bluuebunny/crossref_metadata_2025 huggingface dataset:
SAT542 TDC or Not TDC: Isolated Ectopic Papillary Carcinoma in the Midline Neck with a Benign Native Thyroid
Authors: Fasen Madeline , Kosmiski Lisa
Published: October 2023

Disclosure: M. Fasen: None. L. Kosmiski: None.

Background: Thyroglossal duct carcinoma is a rare entity, occurring in about 1% of all thyroglossal duct cysts (TDC). Several cases have reported PTC within a thyroglossal duct cyst. Initially thought to be a TDC, we present an unusual case of a midline ectopic papillary thyroid carcinoma with absence of features characteristic of a TDC in the context of benign native thyroid tissue. Clinical Case: A 19 year old female presents to the clinic with a progressively growing midline neck mass over the past five years associated with mild dysphagia. Physical exam was notable for 2 x 2 cm mobile nontender midline mass. Neck ultrasound demonstrated a complex cystic lesion measuring 3.8 x 3.4 x 2.5 cm with partial calcification and mildly vascular. The thyroid itself had no nodules. She underwent a Sistrunk procedure with follow-up pathology revealing 1.6 cm classical PTC that extended into surrounding soft tissue and focal invasion into skeletal muscle without a definitive remnant thyroglossal duct lining despite cystic architecture. The differential included PTC completely replacing the thyroglossal duct cyst, PTC arising from ectopic thyroid tissue or metastatic PTC. Due to the unclear origin of the PTC, decision was made to perform total thyroidectomy. Pathology of the thyroid and four lymph nodes were negative for malignancy confirming a PTC origin from an extra-thyroidal remnant. The patient’s course was complicated by post-operative hypocalcemia resolved with calcitriol and calcium carbonate. She is pending discussion with endocrinology regarding adjuvant radioactive iodine. Conclusion: Thyroglossal duct carcinoma, most commonly papillary carcinoma, is a rare condition that should be considered in patients presenting with cystic midline neck masses. Sistrunk surgery should be performed in all cases for tumor removal. Thyroidectomy in individuals with normal thyroid can be considered due to the probability of concomitant intraglandular thyroid cancer and enables management with adjuvant radio-iodine if needed. In this particular case, PTC was found without evidence of a TDC and suggests PTC arose from ectopic thyroid tissue. Ectopic thyroid tissue can undergo malignant transformation along with the native thyroid gland. There are only a few other reports of isolated ectopic thyroid tissue malignancy with a benign thyroid gland.

Presentation Date: Saturday, June 17, 2023
SAT543 A Case of Non-iodine-Avid Papillary Thyroid Cancer With a Rare Distant Metastasis to the Pancreas
Authors: Huliganga Alcain Alistair Marie , C. Isidro Maria Jocelyn
Published: October 2023

Disclosure: A.H. Alcain: None. M.C. Isidro: None.

Papillary Thyroid Carcinoma is the most common type of differentiated thyroid cancer. Distant metastasis is rare occurring only in 5% of patients and typically involves the lungs and bones. Metastasis to the pancreas is extremely rare with few cases reported over the years. We present a case of a 65-year-old female, who presented with sudden onset of abdominal pain. A review of the patient’s medical history revealed a history of a non-iodine avid Papillary Thyroid Carcinoma in 2015. The patient underwent Radioactive Iodine (RAI) ablation therapy twice due to elevated Thyroglobulin (Tg) levels. Despite RAI, Tg levels were still elevated with no recurrence nor metastasis noted on scan. Chemotherapy was offered but the patient opted for Tomotherapy. The patient completed Tomotherapy in 2017 but afterward was lost to follow-up. A CT scan of the abdomen showed findings of a pancreatic tail and body mass (10 x 7 cm) with an invasion of the mid-descending colon with pulmonary nodules which are possibly metastatic. The patient underwent an endoscopic ultrasound-guided biopsy, and pathology showed findings of a pancreatic papillary neoplasm (CK and beta-catenin positive, synaptophysin negative). Chemotherapy was given (FOLFOX) and a PET scan was requested to monitor the response to treatment. However, PET-scan showed FDG-avid (SUV 32.1) mass in the pancreatic tail (7.2 x 7.8 x 13.3 cm), FDG-avid (SUV 17.61) nodules in the lungs, and an ill-defined heterogeneous mass in the left surgical site (2.2 x 2.6 x 5.3 cm). Given that patient had a thyroidectomy in 2015, recurrence was considered. The possibility of probable metastasis to the pancreas was entertained hence re-biopsy was done. Serum Tg levels were elevated (4,115 ng/ml NV: 1.59-50.0) and negative for Anti-Tg. Biopsy showed high-grade neoplasm with papillary features. IHC staining showed positive for CK7, Tg, and TTF-1, and negative for CK20 which was consistent with metastatic papillary thyroid carcinoma. The patient was given Lenvatinib and is at present tolerating the treatment well with evidence of decreasing Tg levels suggesting a response to treatment. This is a case of a rare site of distant metastasis of a non-iodine avid papillary thyroid carcinoma. Targeted therapy such as Tyrosine kinase inhibitors can improve the survival rate of patients with Radioiodine Refractory Thyroid cancers. Metastasis should be considered especially in patients with a history of prior malignancy.

Presentation Date: Saturday, June 17, 2023
SAT544 Abnormal Labs Reveal Metastatic Papillary Thyroid Cancer
Authors: Shahid Muhammad , Bellamy Shannay , Ottley Anroy , Griffith Mindy
Published: October 2023

Disclosure: M. Shahid: None. S. Bellamy: None. A. Ottley: None. M. Griffith: None.

