bluuebunny/crossref_metadata_2025 huggingface dataset:
8257 Pancreatic Neuroendocrine Tumor Presenting as Carcinoid Syndrome
Authors: Phung Don , Saad Bashar
Published: October 2024

Disclosure: D. Phung: None.

Introduction Pancreatic neuroendocrine tumors (NETs) are rare tumors that arise in neuroendocrine cells of the pancreas. These tumors secrete a wide array of hormones. Carcinoid syndrome is a result of well-differentiated neuroendocrine tumors that secrete biologically active amines and peptides that cause the clinical manifestation of flushing, diarrhea, cardiac involvement, and wheezing. Case Presentation A 57-year-old male presented to the clinic for symptoms of tachycardia, shortness of breath, dizziness, and sweating for the past year. He had past medical history of chronic kidney disease, history of previous cardiac arrest, history of previous myocardial infarction, congestive heart failure, hypertension and gastric reflux disease. No history of tobacco, alcohol, or drug consumption. No previous surgeries. Family history with heart disease and prostate cancer in his father. His symptoms began over the course of the past year. Initially began with shortness of breath, chest pain, weight gain which then developed into dizziness with standing, episodes of night time sweating. He had associated headaches that were occurring daily. Vomiting would occur intermittently three to four times weekly. He noted episodes of flushing with rash occurring in the upper chest and bilateral arms. Diarrhea and loose bowel movements would occur occasionally. On examination he had tachycardia with heart rate at 103 BPM. Lung fields clear throughout. Abdomen was soft, nontender, without masses palpated. On biochemical testing chromogranin A was highly elevated and remained elevated upon repeat testing. Initial imaging with CT abdomen and pelvis with contrast was negative. PET scanning confirmed and localized his NET, revealing increased tracer uptake and hypervascularity in the neck of pancreas as well as two regions in the right lower lobe of the liver. Following confirmation and localization of his tumor he was then referred for surgical evaluation and treatment. Discussion In our presented case, the patient presented with symptoms suggestive of carcinoid syndrome which was confirmed biochemically with elevated chromogranin A. Clinical suspicion remains critical in diagnosis of NETs. The patient presented with clinically suspicious carcinoid syndrome, but initial testing with CT scan was negative and required further PET-based tracing to uncover tumors. Our case highlights the importance of clinical examination and acumen in diagnosing neuroendocrine tumors.

Presentation: 6/2/2024
7862 The Paradoxical Role of ERFFI1 in Breast Cancer Progression Is Supported by Its Dynamic Protein Interactome
Authors: Maeve Ocampo Alessandria , Dano Bagamasbad Pia
Published: October 2024

Disclosure: A. Ocampo: None. P.D. Bagamasbad: None.

In breast cancer (BCa), glucocorticoid (GC) therapy is used in anti-emetic and palliative care. However, the effects of GC therapy in BCa are conflicting as it is beneficial for hormone-responsive luminal subtypes while it promotes tumor progression in more aggressive triple-negative BCa (TNBCs). A factor implicated in this paradoxical shift is the feedback inhibitor of epidermal growth factor receptor (EGFR) signaling, ERBB receptor feedback inhibitor 1 (ERRFI1). In BCa cell lines, ERRFI1 expression is directly regulated by GC receptor (GR). More interestingly, ERRFI1 was found to restrict the GC-enhanced proliferation in normal breast epithelia but enhances the GC-mediated pro-tumorigenic effects in highly aggressive TNBC. To identify the mechanism behind the shift in ERFFI1 function through BCa progression, ERRFI1 protein interactions in the luminal, HER2, and TNBC subtypes were analyzed by identifying differentially expressed proteins from each subtype using available proteome and interactome datasets from Integrated Interactions Database and followed by network and clustering analyses through STRING. The ERRFI1 interactome varied across the subtypes, and gene ontology analysis of the protein networks revealed progressive tumorigenic effects from the least aggressive luminal subtype to the most aggressive TNBC. The luminal BCa-ERRFI1 interactome showed metastatic potential that is countered by negative regulation of receptor tyrosine kinase (RTK) signaling. The HER2-ERRFI1 interactome highlighted the amplification of RTK signaling and its possible modulation through SRC while the TNBC-ERRFI1 interactome presents pro-oncogenic proteins implicated in drug resistance, angiogenesis, and EMT. Interestingly, the interactome also revealed a link between EGFR signaling and GR signaling possibly through ERRFI1, EGFR, and SFN. To determine the function of ERFFI1 in EGFR signaling in BCa, we generated stable ERRFI1 knockdown in different breast epithelial cell models through lentiviral transduction. Cells were then treated with EGF followed by gene expression analysis of known EGF-upregulated genes such as MYC, GSK3B, MCL1, and MMP9. We found that ERRFI1 knockdown enhanced the EGF-dependent induction of MYC and MMP9 in normal MCF10A cells and this effect was not observed in the TNBC MDA-MB-468 line, suggesting the loss of ERRFI1-mediated inhibition of EGFR signaling with BCa tumorigenic potential. Taken together, our findings suggest that the progressive loss of anti-tumorigenic function of ERRFI1 may be explained by its changing interactome in BCa molecular subtypes.

Presentation: 6/3/2024
7536 Missed Silent Retroperitoneal Paraganglioma
Authors: Lamichhane Shristi , Price David T , Faria-Briceno Judith J , Kaur Arshpreet
Published: October 2024

Disclosure: S. Lamichhane: None. D.T. Price: None. J.J. Faria-Briceno: None. A. Kaur: None.

