bluuebunny/crossref_metadata_2025 huggingface dataset:
THU505 Severe Acute Hypercortisolism From Stable Pre-existing Lung Nodule
Authors: Raza Nadia , Wagle Sneha , Kiani Rabia Nadeem , Kaput Katie
Published: October 2023

Disclosure: N. Raza: None. S. Wagle: None. R.N. Kiani: None. K. Kaput: None.

A 63-year-old male with uncontrolled hypertension and Rheumatoid arthritis was admitted for acute psychosis, progressive asthenia, and severe refractory hypokalemia. He was afebrile on admission and blood pressure was 151/99 mmHg. Physical examination lacked typical Cushingoid appearance of moon facies, central obesity, or purple striae. Labs showed a potassium of 1.8 (ref: 3.3-5 mmol/L), HbA1c 6.0% (ref<=5.6 %), 24-hour urinary free cortisol of 9438 (ref<=60.0 ug/d) and random ACTH level of 229 (ref:7.7-63.3pg/ml). The presentation was felt to be consistent with ectopic ACTH dependent Cushing's syndrome. He was treated with ketoconazole 400 mg BID, Deep veinous thrombosis prophylaxis and trimethoprim-sulfamethoxazole daily for PJP prophylaxis. CT chest/abdomen/pelvis was performed and showed a 1.9 cm right middle lobe pulmonary nodule. Past records were reviewed and showed a stable lung nodule from 2020 (2.5 years earlier). Elective lung biopsy was discussed, and the patient was discharged home with plan for outpatient biopsy. Prior to his biopsy, he was readmitted with worsening agitation, hypertension, and extremity edema. After extensive discussion with CT surgery, a decision was made to perform robotic-assisted thoracoscopic resection of the right middle lobe with mediastinal lymph node dissection. Post-surgery his BP improved, agitation resolved, and cortisol level declined to 3.4 (ref: 6.0 - 18.4 ug/dL). Final pathology showed a well differentiated neuroendocrine tumor, low grade. Lymphovascular invasion was present, and one lymph node was positive for tumor. ACTH immunostaining was performed and was also positive. Ectopic ACTH dependent Cushing syndrome represents a rare condition, contributing to 5-20% of Cushing’s cases. Lung carcinoid tumor is one of the major causes of ectopic ACTH syndrome and typically resolves with surgery. Unusual in our case is the stability of the lung lesion prior to his acute decompensation and lymph node positivity. To date, we have not identified a reason for the indolent nature of his tumor. He is currently on a hydrocortisone taper and is actively undergoing treatment planning with our multidisciplinary peer review process. Essential to his management is the coordination of multiple providers, which includes complex medical decision making and treatment decisions. In the future, lung carcinoid should be considered in the differential for persons with difficult to control hypertension and a stable pulmonary nodule

Presentation: Thursday, June 15, 2023
THU508 Does Mid-treatment Response To 177Lu-DOTATATE Predict Treatment Outcome In Patients With Neuroendocrine Neoplasms?
Authors: Halperin Reut , Tirosh Amit
Published: October 2023

Disclosure: R. Halperin: None. A. Tirosh: None.

Introduction - Patients with advanced or unresectable neuroendocrine neoplasm (NENs) have limited systemic treatment modalities. Among these, patients with well differentiated (G1 and G2) NENs can be treated with peptide receptor radionuclide therapy (PRRT) treatment with 177Lu-DOTATATE. However, a subset will require further chemotherapy in later stages. Hence, limiting radiation exposure is of paramount importance. However, there are no mid-term predictive factors for response to PRRT. Aims - Assess the utility of mid-treatment (post 2nd cycle) response to PRRT as a potential predictor for final outcome in patients with well-differentiated NENs. Materials and Methods - A retrospective study in a tertiary center, enrolling patients that underwent at least four cycles of PRRT. Data gathered included demographics, tumor grade and stage, treatment response (partial response [PR], stable disease [SD] or progressive disease [PD]) evaluated by 68Ga-DOTATATE PET CT after 2nd and 4th treatment cycle, compared to pretreatment 68Ga-DOTATATE PET CT scan. Results - A total of 30 patients (50% women, age at diagnosis 63.5±1.7 years) completed four PRRT cycles (median, range 4-6). NEN primary site were pancreatic (n=15), small intestine (n=8), lung (n=2) or other (n=5). Final outcome was PR, SD and PD in 15, 13 and 2 patients, respectively. Patients with pancreatic NEN had superior response vs. small intestine NEN (p=0.01). Patients with PR at mid-treatment had higher PR rates at final evaluation than those with mid-term SD (p=0.008). On multivariable model, adjusted for age at diagnosis, grade, NEN type, and medical treatment, mid-treatment outcome was independently associated with final outcome (adjusted odds ratio 9.1, 95% confidence interval 1.4-60.4, p=0.02). Conclusions - Mid-treatment PRRT efficacy can serve as a measure of final outcome in patients with advanced or unresectable well differentiated NEN.

Presentation: Thursday, June 15, 2023
THU523 A Rare Case Of Functional Cervical Paraganglioma: Case Report
Authors: Oliveira Vitória Dupas , Vaccarezza Guilherme Cavazzani , Rodrigues Vieira Alysson Emannuel Neves , Scalissi Nilza Maria , dos Santos Américo Rubens Leite , Lazarini Paulo Roberto , Suehara Alexandre Baba , Olivati Caroline , Lima Jose Viana
Published: October 2023

Disclosure: V.D. Oliveira: None. G.C. Vaccarezza: None. A.E. Vieira: None. N.M. Scalissi: None. A.R. dos Santos: None. P.R. Lazarini: None. A.B. Suehara: None. C. Olivati: None. J.V. Lima: None.