Objective:Abnormal thyroid function studies are commonly referred to Endocrinology for further evaluation. In most cases, once studies are repeated and normal no further work up is considered. It is uncommon to order a thyroid ultrasound if the patient is asymptomatic with repeat normal labs and physical exam. Clinical Case:43 yo female with no significant medical history who presented to Endocrine clinic for evaluation of abnormal thyroid function labs. She denied taking any medications. Review of systems was positive only for a five pound weight gain over three months. Her physical exam was unremarkable. Labs were significant for TSH level of 0.25 uIU/mL (normal range 0.45 - 5.33 uIU/mL), free T4 of 0.57 ng/dL (normal range 0.61 - 1.12 ng/dL). At the initial visit, thyroid function tests, thyroid antibodies, and thyroid ultrasound were ordered. Results included a normal serum TSH , Free T4 and Thyroid Stimulating Immunoglobulin. Thyroid Peroxidase Antibody resulted as detectable at 124 IU/mL (normal value <9 IU/mL). Thyroid ultrasound showed nodules bilaterally; some subcentimeter in size with two meeting criteria for FNA; one in the right mid pole measuring up to 1.8 cm with suspicious features of hypoechogenicity and a feeding blood vessel, and another isoechoic left mid pole nodule measuring up to 1.8 cm. Per pathology, the right mid pole nodule was considered Betheseda Category V, suspicious for Hurtle cell neoplasm or Hashimoto’s thyroiditis, with the possibility of medullary or papillary thyroid carcinoma. The left mid pole nodule was considered Bethesda Category II. Following surgical consultation, the patient underwent total thyroidectomy with right cervical neck dissection. Pathology revealed pT3N1Mx Metastatic Papillary Thyroid Cancer (conventional type) involving the skeletal muscle and one out of six right cervical neck lymph nodes. The resection margins were negative for carcinoma. Post operatively the patient received radioactive iodine treatment and Levothyroxine was initiated. DISCUSSION:In Endocrine practice, the use of thyroid ultrasonography is common. However, the clinician is usually prompted to order an ultrasound due to consistent abnormal thyroid studies revealing thyrotoxicosis and/or abnormal physical exam findings such as nodular goiter. Or in the case of known diagnoses such as thyroid cancer, it is useful for pre and post surgical management. Nonetheless, in some cases, when ordered outside of common practice, unexpected pathology may be discovered. CONCLUSION:This case demonstrated an unexpected finding of metastatic papillary thyroid cancer , despite initial presentation of abnormal thyroid function tests with normal repeat result and physical exam. Thyroid ultrasound was useful in revealing the diagnosis, preventing a delay in treatment.

Presentation Date: Saturday, June 17, 2023
SAT401 The Aftermath Of Pueraria mirifica: A Case Of Hypertriglyceridemia And Necrotizing Pancreatitis In A Non-binary Individual With Surreptitious Use Of Oral Estrogenic Compounds
Authors: Tobolsky Seth , Hayes Frances J , Lo Janet
Published: October 2023

Disclosure: S. Tobolsky: None. F.J. Hayes: None. J. Lo: None.

Background Prescription of gender-affirming hormone therapy (GAHT) has become an increasingly prevalent aspect of endocrine care meriting greater attention from our specialty. We report a case where surreptitious use of an unregulated compound with estrogenic activity in a patient with gender dysphoria resulted in severe hypertriglyceridemia and necrotizing pancreatitis. The compound, Pueraria mirifica, is readily available for purchase online.

CaseThe patient is a 26yo non-binary individual assigned male at birth who presented to the ED with 1.5 days of abdominal pain and vomiting. CT abdomen showed acute necrotizing pancreatitis. On arrival, serum triglycerides 2,559 mg/dl (nl 40-150 mg/dL) and lipase 481U/L (nl 13-60 U/l). The patient reported no alcohol use. Family history of unspecified hyperlipidemia in father. Patient was admitted, made NPO, and started on insulin/dextrose infusions, continued until serum triglycerides dropped to <1,000 mg/dL. Fenofibrate started and extensive nutritional counseling on low-carbohydrate and low-fat diet given.

In absence of clear etiology for hypertriglyceridemia, patient was questioned carefully on supplement use and revealed they took 2 tablets of Pueraria mirifica daily with intent of transitioning without medical guidance given prior negative encounters with healthcare. Patient discharged on fenofibrate 200 mg, atorvastatin 20 mg and omega-3 acid ethyl esters 2 g BID, with plan for endocrinology follow-up for initiation of medically supervised GAHT.

At follow-up on this regimen, LDL was 79 mg/dL and triglycerides 160 mg/dL. Goals of transition were discussed with the patient as was importance of avoiding oral estrogens, prescribed or over-the-counter. Given patient’s desire for partial transition, low dose transdermal estradiol 0.05 mg patch and spironolactone 50mg BID started. On above regimen, estradiol was 179 pg/mL and total testosterone suppressed at 72 ng/dL. The patient’s triglycerides remained <150 mg/dL with no further complications.

ConclusionThis case highlights a potentially fatal complication of hormone use in a transgender individual with likely underlying familial hypertriglyceridemia. It also illustrates how distrust of the medical system led to surreptitious hormone use and emphasizes the need to create a safe, welcoming environment for individuals with gender dysphoria. Finally, it emphasizes the need to interrogate possible surreptitious hormone use in patients with unusual presentations and for endocrinologists to be aware of the need to avoid oral estrogen use in patients with hypertriglyceridemia.

Presentation: Saturday, June 17, 2023
THU539 Pembrolizumab-induced Hypophysitis Occurring Concurrently With Takotsubo Cardiomyopathy
Authors: Nadeem Ifrah , Chaudhry Hammad S , Aslam Sadia , Asif Muhammad , Khan Wahab J
Published: October 2023

Disclosure: I. Nadeem: None. H.S. Chaudhry: None. S. Aslam: None. M. Asif: None. W.J. Khan: None.

