bluuebunny/crossref_metadata_2025_split huggingface dataset:
6702 Management And Complications Of Metastatic Adrenocortical Carcinoma Presenting With Severe Cushing Syndrome
Authors: Rodrigues Sonia , Singh Sumal Amit Kartar 
Published: October 2024

Abstract
Disclosure: S. Rodrigues: None. A.K. Sumal: None.
Background: Metastatic adrenocortical carcinoma (ACC) presenting with Cushing syndrome (CS) is a complicated, aggressive disease that commonly requires multiple adrenal steroidogenesis inhibitors and chemotherapy to achieve hormonal and tumor control. Clinical Case: A 66-year-old man with a history of prostate cancer and hypertension presented with right flank and back pain, worsening type 2 diabetes, profound proximal muscle weakness, and 3+ lower extremity edema to his thighs. CT and PET-CT revealed a 10.9 cm right adrenal mass with pericaval lymphadenopathy and metastatic disease at the L2 vertebral body. Laboratory testing demonstrated evidence of hypercortisolism with elevated 24-hour urinary cortisol excretion (449 mcg/24h; n&lt;45 mcg/24h), and abnormal 1 mg dexamethasone suppression test (cortisol 15 mcg/dL; n&lt; 1.8 mcg/dL) with suppressed ACTH (&lt;6 pg/mL; n=7-63 pg/mL). Surgical resection of the primary tumor was aborted intraoperatively given the discovery of new peritoneal metastases, which were confirmed by biopsy to be metastatic ACC. He was started on mitotane and osilodrostat to manage his severe CS. He was also started on dexamethasone, both to prevent adrenal insufficiency and to avoid influencing serum cortisol measurements used to assess disease control. However, given his significant peripheral edema and weakness, he was functionally unable to receive chemotherapy. Despite rapid uptitration of mitotane and osilodrostat over three weeks, his CS remained uncontrolled, and he was ultimately hospitalized for lower extremity paralysis and septic shock due to pyelonephritis. Repeat imaging revealed severe spinal canal stenosis from an L2 pathologic fracture, as well as worsening hepatic, osseous, peritoneal, and retroperitoneal metastases. After recovery from his septic shock, he was started on chemotherapy with carboplatin and etoposide while hospitalized, but his mitotane was intermittently held due to elevated transaminases. His hospital course was complicated by hypotension requiring pressor support, atrial fibrillation, hemoperitoneum, worsening anasarca, and acute kidney injury requiring continuous renal replacement therapy. Given his worsening condition that precluded him from further chemotherapy or palliative radiation, he elected to pursue comfort care measures and expired shortly thereafter. Conclusion: This case highlights the therapeutic challenges of metastatic ACC presenting with life-threatening CS. Simultaneous use of multiple adrenal steroidogenesis inhibitors is often required for control of hypercortisolism, and chemotherapy is equally necessary to manage tumor burden. However, as in this case, disease-related complications can limit treatment management and result in rapid deterioration. Thus, early diagnosis and prompt treatment of metastatic ACC presenting with CS is critical to prevent morbidity and mortality.
Presentation: 6/3/2024
7662 Mass Spectrometry Imaging Reveals Region-, Age-, And Sex-Specific Effects Of Lipopolysaccharide Administration On Glucocorticoids In Mouse Lymphoid Organs
Authors: Salehzadeh Melody , Khan Shazia , Andrew Ruth , Soma Kiran K 
Published: October 2024