INTRODUCTION: Head and neck paragangliomas (HNPGL) are rare tumors arising from cells associated with parasympathetic ganglia. Catecholamine hypersecretion is founded in less than 5% of the patients. Evidence is growing that about 50% of the HNPGL are associated with hereditary syndromes. CASE REPORT: Male patient, 34 years old, previously healthy, presented with a 1-year history of jaw pain and hypoacusis, associated with progressive symptoms of dysphagia, facial paralysis, dysphonia and hoarseness. He also had a 2-month history of hypertension and palpitations. On physical examination, the patient had deficits in cranial nerves (CN) VII, VIII, IX, X, XI and XII and blood pressure of 150x90mmHg. Head and neck MRI showed an expansive lesion occupying the right jugular foramen extending above the cistern at the cerebellopontine angle and below the carotid space in the ipsilateral infratemporal fossa, reaching 50% of the internal carotid artery and extending into the right internal auditory canal, suggestive of glomus jugulare paraganglioma. Laboratory examination showed normetanephrines 9.1 mmol/L (VR < 0.9), confirming catecholamine-secreting paraganglioma. Next Generation Sequence (NGS) genetic testing evaluating 24 genes (ATM, DLST, EGLN1, EGLN2, FH, EPAS1 (HIF2A), HRAS, KIF1B , MAX, MDH2, MEN1 , MERTK , MET, NF1, RET, SLC25A11, SDHA, SDHAF2, SDHB, SDHC, SDHD, TMEM127, TP53 and VHL) was positive for the pathogenic variant c.166_170del:p.(Pro56Tyfs*5) of the SHDB gene. Patient with no family history of paraganglioma. Alpha-adrenergic blockade was started with doxazosin and, after two weeks, beta-adrenergic blockade with propranolol. After 3 months, he underwent preoperative embolization 48 hours before surgery with total tumor resection. Patient did not require antihypertensive drugs after surgery. CONCLUSIONS: We reported a case of a young patient diagnosed with catecholamine secreting HNPGL that carries pathogenic variant of SHDB.

Presentation: Thursday, June 15, 2023
THU526 Long-term Follow-up Of A Functional Gastroenteropancreatic Tumor Secreting Both Somatostatin And Gastrin
Authors: Zafar Rafia , Syeda Javeria Nasir , Rajamani Krishnakumar
Published: October 2023

Disclosure: R. Zafar: None. J. Syeda: None. K. Rajamani: None.

Introduction: There have been fewer than 200 cases of somatostatinoma reported since 1977. We report a case of a functional Gastroenteropancreatic neuroendocrine tumor (GEP-NET) secreting both somatostatin and gastrin. Clinical Case: A 55-year-old male with diabetes mellitus, chronic diarrhea, gastric ulcer, and cholelithiasis was referred to the endocrinology clinic for poorly controlled diabetes mellitus. He had a history of B-cell lymphoma of the thyroid treated by chemotherapy and radiation. He was found to have two paraduodenal masses by PET CT scan during surveillance for recurrence of lymphoma. Laboratory evaluation revealed elevated levels of insulin, glucagon, gastrin, somatostatin, and chromogranin A on multiple occasions both fasting and random. Ultrasound-guided endoscopic biopsy of the paraduodenal nodules was initially read as a neuroendocrine tumor. Subsequent immunohistochemical staining was positive for both somatostatin and gastrin. The stains were negative for glucagon and insulin. The Ki-67 proliferation index was less than 1%. The patient declined surgical treatment of the paraduodenal tumors. He underwent cholecystectomy for cholelithiasis. Gastric ulcers resolved with the use of proton pump inhibitors. His blood glucose was well controlled with insulin. Sequential CT/PET scans showed no change in the size of paraduodenal masses over a follow-up period of 14 years. Conclusion: GEP-NETs may secrete more than one type of hormone simultaneously. This case highlights a functional GEP-NET with clinical manifestations due to elevated levels of somatostatin and gastrin. Characterization of GEP-NETs by immuno-histochemical staining and hormonal analysis may help direct clinical management. Although many GEP-NETs are managed surgically, this case suggests that the Ki-67 proliferation index and sequential PET or CT scans may guide the nonsurgical management of functional GEP-NETs.

References: 1-Ganda OP et al. "Somatostatinoma": a somatostatin-containing tumor of the endocrine pancreas. N Engl J Med. 1977;296(17):963-7. 2-Hofland, J., Kaltsas, G., & de Herder, W. W. (2020). Advances in the diagnosis and management of well-differentiated neuroendocrine neoplasms. Endocrine Reviews, 41(2), 371-403. 3-M., Öberg, K., Falconi, M., Krenning, E. P., Sundin, A., Perren, A., & Berruti, A. (2020). Gastroenteropancreatic neuroendocrine neoplasms: ESMO Clinical Practice Guidelines for diagnosis, treatment, and follow-up. Annals of oncology, 31(7), 844-860.), 371-403.

Presentation: Thursday, June 15, 2023
THU536 Pseudoglucagonoma Syndrome: A Rare Complication After Partial Pancreatectomy
Authors: Monsour Elio Paul , Badour Sanna , Tuna Kubra Melek , Leey Julio , Lamas Marcos
Published: October 2023

Disclosure: E.P. Monsour: None. S. Badour: None. K.M. Tuna: None. J. Leey: None. M. Lamas: None.