Abstract: Immune checkpoint inhibitors (ICI) are novel medications used to treat a wide range of solid organ tumors and work by stimulating the cellular immune response. With their increasing use, more and more multiorgan side effects including endocrine system are reported in the literature. Prompt recognition of these findings is vital for the safe clinical use of these agents. We report a case of a pembrolizumab-induced triad of hypophysitis, takotsubo cardiomyopathy, and pneumonitis. Case Report: A 72-year-old female with metastatic NSCLC on single therapy with pembrolizumab had received her second session three weeks before the presentation. She presented with progressive dyspnea and generalized weakness but no reported chest pain, fever, or chills. At presentation, she had a BP of 82/62 mmHg, and a pulse rate of 160/min; EKG showed new-onset atrial fibrillation with a rapid ventricular response (RVR) but no acute ischemic changes. Physical examination revealed a pale lady in distress due to shortness of breath. Laboratory analysis revealed hypophysitis with ACTH <5 pg/ml (7.2-63 pg/ml), aldosterone <4 ng/dl (<21ng/dl), TSH 0.26 uIU/ml (0.34-4.94 Uiu/ml), FSH 8.4 mIU/ml (low for age), LH 1.6 mIU/ml (low for age). She was managed with methyl prednisone 60 mg twice daily for seven days, followed by a taper to a final maintenance dose of 5 mg prednisone due to adrenal insufficiency. Unfortunately, two months post-discharge, she passed away at her home due to sudden cardiac death. Discussion: ICI is increasingly used for different malignancies and is frequently linked to various immune-mediated entities simultaneously or at separate times including the pituitary gland. The adverse effects involving the endocrine system are hypo- or hyperthyroidism, hypophysitis, adrenal insufficiency, and type 1 diabetes mellitus. Immune-mediated Takotsubo cardiomyopathy pneumonitis and hypophysitis are treated with systemic steroids with a slow taper and close monitoring of side effects from corticosteroids. Other options include pulse steroids, mycophenolate mofetil, and plasmapheresis on a case-by-case basis. The median onset of hypophysitis and pneumonitis was noted to be 76 and 90 days from the initiation of ICIs, respectively. The mortality rate is relatively high with these complications. Our case report underscores the importance of provider awareness for closely monitoring all patients treated with ICI for various multisystem complications. We anticipate that identifying and reporting these rare complications will help get data for developing monitoring protocols in the future and help other providers recognize these complications in their patients currently on ICI treatment and take appropriate management steps for patient safety.

Presentation: Thursday, June 15, 2023
FRI223 Ectopic ACTH Syndrome
Authors: Sudhakar Shwetha Mallesara , Story Ellen Shannon
Published: October 2023

Disclosure: S. Mallesara Sudhakar: None. E.S. Story: None.

Introduction: Ectopic ACTH Syndrome (EAS) is caused by hypercortisolism from extra-hypophysial tumors. EAS accounts for 10-15 % of Cushing’s Syndrome. Case 1: A 36 year old male with recently diagnosed stage IV well differentiated grade 2 neuroendocrine tumor (NET) of the pancreas with liver metastases developed new hypertension, hyperglycemia, hypokalemia, metabolic alkalosis, fatigue and muscle weakness. There were no obvious signs of Cushing’s Syndrome. ACTH was 679 pg/ml, cortisol 120 ug/ml. MRI pituitary was normal. He required 4 antihypertensives, insulin, and metyrapone was initiated for hypercortisolism. Due to difficulty obtaining medications during the COVID pandemic, intolerance to therapies and lack of improvement in clinical symptoms, decision was made to perform laparoscopic bilateral adrenalectomy. He was started on hydrocortisone and fludrocortisone. Pathology revealed diffuse adrenal hyperplasia. Post-surgery he improved dramatically and was able to discontinue antihypertensives and insulin. Chemotherapy for the underlying tumor was discontinued due to cytopenias. His cancer progressed and he succumbed to disease 10 months from initial diagnosis. Case 2: A 60 year old female presented with severe hypokalemia, metabolic alkalosis, hypercalcemia, cytopenias, HTN, weight loss, muscle weakness, nausea and mental status changes. CT abdomen showed bilateral adrenal hyperplasia. ACTH was 489 pg/ml, cortisol 81 ug/ml. MRI pituitary was unremarkable. PET-CT additionally showed hypermetabolic mediastinal lymph nodes and right upper lobe nodular opacity, and widespread osseous lesions. She was started on ketoconazole and antihypertensives. Bilateral adrenalectomy was considered but could not be performed due to rapid clinical deterioration. Etomidate was initiated. Fine needle aspiration of a mediastinal lymph node showed small cell carcinoma. Patient became too frail to receive systemic chemotherapy and succumbed within 2 weeks of hospitalization. Discussion: Most Ectopic ACTH Syndrome cases are caused by NET of the lung, pancreas and thymus. In children, Ewing’s sarcoma has been reported. Small cell carcinoma of lung, malignant pancreatic NETs, and medullary carcinoma of thyroid often present with metastasis and carry an ominous prognosis. Not all patients have clinical features of classic Cushing's syndrome. The outcome of EAS correlates with tumor type. Optimum treatment is surgical resection of the tumor, often not possible with metastatic disease. Hypercortisolism may be controlled with adrenal enzyme inhibitors and receptor blockers. Bilateral surgical adrenalectomy may be needed when symptoms are not controlled by medical management. Early and rapid control of Cushing’s Syndrome is important to facilitate antineoplastic treatment of the underlying tumor.