Abstract
Disclosure: M. Salehzadeh: None. S. Khan: None. R. Andrew: None. K.K. Soma: None.
Glucocorticoids (GCs) are steroids that are critical for immune function. Immune organs, such as the thymus and spleen, locally produce GCs (i.e., immunosteroids). However, GC concentrations in the thymus and spleen at the cellular level, and how these levels are affected by stress, remain largely unknown. We used state-of-the-art mass spectrometry imaging (MSI) to elucidate the spatial distribution of GCs in the neonatal and adult mouse thymus and spleen 1) at baseline and 2) after an acute stressor. We used MSI to measure 11-deoxycorticosterone (DOC), corticosterone, and 11-dehydrocorticosterone (DHC) in different regions of the thymus (medulla/cortex) and spleen (white/red pulp) after an immunological challenge. We administered lipopolysaccharide (LPS; i.p.) at low (50μg/kg) and high (400μg/kg) doses or saline (vehicle) to male and female C57BL/6J mice at post-natal day (PND) 5 (neonatal) and 90 (adult) (n=6/sex/group/age). 4hr after treatment, we collected thymus and spleen on liquid nitrogen. Cryosections (10μm) were subject to MSI following Girard-T reagent derivatization and α-cyano-4-hydroxycinnamic acid matrix application. Matrix assisted laser desorption/ionisation (MALDI) was used for sampling, coupled to Fourier-transform ion cyclotron mass spectrometry (100μm resolution; positive mode; Bruker 12T SolariX). Adjacent sections were taken to determine histological zones by H&E staining. Preliminary results indicate that LPS increased DOC, corticosterone, and DHC levels by 2- to 9-fold in lymphoid organs at both ages. There was a dose-dependent increase in thymus and spleen GC levels at PND5, but not PND90. At PND5, GC levels were similarly distributed across each tissue in both sexes. In contrast, at PND90, thymic corticosterone levels were greater in males than females in the medulla and cortex. Interestingly, in PND90 thymus, the medulla had greater DHC levels than the cortex only after LPS treatments. In PND90 spleen, GC levels significantly increased after LPS, yet there was no significant difference in GC distribution between sexes or red and white pulp. These results suggest that GC production is uniform across neonatal lymphoid organs. However, in adulthood, the thymus exhibits region-specific GC metabolism. Our results expand knowledge of steroid intracrinology in thymus and spleen and potential effects of environmental stressors (e.g., infectious diseases, toxins) on immune GC responses. Further, our novel MSI method for GC detection in murine lymphoid organs can help inform future techniques in pharmacokinetics for localized thymic and splenic targeting of steroids and steroid modulators.
Presentation: 6/3/2024
5141 Metastatic Adrenocortical Carcinoma
Authors: Anwaar Nida 
Published: October 2024

Abstract
Disclosure: N. Anwaar: None.
Adrenocortical carcinomas are rare and frequently aggressive tumors that may be functional (hormone secreting) and cause Cushing's syndrome and/or virilization or nonfunctional and present as an abdominal mass or as an incidental finding. We report a case of a 72-year-old lady who was presented to the ER with chest pain and elevated blood pressure. CTA was performed to evaluate for aortic dissection, which incidentally found a 5.0 x 3.7 cm right-sided adrenal mass. 1 mg overnight dexamethasone suppression study showed non-suppression of cortisol. The ACTH was suppressed, consistent with the autonomous production of cortisol from the adrenal gland. CT abdomen with adrenal protocol showed an indeterminate suspicious 5.1 x 3.9 cm right-sided adrenal mass. She underwent an adrenalectomy and the final pathology showed adrenocortical carcinoma. Postoperatively she was treated with adjuvant radiotherapy and chemotherapy. A few years later, she developed metastatic lesions and overt Cushing syndrome. She was started on pembrolizumab, which was later discontinued due to poor response and then placed on mitotane. The metastatic disease progressed, and the patient was transitioned to hospice care. Due to tumor’s rarity, the understanding and experience of management modalities are limited. New treatment options may be available in the coming years.
Presentation: 6/1/2024
8191 Navigating The Maze Of Adrenal Insufficiency, A Complex Case Of Late Presentation
Authors: Pereira K N , Sundaram V , Mehta V , Desai K , Agrawal B 
Published: October 2024

Abstract
Disclosure: K.N. Pereira: None. V. Sundaram: None. V. Mehta: None. K. Desai: None. B. Agrawal: None.
Adrenal insufficiency, a rare but potentially life-threatening endocrine disorder, arises from the inadequate production or ineffective response to adrenal hormones, particularly cortisol and aldosterone. It poses diagnostic challenges, especially in individuals with intricate medical histories and manifests as either primary (Addison's disease) or secondary. The subtlety of initial symptoms often leads to a delayed diagnosis, emphasizing the importance of a high index of suspicion among healthcare providers. Timely recognition and intervention are crucial to prevent adrenal crises, which includes severe hypotension, electrolyte imbalances and life-threatening complications. This case report delves into the presentation, diagnosis, and management of primary adrenal insufficiency in a 51-year-old female with a myriad of co-morbidities who presented with persistent low blood pressure, syncope episodes and dizziness both at rest and with exertion, despite being on midodrine with systolic blood pressure readings ranging from 60s to 80s mmHg. She was also noted to be bradycardic and laboratory results showed hyponatremia, hyperkalemia, hypoglycemia and anemia. She was given prompt fluid resuscitation, stress dose steroids and fludrocortisone, leading to a remarkable improvement in blood pressure and overall clinical status. Subsequent testing showed low serum cortisol level and elevated ACTH level, confirming the diagnosis of primary adrenal insufficiency. Continued steroids resulted in significant symptomatic improvement and with no further episodes of hypotension or syncope on ensuing follow ups. This case serves as a poignant illustration for the need for a heightened clinical suspicion, as the symptoms of adrenal insufficiency can often masquerade within the intricate tapestry of comorbidities. When the utilization of midodrine, aimed at managing orthostatic hypotension, did not abate symptoms, it prompted a thorough investigation into the possibility of underlying adrenal dysfunction. This case also highlights the collaborative, multidisciplinary approach in the management of adrenal insufficiency, with endocrinology playing a pivotal role.
Presentation: 6/1/2024
8543 Non-Specific Uptake Of Magnetic Iron Oxide Nanoparticles Into Adrenocortical Carcinoma Cells, Endothelium And Primary Monocytes
Authors: Surya Challapalli Ritihaas , Sorushanova Anna , Hong Cong , John Mullen Nathan , Feely Sarah , Covarrubias-Zambrano Obdulia , Covarrubias Jose , Varghese Sunitha , Hantel Constanza , Owens Peter , O’Halloran Martin , Prakash Punit , Bossmann Stefan H , Conall Dennedy Michael 
Published: October 2024

