid gland, triggered thyroid storm, and caused cardiac event. Rapid correction of the hyperthyroid state is warranted in thyroid storm in addition to aggressive treatments for heart failure, arrhythmias, and myopericarditis. Our patient’s cardiac function improved rapidly after achieving euthyroidism by plasmapheresis. The treatment of hyperthyroidism is critical in preventing the recurrence of myopericarditis.

Presentation: Friday, June 16, 2023
FRI500 Atypical Case Of Undifferentiated Shock
Authors: Vadini Vidhu , Vasistha Prabhav
Published: October 2023

Disclosure: V. Vadini: None. P. Vasistha: None.

Introduction: Shock is encountered frequently in the ICU. Undifferentiated shock, however, poses a diagnostic challenge. The differentials and work up are broad and time sensitive. Endocrinopathies are a known etiology but thyroid cardiomyopathy causing cardiogenic shock is rare. Clinical case: A 78 y old man presented to the ER with hypotension that did not improve after administration of 2.5 L IV fluids. Vasopressors were initiated and he was admitted to the ICU. Patient reported 2-month history of generalized weakness, nausea, vomiting, falls and poor oral intake. Review of systems was notable for 20-pound weight loss in 6 months, dyspnea with exertion, loss of appetite and occasional diarrhea. On exam, patient was afebrile, hypotensive 80/40, PR 87, O2 saturation > 90% on room air. He appeared pale with JVP measured at 11 cm of water. Pulse was irregular, heart sounds normal without murmurs. Bilateral lower extremities were mildly edematous. Strength in lower extremities was 4/5 proximal and distally. Labs were notable for normocytic anemia, troponin 1.05, elevated anion gap 18, lactate 1.8, creatinine 3.3 from a baseline of 1 and BNP 1425. ECG showed sinus rhythm with frequent premature atrial contractions. Chest Xray on admission was unremarkable. Additional labs were negative drug screen, normal cortisol, urinalysis. Blood cultures were sent. Overnight, the patient developed tachycardia and atrial fibrillation with rapid ventricular rate. Cardiology was consulted, bedside echo was suspicious for low left ventricular ejection fraction. The patient was anticoagulated with heparin. TSH was sent. He was requiring 2 vasopressors to maintain MAP>65. CT chest abdomen pelvis was unremarkable except stable pulmonary nodule. Patient became hypoxic on Day 2 of admission, CXR now showed features of pulmonary edema. TSH returned less than 0.01, free T4 4.69 Endocrinology was consulted, methimazole was started for thyrotoxicosis. Formal TTE showed LVEF 20-25% with global reduction in left ventricular contractility, dilated left atrium and mild MR. He was given furosemide for pulmonary edema. TSI and TRAB were positive indicating Grave’s disease. He was successfully transferred out of the ICU. Patient gradually became euvolemic with significant improvement in energy, appetite and functional capacity. He was able to participate in physical therapy and was eventually discharged to rehab. Conclusion: This case addresses an uncommon but potentially life-threatening cause of undifferentiated shock. Physical exam, history and high degree of suspicion are key in early identification and treatment. Although thyroid cardiomyopathy is rare, Grave’s disease is common and ruling our thyrotoxicosis should be included in preliminary work up of undifferentiated shock.

Presentation: Friday, June 16, 2023
FRI504 Ectopic Hyperactive Mediastinal Thyroid Tissue: A Case Report
Authors: Dimech Christina , Jaiswal Gayatri , Bhargava Amit
Published: October 2023

Disclosure: C. Dimech: None. G. Jaiswal: None. A. Bhargava: None.

Ectopic thyroid tissue is usually located along the normal path of the caudal migration of thyroid tissue during embryonic life. Substernal goiters are thought to occur by either the enlargement of ectopic mediastinal thyroid tissue (primary mediastinal goiter) or abnormal extension of thyroid issue into the superior mediastinum (secondary mediastinal goiter). Typically these goiters remain asymptomatic, and rarely result in hyperthyroidism or local compression of the surrounding area. We report a case of an 89-year-old Caucasian female with history of a multinodular goiter status post right hemithyroidectomy, who initially presented for subclinical hyperthyroidism. Further evaluation revealed negative thyroid stimulating antibodies. A thyroid ultrasound demonstrated a surgically absent right lobe, with a small heterogenous left lobe. A nuclear medicine radioactive iodine uptake and scan showed hypermetabolic residual thyroid tissue with a large area of increased radiotracer uptake projecting over the right anterior chest, concerning for ectopic thyroid tissue. A subsequent chest CT without contrast revealed an approximately 5 centimeter partially calcified anterior mediastinal/retrosternal mass. Given the patient’s age and co-morbidities, a decision was made to treat the hyperthyroidism with methimazole and monitor the ectopic tissue for worsening symptoms of compression. In cases with severe compressive symptoms, or difficult to treat hyperthyroidism, a surgical option must be considered.