Introduction: Paragangliomas are rare neuroendocrine tumors comprising about 15-20% of all chromaffin cell tumors and can arise anywhere along the sympathetic and parasympathetic ganglionic chain from skull base to the pelvic floor. About 75% of sympathetic paragangliomas arise in the abdomen out of which majority are functional and secrete catecholamines responsible for the typical clinical features. While the diagnosis is usually made by clinical features and lab elevation of catecholamines, it is estimated that 10-15% of paragangliomas are non-functional and another 10% do not manifest clinically according to the hormone activity, thus posing a significant diagnostic challenge. We report a case of a retroperitoneal paraganglioma diagnosed by biopsy as it was initially missed owing to its silent nature clinically and biochemically. Case report:A 48-year-old smoker with panic disorder, remote history of spontaneous pneumothorax, and exploratory laparotomy for motor vehicle accident visited ER due to left-sided abdominal fullness and weight loss of 10-20 pounds for several months. Review of systems was negative except for mild constipation. He denied taking any medications and BP had been normal. CT abdomen showed a large 13.3 cm mixed cystic and solid mesenteric mass. Core biopsy revealed pheochromocytoma and patient was referred to Endocrinology. Labs showed elevated plasma free metanephrines (MN) 80 pg/ml, normetanephrines (NMN) 190 pg/ml, total MN 270 pg/ml, all less than twice the upper limit of normal and inconclusive, non-elevated 24-hour urine MN and NMN but with inadequate collection, and normal plasma catecholamines. MRI revealed a 13.5 cm mass in the left retroperitoneal sympathetic chain separate from the left adrenal gland and inferior to the left kidney. After pre-op optimization with alpha and beta blocker, patient had an uncomplicated open resection of the mass along with the retroperitoneal lymph nodes (LN). Pathology resulted in 3 benign LNs, a 16.5 cm paraganglioma negative for margin, lymph-vascular invasion, and necrosis. Genetic panel was negative. Follow-up post-surgery at 1 and 3 months with mildly elevated catecholamines and MRI abdomen at 3 months without evidence of recurrent or residual mass and metastasis. PET scan is pending prior authorization. Conclusion: Silent retroperitoneal paragangliomas are exceedingly rare. The diagnosis is often missed when the tumors are asymptomatic, and biomarkers are not elevated. The lack of specific imaging characteristics also adds to the diagnostic challenge. Early recognition can avoid the potential risk of life-threatening hypertensive crisis during surgical intervention. Our case highlights the importance of considering this rare entity in the differential diagnosis of retroperitoneal mass.

Presentation: 6/1/2024
12544 Notch4 And Gbp7 Genetic Contribution To Primary Aldosteronism Pathology
Authors: Mohd Rizam Nurfatin Syazreen , Athirah Pauzi Fatin , Choy Mun-Kit , Williams Simon , Aminuddin Amnani , Abdul Latif Faeezah , Syed Mohammed Nazri Siti Khadijah , Mustangin Muaatamarulain , Chin Tan Geok , Wu Xilin , Ng Elisabeth , Laycock Kate , Sukor Norlela , Bahari Nasruddin Azraai , Jonathan Brown Morris , Keavney Bernard , Aisha Azizan Elena
Published: October 2024

Disclosure: N.S. Mohd Rizam: None. F.A. Pauzi: None. M. Choy: None. S. Williams: None. A. Aminuddin: None. F. Abdul Latif: None. S. Syed Mohammed Nazri: None. M. Mustangin: None. G. Tan: None. X. Wu: None. E. Ng: None. K. Laycock: None. N. Sukor: None. A.B. Nasruddin: None. M.J. Brown: None. B. Keavney: None. E.A. Azizan: None.

Primary aldosteronism (PA) is a common curable cause of hypertension (5-10% cases) yet markedly underdiagnosed. Heredity contributes 25-64% of inter-individual blood pressure variation. Genome-wide association studies have identified a proportion of these genetic factors, whole-genome sequencing (WGS) could provide deeper genetic resolution. We therefore performed WGS on PA patients to elucidate genetic contributors for aldosterone related hypertension. In PA patients of Malay or Black ethnicity, missense mutations in NOTCH4 were frequently encountered (21 of 100). Four of the seven mutations identified were rare (gnomAD allele frequency = 0) and damaging (CADD score >20). The protein is a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 that regulates cell-fate determination. Whereas in Black PA patients or PA patients with no apparent adenoma, an enrichment of two rare missense mutations in GBP7 occurred compared to the global population (7 of 100). The mutations in GBP7 were verified as the encoded protein hydrolyzes GTP to GMP associated with the aldosterone synthesis pathway. Bulk adrenal expression of NOTCH4 and GBP7 were 11.7 and 1.145 transcript per million (TPM) respectively (data acquired from GTex). Single-cell analysis of human adrenals identified NOTCH4 to be expressed mainly in endothelial cells. Co-culturing of the endothelial cell line (HCMEC) with an adrenocortical cell line (HAC15) increased expression of CYP11B2, encoding the aldosterone synthase enzyme, by 1.82+0.37-fold (n=6, p=0.03). Overexpressing NOTCH4 and GBP7 in HAC15 increased CYP11B2 expression by 1.74+0.08-fold (n=16, p=0.000003) and 1.57+0.21-fold (n=24, p=0.001) respectively. In summary, NOTCH4 and GBP7 may highlight a novel pathway in PA pathology.

Presentation: 6/2/2024
8712 Pediatric Adrenocortical Oncocytic Neoplasm With Central Precocious Puberty: A Case Report
Authors: Huzita Claudia H , Lins Wallison M , Beeby Stephanie K , Lopes Roberto I , Denes Francisco T , Claudia Latronico Ana , Polo Marilia , Victor Carolina R , Hoff Ana A , Mendonca Berenice B , Almeida Madson Q , Barisson Villares Fragoso Maria Candida
Published: October 2024

Disclosure: C.H. Huzita: None. W.M. Lins: None. S.K. Beeby: None. R.I. Lopes: None. F.T. Denes: None. A. Latronico: None. M. Polo: None. C.R. Victor: None. A.A. Hoff: None. B.B. Mendonca: None. M.Q. Almeida: None. M.C. Fragoso: None.