Introduction/Background: Necrolytic migratory erythema (NME) is a specific cutaneous eruption associated with glucagonoma, an alpha-cell secreting pancreatic neuroendocrine tumor. Glucagonoma syndrome is a paraneoplastic syndrome characterized by NME, diabetes, stomatitis, anemia, weight loss, and gastrointestinal disturbances. Rarely NME can occur in the absence of an alpha-cell tumor of the pancreas, termed pseudoglucagonoma syndrome, seen in other clinical entities such as hepatic disease and intestinal malabsorption. Here, we describe a rare case of pseudoglucagonoma syndrome as a long-term complication following partial pancreatectomy. Clinical Case: A 45-year-old male with a history of benign pancreatic head cyst s/p partial pancreatectomy, pancreatic exocrine insufficiency, and pancreatogenic diabetes reported a 2-week history of a rash on his bilateral upper and lower extremities that was accompanied with blistering and skin peeling. Associated symptoms included tongue pain, diarrhea, and worsening paresthesias. Medications included subcutaneous insulin aspart, pantoprazole, and pancrelipase. Physical examination revealed a patchy rash with hyperpigmented plaques and shellac-like scales, a smooth red tongue, and symmetric hyperreflexia. Preliminary punch biopsy was concerning for NME; thus, the patient was evaluated for possible glucagonoma. Laboratory evaluation revealed normocytic anemia with hemoglobin of 9.8 mg/dL, plasma glucose of 104 mg/dL, and glucagon level of 103 ng/L (RR: <208 ng/L). MRCP was negative for any pancreatic lesions. The patient was further evaluated for nutritional deficiencies and had strinkingly low vitamin A, D, E, K, B6, serum copper, and zinc levels. Plasma amino acids revealed low phenylalanine and tryptophan levels. He was started on a multivitamin (with minerals) and oral nutritional supplements with resolution of rash and subsequent improvement in symptoms. Final pathology of punch biopsy revealed parakeratosis with dermal edema, most compatible with nutritional deficiency. Discussion and conclusion: The pathogenesis and etiology of NME in glucagonoma and pseudoglucagonoma syndromes are not entirely understood. NME is thought to be multifactorial to multiple (essential) nutrient and vitamin deficiencies, as seen in our patient and other nutrient deficiency dermatoses such as zinc deficiency, necrolytic acral erythema, and pellagra. After further investigation, the patient reported poor adherence to pancrelipase supplementation, likely contributing to his clinical presentation and symptoms. Whereas in glucagonoma, excess glucagon levels cause a state of catabolism and exert its effect on the liver to increase gluconeogenesis via amino acid catabolism leading to deficiency. It is essential for clinicians to be aware of this rare and underrecognized phenomenon.

Presentation: Thursday, June 15, 2023
THU557 Effects Of Two Experimental Monocarbonyl Analogs Of Curcumin (MACs) On Breast Cancer Growth, Migration, And Epithelial-To-Mesenchymal Transition (EMT)
Authors: Stojchevski Radoslav , Hadzi-Petrushev Nikola , Mladenov Mitko , Bogdanov Jane , Velichkovikj Sara , Poretsky Leonid , Avtanski Dimiter B
Published: October 2023

Disclosure: R. Stojchevski: None. N. Hadzi-Petrushev: None. M. Mladenov: None. J. Bogdanov: None. S. Velichkovikj: None. L. Poretsky: None. D.B. Avtanski: None.

Curcumin, a polyphenol found in turmeric (Curcuma longa), has been reported to have a range of potential therapeutic effects, including anti-inflammatory and antioxidant properties. However, curcumin’s poor bioavailability has limited its use in medicine. Monocarbonyl analogs of curcumin (MACs) have been developed to overcome this challenge and have shown promise in various medical applications, including cancer. Our previous experiments in animals showed that these two analogs possess potent antioxidant properties. The aim of this study was to investigate the in vitro effects of two experimental MACs (C66 (C22H16F6O) and B2BrBC (C20H16Br2O)) on breast cancer cell growth and epithelial-to-mesenchymal transition (EMT). Both C66 and B2BrBC significantly suppressed MCF-7 and BT-474 viability shown by MTT assay. These two analogs also suppressed breast cancer cell migration, demonstrated by scratch migration wound-healing assay using MCF-7 and MDA-MB-231 cells. Further, using qRT-PCR, we investigated the effects of C66 and B2BrBC on the expression of various epithelial (E-cadherin, cytokeratin-18) and mesenchymal (snail, slug, fibronectin, and vimentin) genes in MCF-7 cells subjected to EMT induction (a media supplement containing Wnt-5a, TGFβ1, anti-E-cadherin, anti-sFRP1, and anti-Dkk-1 antibodies). Since the EMT-induction media significantly downregulated the epithelial markers’ and upregulated the mesenchymal markers’ mRNA expression, these effects were significantly abolished when C66 or B2BrBC were introduced. Taken together, these data demonstrate that C66 and B2BrBC are potent agents for suppressing breast cancer cell growth and EMT in vitro. Further investigation is needed to determine the potential clinical use of these compounds in breast cancer treatment.

Presentation: Thursday, June 15, 2023
OR05-05 A Novel Model Of Prostate Cancer Suggests Enzalutamide Functions Through The Immune System To Diminish Castration Resistant And Metastatic Growth
Authors: Kregel Steven
Published: October 2023

Disclosure: S. Kregel: None.