Abstract
Disclosure: R. Challapalli: None. A. Sorushanova: None. C. Hong: None. N.J. Mullen: None. S. Feely: None. O. Covarrubias-Zambrano: None. J. Covarrubias: None. S. Varghese: None. C. Hantel: None. P. Owens: None. M. O’Halloran: None. P. Prakash: None. S.H. Bossmann: None. M.C. Dennedy: None.
Adrenocortical carcinoma (ACC), a rare malignancy with a poor prognosis and a survival rate of up to 24 months, requires varied treatments such as surgery, chemotherapy, or radiation. The high recurrence rate emphasizes the need for innovative therapies. Magnetic iron oxide nanoparticles have emerged as promising candidates for cancer treatment due to their versatility in size and shape and the ability to modify their surface for targeted cellular uptake. In our initial investigation, we assessed the uptake of magnetic iron oxide nanoparticles (IONP) by ACC (H295R, HAC15, and MUC1) cells, HUVECs and primary monocytes, incubated with 0, 5, 10, 20, and 50 µg/ml of IONP for 24 hours. The results demonstrated concentration and time-dependent nanoparticle uptake and its impact on cellular viability. The optimal concentration of IONP was identified as 10 µg/ml, subsequently used to evaluate the rate of uptake and intracellular location. The efficiency of IONP uptake by ACC cells decreased when exposed to primary monocytes and an HUVEC layer, as demonstrated through a Transwell migration system. This study revealed insights into the non-specific uptake of IONP by ACC, primarily attributed to the mechanism of macropinocytosis. These preliminary findings lay the groundwork for exploring potential modifications to enhance specific uptake by ACC cells, particularly for applications like magnet-induced thermal ablation or nanobiocontrast.
Presentation: 6/2/2024
6919 Overstimulation Overload- Evidence Of Overuse Of The Cosyntropin Stimulation Test In The Hospital Setting
Authors: Goldberg R , Thelmo F , Ahmed I 
Published: October 2024

Abstract
Disclosure: R. Goldberg: None. F. Thelmo: None. I. Ahmed: None.
Introduction The cosyntropin stimulation test (CST), which utilizes a synthetic adrenocorticotropic hormone (ACTH) analog to stimulate the adrenal glands to release cortisol, is a test used to help define the presence or absence of adrenal insufficiency (AI). In primary and secondary AI, cortisol is inappropriately low (&lt;18 mcg/dL) when measured 30 minutes and 60 minutes after administration of cosyntropin. The aim of this study was to assess utilization of CST in Jefferson hospital enterprise and initiation of steroid therapy based on results. Methods A retrospective analysis, using the Slicer Dicer feature of Epic electronic records (Verona, USA) was performed on all adult hospitalized patients from 5/5/2023 and 9/5/2023. Results 149 CST were performed in the above-mentioned period, 61 patients (41%) were male, and 88 patients (59%) were female. Two were excluded from the study as one test was performed incorrectly, and one study had insufficient sample to produce a result. Of the 147 patients, 47 patients (32.0%) were positive for AI. Five of 20 patients (25%) in the ICU were positive for AI. 42 of the 127 patients (33.1%) on the floor were positive for AI. Of the 47 patients diagnosed with AI, 37 were placed on steroid treatment and ten patients were not started on steroids; despite inadequate stimulation, the patient’s clinical picture was not thought to represent AI. Discussion Our analysis points to a relative overutilization of CST in Jefferson hospitals. This may be due to the relative ease of CST in the hospital setting, and clinicians should be overly cautious about ruling out AI despite the presence of more likely explanations for the clinical scenario. Notably, although several patients in the study met criteria for AI, endocrinology chose not to treat them with steroids, which raises the topic of defining AI in the critically ill patient. The validity of CST and normal cortisol cut-offs in the critically ill remain a topic of intense debate. The results of this study should prompt clinicians to think critically before ordering a CST. Despite strict cutoffs for diagnosis of AI, careful consideration of the clinical scenario should be taken into account before initiating patients on steroid therapy. If the diagnosis of AI is confirmed, patients should be followed closely as an outpatient to ensure proper adjustments to medication regimens are made.
Presentation: 6/2/2024
7705 Paliperidone Induced Central Adrenal Insufficiency: A Case Report
Authors: Shevtsova Inga , Gerstner Steven J 
Published: October 2024