Background: Adrenocortical oncocytic tumors (AOT) originate from the adrenal cortex. In the pediatric age group, they are rare and usually non-functional. Less than 20 cases of functional AOT have been reported and only one developed central precocious puberty. We describe the case of a patient with Li Fraumeni syndrome with germline TP53 pathogenic variant (PV) (p.R337H) who developed functional AOT and then central precocious puberty. ClinicalCase: A 2-year and 9-months old girl presented with pubic hair (Tanner stage P3S1) and clitoromegaly (2.6cm). Hormonal study showed elevated total testosterone (70ng/dL,ref. < 48ng/dL), DHEA-S (13490 ng/mL,ref<194 ng/mL) and a positive overnight 1mg dexamethasone suppression test (Cortisol5,8µg/dL). Abdominal ultrasonography showed a right round adrenal mass, which on magnetic resonance imaging (MRI) was well defined (50mm) and there was no evidence of invasion into adjacent organs or vessels. ChestX-ray and liver ultrasound imaging were normal.TheTP53 p.R337HPV was inherited from her father. The patient underwent a right adrenalectomy and oncocytic adrenocortical tumor was identified by histopathology (Biseglia score2/7, Wieneke score1/9 and Weiss score 5). Immunohistochemistry was positive for p53 and Ki67(13%). Following surgical removal of the tumor, the patient subsequently developed hypothalamic-pituitary activation and demonstrated central precocious puberty (Tanner P3S2 and advanced bone age). She was treated with a gonadotropin-releasing hormone agonist. Hormonal and clinical follow up demonstrated delayed pubertal progression. Discussion: AOT rarely presents with excess hormonal production. Herein we describe the case of the youngest child with functional AOT that developed central precocious puberty after the removal of the tumor. The mechanisms that cause hypothalamic-pituitary activation are not well understood, but prolonged exposure to androgen and then its withdrawal might lead to activation of hypothalamic GnRH pulse generated via a feedback system that has matured during the period of exposure to sex steroids.Therefore, clinical follow up of potential secondary effects of excess hormone secretion after tumor removal is important in pediatric patients with virilizing arenocortical tumor. In addition, considering Li Fraumeni syndrome, the screening of other tumors according to the Toronto protocol is required.

Presentation: 6/2/2024
7206 Perioperative Management of Pheochromocytoma: The Mayo Clinic Florida Experience
Authors: Verma A , Elli F , RAO S , Smith M , Shapiro A , Moshe C , Chadha R
Published: October 2024

Disclosure: A. Verma: None. F. Elli: None. S. Rao: None. M. Smith: None. A. Shapiro: None. C. Moshe: None. R. Chadha: None.

Introduction: Pheochromocytomas are rare, neuroendocrine tumors derived from chromaffin cells of the neural crest, typically within the adrenal medulla. The pathophysiologic effect of primary concern is the uncontrolled release of catecholamines into the bloodstream, which carry risk for episodic hypertension, palpitations, and life-threatening crises. Preoperative preparation with drugs that block adrenergic receptors is utilized to improve hemodynamic oscillation force and surgical outcomes. Widely used premedication include alpha-blockers, beta-blockers, and calcium channel blockers. Despite adequate pretreatment, hemodynamic instability continues to evoke massive risk. The objective of this study was to assess the incidence of intraoperative hypertensive episodes in patients undergoing robotic assisted laparoscopic adrenalectomy. Methods: This study is an observational retrospective analysis of patients who underwent elective laparoscopic robotic-assisted adrenalectomies from February 2019 to April 2023. 17 patients total patients were included. Preoperative information included age, BMI, ASA physical classification, preoperative blockade regiment, and urine metanephrines. Intraoperative information included operation duration, tumor size, intraoperative anti-hypertensives, and hypertensive spikes defined as a SBP greater than 175 mmHg for 5 consecutive minutes. Data analysis was performed to obtain frequency counts (%), means (standard deviations), and median (range) as appropriate. Results: The mean age at the time of surgery was 57.12 ± 17.2 years. The majority of patients (76%) were ASA status class III. 7 of the 17 patients did not have active pheochromocytoma based on symptomatology, the incidental diagnoses being made by imaging and workup. The average tumor diameter was 3.90 ± 1.8, with a range of 2.0 - 8.0. Mean operative time was 153.76 ± 53.9 minutes. Preoperative urinary metanephrines were observed to have a mean of 1,248.44 ± 2,866.9 pg/mL. In terms of preoperative preparation, 65% of patients received Doxazosin, and 29% of patients received an alternative anti-hypertensive. Yet, 64.7% of patients were found to have at least 1 intraoperative hypertensive spike Conclusion: Despite premedication with anti-hypertensives, a significant percentage of patients experienced intraoperative hemodynamic instability. This emphasizes the importance of anesthesiologist preparation for intraoperative hypertension management to aggressively prevent hypertensive crises. In addition, it questions the routine use of alpha blockade for all cases preoperatively as has been suggested in certain studies, and whether or not it should be driven by other patient characteristics.

Presentation: 6/1/2024
8563 Pheochromocytoma Screening In A Patient With Neurofibromatosis Type I And Medication-Resistant Hypertension
Authors: Mora Eduardo , Bolduc Aaron , Elshimy Ghada
Published: October 2024

Disclosure: E. Mora: None. A. Bolduc, MD: None. G. Elshimy: None.