Background: There exists a tremendous need for establishing prostate cancer (PCa) murine models capable of recapitulating the progress of human PCa. By itself, the murine prostate does not form sporadic tumors and is anatomically and developmentally different from the human prostate. Engineered mouse models, however, lack the heterogeneity of human disease, are often driven in a contrived manner, and rarely (if ever) establish metastatic growth. Human xenografts represent an alternative, but they rely on tumor growth in an immunocompromised host, thus preventing the study of tumor-immune interactions and immunotherapies. Accordingly, we generated PCa xenograft models in a murine system with an intact human immune system (huNOG mice) to test the hypothesis that humanizing tumor-immune interactions would improve modeling of metastatic PCa as well as our ability to model the impact of hormonal and immunotherapies. Methods: Male huNOG and huNOG-EXL mice were produced at Taconic Biosciences by engrafting juvenile NOG mice with human CD34+ hematopoietic stem cells. These mice stably maintained multiple human cell lineages, including functional human T-cells. We utilized two human PCa xenograft cell line models transduced with luciferase to assay organ-specific metastatic growth. First, castrated and intact control mice were injected subcutaneously with 22Rv1 cells. When tumors reached >100 mm3, half of the castrated mice were treated with enzalutamide (enza), and tumor growth was then monitored to endpoint. Additionally, VCaP tumor-bearing mice were castrated when the tumors reached ∼200 mm3, and once the tumor grew back, they were randomized and treated with enza and/or the anti-PD-1 antibody, pembrolizumab (pembro) as well as with vehicle controls. At sacrifice, organs were ex vivo analyzed for metastatic growth, tumor infiltrating lymphocytes, and splenic immune reconstitution. Results: In 22Rv1 tumor-bearing mice, subcutaneous tumor size was not significantly altered across conditions. However, the extent and growth at the secondary sites differed markedly in castrate huNOG vs conventional NOG mice treated with enza. VCaP xenograft tumors showed marked decreases in growth with enza and pembro treatments in huNOG mice, while no effect was observed with either of these treatments in NOG mice. Furthermore, immune responses to enza treatment in huNOG and NOG mice were distinct, as enza treatment only increased intra-tumor CD3+ T-cells as well as CD3+ T-cell activation in huNOG mice. Conclusions: These results illustrate, to the best of our knowledge, the first model of human PCa that metastasizes to clinically relevant locations, has an intact human immune system, and responds to standard-of-care hormonal therapies in a manner similar to responses observed under clinical settings.

Presentation: Thursday, June 15, 2023
SAT634 The Androgen Receptor Does Not Directly Regulate The Transcription Of DNA Damage Response Genes
Authors: Hasterok Sylwia , Scott Thomas G , Roller Devin G , Spencer Adam , Dutta Arun B , Sathyan Kizhakke Mattada , Frigo Daniel E , Guertin Michael J , Gioeli Daniel
Published: October 2023

Disclosure: S. Hasterok: None. T.G. Scott: None. D.G. Roller: None. A. Spencer: None. A.B. Dutta: None. K. Sathyan: None. D.E. Frigo: None. M.J. Guertin: None. D. Gioeli: None.

The clinical success of combined androgen deprivation therapy (ADT) and radiation therapy (RT) in prostate cancer (PCa) created interest in understanding the mechanistic links between androgen receptor (AR) signaling and the DNA damage response (DDR). Convergent data have led to a model where AR both regulates, and is regulated by, the DDR. Integral to this model is that the AR regulates the transcription of DDR genes both at steady state and in response to ionizing radiation (IR). In this study, we sought to determine which immediate transcriptional changes are induced by IR in an AR-dependent manner. Using PRO-seq to quantify changes in nascent RNA transcription in response to IR, the AR antagonist enzalutamide, or the combination of the two, we find that enzalutamide treatment significantly decreased expression of canonical AR target genes but had no effect on DDR gene sets in PCa cells. Surprisingly, we also found that the AR is not a primary regulator of DDR genes either in response to IR or at steady state in asynchronously growing PCa cells. Our data indicate that the clinical benefit of ADT and RT is not due to the direct regulation of DDR gene transcription by AR and that the clinical benefit of this therapeutic combination is instead likely due to both treatments independently reducing tumor cell fitness.

Presentation: Saturday, June 17, 2023
SAT636 Obesity And Aging Interactions Modify The Breast Tissue Microbiome Influencing Cancer Risk
Authors: Iyengar Neil M , Chiba Akiko , Howard-McNatt Marissa , Thomas Alexandra , Soto-Pantoja David R , Cook Katherine Loree
Published: October 2023

Disclosure: N.M. Iyengar: None. A. Chiba: None. M. Howard-McNatt: None. A. Thomas: None. D.R. Soto-Pantoja: None. K.L. Cook: None.

Obesity is one of the few modifiable risk factors for postmenopausal breast cancer. While obesity influences on the gut microbiome are established, the effect of diet and adiposity on tissue resident microbiome populations are underexplored. Studies have shown that breast tissue has a distinct microbiome, which is shifted in the presence of tumors or diet. However, whether obesity and menopause modify the breast microbiome is unknown. Using a cohort of non-cancerous breast tissue samples (n=80) taken at surgery from women that underwent mastectomy for breast cancer, we now demonstrate that obesity and aging interact to shift the breast microbiome. DNA isolated from breast tissue collected at surgery was used to perform V3-V4 amplicon 16S bacterial sequencing. Breast tissue from postmenopausal women with obesity (mean BMI 34.7 ±3.7) displayed a significantly higher α-diversity than breast tissue from postmenopausal lean women (mean BMI 21.9 ±1.7). Postmenopausal women with obesity also displayed a significantly different β-diversity than all other groups (Bray-Curtis; PERMANOVA p<0.02). At the species level, breast tissue from postmenopausal women with obesity had a significantly elevated Akkermansia mucinphila proportional abundance (5.6%) when compared with all other groups (0.05-0.3% proportional abundance), demonstrating obesity and menopause interact to modify the breast tissue microbiome. Akkermansia muciniphila is a mucin-degrading bacteria. Breast tumors display aberrant mucin glycosylation and abundance, which previously were shown to promote carcinogenesis. Staining ER+ breast tumors for mucin-1 from patients with or without obesity indicates patient BMI positively correlates with tumor mucin-1 abundance, suggesting obesity regulation of mucin and/or mucin-degrading bacteria may promote breast tumorigenesis. To determine physiological relevance of breast Akkermansia muciniphila abundance, Western diet-fed MMTV-PyMT mice were intra-nipple injected with saline or Akkermanisa muciniphila bacteria into the mammary gland (MG) at 5, 7, and 9 weeks of age and palpated weekly for tumor formation. Elevated MG Akkermansia presence was associated with increased mammary tumorigenesis and multiplicity. Tumor mucin-1 was decreased with A. muciniphila administration. Flow cytometry analysis of single cell suspensions of breast tumors indicate A. muciniphila modified infiltrating immune populations. Overall, these results suggest obesity and aging may interact to enrich breast mucin-degrading bacteria abundance as a risk factor for postmenopausal breast cancer.