Presentation: Friday, June 16, 2023
FRI558 Hidden Cause Of Decreased Fertility Rate During Grave’s Disease
Authors: Kutchukhidze Tinatin , Khurodze Tea
Published: October 2023

Disclosure: T. Kutchukhidze: None. T. Khurodze: None.

Introduction: Thyroid autoimmune disorders interfere with the physiology of reproduction, cause premature ovarian aging, and mimic the early stage of menopause. Recently, no specific research was made to measure Grave’s disease and infertility rates in young patients. Case Report: Due to an inability to conceive for two years, a 24-year-old Caucasian female was referred to the clinic with typical symptoms and complaints of Grave's disease. She has a family history of Grave’s disease and Diabetes mellitus. Ultrasound confirmed the presence of a highly vascularized non-homogeneous hyperplastic thyroid gland. A thyroid scan with Tc99m revealed generalized increased uptake. Laboratory investigations showed a decrease in TSH-<0.005mIU/ml (n.0.4mIU/ml - 4.0mIU/ml), elevated FT4-31.8 pmol/l (n.8.0pmol/l-22.0pmol/l), FT3- 9.69pmol/l (n3.4 pmol/l-6.76pmol/l) and positive Anti-TG -190.05 AU/ml (n>150), Anti-TPO -75.7 IU/ml (n>75) Anti-TSHR-27.3 IU/l (n>1,5). Prolactin and gonadal hormones were within normal limits AMH - 1.8 ng/ml(n1.52ng/ml-9.95ng/ml), FSH- 6mIU/ml(n3.9mIU/ml-12.4mIU/ml). The patient was started on Methimazole and Beta-blocker. While decreasing the Methimazole dosage for further discontinuation, disease recurrence developed, and a total thyroidectomy was performed. Postoperatively, the patient was maintained on Levothyroxine. After 6 months of follow-up due to irregular Levothyroxine intake, the patient reached a hypothyroid status, during which, the patient had 2 consecutive spontaneous pregnancies, from which, one ended with spontaneous miscarriage in the early weeks of pregnancy and another, ectopic pregnancy treated with right salpingectomy. HSG confirmed weak left fallopian tube patency. After several months of keeping TSH below 2.5 mIU/ml, IVF treatment was scheduled. The results of the infertility workup showed a decrease in ovarian reserve AMH - 0.163ng/ml (n1.52ng/ml-9.95ng/ml), FSH-16.23 mIU/ml(n3.9mIU/ml-12.4mIU/ml), due to it, modified natural cycle IVF was performed. She received 2 oocytes and 2 embryos. One high-grade blastocyst was transferred in a fresh cycle that ended with pregnancy and delivery. The child was born without a genetic disorder but with natal teeth. Conclusion: This is a rare case of infertility with diminished ovarian reserve due to Grave’s disease. A pregnancy was reached by proper correction of thyroid hormonal parameters and modified natural cycle IVF. It indicates a possible need for close monitoring of the functional ovarian reserve in patients planning pregnancy even in the young age group.

Presentation: Friday, June 16, 2023
SAT546 Papillary Thyroid Cancer Surveillance: Thyroglobulin Levels Affected by HAMA
Authors: Perez Julienne Sanchez , Obeid Michele , Fariduddin Maria , Toft Daniel Joseph
Published: October 2023

Disclosure: J. Sanchez Perez: None. M. Obeid: None. M. Fariduddin: None. D.J. Toft: None.

Introduction: Thyroglobulin (TG) measurement is a major means of detecting recurrence of previously treated differentiated thyroid cancers. Human-Anti Mouse Antibodies (HAMA) can interfere with lab measurements of TG levels and affect clinical decisions and treatment for these cancers.Clinical Case: A 65-year-old female was diagnosed with papillary thyroid cancer (PTC). Surgical pathology following total thyroidectomy demonstrated a tumor of 3.5 cm in its greatest dimension, unifocal, without invasion of locoregional tissue classified as Stage I (pT2N0M0) per AJCC 8th edition. Radioiodine whole body scan (WBS) demonstrated iodine uptake in the neck and 126.5 mCi of I-131 was given. In surveillance 5 years later, TSH was found to be 0.17 mcIU/ml (ref range: 0.35 - 4.00) TG 64.7 ng/ml (ref range: 1.3 - 31.8 ng/mL), and anti-Tg antibodies were undetectable. Neck US consistently showed nonspecific findings of stable small nodes with normal morphology in both supraclavicular regions. Given elevated TG levels, 250 mCi of I-131 was given. Follow-up TG levels ranged from 27.8 to 36.4 ng/ml. A repeat WBS did not reveal any uptake, but as TG remained elevated, I-131 (238 mCi) was again given. Subsequent TG throughout the following 15 years ranged from 2.8 - 58.6 ng/ml. Repeat Neck US only showed benign-appearing lymph nodes. WBS did not have any focal activity to suggest recurrent disease and PET/CT did not show any abnormal FDG uptake. The persistently high TG levels without clinical evidence of tumor recurrence raised the suspicion of lab interference. The serum sample was treated with a blocking reagent that contained mouse immunoglobulin after which the TG level decreased to 2.7 ng/ml compared to untreated value of 20.5 ng/ml.Conclusion: HAMA are human antibodies against mouse antibodies which are believed to develop in humans from direct contact with rodents, including mice, and from the recent increase in the use of mouse monoclonal antibodies for diagnostic and therapeutic purposes. These antibodies implicate an unexpected source of interference in immunoassays, as seen in our patient, which can confound laboratory results and create a clinical dilemma. This patient with PTC had a complete radiological response after surgery, but an incomplete biochemical response which caused the patient to be given a total of 614 mCi of I-131. This case highlights the importance of recognizing the possible presence of HAMA when analyzing TG levels, particularly when the TG levels are used for treatment decisions.