Presentation: Friday, June 16, 2023
THU555 Stress Induced AIPB Expression In Triple Negative (ER-/PR-/Her2-) Breast Tumors Reduces Estradiol
Authors: Patrawala Mahjabin , Bose Himangshu S
Published: October 2023

Disclosure: M. Patrawala: None. H.S. Bose: None.

In the United States, 1 in 8 women will develop invasive breast cancer in their lifetimes, and currently, more than 3.8 million individuals are survivors. Breast cancers are hormonally regulated and are categorized ER+/PR+/HER2-, ER-/PR-/HER2+, ER+/PR-/HER2-, and ER-/PR-/HER2-. In patients with Estrogen Receptor positive (Er+) and Progesterone Receptor positive (PR+), these receptors are used for targeted therapy. However, about fifteen percent of patients are diagnosed with triple-negative breast cancer. Currently, there are no molecular therapies for this cancer and only 20% of the cases respond to chemotherapy, so new prognostic markers and therapies are necessary. Aromatase, the rate limiting enzyme catalyzes testosterone to estradiol, is expressed in the ovaries of pre-menopausal women and increases 20-fold in peripheral tissues and fat bodies, like breast, in post-menopausal women contributing to tumor growth. We observed “Aromatase Interacting Partner in Breast (AIPB)” overexpression inhibits aromatase activity resulting by decreasing in estradiol. In triple-negative breast cancer, patients have a more than ten-fold decline in the expression of AIPB compared to ER+/PR+/Her2- breast tumors. Patients diagnosed with triple-negative breast cancer are profoundly stressed considering the low survival rate, which induces higher cortisol synthesis. We hypothesize the stressor will change the expression of AIPB in the tumor cells which will possibly reduce estradiol synthesis. The stress was emulated using a laboratory model in which a heat shock of 42° was delivered for varying periods (0,15,30,45 minutes). The model was used on engineered triple-negative tumor cells which conditionally overexpress AIPB with the addition of tetracycline. We observed MDA-MD-231 cells had a 50% reduction of estradiol from 160 ng/ml to 100 ng/ml following stress for 45 minutes. Interestingly MDA-MD-231-AIPB cells synthesized only 62 ng/ml, which is an 18.75% reduction. On addition of doxycycline, the estradiol level was further decreased to 47 ng/ml, which is about 29.4%. Western blot with a CT antibody of the MDA-MB-231-AIPB cells showed an increase in AIPB expression at the maximum level when stress was performed in combination with doxycycline. Aromatase is absent in triple-negative breast cancer, so we conclude aromatase independent action AIPB in these triple-negative tumorigenic cells plays a crucial role in estradiol synthesis. With our current data, we can suggest a model in which stimulating higher expression of AIPB in patients can provide them with better and longer lives.

Presentation: Thursday, June 15, 2023
THU556 Targeting Breast Cancer Stem Cells With Oncolytic Virus
Authors: Roman Ortiz Natasha Ivelisse , Danthi Pranav , Ostrander Julie Hanson
Published: October 2023

Disclosure: N.I. Roman Ortiz: None. P. Danthi: None. J.H. Ostrander: None.

Breast cancer is the second leading cause of cancer deaths among women in the United States. Estrogen receptor positive [ER+] breast cancer has a more favorable prognosis; however, patients can experience recurrence for many years after initial diagnosis. Breast cancer stem cells (BCSC), which are dormant and exist as a minority sub-population (0-5%), drive recurrence, metastasis and resistance to therapies that primarily target rapidly proliferating tumor cells. Current treatments are insufficient to cure metastatic ER+ breast cancer and there are no FDA approved therapeutics that target BCSC. Mammalian orthoreovirus (MRV) is an oncolytic virotherapy tested in clinical trials for many cancer types including metastatic breast cancer. MRV was found to be safe, but efficacy limited as a monotherapy. In our studies we compared several laboratory MRV strains (T1L, R2) to the strain most similar to Reolysin, which is being tested in clinical trials (i.e. T3D). Our studies suggest that T3D is less effective in killing ER+ breast cancer cells and BCSCs. We propose to generate a novel MRV strain with enhanced BCSC-targeting capacity using forward genetic approaches by serially passaging MRV strains in BCSC enriched 3D tumorsphere cultures of MCF-7 Paclitaxel resistant (TaxR) cells to generate a selective oncolytic virus. Preliminary data has shown that serially passaged (SP) MRV strains (T1L SP, R2 SP) are more effective in decreasing cell viability and inhibiting tumorsphere formation compared to the parental (P) strains (T1L P, R2 P). We anticipate these studies will lead to an improved MRV oncolytic virotherapy that will be combined with clinically relevant inhibitors, such as CDK4/6 inhibitors and anti-estrogens, to prevent and treat therapy-resistant ER+ breast cancer.

Presentation: Thursday, June 15, 2023
OR05-02 Silencing Of Adenylosuccinate Lyase Impairs Growth And Perturbs Mitochondrial Function Of Endocrine Therapy Resistant Breast Cancer Cells
Authors: Yadav Anil K , Jin Lu , Clarke Robert , Sengupta Surojeet
Published: October 2023

Disclosure: A.K. Yadav: None. L. Jin: None. R. Clarke: None. S. Sengupta: None.