Presentation: Saturday, June 17, 2023
FRI241 Late Diagnosis Of Non-classical CAH In An Elderly Male Previously Diagnosed With Estrogen Producing Adrenal Tumor
Authors: Kaval Roopitha , Subauste Jose
Published: October 2023

Disclosure: R. Kaval: None. J. Subauste: None.

In 2013 a 66-year-old Caucasian male presented to the VA outpatient endocrinology clinic to establish care; the patient carried a diagnosis of estrogen producing left adrenal tumor in 1989 at the age of 42 at an outside facility. On review of records the patient was initially worked up for hypogonadism and was noted to have an elevated estrogen level and a “left adrenal tumor”. He subsequently underwent an unilateral left adrenalectomy for treatment and pathology reported with benign tumor findings. Following surgery, the patient was started on steroid and mineralocorticoid replacement for primary adrenal insufficiency (PAI) and topical testosterone gel for hypogonadism. The question was raised as to why this patient had PAI as he had an intact right adrenal gland on CT scan. On laboratory work-up in 2006 the patient had baseline cortisol of 3.4 ug/dl, ACTH was elevated at 99 pg/ml [7.2- 63.3], and adrenal antibodies (21-OH antibody] were negative. Renin was 2.35 ng/ml/hr [0.167-5.380], Estradiol was 41.8 pg/ml [7.6 - 42.6], LH was low at 0.20 mIU/ml [1.2-8.6] and total testosterone was low at 2.2 ng/ml [1.8-7.8]. Repeat testing yielded ACTH that was elevated at 686.7 pg/ml [7.2- 63.3], electrolytes including sodium and potassium were normal. On physical examination the patient had hyperpigmented skin, normal height, weight and otherwise unremarkable. On CT scan of the abdomen the right adrenal gland was mildly diffusely enlarged. In 2019, 30 years after his initial diagnosis the team questioned whether the adrenal tumor was truly an estrogen producing tumor. As a result, 17-OH progesterone was obtained, and the unstimulated value resulted as 3522 ng/dl [27-199]. With the elevated 17 OH >1000 ng/dL this was diagnostic for Non-classical CAH. The unilateral adrenalectomy likely unmasked the underlying impairment of cortisol production leading to primary AI that is seen with Non-classical CAH patients. The patient was lost to follow up during the pandemic, hence we were not able to perform and further testing.

Presentation: Friday, June 16, 2023
FRI246 A Rare Case Of An Adrenal Gland Hemangioma In A 68-year-old Female
Authors: Daas Rana , Logan Sarah , Voss Rachel , Tarasova Valentina , Glushko Tetiana , Prera Juan Hernandez , Salgado Sarimar Agosto , Hallanger-Johnson Julie , Veloski Colleen
Published: October 2023

Disclosure: R. Daas: None. S. Logan: None. R. Voss: None. V. Tarasova: None. T. Glushko: None. J. Hernandez Prera: None. S. Agosto Salgado: None. J. Hallanger-Johnson: None. C. Veloski: None.

Background: Adrenal gland hemangiomas are extremely rare, with less than one hundred cases reported in the literature. Although benign and usually asymptomatic, they can be confused with adenomas, pheochromocytomas, or malignant adrenal tumors and preoperative diagnosis is challenging. Clinical Case: A 68-year-old female with a history of breast cancer completes an abdominal/ pelvic MRI due to abdominal and back pain that reveals a 1.4 cm right adrenal mass with T2 bright enhancement prompting concern for pheochromocytoma, lipid poor adenoma, or metastasis. An adrenal protocol contrast CT abdomen redemonstrated a 1.3 cm brightly enhancing right adrenal nodule with precontrast Hounsfield units (HU) of 35, postcontrast HU of 236, and delayed HU of 81. Absolute washout was 77.1%, consistent with an adenoma, however, the enhancement profile was also concerning for pheochromocytoma. Labs showed ACTH 15.2 pg/mL (7.2 - 63.3 pg/mL), cortisol 14.7 ug/dL (3.7 - 19.4 ug/dL), dexamethasone suppression test with cortisol 1.3 ug/dL (3 – 41 ug/dL), aldosterone 12 ng/dL (4.0 - 31.0 ng/dL), renin 0.1 ng/mL/hr (0.5 - 4.0 ng/mL/hr), potassium 4.0 mmol/L (3.4 - 4.5 mmol/L), DHEA-S 122 ug/dL (9 - 246 ud/dL), total testosterone 41.38 ng/dL (3.00 – 41.00 ng/dL), free testosterone 3.7 pg/mL (0.6 - 3.8 pg/mL), plasma normetanephrines 0.82 nmol/L (0 - 0.89 nmol/L), and plasma metanephrines 0.14 nmol/L (0 - 0.49 nmol/L), 24-hour urine: norepinephrine 47 ug/d (14 – 120 ug/d), epinephrine <4 ug/d (1 – 14 ug/d), dopamine 236 ug/d (71 – 485 ug/d), metanephrines 86 ug/d (36 – 229 ug/d), and normetanephrines 258 ug/d (95 – 650 ug/d). The patient was asymptomatic, without high blood pressure, tachycardia, or hypokalemia. Despite the unremarkable lab workup, surgical excision of the nodule was recommended due to concern for silent pheochromocytoma or metastasis given the imaging findings and history of breast cancer. She was pretreated with doxazosin and had a right adrenalectomy. Pathology revealed a 1 cm hemangioma involving the periadrenal adipose tissue with ERG positive, CD31 positive, and D2-40 negative immunohistochemical staining. She was monitored post-operatively for transient hypotension and tachycardia and was discharged in stable condition. Conclusion: The differential diagnosis for adrenal gland incidentalomas is quite broad, however, patient history, along with laboratory and imaging studies, can help guide management. Adrenal gland hemangiomas are rare, non-functional, and have a propensity to bleed, but are benign and have a good prognosis.