Title: Pheochromocytoma Screening in a Patient With Neurofibromatosis Type I and Medication-Resistant Hypertension Background: Patients with neurofibromatosis type I (NF1) have a higher risk of pheochromocytoma and it may be missed if no screening done, thus placing the patient at risk of stroke and/or myocardial infarction. The prevalence of pheochromocytoma in patients with NF1 is 2.9% according to a retrospective cohort study by Gruber et al. We present a case of biochemically silent pheochromocytoma in a patient with NF1 and resistant hypertension Clinical case: A 74-year woman with NF1 presented with episodic headaches and labile systolic blood pressure (BP) in the 170-200s mm Hg on three different antihypertensives consistent with pheochromocytoma. Initial tests for renal artery stenosis and pheochromocytoma showed normal plasma MN (0.43 nmol/L, n< 0.50 nmol/L) and NM (0.86 nmol/L, n< 0.90 nmol/L), and normal flow in both renal hila by color Doppler and no large suprarenal masses identified on retroperitoneal US. Duplex imaging of the bilateral kidneys showed no evidence of renal artery stenosis. CT of abdomen/pelvis with and without IV contrast showed a 1.6 cm nodule on Right (RT) adrenal gland that measured 36 HU on unenhanced phase with an absolute washout of 67%. No discrete nodule in Lt adrenal gland. Dotatate PET/CT revealed a Rt adrenal nodule with elevated asymmetric activity (measured 28.1 standardized uptake values (SUV), n for liver: max 12.3, spleen: max 23.5) relative to the normal physiologic activity of the Leftt adrenal gland, which is concerning for pheochromocytoma. The patient was then referred to our endocrine clinic for further evaluation 6 months after the initial presentation. Labs showed normal aldosterone (5.8 ng/dL, n≤39.2 ng/dL), cortisol (7.66 mcg/dL, n: 3.09-22.40 mcg/dL), ACTH (20 pg/mL, n: 7.2-63 (AM collection), and DHEA-S (28 mcg/dL, n:5.3-124 mcg/dL). Normal repeat plasma MN (0.38 nmol/L, n< 0.50 nmol/L) and NM (0.46 nmol/L, n< 0.90 nmol/L). Repeat CT adrenal washout redemonstrated 1.4 cm Rt adrenal nodule that measured 39 HU on non- contrast image with an absolute washout of 68%. Patient will have a surgical resection of the Rt adrenal biochemically silent pheochromocytoma next week and she has been receiving an alpha-blocker prior to surgery to decrease risk for labile BP. Discussion and Conclusion: This case illustrates how CT and DOtatate scan findings can alert providers to the presence of a pheochromocytoma, even in biochemically negative patients. We recommend pheochromocytoma screening in all patients with NF1 to prevent delayed diagnosis and complications of untreated pheochromocytoma.

Presentation: 6/1/2024
7783 Pheochromocytoma Unusually Presenting As Intestinal Pseudo-Obstruction: A Case Report
Authors: Chua Jessa Marie V , Cunanan Elaine C , Sazon Joseph Francis G , Reyes Joannalyn L
Published: October 2024

Disclosure: J.V. Chua: None. E.C. Cunanan: None. J.G. Sazon: None. J.L. Reyes: None.

Introduction: Pheochromocytoma is a rare neuroendocrine tumor that arises from the adrenal medulla. It may present with a variety of symptoms that can resemble other diseases as a result of the effects of catecholamine overproduction on the different organ systems of the body, occasionally making diagnosis difficult and delaying appropriate treatment.Intestinal pseudo-obstruction is an unusual presentation of pheochromocytoma from the effects of excessive catecholamines on the gastrointestinal system, resulting in decreased peristalsis with constriction of the sphincter muscles, consequently prolonging intestinal transit time. Currently, there is no available data on its incidence or prevalence rate. Clinical Case: This is a case of a 50-year-old Filipino male initially presenting with abdominal pain and enlargement with inability to pass stool and flatus, not relieved by laxatives, enemas, and nasogastric and rectal tube decompression. Abdominal radiograph revealed segmental ileus versus partial large bowel obstruction, while abdominal CT scan showed fecal impaction and an incidental finding of an enhancing adrenal mass on the left adrenal gland. Colonoscopy findings were unremarkable. Laboratory workup demonstrated elevated 24-hour urine metanephrine levels with a value of 44.62 mg/24 hours (normal value: 0-1.0 mg/24 hours). The patient was initially managed conservatively, but no improvement in symptoms was noted. Pre-operative preparation was done with terazosin and intravenous saline infusion, and the patient then underwent left open adrenalectomy with bowel decompression, which provided resolution of symptoms and resumption of regular bowel movement post-operatively. The final result of the histopathologic examination confirmed the diagnosis of pheochromocytoma. Conclusion: Gastrointestinal symptoms such as ileus and pseudo-intestinal obstruction are uncommon presentations of pheochromocytoma. A high index of suspicion is necessary among patients presenting with these symptoms, and pheochromocytoma should be considered as part of the differential diagnosis.

Presentation: 6/1/2024
7094 Post Unilateral Adrenalectomy Hyporeninemic Hypoaldosteronism: Requiring Long Term Fludrocortisone In Managing Hyperkalemia And Renal Dysfunction
Authors: Rani Richa , Bidani Khyati , Roy Roopa
Published: October 2024

Disclosure: R. Rani: None. K. Bidani: None. R. Roy: None.