Abstract
Disclosure: I. Shevtsova: None.
Introduction: Atypical antipsychotics reduce ACTH and control secretion in healthy subjects. However, the clinical significance of it is still unclear with only a few case reports tying antipsychotics to clinically relevant adrenal insufficiency. Case: A 32-year-old male with schizoaffective and polysubstance abuse disorders was admitted to a hospital with a complex right hand infection complicated by MRSA bacteremia, and native mitral and tricuspid valves infective endocarditis. To control the source of infection, the patient underwent multiple surgical interventions and the bacterial endocarditis required a prolonged course of IV antibiotics. The patient’s mental health negatively affected his hospital course. He was diagnosed with a schizoaffective disorder several years ago, and his mental disease has been difficult to control. There were multiple ED visits and hospitalizations for mental health issues due to significant positive and negative symptoms, substance abuse and medication noncompliance. For the last several months, the patient had not taken his medication (paliperidone). Initially, the patient displayed impulsive, aggressive, and irrational behavior caused by substance withdrawal and uncontrolled mental health illness. Paliperidone was restarted with great clinical response within 5-6 days. On week 2, the patient developed prominent symptomatic hypotension, extreme fatigue, and sleepiness. The repeat blood count was within normal limits, and chemistry showed normal electrolyte levels. Transesophageal echocardiography showed resolution of vegetation, normal ventricles and valves functions. Morning cortisol level was low, 1.58 ug/dl (3.2-22.4 ug/dl) with significant increase to 23.07 ug/dl after cosyntropin stimulation. ACTT level was inappropriately borderline low, 7.8pg/ml (7.2-63 pg/ml) and 21 hydroxylase antibodies were negative. Considering all the findings, a confident clinical diagnosis of central adrenal insufficiency was made. MRI of pituitary gland did not reveal any pathology. Drug induced central adrenal inefficiency became a primary working diagnosis. Paliperidone was discontinued. After 2 days, there was improvement in vital signs and other symptoms of adrenal insufficiency. This established a potential association between adrenal insufficiency and paliperidone. Unfortunately, the patient became restless and agitated again after withholding paliperidone for 5 days, so it was resumed. Adrenal insufficiency was treated with hormonal replacement therapy. Conclusion: This is the first case demonstrating possible paliperidone induced central adrenal insufficiency. It is important to note that even relative adrenal insufficiency caused by atypical antipsychotic might be life-threatening in a high stress state, such as sepsis. This needs to be recognized in a timely manner and managed appropriately.
Presentation: 6/2/2024
6574 Pheochromocytoma In A Patient With ESRD; Clinical Challenges And Lessons From A Successful Evaluation
Authors: Anthony Younes Sam , Sayed Alaa , Selk Karen , Willard Lauren A 
Published: October 2024