Presentation: Friday, June 16, 2023
SAT024 Contribution of 11-Ketotestosterone and 11-Ketodihydrotestosterone to Castration-Resistant Prostate Cancer
Authors: Abu-Lebdeh Haitham S , Heshmati Hassan M
Published: October 2023

Disclosure: H.S. Abu-Lebdeh: None. H.M. Heshmati: None.

Background: Prostate cancer is among the most common malignancy in men and represents the second most common cause of cancer-related mortality among men in the US. Androgen-deprivation therapy with surgical or medical castration is widely used to treat hormone-sensitive prostate cancer. Disease progression despite androgen-deprivation therapy is a state defined as castration-resistant prostate cancer that is associated with poor survival rate. This review presents an update on the contribution of two adrenal androgens, 11-ketotestosterone and 11-ketodihydrotestosterone, to the castration-resistant prostate cancer. Methods: A systematic search of literature was conducted using the search terms prostate cancer, testosterone, dihydrotestosterone, adrenal androgens, 11-ketotestosterone, 11-ketodihydrotestosterone, androgen-deprivation therapy, castration, and castration-resistant prostate cancer. Results: In 2022, around 268,490 new cases of prostate cancer were diagnosed in the US with a mortality of 34,500 cases. Although androgen-deprivation therapy with castration is efficient at the beginning, most patients develop a state of castration resistance usually after 2-3 years as a result of the reactivation of androgen-receptor signaling despite low testosterone levels. The adrenal glands produce significant amounts of steroid hormones and metabolites. Among them, 11-ketotestosterone and 11-ketodihydrotestosterone are potent and efficacious androgens with potentially longer activity compared to testosterone and dihydrotestosterone because they are metabolized at a lower rate. Dihydrotestosterone derived from the metabolism of adrenal androgens (e.g., androstenedione and dehydroepiandrosterone) and especially 11-ketotestosterone and 11-ketodihydrotestosterone are important contributors to castration-resistant prostate cancer. In these cases, adrenal suppression with drugs causing a decrease in adrenal androgen production may improve the effectiveness of the androgen-deprivation therapy. Conclusion: In most patients with prostate cancer, androgen-deprivation therapy loses its effectiveness after 2-3 years leading to a state of castration-resistant prostate cancer. Two potent and highly efficacious androgen-receptor agonists of adrenal origin, 11-ketotestosterone and 11-ketodihydrotestosterone, are predominant androgens after castration and play an important role in the development and progression of castration-resistant prostate cancer. Their measurement in blood can be of clinical value during androgen-deprivation therapy. Concomitant treatment aimed to block the production of adrenal androgens is of potential interest in the management of these patients, but more studies are necessary to further investigate the benefits and adverse effects of this approach.

Presentation: Saturday, June 17, 2023
SAT271 Ligand Induced GR Heterodimerization With MR In Living Cells
Authors: Sueyoshi Tatsuya , Perera Lalith , Cidlowski John A
Published: October 2023

Disclosure: T. Sueyoshi: None. L. Perera: None. J.A. Cidlowski: None.

We have established methods for monitoring heterodimer formation between GR and MR in living cells upon the addition of ligands. Two protein fragments derived from NanoBit luciferase (Small Bit peptide composed of 11 amino acids and Large Bit peptide sized 17.6 kDa) can form functional enzyme when protein-protein interaction brings these fragments close proximity. Utilizing the enzyme fragments for fusion protein partners for the hormone receptors, we have constructed expression plasmids for every combination of receptor and enzyme fragments comprising N-terminal or C-terminal fusion proteins. GR and MR fusion proteins with the luciferase fragments were expressed in HEK293 cells and the enzyme activities were determined in time course before and after the addition of ligands (dexamethasone and aldosterone). We observed robust increases of NanoBit luciferase activity in GR and MR transfected cells less than 20 min after the addition of ligands suggesting the heterodimer was formed in the time period. Similar assays detected these receptors formed homodimer after the addition of ligand for each receptor suggesting homodimer and heterodimer co-exists when appropriate ligands are in this assay system. DNA binding null mutations of GR DNA binding domain effectively abolished GR homodimers but not GR - MR heterodimers suggesting mechanistical differences between the homodimer and heterodimer formation. Based on the results only C-terminal NanoBit fusion receptors showed positive heterodimerization-induced enzyme activity, we proposed ligand binding domain 3D structure heterodimer models and found amino acid residues in helix 9, helix 10, and near C-terminus are involved in the heterodimer interaction interface. Thus, this method will be a powerful tool for analyzing molecular mechanisms of GR - MR heterodimer formation in living cells.

Presentation: Saturday, June 17, 2023
SAT323 Management Of Severe Cushing’s Syndrome Due To Cortisol Secreting Adrenal Tumor In A Critically Ill Patient
Authors: Obeid Hiba , Buras Eric Dale , Else Tobias
Published: October 2023

Disclosure: H. Obeid: None. E.D. Buras: None. T. Else: None.