Adrenalectomy, seen as a potentially curative measure for unilateral aldosterone-producing adenoma (APA), targets both biochemical and clinical resolution. However, postoperative challenges may arise, including acute renal failure and hyperkalemia, due to inadequate aldosterone secretion, a consequence of prolonged suppression of the renin-angiotensin-aldosterone system (RAAS) on the contralateral side. Our case underscores the postoperative challenge of isolated aldosterone deficiency leading to renal function deterioration and hyperkalemia, necessitating fludrocortisone therapy. We are presenting case of 71-year-old male with a history of uncontrolled hypertension for over 30 years with hypokalemia (taking KCL 20mEq daily). Initial laboratory findings revealed elevated aldosterone levels 79ng/dL and an aldosterone-to-renin ratio (ARR)> 20, K- 3.2mmol/L, creatinine 1.32mg/dl, Na-145 mmol/L with normal cortisol and plasma metanephrines levels. CT abdomen disclosed a 21 x 18 mm right adrenal adenoma, with subsequent confirmation of lateralization through Adrenal vein sampling. The patient underwent right adrenalectomy. Two weeks post-surgery, he presented to the emergency department with symptoms of fatigue and weakness. Laboratory results indicated hyperkalemia (K- 6.5 mmol/L) and elevated creatinine (3.52mg/dl) with undetectable aldosterone and renin levels. Urinalysis and CT abdomen ruled out other causes of acute renal injury. Initial management included intravenous fluids and Potassium supplementation. However, due to persistent hypokalemia, the patient was initiated on fludrocortisone (0.1 mcg daily). Subsequent follow-up demonstrated improvement in renal function and potassium levels, however, his aldosterone and renin levels remain undetectable. Hyperkalemia incidence post-adrenalectomy in primary aldosteronism (PA) ranges from 6.3% to 29.1%. Notably, older age and preexisting impaired renal function, particularly in cases with prolonged hypertension are identified as potential risk factors for postoperative hyperkalemia and renal failure. Understanding the potential for a further decline in the glomerular filtration rate (GFR) post-surgery becomes crucial. This decline might manifest as a transient or permanent issue, necessitating prolonged fludrocortisone treatment. This case highlights the importance of tailored preoperative assessment and postoperative management to mitigate complications in high-risk populations.

Presentation: 6/1/2024
7859 Primary Hyperaldosteronism And Mild Autonomous Cortisol Secretion (MACS) In Adrenal Incidentaloma
Authors: Chanturishvili Ketevan , Gvazava Qetevan , Zavrashvili Nino
Published: October 2024

Disclosure: K. Chanturishvili: None. Q. Gvazava: None. N. Zavrashvili: None.

An adrenal incidentaloma is a mass lesion greater than 1 cm in diameter, discovered by radiologic examination, performed for another reason. Widespread use of imaging studies in everyday clinical practice has led to the increased rates of adrenal incidentalomas. Two main questions arise after discovering adrenal mass: is it malignant or benign, and is the mass hormonally active?We present a case of a 55 years old male, with a history of obesity (BMI 35).He had no significant past medical history and was not taking any medications.He presented to our clinic with an upper respiratory tract infection and shortness of breath. Chest CT was done to evaluate for possible pneumonia, where 46 x 30 cm adrenal incidentaloma with -5 HU was discovered.He was referred to our department for endocrine evaluation.Initial assessment revealed previously unknown hypertension with left ventricular hypertrophy. Laboratory workup revealed high aldosterone, suppressed renin, low normal ACTH and DHEA-S, positive 1-mg overnight dexamethasone suppression test (DST- 2.66 ug/dL) and 8-mg DST (2.26 ug/dL).Additionally, the metabolic panel showed prediabetes and hyperlipidemia.Diagnosis of adrenal macroadenoma with cortisol and aldosterone co-secretion was made.Unilateral adrenalectomy was planned. Possible postoperative adrenal insufficiency has been established. Recommendation for proper glucocorticoid coverage was given.In conclusion, evaluation of the functional status of adrenal tumors is essential to uncover hidden medical issues, as s well as to properly guide the patient for intra and postoperative management, avoiding the risks of adrenal insufficiency with proper glucocorticoid coverage. Surgical management of hormonally active adrenal incidentalomas, especially larger >2.4 cm, has potential benefit of improving and preventing metabolic abnormalities: hyperglycemia, dyslipidemia as well as comorbidities such as obesity, hypertension and osteoporosis.

Presentation: 6/1/2024
6629 Pure Androgen Secreting Adrenal Adenoma In A Premenopausal Woman
Authors: Syed S , Patel S B
Published: October 2024

Disclosure: S. Syed: None.

Background: Pure androgen secreting adrenal adenomas are extremely rare; most of the reported cases occur in post-menopausal women, with significant virilization of acute onset and are usually malignant. Here we present a case of an androgen secreting adrenal adenoma found in a young female with regular menstrual cycles and hirsutism. Clinical Case: A 27-year-old female with no significant past medical history was referred to Endocrinology clinic for evaluation of elevated testosterone level noted on a routine OBGYN exam. Patient had miscarriage six months prior to initial endocrine clinic visit. She had a routine follow up visit with her gynecologist after miscarriage and noted to have mild male pattern hair growth on her chin, worse after stopping birth control pills two years ago. Patient had menarche at 14 years of age and had regular menstrual cycle until started birth control pills. The skin examination revealed coarse male pattern hair on chin. Scattered acne was present on back. No signs of hypercortisolism were present. Labs done at time of initial consultation showed unremarkable comprehensive metabolic panel, thyroid and gonadotropic hormones. Testosterone was elevated at 122ng/dl (0-75ng/dl). Pelvic ultrasound done in the year prior showed normal uterus and adnexal structures. Further work up showed elevated DHEAS 781 µg/dL (18-391 µg/dL) and normal 17 OH progesterone and androstenedione levels. MRI abdomen with and without contrast done at outside facility showed a 4 cm x 3.3 cm x 4.1 cm well-circumscribed round shaped, mildly heterogeneously enhancing mass arising from right adrenal gland, with restricting diffusion, no signal dropout in out-of-phase imaging. Normal ovaries were noted. Given the large size of lesion, adrenalectomy was recommended. Patient underwent laparoscopic right adrenalectomy. The histologic features on pathology specimen were consistent with an adrenal cortical adenoma. No evidence of malignancy was seen (based on modified Weiss criteria). 3 weeks post op labs showed Testosterone level reduced to 19 ng/dl (0-75ng/dl) and DHEAS 138 ug/dl (18-391 µg/dL). Patient is recovering from recent childbirth. Conclusion: In adults, pure androgen secreting adrenal tumors are extremely rare. Diagnosis of malignancy is made with histopathological examination and Weiss score calculation. Our patient has unique presentation of having mild hirsutism in setting of regular menstrual cycles with no other symptoms of virilization and is noted to have unexpectedly large adrenal adenoma. Given the size of adenoma, there was concern for adrenal cortical carcinoma, however histological examination was consistent with a benign lesion.