The estrogen receptor positive (ER+) subtype comprises of ∼80% of all breast cancers and is the major contributor to cancer related deaths in women. While ER+ breast cancers respond to treatment with endocrine therapies (ET) such as tamoxifen, Fulvestrant and aromatase inhibitors, a major limitation is emergence of resistance to ET resulting from adaptive pathways that promote relapse and disease progression. Hence, there is an urgent need for identification and validation of new molecular targets for potential therapeutic treatment of ET resistant-ER+ breast cancer. Here, we have determined the role of adenylosuccinate lyase (ADSL), a crucial enzyme involved in the de novo purine synthesis pathway, as a potential molecular target for ER+ breast cancer cells. ADSL enzyme catalyzes two non-sequential steps in de-novo purine synthesis pathway that produces aminoimidazole carboxamide ribonucleotide (AICAR) and adenosine monophosphate (AMP); fumarate is generated as a byproduct. We observed higher protein expression of ADSL in LCC9 (endocrine therapy crossresistant cells) when compared with LCC1 or MCF-7 (antiestrogen sensitive) cells. Additionally, T47D-4HT cells (also endocrine therapy resistant) also expressed modestly higher ADSL protein level in comparison to its parental endocrine therapy sensitive T47D-A18 cells. Notably, siRNA-mediated knockdown of ADSL in both LCC9 and T47D-4HT cells leads to strong inhibition of cell proliferation, long-term colony, and spheroid formation. Furthermore, ADSL depletion in LCC9 increased the accumulation of cells in G0/G1 phase along with elevated protein expression of cyclin D1. In T47D-4HT cells, ADSL knockdown caused cells to accumulate in S-phase, with a reduction of total cyclin D1 protein levels. Further investigation revealed that ADSL knockdown decreased ATP levels and mitochondrial membrane potential in both LCC9 and T47D-4HT cells and significantly reduced the basal oxygen consumption rate (OCR) and maximal respiration capacity. Notably, addition of AICAR (100 µM) to ADSL deficient LCC9 cells partially rescued cell proliferation, colony formation, and restored the mitochondrial membrane potential. In clinical datasets higher expression of ADSL transcripts correlates with poor relapse free survival in ER+ breast cancer patients treated with endocrine therapies. Overall, our results indicate that ADSL-mediated de novo purine synthesis plays an important role in growth and proliferation of endocrine therapy resistant ER+ breast cancer cells through mitochondrial function. Therefore, targeting ADSL is a novel potential therapeutic approach for ER+ endocrine resistance breast cancer.

Presentation: Thursday, June 15, 2023
FRI224 A Rare Case Of Recurrent Paraganglioma Presented With Liver Metastasis
Authors: Gupta Eisha , Al Mushref Mazen
Published: October 2023

Disclosure: E. Gupta: None. M. Al Mushref: None.

Malignant Paragangliomas (PGLs) and Pheochromocytomas (PCC) are extremely rare. Approximately 10% of PCCs and 25% of PGLs are metastatic. Metastatic PGLs typically occur in patients with predisposing genetic mutations. We present a case of recurrent metastatic PGL in a young female with no known genetic predisposition to metastatic disease occurring after surgical resection. Our patient is a 28-year-old female with a history of PGL status post left adrenalectomy and nephrectomy two and a half years prior who presented to the ED for abdominal pain. She was first diagnosed after being admitted for hypertensive emergency. During time of diagnosis, plasma and urinary metanephrines were significantly elevated at 1.13 nmol/L and 907 ug/gCr respectively and plasma and urinary normetanephrines were elevated at 80.2 nmol/L and 52043 ug/gCr respectively. MRI showed a 16 cm left retroperitoneal mass and MIBG scan showed increased uptake in the mass however no evidence of metastatic disease was noted then. The patient had immigrated from Haiti. Her mother had passed away at age 20 of unknown cause and her father has no known history. Genetic testing was negative for hereditary gene mutations including multiple SDHDs, VHL, NF1, MEN1 and MAX. Surgical exploration showed a giant left retroperitoneal neoplasm involving the left kidney and left adrenal and both organs were resected. Pathology revealed PGL, focally extending to peripheral specimen margin and benign retroperitoneal lymph nodes and soft tissues. Post-resection meta- and normetanephrines levels were normal. Unfortunately, the patient was lost to follow up after surgery. On this admission, she endorsed right lower quadrant abdominal pain. Plasma normetanephrine was 1.72 nmol/L, metanephrine was normal, and chromogranin A level was elevated at 545 ng/mL. CT scan revealed multiple hepatic lesions and MIBG scan further showed new increased uptake suggesting metastasis. The patient was asymptomatic and blood pressure remained normal during her hospitalization. Due to concerns of recurrent PGL with metastasis, she established care with Oncology for initiation of treatment. PGL is an extremely rare neuroendocrine tumor and is closely related to PCC. Sympathetic PGLs cause catecholamine surge symptoms but low volume disease may remain asymptomatic. Genetic predisposition is common in malignant PGL particularly succinate dehydrogenase mutation subunit B. Patients should be closely followed up to screen for recurrence and genetic testing should also be done. In our patient’s case, despite surgical resection and negative genetic testing, she developed recurrence of the PGL with new metastasis emphasizing the importance of close surveillance in the case of PGL to monitor for recurrence.

Presentation: Friday, June 16, 2023
OR05-04 Growth Hormone Receptor Antagonism Markedly Improves Therapeutic Response In Mouse Models Of Melanoma, Liver Cancer, Pancreatic Cancer And Cholangiocarcinoma
Authors: Basu Reetobrata , Kulkarni Prateek , Ortiz Silvana Duran , Davis Emily , Kopchick John Joseph
Published: October 2023

Disclosure: R. Basu: None. P. Kulkarni: None. S. Duran Ortiz: None. E. Davis: None. J.J. Kopchick: None.