Introduction: Severe Cushing’s syndrome is associated with multiple life threatening complications. Clinical Case: A 69 year-old man with Cushing’s syndrome was admitted to the hospital with septic shock due to bacteremia with necrotic left lower extremity infection. He required above knee amputation. His hospital course was complicated with invasive pulmonary Aspergillosis and ventilator associated pneumonia. He developed acute kidney injury that required dialysis, altered mental status, deep venous thrombosis bilateral pulmonary embolisms, bleeding duodenal ulcer and retroperitoneal hematoma. Prior to admission: Random cortisol was 31.7 mcg/dL (Normal: 4.8-19.5 mcg/dL), AM Cortisol following 1 mg oral dexamethasone was 47 mcg/dL (Normal: <1.8 mcg/dL), DHEA-s was 210 mcg/dL (normal: 33.6-249 mcg/dL) and 24 hour urine free cortisol was 622 mcg/day (Normal: <60 mcg/day). ACTH was undetectable. An FDG-PET scan showed a 6.5 centimeters hypermetabolic left adrenal mass with internal coarse calcifications but no evidence of metastasis. Etomidate drip, Metyrapone and Osilodrostat were tried to lower excess cortisol production. During admission while on Osilodrostat: Cortisol level: 20 mcg/dL (normal: 8-19 mcg/dL). Deoxycorticosterone: 53 ng/dL (Normal: 2-19 ng/dL). 11-Desoxycortisol: 580 ng/dL (Normal: 12-158 ng/dL). 17-alpha-hydroxyprogesterone: 45 ng/dL (Normal: 27-199 ng/dL).

Surgery was considered, but adrenalectomy was deemed high risk and not pursued. Therefore, the patient underwent computed tomography (CT) cryoablation of the left adrenal gland. Labs following cryoablation: Cortisol: 7.7 mcg/dL. Deoxycorticosterone: 10 ng/dL. 11-Desoxycortisol: 34 ng/dL. 17-alpha-hydroxyprogesterone: 25 ng/dL. The procedure was complicated by T11/T12 intercostal artery injury leading to hemothorax. He was continued on physiologic doses of hydrocortisone. On follow up 4 weeks following discharge, he had complete resolution of hypercortisolism symptoms. A repeat whole body PET scan showed persistent FDG-avid neoplasm in left adrenal area, as well as metastasis in the liver and the duodenum. Conclusion: It is critical to control hypercortisolism in patients with Cushing’s syndrome. Several medications can be used. Surgical adrenalectomy remains the gold standard for treatment. CT-guided cryoablation of the adrenal tumor is a reasonable alternative when patient is not a surgical candidate. However, it is not a completely benign procedure as it can be associated with complications. Our treatment approach improved short term outcome for our patient, but did not provide long term benefit since he developed metastasis.

Presentation: Saturday, June 17, 2023
THU433 Spontaneous Vertebral Fractures In The Setting Of Prolonged CRRT
Authors: Akanbi Folake , Kutahyalioglu Merve , Gogineni Preethi , Raja Sobia
Published: October 2023

Disclosure: F. Akanbi: None. M. Kutahyalioglu: None. P. Gogineni: None. S. Raja: None.

Introduction: Bone resorption and hypercalcemia due to prolonged immobilization are known complications in critically ill patients. This is more pronounced in patients with high bone turnover rates such as in secondary hyperparathyroidism. In this case report, the chelation of calcium by citrate masked the immobilization hypercalcemia, resulting in marked bone loss and spontaneous vertebral fractures in the context of normal calcium levels. Case report: 23 year old man with no past medical history was seen on account of concerns for calcium loss from his bones as he was on CRRT, for 4 months and the amount of calcium in the extracorporeal circuit was more than expected. He had presented with new onset systolic heart failure (EF 10%) secondary to fulminant post-COVID-19 myocarditis, and renal failure due to acute tubular necrosis. CRRT with citrate dextrose anticoagulation was initiated at presentation. He had received pulse dose prednisone for presumed post-viral myocarditis. He was awaiting heart and kidney transplantation. Greater than average calcium clearance during CRRT prompted workup for hypercalcemia. He denied personal or family history of hypercalcemia, renal stones, fractures, dental issues or hyperparathyroidism. He reported eating adequate amounts of dairy products. Labs showed corrected calcium 9.3 (8.6-10.3 mg/dl), elevated PTH 189 (10-65 pg/ml), low serum protein and albumin, and low 25OHVD that was 14 (25-100 ng/mL) on presentation and actively being replaced with ergocalciferol. Phosphorus, magnesium, liver and thyroid function were normal. The patient had complained of back pain after being immobile for 3 months. MRI showed subacute vertebral fractures of T12 and L1. Thereafter, spine X-ray showed multiple vertebral fractures of L2-L5. Beta CTX was 4153 (120-946 pg/ml) and DXA scan revealed low bone density for age with Z score -3.7 in the femoral neck, invalid in the spine due to the fractures, felt to be the source of high extracorporeal calcium concentration. A dose of Denosumab was given for treatment with improvement of calcium clearance during CRRT. Discussion: Acute fractures and infrequently, prolonged immobilization cause hypercalcemia with suppression of PTH. In our patient who was critically ill and immobilized for 4 months, the use of CRRT maintained normocalcemic blood levels, and renal failure with vitamin D deficiency caused secondary hyperparathyroidism. Only the declining requirements for calcium replacement during CRRT prompted workup for hypercalcemia that lead to identification of significant vertebral fractures and treatment. Declining need for calcium replacement during CRRT should prompt investigation and treatment of disorders of hypercalcemia and metabolic bone disorders in this patient population.

Presentation: Thursday, June 15, 2023
THU440 A Case Of Osteomalacia In A Young Adult Female With Premature Ovarian Insufficiency
Authors: Kasimoglu Ismail Hakki , Vu Timothy , Dai-Ju Jenny Qian
Published: October 2023

Disclosure: I.H. Kasimoglu: None. T. Vu: None. J.Q. Dai-Ju: None.