Presentation: 6/1/2024
8034 Putting the Pieces Together: Carney Complex, A Hyper-Rare Congenital Neoplastic Syndrome
Authors: Fontanazza Gia , Conforti Anthony R , Bird Kimberly , Caplan Michael
Published: October 2024

Disclosure: G. Fontanazza: None. A.R. Conforti: None. K. Bird: None. M. Caplan: None.

Intro: Carney complex (CNC) is an autosomal dominant disorder characterized by multisystem neoplasia that primarily affects the thyroid, pituitary, and adrenal glands. Its prevalence is not well established, as only 750 cases have been reported worldwide. This condition arises when an inactivating PRKAR1A gene mutation results in dysregulated cell proliferation and tumorigenesis. Complications include the potential for malignant transformation and systemic manifestations, necessitating comprehensive management and ongoing surveillance of disease progression. Case: The patient is a 58-year-old woman who initially presented as a teenager with complaints of hirsutism, truncal obesity, and violaceous abdominal striae. Initial workup revealed a low-dose dexamethasone suppression test that resulted in a non-suppressed cortisol levels. She also had undetectable adrenocorticotropic hormone (ACTH) levels. Imaging revealed no pituitary masses and demonstrated slight bilateral adrenal enlargement without adenomas. Despite these results, she was empirically treated for presumed pituitary-dependent Cushing's disease and received external beam radiation. Despite treatment, she continued to have episodes of hypercortisolism that were apparent clinically and biochemically. Over time, she developed a cardiac myxoma with six cerebrovascular accidents and multiple benign tumors. As an adult, she underwent extensive endocrine evaluation, which revealed urine cortisol excretion that paradoxically rose in response to dexamethasone. ACTH levels were always undetectable, even when she was significantly hypercortisolemic. Genetic testing revealed a homozygous mutation in the melanocortin-2 receptor (MC2R). Accordingly, she elected to have a bilateral adrenalectomy and was started on hydrocortisone and fludrocortisone. Discussion: The patient exhibited ACTH-independent micronodular adrenal hyperplasia and its most frequent variant, primary pigmented nodular adrenocortical disease. Bilateral pigmented nodular hyperplasia is a finding which can occur in association with CNC and cause episodic hypercortisolism. These patients have been shown to respond to dexamethasone with a paradoxical increase in glucocorticoid excretion. While management requires ongoing surveillance, this patient had not been diagnosed until later in life and did not have regular screening. When speculating on the late detection, her story reflects the parable of the blind men and the elephant: endocrinology managed Cushing's disease, cardiology managed atrial myxoma, and oncology managed osteochondromyxomas. Limited perspective with specialized management and an inability to see the whole picture led to prolonged diagnosis with unfortunate sequelae. This report encourages physicians to develop perspective awareness and to consider the entire picture when treating patients.

Presentation: 6/2/2024
8239 Recurrent Superior Laryngeal Nerve Glucocorticoid Injections: A Likely Cause Of Secondary Adrenal Insufficiency In An Otherwise Healthy Man
Authors: Lorin A , Pranger M C , Park J M , Clutter C A
Published: October 2024

Disclosure: A. Lorin: None. M.C. Pranger: None. J. Park: None. C.A. Clutter: None.

Background: Secondary adrenal insufficiency is well described in the literature with various offending agents implicated. Superior laryngeal nerve (SLN) glucocorticoid injections, however, have rarely been recorded as causal agents of secondary adrenal insufficiency. We present a case of a generally healthy man with secondary adrenal insufficiency after chronic administration ofsuperior laryngeal nerve glucocorticoid injections without other identifiable etiologies. Clinical Case: A 68-year-old man with no significant medical history presented to endocrinology clinic due to persistent nausea and severe fatigue. His initial labs were notable for morning cortisol of 1.66 mcg/dL (5-25) and an undetectable ACTH (<3.2 pg/mL, 10-60) suggestive of adrenal insufficiency. FSH/LH, testosterone, FT4, and IGF-1 were otherwise normal. On initial review of his medication history, the only glucocorticoid exposure appeared to be intranasal beclomethasone, with remote courses of oral prednisone. Further history revealed that the patient was receiving superior laryngeal nerve glucocorticoid injections for chronic cough every three weeks for over a year. The injection consisted of 1:1 mixture of 1 mL of triamcinolone acetonide 200 mg/5 mL and local anesthetic, which is equivalent to triamcinolone 40 mg or hydrocortisone 200 mg. Given the volume and chronicity of the glucocorticoid injections, the patient developed secondary adrenal insufficiency as above. Since the diagnosis, the patient discontinued SLN glucocorticoid injections and was placed on physiologic hydrocortisone replacement, with gradual recovery of his HPA axis. Conclusions: Sequelae of percutaneous glucocorticoid injection into the superior laryngeal nerve for treatment of chronic cough are not well documented in terms of their effects on the HPA axis. While an effective and increasingly common treatment for chronic cough, SLN glucocorticoid injection has the potential to cause suppression of the HPA axis and cause secondary adrenal insufficiency. Excess glucocorticoid appeared to solely inhibit ACTH production, as the other anterior pituitary hormones were not affected. Understanding consequences of glucocorticoid use in any formulation is important when considering such therapies, as these may alter normal HPA function with recurrent dosing. Recovery from a disrupted HPA axis may be achieved with the use of physiologic doses of hydrocortisone replacement in the case of secondary adrenal insufficiency.