Presentation Date: Saturday, June 17, 2023
SAT547 Hereditary Paraganglioma: The Rare Co-Existence Of Two Genetic Syndromes Associated With PPGL-pheochromocytoma
Authors: Samuel Kelara
Published: October 2023

Disclosure: K. Samuel: None.

Hereditary Paraganglioma: the rare co-existence of two genetic syndromes associated with PPGL-Pheochromocytoma Kelara Samuel MD, Bryan McIver MD, Colleen Veloski MD, Julie Hallanger-Johnson MD, Valentina D. Tarasova, John Tourtelot MD, George Q. Yang MD, Sarimar Agosto-Salgado MD Background: Paragangliomas are neuroendocrine tumors arising from neural crest chromaffin cells of the autonomic ganglia and can be parasympathetic or sympathetic in nature. Approximately 30 percent of all paragangliomas are hereditary either associated with familial paraganglioma syndromes and other autosomal dominant syndromes, such as multiple neuroendocrine neoplasia 2A and 2B, neurofibromatosis type 1, and von Hippel Lindau disease.Case: A 73-year-old Hispanic female with a past medical history of hypothyroidism, hypertension, hyperlipidemia, and Lupus presented with a large neck mass of 11 years of evolution. An evaluation revealed a large near 12cm hypervascular, hyperenhancing left neck mass that encased the distal common carotid artery, carotid bifurcation, and internal and external carotid arteries and their branches. The multidisciplinary team recommended, given the tumor's extent, a non-surgical localized treatment consisting of radiation. Clinically, the patient had compressive symptoms, including tenderness over the tumor region, hoarseness, dysphagia, and changes in phonation. The patient also had a positive family history of paraganglioma in her grandson and nephew, but specific genetic alteration data from relatives was unavailable. Plasma normetanephrines were 0.68 (normal range 0-0.89), and plasma metanephrines were 0.23 (normal range 0-0.49). Genetic testing was positive for germline alterations in both SDHB p.Q214 and NF1 c.2970_2972delAAT. At this time, there is no evidence of metastatic disease and no clinical manifestations of NF1, suggesting a mild neurofibromatosis phenotype. Restaging imaging revealed an ongoing partial response to radiation and clinically patient has noted a significant improvement in the prior compressive symptoms. Conclusion: We present a case where we see an uncommon presentation of a non-secretory, hereditary paraganglioma with two concomitant rare genetic syndromes. This case highlights the importance of genetic testing for patient-appropriate tumor surveillance and family counseling implications.

Presentation Date: Saturday, June 17, 2023
SAT570 Thyroid Lymphoma In A Patient With Hashimoto’s Thyroiditis
Authors: Aggarwal Tanya , Reyes Stephanny , Glitza Oliva Isabella C , Korytnaya Evgenia
Published: October 2023

Disclosure: T. Aggarwal: None. S. Reyes: None. I.C. Glitza Oliva: None. E. Korytnaya: None.