Abstract
Disclosure: S. Younes: None. A. Sayed: None. K. Selk: None. L.A. Willard: None.
Introduction: Pheochromocytomas are rare tumors that arise from the chromaffin cells in the adrenal medulla, that secrete norepinephrine, epinephrine and dopamine. Common presentations include resistant hypertension (HTN) and adrenergic spells with headaches, sweating and tachycardia. The literature has few cases of pheochromocytoma in the setting of end stage renal disease (ESRD). Case: A 46-year-old male with a history of resistant HTN on amlodipine, lisinopril, and labetalol, complicated by ESRD on hemodialysis (HD) and secondary hyperparathyroidism initially presented with gross hematuria. The patient reported sporadic, intermittent headaches associated with palpitations and sweating. A renal ultrasound revealed a left-sided complex renal cystic mass. CT abdomen/pelvis demonstrated an enhancing left adrenal lesion and MRI abdomen/pelvis confirmed an enhancing 4.6 x 2.8 cm adrenal mass. Laboratory studies revealed elevated normetanephrine of 1186 pg/mL (ref &lt;149 pg/mL), elevated metanephrine at 139 pg/mL (ref &lt;57 pg/mL) and elevated epinephrine at 128 pg/mL (ref &lt;95 pg/mL). Given the laboratory and imaging findings in conjunction with clinical presentation, an excision of the adrenal mass was set. Two weeks prior to the surgery, alpha blockade was started with doxazosin 1mg daily with a goal blood pressure &lt;130/80. He was admitted to the hospital with a goal to keep him 1-1.5kg above his dry weight. His dry weight was 81.5kg close to admission weight, so he was started on gentle IV hydration. He had a left robotic assisted adrenalectomy and was given stress dose steroids and a steroid taper given no preoperative Cushing’s screen was completed. No postoperative complications reported, and doxazosin was discontinued. 2 weeks later, he reported his adrenergic spells had resolved. Surgical pathology confirmed pheochromocytoma and he was referred for genetic consultation. Conclusion: Although there is little in the literature regarding management of a pheochromocytoma in patients with ESRD, similar principles of management in patients with normal renal function apply, including blood pressure control, alpha blockade, and establishment of euvolemia with recommendation of a high-sodium diet and 1-2 liters of saline the day prior to the procedure. This case highlights successful perioperative management with traditional use of alpha blockade but also incorporated maintaining the patient 1-1.5 kg above their dry weight for surgery to limit postoperative hypotension.
Presentation: 6/3/2024
7305 Pheochromocytoma Presenting With Resistant Hyperglycemia
Authors: Economou Magdalene , Devine Alma 
Published: October 2024

Abstract
Disclosure: M. Economou: None. A. Devine: None.
Background: Pheochromocytoma is a rare catecholamine producing tumor arising from the adrenal gland. Impaired glucose tolerance is a well-recognized hormonal and metabolic manifestation of pheochromocytoma caused by catecholamine excess [1]. Insulin resistance requiring very high doses of insulin in association with pheochromocytoma is, however, rare. Here we report a case of pheochromocytoma in a woman with diabetes mellitus that proved difficult to control despite high-dose insulin therapy. Case presentation: A 72-year-old woman with a longstanding history of type 2 diabetes mellitus, uncontrolled hypertension, hyperlipidemia and CVA presented to the hospital after she was found to have a hemoglobin of 7.0 ng/mL on routine labs. Notably, over the past 4 years, her insulin requirement gradually increased from 20 units/day to 50 units/day despite an A1c level of 6.1%. On presentation, our patient was hypertensive to 170/90 with limited response to multiple antihypertensive medications. Additionally, her glucose was severely uncontrolled, fluctuating between 200-500 mg/dL. Within days, the patient’s total daily insulin requirement increased tremendously to as much as 300 units/day. As part of her anemia workup, she underwent a contrast-enhanced CT abdomen & pelvis which identified a left adrenal mass measuring 2.2 x 2.8 x 2.9 cm. Further evaluation with MRI confirmed an adrenal mass suspicious for pheochromocytoma. Evaluation of plasma hormone levels revealed an elevated normetanephrine level of 7.10 nmol/L (normal: less than 0.89 nmol/L). Furthermore, the 24-h urinary normetanephrine level and chromogranin A levels were elevated to 145 mcg/day and 1203 ng/mL, respectively. Initial treatment with alpha and beta blockade improved blood pressure but glucose levels remained persistently elevated. The patient underwent left laparoscopic adrenalectomy and pathology revealed pheochromocytoma, measuring, 3.2 cm in diameter, with stains positive for CD56, synaptophysin and chromogranin. Surgical resection margins were negative for tumor. Postoperatively, insulin requirements returned to roughly that of her baseline, 40 units/day. Conclusion: Impaired glucose tolerance is a known phenomenon associated with pheochromocytoma. Despite this, it is unusual to see an insulin requirement rise as abruptly and drastically as seen in this case. Our patient, with relatively controlled diabetes had an enormous increase in her insulin requirement during her hospital course as evidenced by her insulin regimen which increased sixfold. This case highlights the importance of maintaining a high degree of suspicion for pheochromocytoma in patients with a sudden rise in insulin requirement and uncontrolled hypertension. Reference: (1) Ronen JA, Gavin M, Ruppert MD, Peiris AN. Glycemic Disturbances in Pheochromocytoma and Paraganglioma. Cureus. 2019 Apr 27;11(4): e4551.
Presentation: 6/3/2024