Presentation: 6/3/2024
8092 Senecence Cell Accumulation In Cushing Syndrome
Authors: Alexandra Hanzu Felicia , Abbas Maha , Diaz-Catalan Daniela , Maria Santillan Cintia , Capo Julia , Casals Gregori , Macip Salvados
Published: October 2024

Disclosure: F.A. Hanzu: None. M. Abbas: None. D. Diaz-Catalan: None. C.M. Santillan: None. J. Capo: None. G. Casals: None. S. Macip: None.

Background: Senescence is a terminal differentiation state that can be induced in cells in response to different stresses, including exposure to glucocorticoids. Accumulation of senescent cells in tissues induce functional impairment of different organs and age-related pathologies, due to the secretion of factors that create a pro-inflammatory microenvironment and induce further senescence in neighbour cells.Aim: We hypothesize that persistence of senescent cells in glucocorticoid target tissues can mediate pathological changes long time after cure of Cushing syndrome (CS). Quantifying the presence of these cells could have prognostic value and allow the stratification of patients into groups that could receive senotherapies (drugs specific to reduce senescent cell accumulation) as adjuvant treatment. Methods: Fractionation and unbiased mass spectrometry screen to detect proteins related to senescence in glucocorticoid target tissues (muscle, brown and white adipose tissue, liver, adrenals, hypothalamus and pituitary) and plasma in 12 weeks old male C5BL/6J mice with active CS induced by chronic oral cortiscosterone administration (5 weeks) and mice with cured CS (10 weeks after treatment) as compared to CTR mice. Proteins have been extracted by digestion of the tissue samples and tryptic peptides measured by OPA assay prior to be injected on column to a Waters nanoacquity nanoUPLC coupled to a Waters Synapt G2Si. Data has been acquired using Ion mobility enabled data independent acquisition (HDMSE). Results: Raw data extraction and analysis using Progenesis QI for Proteomics identified a tissue-specific profile of proteins linked to senescence and/or ageing persistent after remission of CS in target mice tissue, which can be used for diagnostic and therapeutic purposes.

Presentation: 6/3/2024
7392 Unilateral Adrenal Embolization In Cushing Disease-A Lifesaving Emergent Procedure
Authors: Sadiq M , Irshad B , Haider A
Published: October 2024

Disclosure: M. Sadiq: None. B. Irshad: None. A. Haider: None.

Case presentation: A 59-year-old female was diagnosed with Cushing Disease (CD) thirteen years ago with symptomatic hypercortisolism. Hypokalemia and elevated 24-hour urine cortisol (392 ug/24 hr, n 0-50 ug/24 hr) were noted at the time of diagnosis. Following LDDST, morning cortisol was 30.5 ug/dl, and HDDST showed greater than 50% suppression. A pituitary macroadenoma with bilateral cavernous sinus extension was noted on MRI Sella. Due to cavernous sinus invasion, she was not considered a surgical candidate and underwent Gamma knife radiation. 24-hour urine cortisol decreased significantly (20 ug/24 hours). Two years follow-up MRI brain showed an empty Sella and AM cortisol was noted to be normal at 12.2 ug/ dl with no evidence of AI. She was lost to follow-up and reestablished almost ten years after her initial gamma knife and was symptomatic from hypercortisolism. 24-hour urine cortisol at 85.4 mcg/24 hr, abnormal salivary cortisol x 2 (0.24 and 0.20 mcg/dl n < 0.09 mcg/dl) confirming hypercortisolism. MRI of Sella showed recurrent adenoma with bilateral sellar masses. She was referred to Neurosurgery and was started on Ketoconazole and Paseriotide once-monthly injections. She developed new onset diastolic heart failure & upper GI bleeding, requiring hospitalization. High ACTH level of 668 pg/ml (n. 6.6- 65 pg/ ml). 8 am cortisol was 107.6 ug/dl which was suppressed to 16.1 after 8 mg overnight Decadron. Repeat Gamma knife was planned but due to her decline, it was decided to do unilateral adrenal artery embolization to reduce hypercortisolism. IR-guided adrenal artery embolization of the left middle & inferior adrenal arteries was performed. She required stress dosing of HC post-embolization which was tapered off while monitoring 8 am cortisol which started to rise & 24-hour cortisol levels were noted to be normal (51.2 mcg/24 H) on post-embolization day eight. Gamma knife radiation treatment was performed a month later after which she was noted to have GWS and required Hydrocortisone 15/10 mg twice daily, which she has been taking to date. 24-hour urine cortisol remains normal at 11.8 mcg/24 h. Discussion: Treatment for CD is primarily surgical. Radiotherapy is a second-line alternative in tumors that are non-amenable to surgery. Radiotherapy takes time to achieve its full effect. Cushing Disease patients with significant hypercortisolism and resultant complications require urgent treatment. Unilateral Adrenalectomy is described in literature to curb the cortisol burden . Similarly Unilateral Adrenal artery embolization offers less invasive approach to treat patients considered unfit for surgery. Conclusion: Unilateral adrenal artery embolization can be considered a bridging treatment in CD to reduce cortisol burden and improve the metabolic profile following which a more definitive treatment such as repeat surgery or radiotherapy can lead to long-term remission.

Presentation: 6/1/2024
12386 Unilateral Spontaneous Adrenal Hemorrhage In Pregnancy
Authors: Gondhi A , Campana M , Riofrio M , Fazendin J , Vodopivec D
Published: October 2024

Disclosure: A. Gondhi: None. M. Campana: None. M. Riofrio: None. J. Fazendin: None. D. Vodopivec: None.