Background:Primary thyroid lymphoma (PTL) accounts for < 5% of thyroid malignancies. Patients with Hashimoto’s thyroiditis (HT) are at greater risk for developing PTL, with a relative risk of 67 compared to those without thyroiditis. The most common and more aggressive subtype of PTL is diffuse large B cell lymphoma (DLBCL) which is found in more than 50% of the cases, followed by MALT lymphoma and follicular lymphoma (FL), which represents only about 10% of cases. PTL can be classified as a nodular, diffuse, or mixed type based upon ultrasound (US) findings. Diffuse type PTL presents the biggest diagnostic challenge due to resemblance to thyroiditis on US imaging. Certain US features such as enhanced posterior echoes, markedly hypoechoic appearance of thyroid tissue and linear echogenic strands are suggestive of diffuse type PTL but can also be seen in HT. Positive predictive value for US was only 33.7% for diffuse type of PTL. Diagnosis of PTL is ultimately established by biopsy with immunophenotypic assessment. Management of PTL includes chemotherapy, radiation therapy or combined modality treatment. Given sensitivity of PTL to radiation and chemotherapy, surgery is rarely performed and is reserved only for alleviation of severe compressive symptoms in aggressive disease or protection of airway. Case Presentation: A 58-year-old female with 10-year history of HT, hypothyroidism and goiter underwent total thyroidectomy due to worsening compressive symptoms in her neck. She denied weight loss, fevers, or night sweats. Preoperative US showed enlarged heterogenous hypoechoic thyroid gland with echogenic strands and normal vascularity, consistent with the appearance in HT. Surgical pathology unexpectedly showed extensive follicular hyperplasia, focal grade 3b FL (80%), and large foci of DLBCL arising within FL (20%). Background changes of oncocyte metaplasia and lymphocytic infiltrates consistent with Hashimoto Thyroiditis were described. Both cytogenic FISH studies as well as immunohistochemistry failed to reveal MYC and BCL2 and/or BCL6 rearrangements. Positron emission tomography (PET) scan showed mild to moderately fluorodeoxyglucose- avid lymph nodes in the right superior mediastinal, right superior paratracheal and left neck region. The patient has completed 6 cycles of R-CHOP chemotherapy with complete response as evidenced by normal follow up PET imaging. Conclusion:PTL is a rare malignancy and less than 1% patients with Hashimoto’s thyroiditis develop thyroid lymphoma. Diffuse- type PTL should be included in the differential diagnosis while managing patients with HT who present with worsening compressive symptoms involving aerodigestive tract and rapid enlargement of goiter and have markedly hypoechoic thyroid gland with heterogenous internal echoes and posterior acoustic enhancement on US images.

Presentation: Saturday, June 17, 2023
SAT571 When Two Is Too Few: Bethesda IV Pathology On Repeat Thyroid Fine Needle Aspiration
Authors: Godar Cassandra M , Spiro Andrew J , Shakir Mohamed K M , Hoang Thanh D
Published: October 2023

Disclosure: C.M. Godar: None. A.J. Spiro: None. M.K. Shakir: None. T.D. Hoang: None.

Background: The 2015 American Thyroid Association Guidelines for Adult Patients with Thyroid Nodules provide a strong recommendation against routine ultrasound surveillance of thyroid nodules for which two benign fine needle aspiration (FNA) cytology results have been previously obtained. Strict adherence to these guidelines may hinder detection of malignancy, especially in large nodules where there is potential to miss heterogeneous pathology based on sampling technique.

Clinical Case: A 36-year-old female was evaluated for surveillance of a large non-toxic multinodular goiter. Thyroid ultrasound demonstrated a dominant right thyroid nodule greater than 7 centimeters in size. The patient had undergone FNA of this nodule in 2014 and 2019 with Bethesda II (benign) cytopathology results.

A chest x-ray showed tracheal deviation without evidence of narrowing. She noted a sensation of neck pressure without dysphagia or shortness of breath. She denied fatigue, heat or cold intolerance, hand tremor, or pretibial myxedema. She denied a family history of thyroid cancer or any history of neck irradiation. Due to new compressive symptoms a repeat FNA was performed. Three passes were performed with adequate samples, and the final FNA cytopathology demonstrated a Hurthle cell oncocytic-type follicular neoplasm with Bethesda IV classification. The sample was submitted for ThyGeNEXTTM and ThyraMIRv2TM molecular testing, which returned with NRAS q61R mutation of moderate-to-high risk of malignancy (65-75%). The patient was subsequently referred for total thyroidectomy with pending surgery date.

Discussion: The current ATA guidelines offer a cost-effective surveillance strategy for the vast majority of patients with thyroid nodules. False negative FNA results are rare and are reported to occur in about 1% of cases1. As in this vignette, it is reasonable to perform an additional FNA after two consecutive Bethesda II results in nodules with clinically significant growth, new compressive symptoms, or if there is concern for incomplete sampling in nodules of large size. During an FNA, care should be taken to gently move the needle at various angles to capture follicular cells from different areas within a nodule. Large nodules should be sampled via multiple, separate skin entry points when feasible. Judicious use of repeat FNA along with these sampling techniques may help to prevent under-diagnosis in nodules containing multifocal areas of heterogeneous pathology.

Reference: 1) Durante C, Costante G, Lucisano G, Bruno R, Meringolo D, Paciaroni A, Puxeddu E, Torlontano M, Tumino S, Attard M, Lamartina L, Nicolucci A, Filetti S. 2015. The natural history of benign thyroid nodules. JAMA 313:926-935

Presentation: Saturday, June 17, 2023