A major hurdle in tackling cancer, the second biggest cause of human mortality, is resistance to therapy. Human growth hormone (GH) mediated activation of the growth hormone receptor (GHR) promotes the initiation and invasive progression of several types of human cancers, known since 1950. Recently, through a series of mechanistic studies using in vitro models and in silico analyses of human cancer patient databases, we have identified a covert role of GH in promoting cancer drug resistance via direct upregulation of: (i) the expression of ATP-binding cassette containing multi-drug transporters (ABC transporters) leading to increased drug efflux, (ii) the epithelial-to-mesenchymal transition (EMT) associated gene expression program, and (iii) the mediators of fibrosis and extracellular matrix remodeling. Additionally, based on the known effects of GH and robust expression of GHR in multiple cell types that constitute the tumor microenvironment, autocrine / paracrine GH putatively exerts potent tumor supportive actions. Therefore, we hypothesized that combining GHR antagonist to chemotherapy can markedly improve therapeutic outcome in human cancers. Melanoma and liver cancer jointly and annually constitute >150,000 patients and >60,000 deaths in the US, much due to resistance to therapy. We used a syngeneic murine model of both cancers using C57BL6 mice transgenic for a GHR antagonist (GHA mice) compared against wild-type (WT) counterparts implanted with either B16F10 melanoma or Hepa-1-6 hepatoma cells. GHA expression drastically sensitized melanoma tumors to cisplatin treatment and hepatoma tumors to sorafenib treatment. Additionally, the five-year survival rates of pancreatic cancer and cholangiocarcinoma are a dismal 10% in 2022, indicating an urgent need for new therapeutic approaches for both of these devastating diseases. For this, we used Nude mice for human pancreatic cancer xenografts treated +/- GHA (Pegvisomant and another in development at our laboratory) combined with gemcitabine. Combination of GHA markedly sensitized pancreatic cancer xenografts to gemcitabine in Nude mice, leading to ∼40% of mice being tumor-free at the end of study. GHA similarly also sensitized human cholangiocarcinoma xenografts in Nude mice to gemcitabine-cisplatin therapy. In all cases, GHA led to a marked reduction in gene expression of multidrug efflux transporters, EMT markers, and fibrosis mediators. Collectively, our data provides strong pre-clinical validation for treatment regimens combining GHR antagonist and chemotherapy leading to highly efficacious tumor clearance.

Presentation: Thursday, June 15, 2023
FRI231 Pheochromocytoma - A Silent Killer
Authors: Le Kelly , Shakeel Hira , Sheehan Mary Theresa , Sen Sabyasachi , Paal Edina
Published: October 2023

Disclosure: K. Le: None. H. Shakeel: None. M.T. Sheehan: None. S. Sen: None. E. Paal: None.

Background: Pheochromocytoma, a neuroendocrine tumor that develops in the adrenal medulla, can be fatal to patients who have to undergo surgery if left undiagnosed. It often presents with episodic headache, palpitations, sweating and paroxysmal hypertension (HTN). However, some patients can be asymptomatic, making the diagnosis challenging in an acute setting. Clinical Case: A 59-year-old male with a past medical history of previously well-controlled Type 2 Diabetes Mellitus, HTN, and hyperlipidemia was referred to the emergency department by his primary care physician due to an elevated blood glucose level associated with symptoms of polyuria, polydipsia, and increased fatigue. Upon arrival, blood glucose level was 603 mg/dl with an elevated beta-hydroxybutyrate (a ketone body) of 1.35 mmol/L (reference 0.00-0.24), but a normal anion gap and acidic pH. He was admitted for further glycemic control with IV fluids and subcutaneous insulin. Hemoglobin A1C was 15.5% on admission, which had markedly increased from 6.9% six months prior when patient was on metformin alone. The patient attributed his worsening glycemic control to dietary indiscretion. Given the rapid increase in A1C and uncontrolled glucose level, a CT abdomen/pelvis was done to rule out a pancreatic tumor. No pancreatic tumor noted, but a 4.7 x 5.2 x 5.3 cm right adrenal mass was seen (CT abdomen showed a large right adrenal mass with peripheral enhancement and necrotic center characteristics). Further testing revealed markedly elevated normetanephrine levels of 2583 pg/ml (normal < 148) with a slight increase in metanephrines 73 pg/mL (normal <57). Levels of aldosterone, plasma renin activity, DHEAS and midnight cortisol were within normal limits. Interestingly, prior to admission, patient’s BP was not controlled (ranges 140s-170s/60s-90s) even on three antihypertensives (Hydrochlorothiazide (HCTZ), Valsartan, & Amlodipine). HCTZ was discontinued and Prazosin was initiated prior to surgery to control intra-operative hypertension. The patient underwent right adrenalectomy without complications. On discharge he was maintained on Prazosin, valsartan, and amlodipine for hypertension and Lantus 28-unit qAM along with Aspart 4-unit premeal for diabetes. Four months post-operatively, normetanephrine (121 pg/ml) and metanephrine (25 pg/ml) levels were within normal limits. In addition, A1c went down to 6.2% on a much lesser regimen of hypoglycemic agents (Lantus 15 units qAM & Metformin only) and antihypertensive regimen went down to amlodipine with BP well controlled, ranging from 130s-140s/60s-80s. Conclusion: This case highlights the importance of familiarity with the different presentations of pheochromocytoma (i.e. uncontrolled and challenging hyperglycemia, persistent uncontrolled hypertension, without any obvious physical signs) to healthcare providers as it can be mistreated if left undiagnosed.

Presentation: Friday, June 16, 2023
FRI232 Importance Of Rapid Treatment Initiation In Ectopic Cushing Syndrome: Abstract
Authors: Mendez Dianelys , Fernandez Maria Gabriela , Selen Daryl J
Published: October 2023

Disclosure: D. Mendez: None. M.G. Fernandez: None. D.J. Selen: None.