Unilateral Spontaneous Adrenal Hemorrhage In Pregnancy Introduction: Spontaneous adrenal hemorrhage (SAH) in pregnancy is a rare and under recognized entity with an incidence of 0.14% - 1.1%, mostly unilateral. We present a case of unilateral SAH managed with adrenalectomy during pregnancy. Case presentation: A 24-year-old 14-weeks pregnant woman was referred for right flank pain and nausea due to right adrenal lesion. Medical history significant for 4 first trimester miscarriages and family history of Breast cancer and Uterine cancer in mother, Pancreatic cancer in multiple family members on paternal side. She was hemodynamically stable. Abdominal-US showed right adrenal lesion. Non-contrast MRI abdomen showed a large collection in the right adrenal gland measuring 9.6cm x 9cm. Ability to assess for underlying lesion challenging given the amount of blood products and lack of IV contrast. Laboratory analysis showed an appropriately suppressed cortisol with 1 mg overnight dexamethasone suppression test (cortisol 1.3 mcg/dl, N<1.8 mcg/d Dexamethasone level 332 ng/dl, N<180-550 ng/dl), normal DHEA-S (135 mcg/dl, N=18-391mcg/dl), non-suppressed ACTH (18 pg/ml, N 7.2-63 pg/ml), normal aldosterone (8.1 ng/dl, N=3-39.2 ng/dl) with a non-suppressed renin (17.8 pg/ml, N=4.2-52.2 pg/ml), normal fractionated plasma metanephrines (Free metanephrines <0.2 nMol/L, N<0.0.5nMol/L Free normetaphrines <0.2 nMol/L, N<0.9nMol/L), negative Antiphopholipid antibody testing (Beta 2 Glycoprotein I IgM <2 U/ml, N<20U/ml, Beta 2 Glycoprotein I IgG 2.2 U/ml, N<20U/ml). The patient underwent a laparoscopic converted to open right adrenalectomy. Pathology showed a 9.6cm adrenal gland with organizing hematoma, vascular congestion, and hemorrhage. It also showed periadrenal adipose tissue with atypia, MDM2 gene amplification by FISH negative – ruling out liposarcoma. Post-operatively, her symptoms resolved without complications to the pregnancy. Differentials for adrenal hemorrhage in this pregnant patient include: 1) underlying adrenal tumor (most commonly pheochromocytoma), 2) coagulopathy (e.g. antiphospholipid syndrome), and 3) pregnancy-related adrenal hemorrhage (rare, mostly unilateral due to increased vascular flow to the adrenal gland and the hypercoagulability). After evaluating the adrenal functionality, APLAS and assessing the malignant potential with imaging studies; conservative management is appropriate in stable patients. Our patient underwent surgery due to recurrent intractable pain, and uncertainty regarding malignant potential of the adrenal mass given history of multiple cancers in the family. Conclusion: Our case highlights that when indicated, adrenalectomy in the II trimester is a safe and effective option in pregnancy. Individualized treatment should be chosen for each patient following shared decision-making.

Presentation: 6/1/2024
6999 Utilizing Machine Learning for One-Step Diagnosis Of Adrenal Diseases: Integrating Clinical, Serum Steroid, And Body Composition Data
Authors: Park S , Noh J , Kim J , Kim T , Seo H , Choo J , Choi M , Kim J
Published: October 2024

Disclosure: S. Park: None. J. Noh: None. J. Kim: None. T. Kim: None. H. Seo: None. J. Choo: None. M. Choi: None. J. Kim: None.

Background: With the increasing incidence of adrenal incidentalomas, the precise diagnosis of subtypes, such as mild autonomous cortisol secretion (MACS), adrenal Cushing’s syndrome (ACS), primary aldosteronism (PA), pheochromocytoma and paraganglioma (PPGL), or nonfunctioning adrenal adenomas (NFA) is becoming more critical. However, the process of making accurate diagnoses remains intricate and challenging. This study aims to explore a streamlined, one-step method for diagnosing adrenal nodules, employing a machine learning (ML) model that integrates clinical data (CL), serum steroid profiles (SSP), and computed tomography-based body composition data (BC). Methods: We utilized ML models for subtyping adrenal diseases within a cohort of 641 patients (comprising MACS=141, ACS=64, PA=265, PPGL=78, and NFA=93), incorporating 37 CL, 64 SSP, and 15 BC features. Patients were randomly split into training and test cohorts at a 4:1 ratio, with each disease proportionally represented. The ML-based pipeline involved ML model selection, outlier detection, feature selection, and re-sampling algorithm. An ML model was developed to classify each of the five distinct adrenal diseases individually. In addition, separate ML models were also developed and optimized for individual comparisons between NFA and each of the other four diseases. The performance was evaluated using balanced accuracy, sensitivity, specificity, area under the curve (AUC), and F1 score. Results: The OneVsRest Classifier exhibited the best performance in the multi-class classification of the five adrenal diseases, achieving a balanced accuracy (0.78), sensitivity (0.77), specificity (0.93), and an AUC of 0.89. In this process, 10 CL features and 39 SSP features were utilized, whereas BC did not yield significant features. Using only SSP, the ML model achieved a balanced accuracy of 0.71 and an AUC of 0.89, whereas the ML model using only CL demonstrated a relatively lower accuracy of 0.58 and an AUC of 0.82. In models comparing MACS, ACS, PA, and PPGL with NFAs, the accuracies were 0.85, 0.94, 0.78, and 0.86, respectively, with AUCs of 0.96, 0.99, 0.90, and 0.94, respectively. The ML model differentiating between NFA and the other functioning adrenal diseases exhibited an accuracy of 0.75 and an AUC of 0.79 Conclusion: We have developed a highly sensitive and specific one-step ML model for differentiating adrenal diseases using CL, SSP, and BC. This approach is anticipated to facilitate precise diagnoses of adrenal nodules, thereby enhancing patient care and improving clinical outcomes.

Presentation: 6/2/2024