Background: Osteomalacia is a condition due to inadequate mineralization during the bone-remodeling process. Common causes of bone demineralization include Vitamin D deficiency and low calcium intake. Consequently, the treatment often involves both Vitamin D and calcium supplementation, corresponding dietary modifications, and adequate exposure to sunlight. Clinical Case: 34-year-old female with past medical history of sickle cell disease s/p allogenic bone marrow transplant in 11/2020, brain toxoplasmosis infection 3/2021, secondary amenorrhea due to premature ovarian insufficiency diagnosed in 12/2021, was referred to endocrinology for management of osteomalacia. Dexa Scan from 11/2021 reported lower bone density than expected compared with the same age/gender group (Z-Scores: Left Hip – 0.3, Neck –1.4, and L1-L4 –3.6). Vitamin D 25-OH level was 8.3 (n>30) ng/mL and serum calcium level as low as 5.8 (n8.6-10.3) mg/dL in 3/2021, PTH-I elevated to 459 (n10-68) pg/mL, alkaline phosphatase elevated to 166 (n34-104) U/L. The patient was encouraged to increase Vitamin D3 to 4000 iu daily and calcium intake to 1200 mg daily. After discussion with patient of benefits and risks of hormone replacement, patient was started on very low dose of estradiol patch (0.025mg/day) for concern of prior history of pulmonary embolism, and progesterone 100 mg oral daily 3/2022. Vitamin D 25-OH, PTH, serum and 24 hr urine calcium have been within normal range since 9/2022. Dexa Scan from 11/2022 showed significant improvement of bone density (32.0% increase of lumbar spine, 11.2% increase of left hip). This case of osteomalacia resulting from Vitamin D deficiency and subsequent secondary hyperparathyroidism demonstrates that it is imperative to recognize and treat Vitamin D deficiency because it restores bone strength and prevents fractures while simultaneously correcting biochemical abnormalities (1). This case is also interesting as the patient still carries an increased risk of bone density loss complicated by underlying premature ovarian insufficiency and hypoestrogenic state. Thus, by providing patients with the appropriate Vitamin D and calcium supplementation recommendations along with hormone replacement therapy in young adults, it is possible to rehabilitate their overall bone health as well as reduce future risks of fractures. Conclusion: Adequate Vitamin D and calcium supplementation is important for the management of osteomalacia. In patients with premature ovarian insufficiency, it is even more imperative to promote supplementations, dietary modifications, and sunlight exposure in conjunction with traditional agents of hormonal therapy to promote overall bone health.

Reference: 1) Bhan A., et al. Osteomalacia as a result of vitamin D deficiency. Endocrinol Metab Clin North Am. 2010;39(2):321–331. 10.1016/j.ecl.2010.02.001

Presentation: Thursday, June 15, 2023
THU443 Acute Iridocyclitis Associated With Intravenous Zoledronic Acid
Authors: Ankireddypalli Anvitha Reddy , Sibley Shalamar Dionne
Published: October 2023

Disclosure: A.R. Ankireddypalli: None. S.D. Sibley: None.

Introduction: Bisphosphonates are widely used for osteoporosis. Intravenous (IV) zoledronic acid (ZA) is frequently prescribed in cases of oral bisphosphonate intolerance or noncompliance. Well known immediate ZA side effects include flu-like symptoms such as nausea, myalgias and fever. Here we report a case of a rare side effect of acute anterior uveitis following initial ZA dosing. CASE: A 71-year-old female was diagnosed with osteoporosis; DEXA scan had lowest T score of -2.6 at the lumbar spine. Vitamin D level was 10 ng/mL. She received calcium and vitamin D supplementation. Two months later vitamin D level was 31 ng/mL. ZA was recommended due to difficulty with adherence to oral bisphosphonate. Five days after infusion she presented to our emergency department (ED) with progressive symptoms of bilateral eye itching, redness, excessive tearing, blurry vision, photosensitivity, floaters, pain and headaches that had begun 1 day post infusion. She’d had 2 prior outside ED visits for these symptoms and received polymyxin B and later ofloxacin eye drops which did not relieve them. She denied fever, chills, arthralgias and myalgia. She denied any prior known autoimmune disorder or prior history of eye symptoms. On examination she was afebrile and had bilateral conjunctival injection, excess tearing and watery discharge. She was discharged with olopatadine eye drops and cetirizine, diagnosed with allergic conjunctivitis, and referred to ophthalmology. On ophthalmic exam 7 days after her infusion, visual acuity was 20/60 in the right eye, and 20/60 in the left eye. Intraocular pressure was 12 mmHg in the right eye and 16 mmHg in the left eye. Slit lamp eye exam showed diffuse conjunctival injection of the right eye, mild corneal endothelial folds, and flare with cells in anterior chamber and synechiae posterior to the iris. Right acute iridocyclitis was diagnosed, she received prednisolone eye drops and cyclopentolate eye drops. Symptoms improved in 1 week with almost complete resolution after 3 weeks of therapy. She has not had a recurrence of these symptoms; she has declined future treatment with ZA. Conclusion: ZA-associated ocular inflammation is a rare but serious side effect. This adverse effect has been hypothesized to be associated with increased levels of pro-inflammatory cytokines including Interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-alpha. As with other acute phase reactions to ZA, it does not appear that ocular inflammation tends to recur with subsequent ZA. Optimizing vitamin D levels prior to treatment may help to prevent this condition. There is some evidence for higher rates of acute phase reaction in patients with lower levels of vitamin D but this patient’s vitamin D status was adequate at the time of treatment. Clinicians should be aware of the rare occurrence of post-ZA ocular inflammation. Early recognition and prompt treatment are essential.

Presentation: Thursday, June 15, 2023