Background: Endogenous Cushing syndrome may result from an ectopic non-pituitary tumor. Severe hypercortisolism has high mortality, so prompt medical management to acutely decrease cortisol levels is necessary when no surgical options are available. Clinical Case: A 67-year-old male presented to the hospital with four weeks of fatigue and was found to have a right hilar mass with unsuppressed cortisol levels for which an ectopic tumor was suspected. On initial evaluation, the patient presented with hypokalemia, acute kidney injury, and metabolic alkalosis. In addition, a CT of the chest and abdomen with contrast revealed a right hilar mass with multiple liver lesions concerning for metastasis. These findings prompted workup for hypercortisolism, including 1mg and 8 mg dexamethasone suppression tests. Both tests demonstrated unsuppressed cortisol levels above 150 (reference range [RR] 5.5-20 ug/dl and assay maximum>150) and elevated 24-hour urinary cortisol of 8125 (RR <60 ug/dl), suspicious for an ACTH-secreting tumor. Subsequently, he underwent a liver biopsy to characterize the tumor further and was started on Bactrim for Pneumocystis pneumonia prophylaxis. Metyrapone and osilodrostat were considered for treatment but not available at our facility such that treatment was initiated with ketoconazole 200 mg orally twice daily with subsequent dose titration. He had a mild elevation of AST 52 (RR 7-42 IU/L) and ALT 52 (RR 10-45); therefore, his liver profile was monitored daily due to his elevated risk for hepatotoxicity. With the initiation of ketoconazole, cortisol serum levels decreased to 145 ug/dl after two days of treatment. The pathology report revealed small lung cell carcinoma as the etiology for ectopic Cushing’s syndrome, for which the oncology team-initiated etoposide and carboplatin. Unfortunately, on day 6 of the initiation of treatment, the patient rapidly deteriorated and passed away from pneumonia and septic shock. Conclusion: Severe hypercortisolism leads to an immunosuppressed state resulting in high mortality. Therapeutic options depend significantly on the accessibility of first-line treatment options and prompt initiation of medical treatment. When no other agents are available, ketoconazole should be started at high doses despite the mild elevation of liver enzymes with close monitoring of LFTs. While it is unclear if the patient’s deterioration was due to his cancer burden, chemotherapy, severe hypercortisolism, or a combination, given that osilodrostat and metyrapone are first-line treatment options, standardized systems should be reviewed in hospitals for faster acquisition of these medications to avoid delays in treatment initiation. In addition, the decision to transfer patients to the intensive care unit for etomidate infusion while awaiting the acquisition of the above medications should be considered promptly.

Presentation: Friday, June 16, 2023
FRI242 Primary And Secondary Adrenal Insufficiency Post Transsphenoidal Surgery In Patient On Abiraterone Therapy
Authors: Akande Rukayat Olabisi , Abramowitz Jessica , Mirfakhraee Sasan
Published: October 2023

Disclosure: R.O. Akande: None. J. Abramowitz: None. S. Mirfakhraee: None.

Introduction: This case report describes the co-existence of primary and secondary adrenal insufficiency in a patient who received abiraterone therapy for metastatic prostate cancer and had transsphenoidal surgery for symptomatic pituitary adenoma. It sheds light on the presentation of the patient and explains the subsequent management. Clinical Case: A 67-year-old man with a history of metastatic prostate cancer (status post prostatectomy and radiation) and recent transsphenoidal surgery for pituitary adenoma presented with 3+ pedal edema. The patient had been discharged on hydrocortisone as per neurosurgery protocol and continued abiraterone after his transsphenoidal surgery. His pedal edema started two months after discharge. He denied fatigue, nausea, and dizziness. His vital signs and electrolytes, including serum potassium, were within normal limits. The patient was diagnosed with mineralocorticoid excess in the context of combined primary and secondary adrenal insufficiency. His hydrocortisone was changed to prednisone 5mg daily and his pedal edema subsequently resolved. Conclusion: Abiraterone, a hormonal therapy for the treatment of metastatic prostate cancer, is an irreversible inhibitor of CYP17, a microsomal enzyme with 17 alpha-hydroxylase and 17,20-lyase activities. This inhibition reduces cortisol and androgen concentrations while stimulating ACTH production. Thus, abiraterone use led to primary adrenal insufficiency in this patient. As a result of the 17 alpha-hydroxylase and 17,20-lyase pathway inhibition, there is increased production of deoxycorticosterone, which can lead to fluid retention. This patient was post pituitary surgery with partial secondary adrenal insufficiency and received hydrocortisone postoperatively as an appropriate glucocorticoid replacement in this setting. He developed pedal edema due to mineralocorticoid excess from abiraterone use while on hydrocortisone therapy. He was placed on prednisone, a more potent synthetic glucocorticoid than hydrocortisone, with subsequent rapid resolution of his edema.

Presentation: Friday, June 16, 2023
SAT290 Course of SARS-CoV-2 Infection In Patients With Congenital Adrenal Hyperplasia
Authors: Javaid Rida , Kollender Sarah , Moon Amy , Merke Deborah P
Published: October 2023

Disclosure: R. Javaid: None. S. Kollender: None. A. Moon: None. D.P. Merke: Research Investigator; Self; Diurnal, Neurocrine Biosciences.

Patients with primary adrenal insufficiency (PAI) are at risk for life-threatening adrenal crises, most often triggered by illness. Prior studies suggest possible inefficient immune response in PAI, especially in patients with autoimmune Addison’s disease. Starting in December 2019, the pandemic due to the novel SARS-CoV-2 coronavirus created many challenges in patient management. Data regarding COVID-19,risk of severe illness, and proper prevention of adrenal crisis in patients with PAI due to congenital adrenal hyperplasia (CAH) are lacking.Objective:To describe the experience of patients with PAI due to CAH who acquired COVID-19 in a large cohort study.Methods:Questionnaires and retrospective chart reviews were performed for all patients enrolled in a Natural History Study at the National institute of Health (NCT00250159) who reported COVID-19 infection from March 2019 until November 2022.Results:42 patients with CAH (25 salt-wasting 21OHD, 13 simple virilizing 21OHD, 1 nonclassic 21OHD, 3 P450 SCC deficiency) reported 46 episodes of COVID-19 infections (12 pediatric, 34 adult), 16 were before nationwide vaccine distribution. Of the 30 responses post vaccine, 23 were vaccinated and 7 were unvaccinated. Patients were instructed to stress dose according to standard guidelines for general illnesses. In 21 episodes, patients did not stress dose; in 25 episodes, patients stress dosed orally (1 to 15days); in 6 episodes, patients received intramuscular Solucortef injections. Two patients (8 y.o., 63 y.o.) were hospitalized. One patient with salt-wasting CAH and asthma developed long COVID following 2COVID-19 episodes. Patient risk factors for COVID-19 included: 6 obese (BMI > 30), 2 tobacco users, 1 with concomitant type 1 diabetes mellitus. COVID-related symptomatology was similar to national trends. Early in the pandemic, patients were more likely to have loss of taste and smell, as well as GI symptoms, and later in the pandemic, patients were more likely to experience cough, sore throat, tiredness, and body aches. Data analysis underway.Conclusion:Patients with PAI due to CAH do not appear to be at greater risk of acquiring COVID-19 and do not have higher risk of complications triggered by COVID-19 infection than the general population. Standard glucocorticoid stress dosing guidelines are appropriate in the setting of COVID-19. Glucocorticoid stress dosing is not recommended if the patient is without fever or gastrointestinal symptoms.

Presentation: Saturday, June 17, 2023
SAT294 Effectiveness Of Electronic Consults For Immune Related Endocrine Toxicities In Reducing Appointment Access Time And Preventing Hospital Admissions
Authors: Diamond Carrie , Patolia Harsh , Phinney Donna , Shariff Afreen
Published: October 2023

Disclosure: A.I. Shariff: Consulting Fee; Self; Bristol-Myers Squibb. Speaker; Self; Merck.

Background: Endocrine irAEs are noted in 4% to 14.6% of ICI treated patients leading to 12.2% of irAE related admissions.1Delayed access, diagnosis and management are often causes of preventable hospital admissions in cancer patient.2 3 Herein, we describe a single-institution experience with an e- consult platform from oncology to endocrinology as a cost effective and high impact solution to this limitation. Methods: Between 5/1/2020 to 11/1/2021 patients who received ICI were included in a retrospective observational cohort study. Data collection included patient demographic, cancer, treatments, irAE and appointment specifics. Results: 102 e-consults were reviewed during the study period. Thyroiditis was noted as the most common irAE while NSCLC, and pembrolizumab use were most commonly noted in the cohort. 88 and 60 consults received diagnostic and treatment recommendations respectively. Reduction in median time to appointment was lowered from 60.5 days to 38.50 days. Among e-consulted patients, 2 (2.23%) required hospitalization for further evaluation and management. This is a reduction from previous data at the same institution (2007- 2017) where 11% endocrine toxicities were admitted. With an average length of stay approximated to 6.4 days at $3,142 per day, a total of $100,544 was saved as a result of the consult service.1 We also noted that these e-consults were poorly reimbursed by all payers, and current average reimbursement ranged from $15- $32/ consult.4Conclusion: This study underscores the impact and effectiveness of e consults as a tool for timely recommendations and improving access leading to reduction in health care utilization. To support e-consults, the effort-payment mismatch must be addressed by health systems and payers that can propel integration and scalability of these effective services across oncology and other subspecialty practices to enhance access and mitigate gaps in specialty care provided to cancer patients.

Presentation Date: Saturday, June 17, 2023
SAT298 Adrenal Insufficiency Presenting With Isolated Severe Hyponatremia: A Case Series
Authors: Shafi Amtul , Berardo Jeronimo , Hwang Jessica
Published: October 2023

Disclosure: A. Shafi: None. J. Berardo: None. J. Hwang: None.

Background: Adrenal insufficiency (AI) is an overlooked cause of severe hyponatremia (defined as serum Na <120); especially when it is not accompanied by other classic features (i.e., hypotension, hypoglycemia or other electrolyte dysfunction) leading to delayed diagnosis, treatment and increased length of hospital stay (LOS).Case series: We report 14 cases (9 distinct patients) of hospital admission for severe hyponatremia either on presentation or during course of hospitalization attributable to adrenal insufficiency. Four of the nine patients had multiple admissions. These cases were divided into 2 groups based on if they were newly diagnosed (n=6) or had a known diagnosis (n = 8) of AI. Mean age was 56 for both groups, serum Na was 117 vs 114, systolic BP was 126 vs 123. Endocrine was consulted on day 4.5 vs 1.8 and hydrocortisone was started on day 4.8 vs 1.3 resulting in length of stay 8 vs 5 days, respectively. 80% of the subjects also had hypothyroidism with a mean free T4 of 0.87 vs 0.71. In the newly diagnosed group, cortisol was checked on day 3.5. The majority (86%) of admissions were attributed to a secondary adrenal insufficiency crisis. Conclusion: This case series presents several important conclusions which impact endocrine consultation, treatment and length of hospital stay. A) Despite various hyponatremia guidelines suggesting ruling out AI and hypothyroidism before empirical diagnosis of SIADH, there can still be delay in checking cortisol status. B) AI presentation can lack hemodynamic instability or other electrolyte abnormalities so a high clinical index of suspicion should be exercised in diagnosing this potentially fatal condition when encountering isolated severe hyponatremia. C) There is a significant rate of readmission in cases of severe hyponatremia related to adrenal insufficiency.

Presentation: Saturday, June 17, 2023